The DOI matches its Crossref record; 455 of the 460 references it cites were found in a registry or an index, and 1 are not checked yet; 43 of the 549 sources its claims cite were checked for support.
Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health
Open accessAbstract
Abstract Recent insights into the bioactivation and signaling actions of inorganic, dietary nitrate and nitrite now suggest a critical role for the microbiome in the development of cardiac and pulmonary vascular diseases. Once thought to be the inert, end‐products of endothelial‐derived nitric oxide (NO) heme‐oxidation, nitrate and nitrite are now considered major sources of exogenous NO that exhibit enhanced vasoactive signaling activity under conditions of hypoxia and stress. The bioavailability of nitrate and nitrite depend on the enzymatic reduction of nitrate to nitrite by a unique set of bacterial nitrate reductase enzymes possessed by specific bacterial populations in the mammalian mouth and gut. The pathogenesis of pulmonary hypertension (PH), obesity, hypertension and CVD are linked to defects in NO signaling, suggesting a role for commensal oral bacteria to shape the development of PH through the formation of nitrite, NO and other bioactive nitrogen oxides. Oral supplementation with inorganic nitrate or nitrate‐containing foods exert pleiotropic, beneficial vascular effects in the setting of inflammation, endothelial dysfunction, ischemia‐reperfusion injury and in pre‐clinical models of PH, while traditional high‐nitrate dietary patterns are associated with beneficial outcomes in hypertension, obesity and CVD. These observations highlight the potential of the microbiome in the development of novel nitrate‐ and nitrite‐based therapeutics for PH, CVD and their risk factors. Graphical abstract Figure. No caption available. HighlightsThe microbiome may influence pulmonary hypertension via nitrogen oxide signaling.Oral microbiota are necessary for nitrate reduction to vasoactive nitrogen oxides.Dietary nitrate and nitrite are major sources of exogenous nitrogen oxides.Dietary nitrate in vegetables exerts pleiotropic, beneficial nitrogen oxide effects.Diet and probiotic therapy can alter beneficial nitrate and fatty acid metabolism.
Verified 2026-10-09 · 1 reference not checked yet
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TL;DR
This review argues that dietary nitrate and nitrite are bioactivated by oral and gut microbial nitrate reductases to nitrite, nitric oxide, and other bioactive nitrogen oxides that support cardiac and pulmonary vascular health. It synthesizes preclinical and clinical evidence linking this enterosalivary pathway to blood pressure, endothelial function, exercise capacity, and pulmonary hypertension, while noting that no studies directly link the microbiome, nitrate bioavailability, and PH.
Key findings
- In the enterosalivary nitrate circulation, approximately 25% of circulating nitrate is sequestered into salivary glands and concentrated in saliva up to 20 times plasma levels; oral bacteria reduce nitrate to nitrite. Chlorhexidine mouthwash decreased oral nitrite by 90% (p<0.001), plasma nitrite by 25% (p=0.001), and increased blood pressure by 2–3.5 mmHg in proportion to decreased plasma nitrite (R2=0.56, p=0.002) in humans.
- At least 19 studies in hypertensive, overweight, and other patient populations showed blood pressure reduction with nitrate supplementation; nitrate/nitrite prevented or reversed endothelial dysfunction in mice and in healthy, hypertensive, obese, hypercholesterolemic, and peripheral arterial disease individuals. In HFpEF, a single dose of beetroot juice (12.9 mmol nitrate) increased cardiopulmonary exercise testing performance by 14% in 17 patients, and 1 week of daily beetroot juice (6.1 mmol nitrate) improved submaximal aerobic endurance by 24%.
- No human clinical studies have tested oral nitrate or nitrite in PH, but animal data show nitrite is a selective pulmonary vasodilator, inhibits hypoxia- and monocrotaline-induced PH in rats, and dietary nitrate prevented pulmonary vascular remodeling and right ventricular hypertrophy in wild-type and endothelial NOS-deficient mice.
- The oral cavity contains an estimated 50–100 billion bacteria and nearly 700 identified species; high nitrate reducers include Firmicutes (Staphylococcus, Streptococcus, Veillonella) and Actinobacteria (Actinomyces). Periodontal disease, xerostomia, and gut Firmicutes:Bacteroidetes shifts are associated with inflammation and altered NO signaling, but no studies directly link oral/gut microbial community features, nitrate bioavailability, and PH development.
Methods
- Narrative review, not a systematic review, synthesizing preclinical and clinical literature on the nitrate-nitrite-NO pathway, oral and gut microbiome, pulmonary hypertension, cardiovascular disease, diet, probiotics, and antimicrobials.
- Discusses bacterial nitrate reductase pathways (respiratory denitrification via nar/nap, dissimilatory nitrate reduction to ammonia, assimilatory nitrate reduction), nitrate transport (NarK/NarU), and regulation by oxygen, nitrate, pH, and oral/gut oxygen gradients.
- Reviews dietary nitrate sources and intakes: DASH-related nitrate blood pressure effects began at about 160 mg/day vegetable nitrate; DASH-compliant diets estimated 174–1222 mg/day; average U.S. intake 40–100 mg/day, Europe 30–180 mg/day, and traditional Japanese diet >1100 mg/day for a 60 kg person.
Limitations
- Stated: there have been no human clinical studies testing oral nitrate or nitrite in PH; no studies directly link oral/gut microbial community features, nitrate bioavailability, and PH development; mechanisms of microbial nitrate reduction and contributions to enterosalivary nitrite/NO remain uncertain; identification of major nitrate-reducing bacteria varies with methodological factors.
- Stated: safety of brief and chronic supplemental nitrate/nitrite in PH and dysfunctional NO signaling must be ascertained; carcinogenic potential of nitrite is contextual, depending on interactions with amines/amides versus plant polyphenols and ascorbate.
- Evident from the text: the review is narrative and largely synthesizes animal/preclinical and associative human data; proposed prebiotic, probiotic, and targeted antimicrobial strategies for PH are speculative and not directly tested in PH.
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Claims the paper makes
170 Not checked yet · 35 Own interpretation · 18 No basis given · 10 Partly supported · 3 Supported so far · 1 Supported · 1 Mixed support · accuracy not yet measured
Some cited sources support this claim and some don’t — read each source’s verdict below.
In the paper
“while nitrate supplementation prevents or limits ischemia-reperfusion injury and endothelial dysfunction in both animal[98,120–124] and human[97,125] models of ischemia-reperfusion.”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Microbial Nitrate Reduction to Nitrite and NO is Physiologically Important > Blood Pressure & Endothelial Health
What the sources say
- Partly supportedcites [98] Hendgen-Cotta, 2012, Dietary nitrate supplementation improves revascularization in chronic ischemia, Circulation sourceExperimental — accuracy not yet measured
The Results section on chronic hind-limb ischemia reports improved perfusion in nitrate-treated mice, and the Discussion reports reduced myoblast apoptosis. But this was a mouse model of chronic ischemia, not an ischemia-reperfusion experiment; the paper does not demonstrate prevention of endothelial dysfunction or report such effects in humans. (LLM, conf=0.86)
- Partly supportedcites [120] Webb, 2004, Reduction of nitrite to nitric oxide during ischemia protects against myocardial ischemia-reperfusion damage, Proc. Natl. Acad. Sci. sourceExperimental — accuracy not yet measured
The paper’s opening summary and Discussion (page numbers unavailable) report that nitrite infusion reduced infarct size and improved cardiac function after ischemia–reperfusion in isolated rat hearts. The administered substance was nitrite, not nitrate. The paper also tested NO production in human heart tissue, but did not show that supplementation prevented injury or endothelial dysfunction in humans; it did not establish an endothelial-dysfunction benefit in the rat model either. (LLM, conf=0.90)
- Disputedcites [121] Duranski, 2005, Cytoprotective effects of nitrite during in vivo ischemia-reperfusion of the heart and liver, J. Clin. Investig. sourceExperimental — accuracy not yet measured
The paper’s Discussion identifies nitrite—not nitrate—as the treatment that protected mice from liver and cardiac ischemia-reperfusion injury. In the myocardial results, nitrate was the control against which nitrite significantly reduced infarct size. The paper does not report protection from endothelial dysfunction or test ischemia-reperfusion injury in humans. (LLM, conf=0.86)
Checked by a reasoning model — may be wrong.
- Partly supportedcites [122] Shiva, 2007, Nitrite augments tolerance to ischemia/reperfusion injury via the modulation of mitochondrial electron transfer, J. Exp. Med. sourceExperimental — accuracy not yet measured
The Results section, “Oral nitrite administration confers resistance to hepatic and cardiac I/R injury,” reports reduced injury in mice given oral sodium nitrite. This supports the animal ischemia-reperfusion injury portion, but the administered compound was nitrite, not nitrate; the paper does not establish prevention of endothelial dysfunction or report a human model. (LLM, conf=0.87)
- Partly supportedcites [123] Kumar, 2008, Chronic sodium nitrite therapy augments ischemia-induced angiogenesis and arteriogenesis, Proc. Natl. Acad. Sci. USA sourceExperimental — accuracy not yet measured
The Abstract reports that sodium nitrite protects against acute ischemia–reperfusion injury in the heart and liver, supporting the injury portion of the animal-model claim. This paper studies nitrite, not nitrate supplementation, and its Results concern blood flow and angiogenesis in ischemic mice rather than prevention of endothelial dysfunction. The human-model claim is attached to separate citations in the citing sentence. (LLM, conf=0.86)
- Partly supportedcites [124] Ashmore, 2014, Dietary nitrate increases arginine availability and protects mitochondrial complex I and energetics in the hypoxic rat heart, J. Physiol. sourceExperimental — accuracy not yet measured
The Results and Discussion report that dietary nitrate protected cardiac energetics and reduced oxidative stress in rats exposed to sustained hypoxia. That supports a protective effect in an animal heart model, but the study did not test ischemia-reperfusion injury or measure endothelial dysfunction. Its Introduction discusses ischemia-reperfusion protection by nitrite, rather than demonstrating that effect for nitrate supplementation. (LLM, conf=0.86)
- Supportedcites [97] Webb, 2008, Acute blood pressure lowering, vasoprotective, and antiplatelet properties of dietary nitrate via bioconversion to nitrite, Hypertension source
The Methods (FMD study) describe a human forearm ischemia-reperfusion model in healthy volunteers given beetroot juice. The Results (Dietary nitrate protects against endothelial dysfunction) report that beetroot juice prevented the ischemia-induced loss of endothelial function. This supports the human-model portion to which this citation is attached. (LLM, conf=0.90)
- Partly supportedcites [125] Ingram, 2013, Low-dose sodium nitrite attenuates myocardial ischemia and vascular ischemia-reperfusion injury in human models, J. Am. Coll. Cardiol. sourceExperimental — accuracy not yet measured
The Abstract and Conclusions report that sodium nitrite protected against vascular ischemia-reperfusion injury and endothelial dysfunction in human subjects, but only when administered before ischemia. The study used sodium nitrite infusion, not nitrate supplementation; the animal-model portion of the citing sentence is attached to other citations. Page numbers are not provided for these passages in our copy. (LLM, conf=0.89)
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Despite the diversity of patients who develop PH, many share a common link to the metabolic syndrome[4,12–14].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Dysfunctional Nitric Oxide Signaling underlies Pulmonary Hypertension Pathogenesis > Pulmonary Hypertension
What the sources say
- Could not verifycites [4] Lai, 2014, Pulmonary arterial hypertension: the clinical syndrome, Circ. Res. sourceExperimental — accuracy not yet measured
The Abstract lists several conditions associated with PAH but does not identify metabolic syndrome as a common link among patients with PH. A search for metabolic syndrome and related terms found discussion of cellular glycolytic metabolism in “Tests to evaluate prognosis,” which does not establish the claimed patient-level association. No page numbers were provided for these passages. (LLM, conf=0.75)
- Supportedcites [12] Robbins, 2009, Association of the metabolic syndrome with pulmonary venous hypertension, Chest source
The Abstract reports that 94.1% of patients with pulmonary venous hypertension and 34.3% of those with pulmonary arterial hypertension had at least two features of metabolic syndrome. This supports the claim that many patients with pulmonary hypertension share a link to metabolic syndrome, although the figures concern patients in this referral cohort and metabolic-syndrome features rather than a diagnosis of the syndrome in every patient. (LLM, conf=0.87)
- Not checked yetcites [13] Thenappan, 2011, Clinical characteristics of pulmonary hypertension in patients with heart failure and preserved ejection fraction, Circ. Heart Fail. source
- Not checked yetcites [14] Pugh, 2011, Unrecognized glucose intolerance is common in pulmonary arterial hypertension, J. Heart Lung Transplant.
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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- Could not verify
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“Nitrite metabolism can be activated by hypoxia, low pH and reactions with metalloproteins[50–58].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > The nitrate-nitrite-NO Pathway & Enterosalivary Circulation of Nitrate as ‘Alternate’ Source of NO Signaling
What the sources say
- Not checked yetcites [50] Ignarro, 1981, Mechanism of vascular smooth muscle relaxation by organic nitrates, nitrites, nitroprusside and nitric oxide: evidence for the involvement of S-nitrosothiols as active intermediates, J. Pharmacol. Exp. Ther. source
- Not checked yetcites [51] Cosby, 2003, Nitrite reduction to nitric oxide by deoxyhemoglobin vasodilates the human circulation, Nat. Med. source
- Not checked yetcites [52] Gladwin, 2005, The emerging biology of the nitrite anion, Nat. Chem. Biol. source
- Supportedcites [53] Huang, 2005, Enzymatic function of hemoglobin as a nitrite reductase that produces NO under allosteric control, J. Clin. Investig. source
The Reaction 1 section links nitrite reduction by hemoglobin to deoxygenation and protons. The Figure 2 section reports that decreasing pH increased nitrite reduction and NO generation, while Physiological implications for hypoxic vasodilation describes nitrite reduction by hemoglobin, myoglobin, and other heme proteins at low oxygen tension. Page numbers were not supplied in our copy. (LLM, conf=0.91)
- Not checked yetcites [54] Dalsgaard, 2007, Nitrite-dependent vasodilation is facilitated by hypoxia and is independent of known NO-generating nitrite reductase activities, Am. J. Physiol. Heart Circ. Physiol. source
- Not checked yetcites [55] Dejam, 2007, Nitrite infusion in humans and nonhuman primates: endocrine effects, pharmacokinetics, and tolerance formation, Circulation source
- Supportedcites [56] Gladwin, 2008, The functional nitrite reductase activity of the heme-globins, Blood source
In “Role of myoglobin and the heme-globin family as functional nitrite reductases” (page unavailable), the paper says falling oxygen levels enable nitrite reduction by deoxyhemoglobin and deoxymyoglobin, and that a drop in tissue pH accelerates the myoglobin reaction. Hemoglobin and myoglobin are heme-containing metalloproteins, so the passage supports all three parts of the claim. (LLM, conf=0.93)
- Supportedcites [57] Bueno, 2013, Nitrite signaling in pulmonary hypertension: mechanisms of bioactivation, signaling, and therapeutics, Antioxid. Redox Signal. source
The “Mechanisms of Nitrite Bioactivation” section describes nitrite conversion to NO at low pH and reactions involving metal-containing proteins. The “Endothelial Cells” section states that nitrite reduction is enhanced during hypoxia. (LLM, conf=0.93)
- Supportedcites [58] Kim-Shapiro, 2014, Mechanisms of nitrite bioactivation, Nitric Oxide source
The Abstract identifies protein-mediated nitrite reduction as a major bioactivation pathway and says these conversions occur preferentially under hypoxic and acidic conditions. The History section on heme proteins further explains the dependence on low oxygen saturation and pH in hemoglobin-mediated nitrite reduction. (LLM, conf=0.94)
plaindirect- Asserted: passes — The authors put it forward as true.
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The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“although more recent evidence in both infants and adults suggests that exceptionally high concentrations of nitrite (and well beyond the <75mg nitrite necessary to achieve blood pressure effects) would be necessary to pose a significant threat to safety[25,51,72,113,155–158].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Safety of Inorganic Nitrate and Nitrite
What the sources say
- Not checked yetcites [25] Lundberg, 2008, The nitrate-nitrite-nitric oxide pathway in physiology and therapeutics, Nat. Rev. Drug Discov. source
- Not checked yetcites [51] Cosby, 2003, Nitrite reduction to nitric oxide by deoxyhemoglobin vasodilates the human circulation, Nat. Med. source
- Partly supportedcites [72] Delmastro-Greenwood, 2015, Nitrite and nitrate-dependent generation of anti-inflammatory fatty acid nitroalkenes, Free Radic. Biol. Med. sourceExperimental — accuracy not yet measured
The Materials and Methods (Study Population; page unavailable) report that healthy adult volunteers received 20 mg sodium nitrite and that monitored vital signs and methemoglobin levels remained normal. This supports short-term safety at that studied dose, but the paper does not establish a safety threshold at exceptionally high nitrite concentrations, address infants, or identify a <75 mg dose needed for blood-pressure effects. (LLM, conf=0.86)
- Partly supportedcites [113] Kapil, 2015, Dietary nitrate provides sustained blood pressure lowering in hypertensive patients: a randomized, phase 2, double-blind, placebo-controlled study, Hypertension sourceExperimental — accuracy not yet measured
The Results report blood-pressure lowering and no serious adverse events in adults given dietary nitrate; they also report no change in methaemoglobin concentrations. The Discussion says neither this study nor cited studies with micromolar plasma nitrite showed clinically significant methaemoglobinaemia. The paper does not study infants, establish a <75 mg nitrite dose for blood-pressure effects, or determine how high nitrite concentrations must be to pose a significant safety threat. (LLM, conf=0.86)
- Partly supportedcites [155] Ahluwalia, 2016, Dietary Nitrate and the epidemiology of cardiovascular, J. Am. Heart Assoc. sourceExperimental — accuracy not yet measured
The “Nitrite and Infant Methemoglobinemia” section (page unavailable) says excessive nitrite absorption can harm very young infants, while “Physiological Effects of Exogenous Nitrate and Nitrite” reports blood-pressure lowering from dietary nitrate. The paper does not establish that only exceptionally high nitrite concentrations pose a significant safety threat in both infants and adults, or give a <75 mg nitrite dose for blood-pressure effects; its infant discussion instead emphasizes their particular vulnerability. (LLM, conf=0.82)
- Not checked yetcites [156] Cornblath, 1948, Methemoglobinemia in young infants, J. Pediatr. source
- Not checked yetcites [157] Rathod, 2016, A “green” diet-based approach to cardiovascular health? Is inorganic nitrate the answer?, Mol. Nutr. Food Res. source
- Not checked yetcites [158] Hunault, 2009, Bioavailability of sodium nitrite from an aqueous solution in healthy adults, Toxicol. Lett. source
hedged- Asserted: passes — The authors put it forward as true.
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The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“supporting the idea that biological activity is regulated by multiple forms of nitrate reductase enzymes[192].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > The Oral Microbiome and Bacterial Nitrate Reduction > Local Factors Influence Bacterial Nitrate Reduction
What the sources say
- Partly supportedcites [192] Schreiber, 2010, Denitrification in human dental plaque, BMC Biol. sourceExperimental — accuracy not yet measured
The Background (page unavailable) describes nitrate reduction as part of a sequence mediated by different enzymes, including a nitrate reductase. It does not say that multiple forms of nitrate reductase regulate biological activity; the other reductases listed act on nitrite, nitric oxide, or nitrous oxide. (LLM, conf=0.82)
hedgeddirect- Asserted: passes — The authors put it forward as true.
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- Partly supported
Every source the paper cites for this claim was checked and supports it.
In the paper
“Conversely, microbiota isolated from dental plaque were capable of denitrification under aerobic conditions, supporting the idea that biological activity is regulated by multiple forms of nitrate reductase enzymes[192].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > The Oral Microbiome and Bacterial Nitrate Reduction > Local Factors Influence Bacterial Nitrate Reduction
What the sources say
- Supportedcites [192] Schreiber, 2010, Denitrification in human dental plaque, BMC Biol. source
The Results section (‘Dental plaque mediates aerobic denitrification’) reports N₂ production from dispersed dental plaque incubated in air-saturated medium. It also reports nitrate consumption and denitrification intermediates in the presence of oxygen, supporting the attributed claim. (LLM, conf=0.94)
plain- Asserted: passes — The authors put it forward as true.
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- Supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“it is unlikely they significantly contribute to the enterosalivary circulation given that the majority of nitrate and nitrite are absorbed in the proximal small intestine[233,270].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > The Oral Microbiome and Bacterial Nitrate Reduction > Local Factors Influence Bacterial Nitrate Reduction
What the sources say
- Partly supportedcites [233] Tiso, 2015, Nitrate reduction to nitrite, nitric oxide and ammonia by gut bacteria under physiological conditions, PLoS One sourceExperimental — accuracy not yet measured
The Introduction (page unavailable) says dietary nitrate is usually well absorbed in the upper intestinal tract, supporting the premise of the citing sentence. But it also says about one-third reaches the lower intestine, and the Conclusions say the significance of intestinal bacterial nitrate conversion remains to be established. The paper does not conclude that distal gut bacteria make an insignificant contribution to enterosalivary circulation. (LLM, conf=0.82)
- Not checked yetcites [270] Hezel, 2015, The oral microbiome and nitric oxide homoeostasis, Oral Dis. source
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“there is evidence that particular population changes are associated with pathologies that confer an increased risk of developing PH and other vascular disease, including obesity[273–275], diabetes[276], and insulin resistance[277].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Dysbiosis of the Microbiome in Pulmonary hypertension & Vascular Disease > The Oral Microbiome and ph
What the sources say
- Partly supportedcites [273] Bäckhed, 2007, Mechanisms underlying the resistance to diet-induced obesity in germ-free mice, Proc. Natl. Acad. Sci. sourceExperimental — accuracy not yet measured
The Discussion reports changes in gut microbial populations in obese versus lean mice and humans, supporting the obesity-related part of the citation. It does not establish changes in the oral microbiota or a link to pulmonary hypertension (PH) or other vascular disease. The adjacent diabetes and insulin-resistance claims have separate citations in the citing sentence. (LLM, conf=0.86)
- Partly supportedcites [274] Turnbaugh, 2009, A core gut microbiome in obese and lean twins, Nature sourceExperimental — accuracy not yet measured
The Abstract reports differences in gut bacterial populations between obese and lean individuals, supporting the obesity association for which this source is cited. It examines fecal communities, not oral microbiota, and does not establish a link between those changes and pulmonary hypertension or other vascular disease. The separately cited diabetes and insulin-resistance claims are outside this source’s citation. (LLM, conf=0.88)
- Not checked yetcites [275] Turnbaugh, 2008, Diet-induced obesity is linked to marked but reversible alterations in the mouse distal gut microbiome, Cell Host Microbe source
- Partly supportedcites [276] Wen, 2008, Innate immunity and intestinal microbiota in the development of Type 1 diabetes, Nature sourceExperimental — accuracy not yet measured
The paper’s Abstract reports that changes in intestinal microbiota affect type 1 diabetes development in NOD mice, supporting the diabetes-related part of the citation. It studies gut, not oral, microbiota and does not establish a link to pulmonary hypertension or other vascular disease. (LLM, conf=0.88)
- Partly supportedcites [277] Bäckhed, 2004, The gut microbiota as an environmental factor that regulates fat storage, Proc. Natl. Acad. Sci. sourceExperimental — accuracy not yet measured
The Results and Discussion report that gut microbial activity promotes fat storage in mice and speculate that differences in gut microbial ecology may affect predisposition to obesity. This supports the obesity-related part of the citation, but the paper studies gut, not oral, microbiota and does not link microbial changes to PH or other vascular disease. The citing sentence assigns diabetes and insulin resistance to separate citations. (LLM, conf=0.86)
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“protection from ischemia-reperfusion injury[97,98,272]”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Dysbiosis of the Microbiome in Pulmonary hypertension & Vascular Disease > The Oral Microbiome and ph
What the sources say
- Supportedcites [97] Webb, 2008, Acute blood pressure lowering, vasoprotective, and antiplatelet properties of dietary nitrate via bioconversion to nitrite, Hypertension source
The Results report that beetroot juice, a dietary nitrate source, prevented ischemia-reperfusion-induced endothelial dysfunction in the human forearm. The Discussion also reports reduced myocardial infarct damage in mice after increased dietary nitrite and nitrate intake. Page numbers are not available in our copy. (LLM, conf=0.90)
- Partly supportedcites [98] Hendgen-Cotta, 2012, Dietary nitrate supplementation improves revascularization in chronic ischemia, Circulation sourceExperimental — accuracy not yet measured
The Discussion reports previously demonstrated protection by nitrite in ischemia-reperfusion injury. This paper’s own findings concern dietary nitrate improving revascularization in chronic hind-limb ischemia, not protection from ischemia-reperfusion injury. It also does not establish that both nitrate and nitrite were administered orally for that purpose. (LLM, conf=0.86)
- Partly supportedcites [272] Cooke, 2011, Dietary nitrate, nitric oxide, and restenosis, J. Clin. Investig. sourceExperimental — accuracy not yet measured
The section ‘A new role for exogenous nitrites in restoring vascular homeostasis’ reports that sodium nitrite reduced myointimal hyperplasia after vascular injury in animals. It does not establish protection from ischemia-reperfusion injury or report that oral administration of both nitrate and nitrite provides that protection. (LLM, conf=0.82)
plaindirect- Asserted: passes — The authors put it forward as true.
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- Supported
None of the sources cited for this claim have been checked yet.
In the paper
“Despite an explosion of associative studies involving the microbiome and vascular and cardiovascular diseases, few connections have been identified with mechanistic certainty[2,3].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Introduction
What the sources say
plain- Asserted: passes — The authors put it forward as true.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Oral supplementation with inorganic nitrate or nitrate-containing foods exert pleiotropic, beneficial vascular effects in the setting of inflammation, endothelial dysfunction, ischemia-reperfusion injury and in pre-clinical models of PH”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“suggesting a role for commensal oral bacteria to shape the development of PH through the formation of nitrite, NO and other bioactive nitrogen oxides.”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Abstract
hedgedconditional- Asserted: passes — The authors put it forward as true.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“For example, the contribution of the microbiome in the development of pulmonary hypertension (PH) is emerging as a critical mitigating factor.”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Introduction
hedgedconditional- Asserted: passes — The authors put it forward as true.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“The bioavailability of nitrate and nitrite depend on the enzymatic reduction of nitrate to nitrite by a unique set of bacterial nitrate reductase enzymes possessed by specific bacterial populations in the mammalian mouth and gut.”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Abstract
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, there is encouraging evidence for the study of microbe-driven, nitrogen oxide pharmacology in the treatment of several forms of PH.”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Introduction
hedged- Asserted: passes — The authors put it forward as true.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“while traditional high-nitrate dietary patterns are associated with beneficial outcomes in hypertension, obesity and CVD.”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Abstract
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In the paper
“Once thought to be the inert, end-products of endothelial-derived nitric oxide (NO) heme-oxidation, nitrate and nitrite are now considered major sources of exogenous NO that exhibit enhanced vasoactive signaling activity under conditions of hypoxia and stress.”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Abstract
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In the paper
“Recent insights into the bioactivation and signaling actions of inorganic, dietary nitrate and nitrite now suggest a critical role for the microbiome in the development of cardiac and pulmonary vascular diseases.”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Abstract
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In the paper
“Further, recent insight into the biochemical reactions and signaling actions of nitrate, nitrite and nitric oxide reveal that the bioavailability of inorganic nitrate and nitrite, the major sources of exogenous NO, is dependent on the metabolic activity of specific oral microbiota.”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Introduction
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In the paper
“These observations highlight the potential of the microbiome in the development of novel nitrate- and nitrite-based therapeutics for PH, CVD and their risk factors.”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Abstract
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In the paper
“The pathogenesis of pulmonary hypertension (PH), obesity, hypertension and CVD are linked to defects in NO signaling”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Abstract
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In the paper
“It is therefore likely that on some level, PH can be characterized by similar pathogenic mechanisms.”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Dysfunctional Nitric Oxide Signaling underlies Pulmonary Hypertension Pathogenesis > Pulmonary Hypertension
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In the paper
“Pathologically, all types of PH develop via an early, common vasculopathy driven by disproportionate pulmonary vasoconstriction and dramatic remodeling of the endothelium and vessel wall[5,26,27].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Dysfunctional Nitric Oxide Signaling underlies Pulmonary Hypertension Pathogenesis > Nitric Oxide Signaling Dysfunction in Pulmonary Hypertension
What the sources say
- Not checked yetcites [5] Simonneau, 2013, Updated clinical classification of pulmonary hypertension, J. Am. Coll. Cardiol. source
- Not checked yetcites [26] Galiè, 2010, Pulmonary arterial hypertension: from the kingdom of the near-dead to multiple clinical trial meta-analyses, Eur. Heart J. source
- Not checked yetcites [27] Sitbon, 2012, Pathways in pulmonary arterial hypertension: the future is here, Eur. Respir. Rev. source
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In the paper
“Similarly, vascular disease, cardiovascular disease (CVD), and metabolic syndrome all share effective loss of NO function[23,35–39].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Dysfunctional Nitric Oxide Signaling underlies Pulmonary Hypertension Pathogenesis > Nitric Oxide Signaling Dysfunction in Pulmonary Hypertension
What the sources say
- Not checked yetcites [23] Förstermann, 2006, Endothelial nitric oxide synthase in vascular disease: from marvel to menace, Circulation source
- Not checked yetcites [35] Napoli, 2009, Nitric oxide and pathogenic mechanisms involved in the development of vascular diseases, Arch. Pharm. Res. source
- Not checked yetcites [36] Kobayashi, 2015, NO-Rich diet for, Nutrients source
- Not checked yetcites [37] Sansbury, 2014, Regulation of obesity and insulin resistance by nitric oxide, Free Radic. Biol. Med. source
- Not checked yetcites [38] Rizzo, 2010, Reduced NO-cGMP signaling contributes to vascular inflammation and insulin resistance induced by high-fat feeding, Arterioscler. Thromb. Vasc. Biol. source
- Not checked yetcites [39] Omar, 2016, Therapeutic effects of inorganic nitrate and nitrite in cardiovascular and metabolic diseases, J. Intern. Med. source
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In the paper
“Nitrite, derived from the oxygen- and NOS-independent, microbial enzymatic reduction of dietary nitrate, has been identified as an important secondary source of NO and other bioactive nitrogen oxides[25].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > The nitrate-nitrite-NO Pathway & Enterosalivary Circulation of Nitrate as ‘Alternate’ Source of NO Signaling
What the sources say
- Not checked yetcites [25] Lundberg, 2008, The nitrate-nitrite-nitric oxide pathway in physiology and therapeutics, Nat. Rev. Drug Discov. source
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In the paper
“Given that most efficacious therapies for the treatment of PH involve targeting of NO signaling[48,49], it is clear that pulmonary vascular health is intimately tied to effective NO bioactivity.”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Dysfunctional Nitric Oxide Signaling underlies Pulmonary Hypertension Pathogenesis > Nitric Oxide Signaling Dysfunction in Pulmonary Hypertension
What the sources say
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In the paper
“Formation of nitrite and propagation of its downstream NO-signaling effects depends on the oral bacterial reduction of inorganic nitrate by a set of bacterial nitrate reductase enzymes (NaRs) that are largely absent from the human genome[73–78].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > The nitrate-nitrite-NO Pathway & Enterosalivary Circulation of Nitrate as ‘Alternate’ Source of NO Signaling
What the sources say
- Not checked yetcites [73] Witter, 1979, Distribution of nitrogen-13 from labeled nitrate and nitrite in germfree and conventional-flora rats, Appl. Environ. Microbiol. source
- Not checked yetcites [74] Sobko, 2005, Gastrointestinal bacteria generate nitric oxide from nitrate and nitrite, Nitric Oxide source
- Not checked yetcites [75] Lundberg, 2004, Inorganic nitrate is a possible source for systemic generation of nitric oxide, Free Radic. Biol. Med. source
- Not checked yetcites [76] Govoni, 2008, The increase in plasma nitrite after a dietary nitrate load is markedly attenuated by an antibacterial mouthwash, Nitric Oxide source
- Not checked yetcites [77] Sparacino-Watkins, 2014, Nitrate and periplasmic nitrate reductases, Chem. Soc. Rev. source
- Not checked yetcites [78] Petersson, 2009, Gastroprotective and blood pressure lowering effects of dietary nitrate are abolished by an antiseptic mouthwash, Free Radic. Biol. Med. source
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In the paper
“Once in the mouth, salivary nitrate undergoes NOS- and oxygen-independent, enzymatic reduction to nitrite.”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > The nitrate-nitrite-NO Pathway & Enterosalivary Circulation of Nitrate as ‘Alternate’ Source of NO Signaling
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In the paper
“In proportion to the dietary load of nitrate, approximately 25% of total circulating nitrate is actively sequestered into salivary glands and concentrated in saliva up to 20 times that in plasma[73,75,82–88].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > The nitrate-nitrite-NO Pathway & Enterosalivary Circulation of Nitrate as ‘Alternate’ Source of NO Signaling
What the sources say
- Not checked yetcites [73] Witter, 1979, Distribution of nitrogen-13 from labeled nitrate and nitrite in germfree and conventional-flora rats, Appl. Environ. Microbiol. source
- Not checked yetcites [75] Lundberg, 2004, Inorganic nitrate is a possible source for systemic generation of nitric oxide, Free Radic. Biol. Med. source
- Not checked yetcites [82] Spiegelhalder, 1976, Influence of dietary nitrate on nitrite content of human saliva: possible relevance to in vivo formation of N-nitroso compounds, Food Cosmet. Toxicol. source
- Not checked yetcites [83] McKnight, 1997, Chemical synthesis of nitric oxide in the stomach from dietary nitrate in humans, Gut source
- Not checked yetcites [84] Xia, 2003, Alterations of nitrate and nitrite content in saliva, serum, and urine in patients with salivary dysfunction, J. Oral Pathol. Med. source
- Not checked yetcites [85] Qin, 2012, Sialin (SLC17A5) functions as a nitrate transporter in the plasma membrane, Proc. Natl. Acad. Sci. USA source
- Not checked yetcites [86] Jin, 2013, Active secretion and protective effect of salivary nitrate against stress in human volunteers and rats, Free Radic. Biol. Med. source
- Not checked yetcites [87] Clodfelter, 2015, The relationship between plasma and salivary NOx, Nitric Oxide source
- Not checked yetcites [88] Wagner, 1983, Metabolic fate of an oral dose of 15N-labeled nitrate in humans: effect of diet supplementation with ascorbic acid, Cancer Res.
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In the paper
“In a process referred to as the enterosalivary nitrate circulation, or the nitrate-nitrite-NO pathway, dietary nitrate is swallowed and rapidly absorbed in the proximal gastrointestinal tract (Figure 1)[79–81].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > The nitrate-nitrite-NO Pathway & Enterosalivary Circulation of Nitrate as ‘Alternate’ Source of NO Signaling
What the sources say
- Not checked yetcites [79] van Velzen, 2008, The oral bioavailability of nitrate from nitrate-rich vegetables in humans, Toxicol. Lett. source
- Not checked yetcites [80] Licht, 1986, Mechanisms for nitrite loss from the stomach, Carcinogenesis source
- Not checked yetcites [81] Duncan, 1995, Chemical generation of nitric oxide in the mouth from the enterosalivary circulation of dietary nitrate, Nat. Med. source
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In the paper
“Formation of and signal transduction by nitrate-derived nitrite, NO and bioactive nitrogen oxides is not a linear progression to NO and cGMP-dependent signaling, as the reference to the enterosalivary nitrate-nitrite-NO pathway might suggest.”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > The nitrate-nitrite-NO Pathway & Enterosalivary Circulation of Nitrate as ‘Alternate’ Source of NO Signaling
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In the paper
“These reactions also lead to the generation of electrophilic nitro-fatty acid (NO2-FA) signaling mediators, including NO2-conjugated linoleic acid (NO2-CLA) and S-nitrosothiol derivatives, all of which can be detected at increased concentrations in the systemic circulation following oral consumption of nitrate[72,92–96].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > The nitrate-nitrite-NO Pathway & Enterosalivary Circulation of Nitrate as ‘Alternate’ Source of NO Signaling
What the sources say
- Not checked yetcites [72] Delmastro-Greenwood, 2015, Nitrite and nitrate-dependent generation of anti-inflammatory fatty acid nitroalkenes, Free Radic. Biol. Med. source
- Not checked yetcites [92] Richardson, 2002, The ingestion of inorganic nitrate increases gastric S-nitrosothiol levels and inhibits platelet function in humans, Nitric Oxide source
- Not checked yetcites [93] Freeman, 2008, Nitro-fatty acid formation and signaling, J. Biol. Chem. source
- Not checked yetcites [94] Schopfer, 2011, Formation and signaling actions of electrophilic lipids, Chem. Rev. source
- Not checked yetcites [95] Bondonno, 2012, Nitrate causes a dose-dependent augmentation of nitric oxide status in healthy women, Food Funct. source
- Not checked yetcites [96] Lundberg, 2013, Biology of nitrogen oxides in the gastrointestinal tract, Gut source
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In the paper
“and 2–3.5mmHg increase in blood pressure that occurred in proportion to decreased plasma nitrite (R2=0.56, p=0.002)[106].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Microbial Nitrate Reduction to Nitrite and NO is Physiologically Important > Blood Pressure & Endothelial Health
What the sources say
- Not checked yetcites [106] Kapil, 2013, Physiological role for nitrate-reducing oral bacteria in blood pressure control, Free Radic. Biol. Med. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Rests on an assumption: The enterosalivary nitrate-nitrite-NO pathway operates similarly in humans and rodents.
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In the paper
“From the standpoint of vascular health, endothelial dysfunction has been associated with decreased circulating levels of nitrite[67,110].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Microbial Nitrate Reduction to Nitrite and NO is Physiologically Important > Blood Pressure & Endothelial Health
What the sources say
- Not checked yetcites [67] Rassaf, 2006, Plasma nitrite reserve and endothelial function in the human forearm circulation, Free Radic. Biol. Med. source
- Not checked yetcites [110] Kleinbongard, 2006, Plasma nitrite concentrations reflect the degree of endothelial dysfunction in humans, Free Radic. Biol. Med. source
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In the paper
“and that antimicrobial mouthwash abolishes this beneficial effect both acutely and chronically (reviewed in:[108,109]).”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Microbial Nitrate Reduction to Nitrite and NO is Physiologically Important > Blood Pressure & Endothelial Health
What the sources say
- Not checked yetcites [108] Siervo, 2013, Inorganic nitrate and beetroot juice supplementation reduces blood pressure in adults: a systematic review and meta-analysis, J. Nutr. source
- Not checked yetcites [109] Hobbs, 2013, The effects of dietary nitrate on blood pressure and endothelial function: a review of human intervention studies, Nutr. Res Rev. source
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In the paper
“along with a 25% decrease in plasma levels (p=0.001)”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Microbial Nitrate Reduction to Nitrite and NO is Physiologically Important > Blood Pressure & Endothelial Health
What the sources say
- Not checked yetcites [106] Kapil, 2013, Physiological role for nitrate-reducing oral bacteria in blood pressure control, Free Radic. Biol. Med. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Studies in Sprague-Dawley rats[78] and normal human volunteers[106] showed that depletion of oral bacterial nitrate reductases by chlorhexidine mouthwash correlated with a 90% decrease in oral nitrite levels (p<0.001) in humans”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Microbial Nitrate Reduction to Nitrite and NO is Physiologically Important > Blood Pressure & Endothelial Health
What the sources say
- Not checked yetcites [106] Kapil, 2013, Physiological role for nitrate-reducing oral bacteria in blood pressure control, Free Radic. Biol. Med. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Rests on an assumption: The enterosalivary nitrate-nitrite-NO pathway operates similarly in humans and rodents.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Extensive evidence supports that microbial bioactivation of nitrate may play a role in the prevention and treatment of systemic vascular pathology and PH.”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Microbial Nitrate Reduction to Nitrite and NO is Physiologically Important
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In the paper
“At least 19 studies in hypertensive, overweight, and other patient populations have been performed, all revealing predictable acute or chronic blood pressure reduction with varying types of nitrate supplementation[107]”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Microbial Nitrate Reduction to Nitrite and NO is Physiologically Important > Blood Pressure & Endothelial Health
What the sources say
- Not checked yetcites [107] Gee, 2016, Dietary nitrate lowers blood pressure: epidemiological, pre-clinical experimental and clinical trial evidence, Curr. Hypertens. Rep. source
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In the paper
“There exists a broad range of redox-derived nitrogen oxides that exert both cGMP-dependent and -independent signaling actions as a result of nitrosative-, nitrative- and oxidative-induced post-translational protein modifications and subsequent changes in protein function and gene expression profiles[100–102].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > The nitrate-nitrite-NO Pathway & Enterosalivary Circulation of Nitrate as ‘Alternate’ Source of NO Signaling
What the sources say
- Not checked yetcites [100] Pereira, 2013, Theredox interplay between nitrite and nitric oxide: from the gut to the brain, Redox Biol. source
- Not checked yetcites [101] Liu, 2015, Nitrite-mediated renal vasodilatation is increased during ischemic conditions via cGMP-independent signaling, Free Radic. Biol. Med. source
- Not checked yetcites [102] Vitturi, 2015, Convergence of biological nitration and nitrosation via symmetrical nitrous anhydride, Nat. Chem. Biol. source
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In the paper
“Given the importance of NO’s effects on the vasculature and the apparent contribution of the enterosalivary nitrate pathway to systemic NO bioavailability, the loss of the ability to reduce nitrate to nitrite and NO is expected to have systemic implications, particularly in situations of systemic or vascular metabolic and inflammatory stress.”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Microbial Nitrate Reduction to Nitrite and NO is Physiologically Important
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In the paper
“Further, dietary nitrate and nitrite confer protection from intimal hyperplasia in rodents[117–119]”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Microbial Nitrate Reduction to Nitrite and NO is Physiologically Important > Blood Pressure & Endothelial Health
What the sources say
- Not checked yetcites [117] Alef, 2011, Nitrite-generated NO circumvents dysregulated arginine/NOS signaling to protect against intimal hyperplasia in Sprague-Dawley rats, J. Clin. Investig. source
- Not checked yetcites [118] Alef, 2012, Nitric oxide and nitrite-based therapeutic opportunities in intimal hyperplasia, Nitric Oxide source
- Not checked yetcites [119] Vavra, 2011, Insights into the effect of nitric oxide and its metabolites nitrite and nitrate at inhibiting neointimal hyperplasia, Nitric Oxide source
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In the paper
“Functional resilience to debilitating diseases such as PH may also be conferred by microbes via improved exercise capacity, oxygen utilization, and myocardial function[126].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Microbial Nitrate Reduction to Nitrite and NO is Physiologically Important > Exercise Capacity & Oxygen Utilization
What the sources say
- Not checked yetcites [126] Bhushan, 2014, Nitrite therapy improves left ventricular function during heart failure via restoration of nitric oxide-mediated cytoprotective signaling, Circ. Res. source
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In the paper
“Microbial reduction of nitrate to nitrite, NO and other bioactive nitrogen oxides may influence more than vascular health alone.”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Microbial Nitrate Reduction to Nitrite and NO is Physiologically Important > Exercise Capacity & Oxygen Utilization
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In the paper
“an effect that over 14 studies have confirmed with reduced VO2 and increased work capacity in response to nitrate during submaximal exercise in healthy individuals[128,129] (reviewed in:[130,131]) and in certain chronic diseases[127,132].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Microbial Nitrate Reduction to Nitrite and NO is Physiologically Important > Exercise Capacity & Oxygen Utilization
What the sources say
- Not checked yetcites [128] Larsen, 2007, Effects of dietary nitrate on oxygen cost during exercise, Acta Physiol. source
- Not checked yetcites [129] Larsen, 2010, Dietary nitrate reduces maximal oxygen consumption while maintaining work performance in maximal exercise, Free Radic. Biol. Med. source
- Not checked yetcites [130] Affourtit, 2015, On the mechanism by which dietary nitrate improves human skeletal muscle function, Front. Physiol. source
- Not checked yetcites [131] Jones, 2014, Dietary nitrate supplementation and exercise performance, Sports Med. source
- Not checked yetcites [127] Pawlak-Chaouch, 2016, Effect of dietary nitrate supplementation on metabolic rate during rest and exercise in human: a systematic review and a meta-analysis, Nitric Oxide source
- Not checked yetcites [132] Berry, 2015, Dietary nitrate supplementation improves exercise performance and decreases blood pressure in COPD patients, Nitric Oxide source
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In the paper
“For example, one study demonstrated that nitrate supplementation offers net decrease in oxygen cost (VO2, mL/kg/min) during moderate and heavy submaximal exercise in healthy adults[127]”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Microbial Nitrate Reduction to Nitrite and NO is Physiologically Important > Exercise Capacity & Oxygen Utilization
What the sources say
- Not checked yetcites [127] Pawlak-Chaouch, 2016, Effect of dietary nitrate supplementation on metabolic rate during rest and exercise in human: a systematic review and a meta-analysis, Nitric Oxide source
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In the paper
“suggesting the critical potential of exploiting the oral microbiome to enhance functional outcomes in patients via mechanisms spanning from improved mitochondrial function to increased vascular and cardiac performance[138].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Microbial Nitrate Reduction to Nitrite and NO is Physiologically Important > Exercise Capacity & Oxygen Utilization
What the sources say
- Not checked yetcites [138] Larsen, 2011, Dietary inorganic nitrate improves mitochondrial efficiency in humans, Cell Metab. source
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In the paper
“and is capable of inhibiting both hypoxia-induced and monocrotaline-induced PH in rats[145].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Microbial Nitrate Reduction to Nitrite and NO is Physiologically Important > Pulmonary Hypertension
What the sources say
- Not checked yetcites [145] Zuckerbraun, 2010, Nitrite potently inhibits hypoxic and inflammatory pulmonary arterial hypertension and smooth muscle proliferation via xanthine oxidoreductase-dependent nitric oxide generation, Circulation source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Current evidence suggests the biological importance of nitrate and its enzymatic and non-enzymatic reaction products in maintenance of vascular health and PH.”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Microbial Nitrate Reduction to Nitrite and NO is Physiologically Important > Pulmonary Hypertension
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In the paper
“In a single experiment using nitrate, dietary supplementation prevented pulmonary vascular remodeling and RVH in both wild-type and endothelial NOS-deficient mice[150]”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Microbial Nitrate Reduction to Nitrite and NO is Physiologically Important > Pulmonary Hypertension
What the sources say
- Not checked yetcites [150] Baliga, 2012, Dietary nitrate ameliorates pulmonary hypertension: cytoprotective role for endothelial nitric oxide synthase and xanthine oxidoreductase, Circulation source
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In the paper
“and in another study, a 24% improvement in submaximal aerobic endurance with 1 week of daily beetroot juice consumption (6.1 mmol nitrate)[151].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Microbial Nitrate Reduction to Nitrite and NO is Physiologically Important > Pulmonary Hypertension
What the sources say
- Not checked yetcites [151] Eggebeen, 2016, One week of daily dosing with beetroot juice improves submaximal endurance and blood pressure in older patients with heart failure and preserved ejection fraction, JACC Heart Fail. source
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In the paper
“These data also support the concept that an intricate and dependent relationship exists between mammals and commensal, oral, nitrate-reducing microbiota in maintaining adequate NO signaling.”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Microbial Nitrate Reduction to Nitrite and NO is Physiologically Important > Pulmonary Hypertension
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Rests on an assumption: The oral microbiome's nitrate-reducing capacity is critical for systemic NO bioavailability in humans.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“indicating an active role for microbial, nitrate-derived nitrite and NO in the development and progression of PH.”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Microbial Nitrate Reduction to Nitrite and NO is Physiologically Important > Pulmonary Hypertension
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In the paper
“These studies support the clinical utility of nitrate in at least some types of PH.”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Microbial Nitrate Reduction to Nitrite and NO is Physiologically Important > Pulmonary Hypertension
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- Rests on an assumption: Animal model findings of nitrate/nitrite benefit in pulmonary hypertension are predictive of human pulmonary hypertension.
In the paper
“Further, in a population of individuals with HFpEF, there was a 14% increase in cardiopulmonary exercise testing performance in 17 patients after a single dose of beetroot juice (12.9 mmol nitrate)[137]”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Microbial Nitrate Reduction to Nitrite and NO is Physiologically Important > Pulmonary Hypertension
What the sources say
- Not checked yetcites [137] Zamani, 2015, Effect of inorganic nitrate on exercise capacity in heart failure with preserved ejection fraction, Circulation source
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In the paper
“In the acute setting, nitrite can bind to hemoglobin and oxidize the ferrous iron in heme to the ferric state, thereby forming methemoglobin (metHgb) and preventing the binding of oxygen[152].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Safety of Inorganic Nitrate and Nitrite
What the sources say
- Not checked yetcites [152] Doyle, 1981, Kinetics and mechanism of the oxidation of human deoxyhemoglobin by nitrites, J. Biol. Chem. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Similarly, little evidence exists to suggest that chronic nitrate or nitrite consumption are directly carcinogenic in humans[159,160].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Safety of Inorganic Nitrate and Nitrite
What the sources say
- Not checked yetcites [159] J.F.W.E. Consultation, Nitrate (and potential endogenous formation of N-nitroso compounds), in: G.J. Speijers, P.A. van den Brandt (Eds.), Safety Evaluation of Certain Food Additives and Contaminants, Geneva. 〈http://www.inchem.org/documents/jecfa/jecmono/v50je05.htm〉, 2003.
- Not checked yetcites [160] IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, IARC monographs on the evaluation of carcinogenic risks to humans. Ingested nitrate and nitrite, and cyanobacterial peptide toxins, IARC Monogr Eval Carcinog Risks Hum. 94, 2010, v–vii–1–412.
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In the paper
“Excitingly, when ingested nitrate and nitrite are rather paired with plant- and fruit-based polyphenols and essential nutrients such as ascorbate, gastric nitrosation is inhibited[162,167,168]”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Safety of Inorganic Nitrate and Nitrite
What the sources say
- Not checked yetcites [162] Vermeer, 2001, Nitrate exposure and the endogenous formation of carcinogenic nitrosamines in humans, Rev. Environ. Health source
- Not checked yetcites [167] Helser, 1992, Influence of fruit and vegetable juices on the endogenous formation of N-nitrosoproline and N-nitrosothiazolidine-4-carboxylic acid in humans on controlled diets, Carcinogenesis source
- Not checked yetcites [168] Bartsch, 1993, Inhibition of nitrosation, Basic Life Sci.
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In the paper
“Indeed, nitrites in combination with dietary amines or amides, such as in red and cured meats, have been linked to stomach and several other cancers[155,157,160,163–166].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Safety of Inorganic Nitrate and Nitrite
What the sources say
- Not checked yetcites [155] Ahluwalia, 2016, Dietary Nitrate and the epidemiology of cardiovascular, J. Am. Heart Assoc. source
- Not checked yetcites [157] Rathod, 2016, A “green” diet-based approach to cardiovascular health? Is inorganic nitrate the answer?, Mol. Nutr. Food Res. source
- Not checked yetcites [160] IARC Working Group on the Evaluation of Carcinogenic Risks to Humans, IARC monographs on the evaluation of carcinogenic risks to humans. Ingested nitrate and nitrite, and cyanobacterial peptide toxins, IARC Monogr Eval Carcinog Risks Hum. 94, 2010, v–vii–1–412.
- Not checked yetcites [163] Cross, 2010, A large prospective study of meat consumption and colorectal cancer risk: an investigation of potential mechanisms underlying this association, Cancer Res. source
- Not checked yetcites [164] Ferrucci, 2010, Meat and components of meat and the risk of bladder cancer in the NIH-AARP diet and health study, Cancer source
- Not checked yetcites [165] Sinha, 2009, Meat and meat-related compounds and risk of prostate cancer in a large prospective cohort study in the United States, Am. J. Epidemiol. source
- Not checked yetcites [166] Dietrich, 2005, A review: dietary and endogenously formed N-nitroso compounds and risk of childhood brain tumors, Cancer Causes Control.
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“suggesting that the mutagenic potential of dietary nitrate and nitrite is likely contextual, depending on the complex interactions between nitrate and nitrite with factors such as the relative content of amines, amides and plant-based, antioxidant substrate[155,169].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Safety of Inorganic Nitrate and Nitrite
What the sources say
- Not checked yetcites [155] Ahluwalia, 2016, Dietary Nitrate and the epidemiology of cardiovascular, J. Am. Heart Assoc. source
- Not checked yetcites [169] Bartsch, 1989, Human exposure to endogenous N-nitroso compounds: quantitative estimates in subjects at high risk for cancer of the oral cavity, oesophagus, stomach and urinary bladder, Cancer Surv.
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In the paper
“Yet, individual bacteria do not act in a vacuum, but rather function in interdependent microbial communities whose conglomerate activity can impact oral and systemic health[183,188,189].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > The Oral Microbiome and Bacterial Nitrate Reduction > Complexity of the Oral Microbiome
What the sources say
- Not checked yetcites [183] Takahashi, 2015, Oral microbiome metabolism: from "Who Are They?" to "What Are They Doing?", J. Dental Res. source
- Not checked yetcites [188] Duran-Pinedo, 2015, Beyond microbial community composition: functional activities of the oral microbiome in health and disease, Microbes Infect. source
- Not checked yetcites [189] Zaura, 2015, Editorial: the oral microbiome in an ecological perspective, Front. Cell. Infect. Microbiol. source
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In the paper
“The bulk of physiologically relevant nitrate reduction occurs via the activity of facultative anaerobic bacteria dwelling in crypts of the posterior dorsum of the tongue[81,200,201].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > The Oral Microbiome and Bacterial Nitrate Reduction > Bacterial Nitrate Reduction
What the sources say
- Not checked yetcites [81] Duncan, 1995, Chemical generation of nitric oxide in the mouth from the enterosalivary circulation of dietary nitrate, Nat. Med. source
- Not checked yetcites [200] Li, 1997, Nitrate-reducing bacteria on rat tongues, Appl. Environ. Microbiol. source
- Not checked yetcites [201] Doel, 2005, Evaluation of bacterial nitrate reduction in the human oral cavity, Eur. J. Oral Sci. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“For instance, nitrite and nitrate are important protective elements of the oral and mucosal immune response, especially in settings of stress and periodontal injury[86,193,231].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > The Oral Microbiome and Bacterial Nitrate Reduction > Local Factors Influence Bacterial Nitrate Reduction
What the sources say
- Not checked yetcites [86] Jin, 2013, Active secretion and protective effect of salivary nitrate against stress in human volunteers and rats, Free Radic. Biol. Med. source
- Not checked yetcites [193] Sánchez, 2014, Total salivary nitrates and nitrites in oral health and periodontal disease, Nitric Oxide source
- Not checked yetcites [231] Lundberg, 2012, Nitrate transport in salivary glands with implications for NO homeostasis, Proc. Natl. Acad. Sci. U.S.A. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Using nitrate supplementation as selective pressure for bacteria capable of nitrate reduction, several studies found proliferation of Veillonella[205], Streptococcus[204], Neisseria[115], Haemophilus[204], and Rothia species[115], all previously identified as high nitrate reducers.”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > The Oral Microbiome and Bacterial Nitrate Reduction > Bacterial Nitrate Reduction
What the sources say
- Not checked yetcites [205] Koopman, 2016, Nitrate and the origin of saliva influence composition and short chain fatty acid production of oral microcosms, Micro. Ecol. source
- Not checked yetcites [204] Hyde, 2014, Characterization of the rat oral microbiome and the effects of dietary nitrate, Free Radic. Biol. Med. source
- Not checked yetcites [115] Velmurugan, 2016, Dietary nitrate improves vascular function in patients with hypercholesterolemia: a randomized, double-blind, placebo-controlled study, Am. J. Clin. Nutr. source
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In the paper
“Similarly, there was decreased NO generation in a polymicrobial culture containing NO-consuming bacteria in rats[217].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > The Oral Microbiome and Bacterial Nitrate Reduction > Local Factors Influence Bacterial Nitrate Reduction
What the sources say
- Not checked yetcites [217] Sobko, 2006, Generation of NO by probiotic bacteria in the gastrointestinal tract, Free Radic. Biol. Med. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Demonstrating the complexity of community metabolism, an ex vivo experiment showed increased nitrate consumption in a polymicrobial culture of mixed high- and low-nitrate reducing bacteria challenged with nitrate compared to one of high-nitrate reducers alone[190].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > The Oral Microbiome and Bacterial Nitrate Reduction > Local Factors Influence Bacterial Nitrate Reduction
What the sources say
- Not checked yetcites [190] Hyde, 2014, Metagenomic analysis of nitrate-reducing bacteria in the oral cavity: implications for nitric oxide homeostasis, PLoS One source
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In the paper
“In both rat and human studies species of Firmicutes (Staphylococcus, Streptococcus and Veillonella) and Actinobacteria (Actinomyces) have been most frequently identified as among the highest nitrate-reducers, while numerous other taxa have also been identified, including Pasteurella, Rothia, Neisseria, Haemophilus, Granulicatella, etc.[190,200–204].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > The Oral Microbiome and Bacterial Nitrate Reduction > Bacterial Nitrate Reduction
What the sources say
- Not checked yetcites [190] Hyde, 2014, Metagenomic analysis of nitrate-reducing bacteria in the oral cavity: implications for nitric oxide homeostasis, PLoS One source
- Not checked yetcites [200] Li, 1997, Nitrate-reducing bacteria on rat tongues, Appl. Environ. Microbiol. source
- Not checked yetcites [201] Doel, 2005, Evaluation of bacterial nitrate reduction in the human oral cavity, Eur. J. Oral Sci. source
- Not checked yetcites [202] Smith, 1999, The microbial generation of nitric oxide in the human oral cavity, Microb. Ecol. ….
- Not checked yetcites [203] Palmerini, 2003, NO synthesis in human saliva, Free Radic. Res. source
- Not checked yetcites [204] Hyde, 2014, Characterization of the rat oral microbiome and the effects of dietary nitrate, Free Radic. Biol. Med. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Yet, despite these varied attempts, there remains a high degree of variability in results depending on numerous methodological factors[206], including source and sampling of sample (saliva versus oral wash versus tongue scraping), direct sampling versus culture, and choice of 16S variable region for sequencing.”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > The Oral Microbiome and Bacterial Nitrate Reduction > Bacterial Nitrate Reduction
What the sources say
- Not checked yetcites [206] Luo, 2016, Effects of specimen collection methodologies and storage conditions on the short-term stability of oral microbiome taxonomy, Appl. Environ. Microbiol. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Mechanistically, much of the toxicity is due to the non-enzymatic protonation of nitrite to HNO2 and NO and subsequent oxidative and nitrosative stress.”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > The Oral Microbiome and Bacterial Nitrate Reduction > Local Factors Influence Bacterial Nitrate Reduction
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In the paper
“In settings of low pH and high nitrate and nitrite concentrations, selected bacteria and bacterial communities capable of nitrate reduction may preferentially survive or expand their population[115,205].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > The Oral Microbiome and Bacterial Nitrate Reduction > Local Factors Influence Bacterial Nitrate Reduction
What the sources say
- Not checked yetcites [115] Velmurugan, 2016, Dietary nitrate improves vascular function in patients with hypercholesterolemia: a randomized, double-blind, placebo-controlled study, Am. J. Clin. Nutr. source
- Not checked yetcites [205] Koopman, 2016, Nitrate and the origin of saliva influence composition and short chain fatty acid production of oral microcosms, Micro. Ecol. source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“Third, it is clear that pH, particularly with regard to stomach acidity, plays an important role in nitrate, nitrite, and NO metabolism.”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > The Oral Microbiome and Bacterial Nitrate Reduction > Local Factors Influence Bacterial Nitrate Reduction
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In the paper
“Indeed, increased production of the weak base, ammonia via nitrate reduction is a well-known strategy for bacteria to alkalinize their cytoplasm and local environment and protect against the potential toxic effects of high concentrations of nitrate, nitrite and NO[238].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > The Oral Microbiome and Bacterial Nitrate Reduction > Local Factors Influence Bacterial Nitrate Reduction
What the sources say
- Not checked yetcites [238] Nascimento, 2009, Correlations of oral bacterial arginine and urea catabolism with caries experience, Oral Microbiol. Immunol. source
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In the paper
“First, H. pylori has been shown to inhibit iNOS expression and NO production by the host macrophage[242].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > The Oral Microbiome and Bacterial Nitrate Reduction > Local Factors Influence Bacterial Nitrate Reduction
What the sources say
- Not checked yetcites [242] Gobert, 2016, The immune Battle against helicobacter pylori infection: NO offense, Trends Microbiol. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Indeed, the expression and activation of bacterial nitrate reductases are tightly regulated via oxygen-dependent and nitrate-responsive mechanisms[77,256].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > The Oral Microbiome and Bacterial Nitrate Reduction > Local Factors Influence Bacterial Nitrate Reduction
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Additionally, acid-reduction is known to reduce gastric production of NO[76,90,254]”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > The Oral Microbiome and Bacterial Nitrate Reduction > Local Factors Influence Bacterial Nitrate Reduction
What the sources say
- Not checked yetcites [76] Govoni, 2008, The increase in plasma nitrite after a dietary nitrate load is markedly attenuated by an antibacterial mouthwash, Nitric Oxide source
- Not checked yetcites [90] Lundberg, 1994, Intragastric nitric oxide production in humans: measurements in expelled air, Gut source
- Not checked yetcites [254] Pinheiro, 2012, Increase in gastric pH reduces hypotensive effect of oral sodium nitrite in rats, Free Radical Biol. Med. source
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In the paper
“These data then suggest that gastric pH may be equally as important in nitrate bioactivation as a viable oral, nitrate reducing microbiome.”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > The Oral Microbiome and Bacterial Nitrate Reduction > Local Factors Influence Bacterial Nitrate Reduction
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In the paper
“has recently been shown to attenuate the blood pressure lowering effects of nitrite in healthy adults[255]”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > The Oral Microbiome and Bacterial Nitrate Reduction > Local Factors Influence Bacterial Nitrate Reduction
What the sources say
- Not checked yetcites [255] Montenegro, 2016, Blood pressure-lowering effect of orally ingested nitrite is abolished by a proton pump inhibitor, Hypertension
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In the paper
“Conversely, areas that have high nitrate reductase activity such as the dorsum of the tongue, gingival plaque and periodontal pockets demonstrate low relative oxygen concentrations (8–13 mmHg, ~1–2%)[81,193,201,266].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > The Oral Microbiome and Bacterial Nitrate Reduction > Local Factors Influence Bacterial Nitrate Reduction
What the sources say
- Not checked yetcites [81] Duncan, 1995, Chemical generation of nitric oxide in the mouth from the enterosalivary circulation of dietary nitrate, Nat. Med. source
- Not checked yetcites [193] Sánchez, 2014, Total salivary nitrates and nitrites in oral health and periodontal disease, Nitric Oxide source
- Not checked yetcites [201] Doel, 2005, Evaluation of bacterial nitrate reduction in the human oral cavity, Eur. J. Oral Sci. source
- Not checked yetcites [266] Hill, 1989
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In the paper
“Biologically important nitrate reduction, therefore, arises from regional interactions between oxygen tension, nitrate concentration, and microbial genetics.”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > The Oral Microbiome and Bacterial Nitrate Reduction > Local Factors Influence Bacterial Nitrate Reduction
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“it rapidly becomes clear that the ability to switch metabolism from aerobic to largely nitrate-driven anaerobic is a requirement for microbial survival[267–269].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > The Oral Microbiome and Bacterial Nitrate Reduction > Local Factors Influence Bacterial Nitrate Reduction
What the sources say
- Not checked yetcites [267] Espey, 2013, Role of oxygen gradients in shaping redox relationships between the human intestine and its microbiota, Free Radic. Biol. Med. source
- Not checked yetcites [268] Matheson, 2000, Regulation of intestinal blood flow, J. Surg. Res. source
- Not checked yetcites [269] Cole, 1996, Nitrate reduction to ammonia by enteric bacteria: redundancy, or a strategy for survival during oxygen starvation?, FEMS Microbiol. Lett. source
boosteddirect- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“What is clear is that the primary determinants of bacterial respiration are the ambient oxygen tension and nitrate concentration at any given point.”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > The Oral Microbiome and Bacterial Nitrate Reduction > Local Factors Influence Bacterial Nitrate Reduction
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In the paper
“despite the capacity of bacteria in the distal GI tract to reduce nitrate[74]”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > The Oral Microbiome and Bacterial Nitrate Reduction > Local Factors Influence Bacterial Nitrate Reduction
What the sources say
- Not checked yetcites [74] Sobko, 2005, Gastrointestinal bacteria generate nitric oxide from nitrate and nitrite, Nitric Oxide source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Second, diffusion of oxygen from the enteral vasculature through the submucosal tissue and into the intestinal lumen creates an incredibly steep oxygen gradient, ranging from 80–100mmHg (~10–13%) in the submucosa and base of the villi, down to only 8–10mmHg (~1–2%) in the overlying mucus layer and an essentially anaerobic luminal center (Figure 4)[233,267].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > The Oral Microbiome and Bacterial Nitrate Reduction > Local Factors Influence Bacterial Nitrate Reduction
What the sources say
- Not checked yetcites [233] Tiso, 2015, Nitrate reduction to nitrite, nitric oxide and ammonia by gut bacteria under physiological conditions, PLoS One source
- Not checked yetcites [267] Espey, 2013, Role of oxygen gradients in shaping redox relationships between the human intestine and its microbiota, Free Radic. Biol. Med. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“In the mouth, regions of high oxygen concentration (20–114mmHg, ~3–15%) are generally expected to be in whole saliva, on the tooth surface, and in dental plaque[266].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > The Oral Microbiome and Bacterial Nitrate Reduction > Local Factors Influence Bacterial Nitrate Reduction
What the sources say
- Not checked yetcites [266] Hill, 1989
hedged- Asserted: passes — The authors put it forward as true.
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In the paper
“that may favor the dissimilatory pathway, leading to ammonia production, alkalization, and nitrogen detoxification[271].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > The Oral Microbiome and Bacterial Nitrate Reduction > Local Factors Influence Bacterial Nitrate Reduction
What the sources say
- Not checked yetcites [271] Vermeiren, 2009, Nitric oxide production by the human intestinal microbiota by dissimilatory nitrate reduction to ammonium, J. Biomed. Biotechnol.
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“the global dependency of enterosalivary nitrate reduction on living oral microbiota to enact its biologic activity[73,99,109].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Dysbiosis of the Microbiome in Pulmonary hypertension & Vascular Disease > The Oral Microbiome and ph
What the sources say
- Not checked yetcites [73] Witter, 1979, Distribution of nitrogen-13 from labeled nitrate and nitrite in germfree and conventional-flora rats, Appl. Environ. Microbiol. source
- Not checked yetcites [99] Woessner, 2016, A stepwise reduction in plasma and salivary nitrite with increasing strengths of mouthwash following a dietary nitrate load, Nitric Oxide source
- Not checked yetcites [109] Hobbs, 2013, The effects of dietary nitrate on blood pressure and endothelial function: a review of human intervention studies, Nutr. Res Rev. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Hence, it is likely that different environmental conditions favor different mechanisms of nitrate reduction and their associated microbial communities.”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > The Oral Microbiome and Bacterial Nitrate Reduction > Local Factors Influence Bacterial Nitrate Reduction
hedgedconditional- Asserted: passes — The authors put it forward as true.
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- The authors state this as an assumption: In a healthy mouth, ATP-generating respiration would predominate.
In the paper
“In hypoxic conditions, respiratory denitrification is the most energetically favorable process that promotes respiration-dependent growth[77].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > The Oral Microbiome and Bacterial Nitrate Reduction > Local Factors Influence Bacterial Nitrate Reduction
What the sources say
- Not checked yetcites [77] Sparacino-Watkins, 2014, Nitrate and periplasmic nitrate reductases, Chem. Soc. Rev. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“the majority of nitrate and nitrite are absorbed in the proximal small intestine[233,270].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > The Oral Microbiome and Bacterial Nitrate Reduction > Local Factors Influence Bacterial Nitrate Reduction
What the sources say
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“oral administration of nitrate and nitrite provides dose-dependent improvement in endothelial dysfunction, inflammation and vascular function[71]”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Dysbiosis of the Microbiome in Pulmonary hypertension & Vascular Disease > The Oral Microbiome and ph
What the sources say
- Not checked yetcites [71] Lara, 2016, Effects of inorganic nitrate and beetroot supplementation on endothelial function: a systematic review and meta-analysis, Eur. J. Nutr. source
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In the paper
“Clinically, nitrate supplementation will reliably produce anti-hypertensive effects[107]”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Dysbiosis of the Microbiome in Pulmonary hypertension & Vascular Disease > The Oral Microbiome and ph
What the sources say
- Not checked yetcites [107] Gee, 2016, Dietary nitrate lowers blood pressure: epidemiological, pre-clinical experimental and clinical trial evidence, Curr. Hypertens. Rep. source
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In the paper
“improved exercise efficiency[127]”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Dysbiosis of the Microbiome in Pulmonary hypertension & Vascular Disease > The Oral Microbiome and ph
What the sources say
- Not checked yetcites [127] Pawlak-Chaouch, 2016, Effect of dietary nitrate supplementation on metabolic rate during rest and exercise in human: a systematic review and a meta-analysis, Nitric Oxide source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“reversal of vascular and ventricular remodeling in several models of PAH[147,150].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Dysbiosis of the Microbiome in Pulmonary hypertension & Vascular Disease > The Oral Microbiome and ph
What the sources say
- Not checked yetcites [147] Pankey, 2012, Effect of chronic sodium nitrite therapy on monocrotaline-induced pulmonary hypertension, Nitric Oxide source
- Not checked yetcites [150] Baliga, 2012, Dietary nitrate ameliorates pulmonary hypertension: cytoprotective role for endothelial nitric oxide synthase and xanthine oxidoreductase, Circulation source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“improved exercise performance in patients with heart failure and HFpEF[135,137,151].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Dysbiosis of the Microbiome in Pulmonary hypertension & Vascular Disease > The Oral Microbiome and ph
What the sources say
- Not checked yetcites [135] Coggan, 2016, Dietary Nitrate and Skeletal Muscle Contractile Function in Heart Failure, Curr. Heart Fail Rep. source
- Not checked yetcites [137] Zamani, 2015, Effect of inorganic nitrate on exercise capacity in heart failure with preserved ejection fraction, Circulation source
- Not checked yetcites [151] Eggebeen, 2016, One week of daily dosing with beetroot juice improves submaximal endurance and blood pressure in older patients with heart failure and preserved ejection fraction, JACC Heart Fail. source
plaindirect- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Based on these findings, there can be little doubt that oral nitrate supplementation exerts profound beneficial vascular effects via microbial-dependent bioactivation in numerous settings closely related to PH and its pathophysiological mechanisms.”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Dysbiosis of the Microbiome in Pulmonary hypertension & Vascular Disease > The Oral Microbiome and ph
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In the paper
“it is likely to be transduced in part by NO and the pleiotropic reactions of secondary nitrogen oxides induced by microbial nitrate reduction and downstream reactions.”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Dysbiosis of the Microbiome in Pulmonary hypertension & Vascular Disease > The Oral Microbiome and ph
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“Yet, despite these localized, periodontal effects on microbial populations, high salivary nitrite concentrations may also exert antimicrobial effects elsewhere in the oral cavity and gut, possibly disrupting community composition or function of biologically beneficial populations of nitrate-reducing bacteria[204,232–237].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Dysbiosis of the Microbiome in Pulmonary hypertension & Vascular Disease > Microbial Communities & Nitrate Bioactivation are Disrupted in Periodontal Disease & Xerostomia
What the sources say
- Not checked yetcites [204] Hyde, 2014, Characterization of the rat oral microbiome and the effects of dietary nitrate, Free Radic. Biol. Med. source
- Not checked yetcites [232] Silva Mendez, 1999, Antimicrobial effect of acidified nitrite on cariogenic bacteria, Oral Microbiol. Immunol. source
- Not checked yetcites [233] Tiso, 2015, Nitrate reduction to nitrite, nitric oxide and ammonia by gut bacteria under physiological conditions, PLoS One source
- Not checked yetcites [234] Rowe, 1979, Nitrite inhibition of aerobic bacteria, Curr. Microbiol. source
- Not checked yetcites [235] Schlag, 2007, Inhibition of staphylococcal biofilm formation by nitrite, J. Bacteriol. source
- Not checked yetcites [236] Zemke, 2014, Nitrite modulates bacterial antibiotic susceptibility and biofilm formation in association with airway epithelial cells, Free Radic. Biol. Med. source
- Not checked yetcites [237] Arora, 2015, Nitric oxide regulation of bacterial biofilms, Biochemistry source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“Significantly, several diseases that share both disproportionately high rates of vascular disease and PH, including Sjögren's and systemic sclerosis[294–297], HIV[7,11], and cystic fibrosis[298] also feature dysregulated salivary flow[299–302] and altered oral microbial populations[224,303–306].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Dysbiosis of the Microbiome in Pulmonary hypertension & Vascular Disease > Microbial Communities & Nitrate Bioactivation are Disrupted in Periodontal Disease & Xerostomia
What the sources say
- Not checked yetcites [294] Battle, 1996, Prevalence of pulmonary hypertension in limited and diffuse scleroderma, Chest source
- Not checked yetcites [295] Bertoni, 2005, Pulmonary hypertension in primary Sjögren's syndrome: report of a case and review of the literature, Clin. Rheumatol. source
- Not checked yetcites [296] Hatron, 2011, Pulmonary manifestations of Sjögren's syndrome, Presse Med. source
- Not checked yetcites [297] Kobak, 2013, The frequency of sicca symptoms and Sjögren's syndrome in patients with systemic sclerosis, Int J. Rheum. Dis. source
- Not checked yetcites [298] Ratjen, 2016, Pulmonary artery hypertension: an underrated disease manifestation in cystic fibrosis?, Lancet Respir. Med. source
- Not checked yetcites [299] von Bültzingslöwen, 2007, Salivary dysfunction associated with systemic diseases: systematic review and clinical management recommendations, Oral Surg. Oral. Med Oral Pathol. Oral Radiol. Endod.
- Not checked yetcites [300] Navazesh, 2009, Effect of HAART on salivary gland function in the Women's Interagency HIV Study (WIHS), Oral Dis. source
- Not checked yetcites [301] López-Verdín, 2013, Differences in salivary flow level, xerostomia, and flavor alteration in Mexican HIV patients who did or did not receive antiretroviral therapy, AIDS Res Treat. 2013 source
- Not checked yetcites [302] da Silva Modesto, 2015, Salivary flow rate and biochemical composition analysis in stimulated whole saliva of children with cystic fibrosis, Arch. Oral Biol. source
- Not checked yetcites [303] Navazesh, 2005, The effect of HAART on salivary microbiota in the women's Interagency HIV study (WIHS), Oral Surg. Oral Med. Oral Pathol. Oral. Radiol. Endod. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Characteristically, disease is accompanied by the transition from symbiotic, facultative microbiota to overgrowth of dysbiotic, anaerobic bacteria together known as the ‘red complex' that reside in the relatively hypoxic subgingival crypts and pockets of the gums[182].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Dysbiosis of the Microbiome in Pulmonary hypertension & Vascular Disease > Microbial Communities & Nitrate Bioactivation are Disrupted in Periodontal Disease & Xerostomia
What the sources say
- Not checked yetcites [182] Kumar, 2016, From focal sepsis to periodontal medicine: a century of exploring the role of the oral microbiome in systemic disease, J. Physiol.
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“What is clear is that inflammation in the localized anaerobic environment of the expanding subgingival crypts, in concert with high salivary nitrate, likely selects for survival and growth of the anaerobic, nitrate-reducing bacteria typical of periodontal disease[193].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Dysbiosis of the Microbiome in Pulmonary hypertension & Vascular Disease > Microbial Communities & Nitrate Bioactivation are Disrupted in Periodontal Disease & Xerostomia
What the sources say
- Not checked yetcites [193] Sánchez, 2014, Total salivary nitrates and nitrites in oral health and periodontal disease, Nitric Oxide source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“Nitrate content in saliva is highly regulated[85,86,193,231].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Dysbiosis of the Microbiome in Pulmonary hypertension & Vascular Disease > Microbial Communities & Nitrate Bioactivation are Disrupted in Periodontal Disease & Xerostomia
What the sources say
- Not checked yetcites [85] Qin, 2012, Sialin (SLC17A5) functions as a nitrate transporter in the plasma membrane, Proc. Natl. Acad. Sci. USA source
- Not checked yetcites [86] Jin, 2013, Active secretion and protective effect of salivary nitrate against stress in human volunteers and rats, Free Radic. Biol. Med. source
- Not checked yetcites [193] Sánchez, 2014, Total salivary nitrates and nitrites in oral health and periodontal disease, Nitric Oxide source
- Not checked yetcites [231] Lundberg, 2012, Nitrate transport in salivary glands with implications for NO homeostasis, Proc. Natl. Acad. Sci. U.S.A. source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Inflammation is a prominent feature of PH that may be mediated by the host-microbe interaction[314,315].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Dysbiosis of the Microbiome in Pulmonary hypertension & Vascular Disease > Inflammation
What the sources say
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“In the injured or diseased gut, inflammation leads to increased production of reactive oxygen species such as superoxide, hydrogen peroxide and hydroxyl radicals and reactive nitrogen oxides such as peroxynitrite, dinitrogen trioxide and nitrogen dioxide[320].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Dysbiosis of the Microbiome in Pulmonary hypertension & Vascular Disease > Inflammation
What the sources say
- Not checked yetcites [320] Szabó, 2007, Peroxynitrite: biochemistry, pathophysiology and development of therapeutics, Nat. Rev. Drug Discov. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“while conversely, reduced microbial diversity is associated with inflammation, obesity, hypertension, and features of metabolic syndrome[311,313,318,319].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Dysbiosis of the Microbiome in Pulmonary hypertension & Vascular Disease > Inflammation
What the sources say
- Not checked yetcites [311] Qin, 2012, A metagenome-wide association study of gut microbiota in type 2 diabetes, Nature source
- Not checked yetcites [313] Le Chatelier, 2013, Richness of human gut microbiome correlates with metabolic markers, Nature source
- Not checked yetcites [318] Cotillard, 2013, Dietary intervention impact on gut microbial gene richness, Nature source
- Not checked yetcites [319] Sun, 2016, The role of intestinal microflora and its possible mechanisms in hypertension, Lipid Cardiovasc. Res.
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Studies suggest that in the gut, greater microbial diversity is associated with protection from inflammation and inflammatory disease[316,317]”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Dysbiosis of the Microbiome in Pulmonary hypertension & Vascular Disease > Inflammation
What the sources say
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Characteristically, dysbiosis of this ratio heralds a shift in microbiota from obligate anaerobes to nitrate-reducing, facultative anaerobes of the Proteobacteria and Firmicutes phyla[333–335].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Dysbiosis of the Microbiome in Pulmonary hypertension & Vascular Disease > Inflammation
What the sources say
- Not checked yetcites [333] Winter, 2013, Host-derived nitrate boosts growth of E. coli in the inflamed gut, Science source
- Not checked yetcites [334] Winter, 2014, Dysbiosis in the inflamed intestine: chance favors the prepared microbe, Gut Microbes source
- Not checked yetcites [335] Verdam, 2013, Human intestinal microbiota composition is associated with local and systemic inflammation inobesity, Obes. (Silver Spring). source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“This shift is particularly notable in the context of inflammatory bowel disease, where massive blooms of pathogenic, nitrate-reducing Salmonella and Escherichia coli are seen in response to inflammation[333,334,338,339].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Dysbiosis of the Microbiome in Pulmonary hypertension & Vascular Disease > Inflammation
What the sources say
- Not checked yetcites [333] Winter, 2013, Host-derived nitrate boosts growth of E. coli in the inflamed gut, Science source
- Not checked yetcites [334] Winter, 2014, Dysbiosis in the inflamed intestine: chance favors the prepared microbe, Gut Microbes source
- Not checked yetcites [338] Stecher, 2007, Salmonella enterica serovar typhimurium exploits inflammation to compete with the intestinal microbiota, PLoS Biol. source
- Not checked yetcites [339] Lundberg, 1994, Greatly increased luminal nitric oxide in ulcerative colitis, Lancet source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Many bacteria are capable of reducing nitrate to nitrite to NO via the denitrification pathway.”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Dysbiosis of the Microbiome in Pulmonary hypertension & Vascular Disease > NO Production
What the sources say
- Not checked yetcites [217] Sobko, 2006, Generation of NO by probiotic bacteria in the gastrointestinal tract, Free Radic. Biol. Med. source
- Not checked yetcites [233] Tiso, 2015, Nitrate reduction to nitrite, nitric oxide and ammonia by gut bacteria under physiological conditions, PLoS One source
- Not checked yetcites [271] Vermeiren, 2009, Nitric oxide production by the human intestinal microbiota by dissimilatory nitrate reduction to ammonium, J. Biomed. Biotechnol.
- Not checked yetcites [278] Sobko, 2004, Gastrointestinal nitric oxide generation in germ-free and conventional rats, Am. J. Physiol. Gastrointest. Liver Physiol. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“suggesting that bacterial nitrate metabolism in the gut is an important selective factor in pathogenic bacterial survival,”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Dysbiosis of the Microbiome in Pulmonary hypertension & Vascular Disease > Inflammation
What the sources say
- Not checked yetcites [323] Scales, 2016, A tale of two sites: how inflammation can reshape the microbiomes of the gut and lungs, J. Leukoc. Biol. source
- Not checked yetcites [337] Vázquez-Torres, 2016, Nitrate, nitrite and nitric oxide reductases: from the last universal common ancestor to modern bacterial pathogens, Curr. Opin. Microbiol. source
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- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“both Lactobacilli and Bifidobacteria have been shown to generate NO from nitrite in culture”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Dysbiosis of the Microbiome in Pulmonary hypertension & Vascular Disease > NO Production
What the sources say
- Not checked yetcites [217] Sobko, 2006, Generation of NO by probiotic bacteria in the gastrointestinal tract, Free Radic. Biol. Med. source
- Not checked yetcites [233] Tiso, 2015, Nitrate reduction to nitrite, nitric oxide and ammonia by gut bacteria under physiological conditions, PLoS One source
- Not checked yetcites [271] Vermeiren, 2009, Nitric oxide production by the human intestinal microbiota by dissimilatory nitrate reduction to ammonium, J. Biomed. Biotechnol.
- Not checked yetcites [278] Sobko, 2004, Gastrointestinal nitric oxide generation in germ-free and conventional rats, Am. J. Physiol. Gastrointest. Liver Physiol. source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“while Lactobacilli, Escherichia coli and Salmonella typhimurium all increase cecal NO production when supplied with nitrate[217,233,271,278].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Dysbiosis of the Microbiome in Pulmonary hypertension & Vascular Disease > NO Production
What the sources say
- Not checked yetcites [217] Sobko, 2006, Generation of NO by probiotic bacteria in the gastrointestinal tract, Free Radic. Biol. Med. source
- Not checked yetcites [233] Tiso, 2015, Nitrate reduction to nitrite, nitric oxide and ammonia by gut bacteria under physiological conditions, PLoS One source
- Not checked yetcites [271] Vermeiren, 2009, Nitric oxide production by the human intestinal microbiota by dissimilatory nitrate reduction to ammonium, J. Biomed. Biotechnol.
- Not checked yetcites [278] Sobko, 2004, Gastrointestinal nitric oxide generation in germ-free and conventional rats, Am. J. Physiol. Gastrointest. Liver Physiol. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Both commensal and pathogenic bacteria possess this capability, although it remains unclear how active these mechanisms are in vivo and exactly what benefit this provides to bacteria.”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Dysbiosis of the Microbiome in Pulmonary hypertension & Vascular Disease > NO Production
What the sources say
- Not checked yetcites [342] Sudhamsu, 2009, Bacterial nitric oxide synthases: what are they good for?, Trends Microbiol. source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Additionally, some bacteria, such as Lactobaciilus[340] and Streptomyces[341], produce NO via a bacterial NOS oxidation of L-arginine, akin to mammalian endothelial NOS function[342].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Dysbiosis of the Microbiome in Pulmonary hypertension & Vascular Disease > NO Production
What the sources say
- Not checked yetcites [340] Morita, 1997, Synthesis of nitric oxide from the two equivalent guanidino nitrogens of L-arginine by Lactobacillus fermentum, J. Bacteriol. source
- Not checked yetcites [341] Kers, 2004, Nitration of a peptide phytotoxin by bacterial nitric oxide synthase, Nature source
- Not checked yetcites [342] Sudhamsu, 2009, Bacterial nitric oxide synthases: what are they good for?, Trends Microbiol. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“At least 50% of intestinal H2S is derived from a set of commensal Proteobacteria, called the sulfate-reducing bacteria (SRB), either by cysteine degradation or a dissimilatory sulfate reduction reaction[345].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Dysbiosis of the Microbiome in Pulmonary hypertension & Vascular Disease > NO Production
What the sources say
- Not checked yetcites [345] Carbonero, 2012, Microbial pathways in colonic sulfur metabolism and links with health and disease, Front. Physiol. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“On one hand, it appears that lower concentrations of endogenously derived H2S exert beneficial cytoprotective, antioxidant and anti-inflammatory actions[344,348–351]”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Dysbiosis of the Microbiome in Pulmonary hypertension & Vascular Disease > NO Production
What the sources say
- Not checked yetcites [344] Singh, 2015, Hydrogen sulfide in physiology and diseases of the digestive tract, Microorganisms source
- Not checked yetcites [348] Liu, 2009, Hydrogen sulfide protects from intestinal ischaemia–reperfusion injury in rats, J. Pharm. Pharmacol. source
- Not checked yetcites [349] Zhao, 2016, Hydrogen sulfide improves colonic barrier integrity in DSS-induced inflammation in Caco-2 cells and mice, Int. Immunopharmacol. source
- Not checked yetcites [350] Motta, 2015, Hydrogen sulfide protects from colitis and restores intestinal microbiota biofilm and mucus production, Inflamm. Bowel Dis. source
- Not checked yetcites [351] Hirata, 2011, Endogenous hydrogen sulfide is an anti-inflammatory molecule in dextran sodium sulfate-induced colitis in mice, Dig. Dis. Sci. source
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“In Western countries, a sub-analysis of the DASH study found that nitrate-mediated blood pressure effects were first seen at daily levels of about 160mg of vegetable-based nitrate[361,371]”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Therapeutic Strategies to Target the Enterosalivary Pathway: Beyond Nitrate Supplementation > Prebiotic therapy: Dietary Interventions
What the sources say
- Not checked yetcites [361] Appel, 1997, A clinical trial of the effects of dietary patterns on blood pressure. DASH Collaborative Research Group, N. Engl. J. Med. source
- Not checked yetcites [371] Obarzanek, 1999, Using feeding studies to test the efficacy of dietary interventions: lessons from the dietary approaches to stop hypertension trial, J. Am. Diet. Assoc. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Specifically, green leafy vegetables appear to be most important in conferring these benefits[369].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Therapeutic Strategies to Target the Enterosalivary Pathway: Beyond Nitrate Supplementation > Prebiotic therapy: Dietary Interventions
What the sources say
- Not checked yetcites [369] Joshipura, 2001, The effect of fruit and vegetable intake on risk for coronary heart disease, Ann. Intern. Med. source
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Green leafy vegetables as well as root vegetables such as beets are known to contain the highest amounts of inorganic nitrate[36,161,370].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Therapeutic Strategies to Target the Enterosalivary Pathway: Beyond Nitrate Supplementation > Prebiotic therapy: Dietary Interventions
What the sources say
- Not checked yetcites [36] Kobayashi, 2015, NO-Rich diet for, Nutrients source
- Not checked yetcites [161] Hord, 2009, Food sources of nitrates and nitrites: the physiologic context for potential health benefits, Am. J. Clin. Nutr. source
- Not checked yetcites [370] Santamaria, 2006, Nitrate in vegetables: toxicity, content, intake and EC regulation, J. Sci. Food Agric. source
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“there is compelling evidence that at least some of the beneficial effects of major dietary initiatives are driven by the enterosalivary nitrate pathway.”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Therapeutic Strategies to Target the Enterosalivary Pathway: Beyond Nitrate Supplementation > Prebiotic therapy: Dietary Interventions
boostedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“with a typical DASH-compliant diet estimated to contain a range of nitrate from 174–1222mg/day[161].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Therapeutic Strategies to Target the Enterosalivary Pathway: Beyond Nitrate Supplementation > Prebiotic therapy: Dietary Interventions
What the sources say
- Not checked yetcites [161] Hord, 2009, Food sources of nitrates and nitrites: the physiologic context for potential health benefits, Am. J. Clin. Nutr. source
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Further work has since identified associations in both diets with high content of alpha linoleic acids (ALA), estimated to make up approximately 24% of total energy intake along with oleic acid in the traditional Mediterranean diet[379–381].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Therapeutic Strategies to Target the Enterosalivary Pathway: Beyond Nitrate Supplementation > Prebiotic therapy: Dietary Interventions
What the sources say
- Not checked yetcites [379] Simopoulos, 2001, The Mediterranean diets: what is so special about the diet of Greece? The scientific evidence, J. Nutr. source
- Not checked yetcites [380] Kafatos, 2000, Mediterranean diet of Crete: foods and nutrient content, J. Am. Diet. Assoc. source
- Not checked yetcites [381] Sandker, 1993, Serum cholesteryl ester fatty acids and their relation with serum lipids in elderly men in Crete and The Netherlands, Eur. J. Clin. Nutr.
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“In a high-fat diet model of PH, Kelley et al. found that mice supplemented with the NO2-FA, nitro-octadecenoic acid, for 6.5 out of 20 weeks on a high-fat diet had reductions in markers of oxidative stress, inflammation, right ventricular remodeling, and degree of pulmonary pressure elevation seen in mice without NO2-FA supplementation on the same high-fat diet[391].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Therapeutic Strategies to Target the Enterosalivary Pathway: Beyond Nitrate Supplementation > Prebiotic therapy: Dietary Interventions
What the sources say
- Not checked yetcites [391] Kelley, 2014, Fatty acid nitroalkenes ameliorate glucose intolerance and pulmonary hypertension in high-fat diet-induced obesity, Cardiovasc. Res. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Under low pH, non-enzymatic reduction of nitrite to NO produces an intermediate nitrogen dioxide radical that can react with dietary, unsaturated, electrophilic fatty acids such as the essential FAs, oleic and linoleic acid, to form nitro-conjugated fatty acids and S-nitrosothiol derivatives[93,384].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Therapeutic Strategies to Target the Enterosalivary Pathway: Beyond Nitrate Supplementation > Prebiotic therapy: Dietary Interventions
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Given such evidence, it stands to reason that the full physiological impact of the enterosalivary nitrate pathway can involve both direct nitrite/NO-mediated and NO2-FA-mediated vascular responses.”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Therapeutic Strategies to Target the Enterosalivary Pathway: Beyond Nitrate Supplementation > Prebiotic therapy: Dietary Interventions
plainconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“it is by no means clear that repopulation by probiotic bacteria must occur to achieve its intended effects[309,407].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Therapeutic Strategies to Target the Enterosalivary Pathway: Beyond Nitrate Supplementation > Probiotics
What the sources say
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“While human and animal studies have established the ability to successfully populate the oral cavity or gastrointestinal tract with specific strains, combinations of bacteria, or bacteria genetically modified to produce enzymes or metabolites[74,404–407]”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Therapeutic Strategies to Target the Enterosalivary Pathway: Beyond Nitrate Supplementation > Probiotics
What the sources say
- Not checked yetcites [74] Sobko, 2005, Gastrointestinal bacteria generate nitric oxide from nitrate and nitrite, Nitric Oxide source
- Not checked yetcites [404] Ridaura, 2013, Gut microbiota from twins discordant for obesity modulate metabolism in mice, Science source
- Not checked yetcites [405] Mekkes, 2014, The development of probiotic treatment in obesity: a review, Benef. Microbes source
- Not checked yetcites [406] Chen, 2014, Incorporation of therapeutically modified bacteria into gut microbiota inhibits obesity, J. Clin. Investig. source
- Not checked yetcites [407] Derrien, 2015, Fate, activity, and impact of ingested bacteria within the human gut microbiota, Trends Microbiol. source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“there is clear potential to treat PH with microbial interventions by modifying either oral or gastrointestinal bacteria.”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Therapeutic Strategies to Target the Enterosalivary Pathway: Beyond Nitrate Supplementation > Probiotics
boostedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“the commonly available probiotic strain, L. rhamnosus, is capable of reducing nitrate to nitrite[217]”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Therapeutic Strategies to Target the Enterosalivary Pathway: Beyond Nitrate Supplementation > Probiotics
What the sources say
- Not checked yetcites [217] Sobko, 2006, Generation of NO by probiotic bacteria in the gastrointestinal tract, Free Radic. Biol. Med. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“producing NO in the gut in response to oral nitrate administration[74,217,278]”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Therapeutic Strategies to Target the Enterosalivary Pathway: Beyond Nitrate Supplementation > Probiotics
What the sources say
- Not checked yetcites [74] Sobko, 2005, Gastrointestinal bacteria generate nitric oxide from nitrate and nitrite, Nitric Oxide source
- Not checked yetcites [217] Sobko, 2006, Generation of NO by probiotic bacteria in the gastrointestinal tract, Free Radic. Biol. Med. source
- Not checked yetcites [278] Sobko, 2004, Gastrointestinal nitric oxide generation in germ-free and conventional rats, Am. J. Physiol. Gastrointest. Liver Physiol. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Based on these findings, it is certainly plausible that L. rhamnosus or other probiotic bacterial strains, alone or in combination, may be able to improve nitrate and nitrite signaling in both the oral cavity and the gut, thus potentially influencing PH.”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Therapeutic Strategies to Target the Enterosalivary Pathway: Beyond Nitrate Supplementation > Probiotics
hedgedconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“and beneficial effects in obesity and metabolic syndrome in humans[405,420].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Therapeutic Strategies to Target the Enterosalivary Pathway: Beyond Nitrate Supplementation > Probiotics
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“and that brushing with even bactericidal toothpaste exerts little to no effect on bacterial nitrate reduction[434].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Therapeutic Strategies to Target the Enterosalivary Pathway: Beyond Nitrate Supplementation > Antibiotic & Antimicrobial Agents
What the sources say
- Not checked yetcites [434] van Maanen, 1996, Modulation of nitrate-nitrite conversion in the oral cavity, Cancer Detect. Prev.
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Conversely, epidemiological studies consistently show that in the general population, good oral hygiene (specifically frequent tooth brushing and mouthwash use) protects against development of hypertension and CVD[431–433].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Therapeutic Strategies to Target the Enterosalivary Pathway: Beyond Nitrate Supplementation > Antibiotic & Antimicrobial Agents
What the sources say
- Not checked yetcites [431] Fujita, 2009, Lower frequency of daily teeth brushing is related to high prevalence of cardiovascular risk factors, Exp. Biol. Med. source
- Not checked yetcites [432] de Oliveira, 2010, Toothbrushing, inflammation, and risk of cardiovascular disease: results from Scottish Health Survey, BMJ source
- Not checked yetcites [433] Choi, 2015, Associations among oral hygiene behavior and hypertension prevalence and control: the 2008 to 2010 Korea National Health and Nutrition Examination Survey, J. Periodontol. source
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Nitrite, for instance, disrupts protective biofilm formation by pathogenic bacteria and is currently under investigation as an adjunct to standard antibiotic therapy[235,236].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Therapeutic Strategies to Target the Enterosalivary Pathway: Beyond Nitrate Supplementation > Antibiotic & Antimicrobial Agents
What the sources say
- Not checked yetcites [235] Schlag, 2007, Inhibition of staphylococcal biofilm formation by nitrite, J. Bacteriol. source
- Not checked yetcites [236] Zemke, 2014, Nitrite modulates bacterial antibiotic susceptibility and biofilm formation in association with airway epithelial cells, Free Radic. Biol. Med. source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“while a recent crossover study in healthy women showed no blood pressure effects with similar treatment[430].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Therapeutic Strategies to Target the Enterosalivary Pathway: Beyond Nitrate Supplementation > Antibiotic & Antimicrobial Agents
What the sources say
- Not checked yetcites [430] Sundqvist, 2016, Antiseptic mouthwash use and effect on resting metabolic rate and blood pressure among healthy females: a randomized, double-blind, crossover study, FASEB J. source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“evidence suggesting that one’s choice in mouthwash (from the strongest bactericidal formulations with chlorhexidine, to weaker ones such as with triclosan or cetylpyridinium, to the widely available and weakest antiseptic formulations) greatly impacts the degree of bacterial nitrate reduction and blood pressure effects[99,429,434]”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Therapeutic Strategies to Target the Enterosalivary Pathway: Beyond Nitrate Supplementation > Antibiotic & Antimicrobial Agents
What the sources say
- Not checked yetcites [99] Woessner, 2016, A stepwise reduction in plasma and salivary nitrite with increasing strengths of mouthwash following a dietary nitrate load, Nitric Oxide source
- Not checked yetcites [429] McDonagh, 2015, The effects of chronic nitrate supplementation and the use of strong and weak antibacterial agents on plasma nitrite concentration and exercise blood pressure, Int J. Sports Med. source
- Not checked yetcites [434] van Maanen, 1996, Modulation of nitrate-nitrite conversion in the oral cavity, Cancer Detect. Prev.
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Nitrite, for instance, disrupts protective biofilm formation by pathogenic bacteria and is currently under investigation as an adjunct to standard antibiotic therapy[235,236].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Therapeutic Strategies to Target the Enterosalivary Pathway: Beyond Nitrate Supplementation > Antibiotic & Antimicrobial Agents
What the sources say
- Not checked yetcites [235] Schlag, 2007, Inhibition of staphylococcal biofilm formation by nitrite, J. Bacteriol. source
- Not checked yetcites [236] Zemke, 2014, Nitrite modulates bacterial antibiotic susceptibility and biofilm formation in association with airway epithelial cells, Free Radic. Biol. Med. source
plain- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“It is clear that these reactions are highly dependent on, and can be readily altered by, oral and gut bacteria separately or in combination.”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Conclusions
boosteddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: unclear — It is unclear why the paper says it holds.
- It may state two separate claims as one. 71
- Probably not a substantial claim. 42
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“For example, obesity, hyperlipidemia, and systemic hypertension are common risk factors for Group I PAH as well as Group II (secondary to left-sided heart failure or PH-heart failure with preserved ejection fraction, HFpEF)[12,15,16], and are also a feature of HIV infection[17,18].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Dysfunctional Nitric Oxide Signaling underlies Pulmonary Hypertension Pathogenesis > Pulmonary Hypertension
What the sources say
- Partly supportedcites [12] Robbins, 2009, Association of the metabolic syndrome with pulmonary venous hypertension, Chest sourceExperimental — accuracy not yet measured
The Study Patients section identifies PAH as Group I and pulmonary venous hypertension (PVH) as Group II. Table 1 in the PVH Patients section reports obesity, hypertension, and hyperlipidemia in both groups, but they were substantially more prevalent in PVH; hyperlipidemia occurred in only 17% of PAH patients. The paper describes these as observed features, not established risk factors for both groups. The separate HIV clause is attached to other citations. (LLM, conf=0.87)
- Partly supportedcites [15] Lai, 2016, SIRT3-AMP-activated protein kinase activation by nitrite and metformin improves hyperglycemia and normalizes pulmonary hypertension associated with heart failure with preserved ejection fraction, Circulation sourceExperimental — accuracy not yet measured
The Introduction and Discussion (pages not provided) identify obesity and hypertension as common comorbidities of Group II PH associated with HFpEF. They do not identify hyperlipidemia as a risk factor or establish that all three are common risk factors for Group I PAH; instead, they report a higher prevalence of obesity and hypertension in PH-HFpEF than in PAH. The HIV clause has separate citations and is not attributed to this source. (LLM, conf=0.86)
- Partly supportedcites [16] Burger, 2011, Comparison of body habitus in patients with pulmonary arterial hypertension enrolled in the registry to evaluate early and long-term PAH disease management with normative values from the national health and nutrition examination survey, Mayo Clin. Proc. sourceExperimental — accuracy not yet measured
The discussion (page not provided) reports more obesity in some Group I PAH subgroups and more statin use and systemic hypertension among obese patients. It treats these comorbidities as possible, not established, PAH risk factors; it does not directly report hyperlipidemia or assess Group II PH. The HIV clause has separate citations in the citing sentence and is not attributed to this source here. (LLM, conf=0.88)
- Supportedcites [17] Nix, 2014, Metabolic syndrome, diabetes, and cardiovascular risk in HIV, Curr. HIV/AIDS Rep. source
The citation is attached to the claim that these conditions occur in people with HIV, not to the PAH risk-factor claim supported by the earlier citations. The Metabolic Syndrome section (page unavailable) describes abdominal obesity and dyslipidemia in HIV-associated lipodystrophy and reports hypertension alongside adverse lipid levels in HIV cohorts. It does not establish that HIV increases obesity relative to people without HIV, but the citing sentence does not make that comparison. (LLM, conf=0.86)
- Not checked yetcites [18] Jantarapakde, 2014, Prevalence of metabolic syndrome among antiretroviral-naive and antiretroviral-experienced HIV-1 infected Thai adults, AIDS Patient Care Stds. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Similarly, nitrite administered via inhalation or infusion is a selective pulmonary vasodilator with increased activity in hypoxia[142–144]”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Microbial Nitrate Reduction to Nitrite and NO is Physiologically Important > Pulmonary Hypertension
What the sources say
- Partly supportedcites [142] Blood, 2011, Inhaled nitrite reverses hemolysis-induced pulmonary vasoconstriction in newborn lambs without blood participation, Circulation sourceExperimental — accuracy not yet measured
The Results (page unavailable) show that inhaled nitrite reduced pulmonary vascular resistance in newborn lambs, but intravenous nitrite had minimal effect under the study’s hemolysis conditions. The Discussion (page unavailable) reports pulmonary vasodilation from intravenous nitrite during hypoxia in previous studies, while noting that it was transient and used a higher dose. The paper does not establish that either route has increased vasodilator activity in hypoxia compared with nonhypoxic conditions, or that both routes are selectively pulmonary vasodilators. (LLM, conf=0.88)
- Not checked yetcites [143] Hunter, 2004, Inhaled nebulized nitrite is a hypoxia-sensitive NO-dependent selective pulmonary vasodilator, Nat. Med. source
- Supportedcites [144] Ingram, 2010, Low-dose sodium nitrite vasodilates hypoxic human pulmonary vasculature by a means that is not dependent on a simultaneous elevation in plasma nitrite, Am. J. Physiol. Heart Circ. Physiol. source
The Abstract reports that nebulized nitrite reduced hypoxia-induced pulmonary hypertension in newborn lambs and that intravenous nitrite reduced indexes of pulmonary arterial pressure in hypoxic human volunteers, with no effect observed during normoxia. The Discussion describes nitrite as a pulmonary vasodilator whose action is potentiated by hypoxia and concludes that low-dose sodium nitrite can cause selective vasodilatation in hypoxic vasculature. (LLM, conf=0.88)
plaindirect- Asserted: passes — The authors put it forward as true.
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The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Further diversity exists between the varied micro-ecologies of the mouth[174,178], such as the tooth surface, gingiva, hard and soft palate, and even regionally on the tongue (Figure 2)[173,176,179].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > The Oral Microbiome and Bacterial Nitrate Reduction > Complexity of the Oral Microbiome
What the sources say
- Partly supportedcites [174] Eren, 2014, Oligotyping analysis of the human oral microbiome, PNAS sourceExperimental — accuracy not yet measured
The Results (page unavailable) report distinct microbial communities across oral sites, including plaque, keratinized gingiva, hard palate, and tongue dorsum. The paper does not report sampling the soft palate or comparing regions within the tongue, so those examples are not supported by this source. (LLM, conf=0.86)
- Not checked yetcites [178] Xu, 2015, Oral cavity contains distinct niches with dynamic microbial communities, Environ. Microbiol. source
- Supportedcites [173] Segata, 2012, Composition of the adult digestive tract bacterial microbiome based on seven mouth surfaces, tonsils, throat and stool samples, Genome Biol. source
The citation to this paper is attached to the general claim that oral micro-ecologies differ, not to the later examples of soft palate or regional variation on the tongue. In Results (‘Microbial community structure indicates four distinct community types’ and ‘Comparison of microbial communities from the two tooth surface-associated sites’; page not supplied), the paper reports distinct communities across oral sites, including adjacent tooth-surface niches. (LLM, conf=0.93)
- Supportedcites [176] Aas, 2005, Defining the normal bacterial flora of the oral cavity, J. Clin. Microbiol. source
The Results and Discussion describes distinct bacterial profiles across tooth surfaces, subgingival plaque, hard and soft palates, and different regions of the tongue. It specifically reports considerable differences between the tongue dorsum and lateral tongue surface. The paper studies subgingival plaque rather than gingival tissue itself. (LLM, conf=0.92)
- Not checked yetcites [179] Krishnan, 2016, A practical guide to the oral microbiome and its relation to health and disease, Oral Dis.
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
- Partly supported
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“Elevated rates of generation of these oxidative inflammatory mediators can have direct effects on enterocytes and mucosal integrity, impair NO-dependent vascular function, reduce nitrate and nitrite absorption, and exert selective pressure on bacteria by augmenting innate anti-bacterial effects[204,233,321–324].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Dysbiosis of the Microbiome in Pulmonary hypertension & Vascular Disease > Inflammation
What the sources say
- Not checked yetcites [204] Hyde, 2014, Characterization of the rat oral microbiome and the effects of dietary nitrate, Free Radic. Biol. Med. source
- Partly supportedcites [233] Tiso, 2015, Nitrate reduction to nitrite, nitric oxide and ammonia by gut bacteria under physiological conditions, PLoS One sourceExperimental — accuracy not yet measured
Split into 2 atoms — 0 confirmed, 2 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Could not verifycites [321] Jädert, 2014, Preventive and therapeutic effects of nitrite supplementation in experimental inflammatory bowel disease, Redox Biol. sourceExperimental — accuracy not yet measured
The Introduction discusses mucosal integrity and nitrate/nitrite absorption, while the Discussion describes epithelial injury and inflammatory defects in the microcirculation. Neither section attributes those effects to elevated generation of oxidative inflammatory mediators, or says those mediators reduce nitrate/nitrite absorption or select for bacteria. Searches for oxidative mediators, impaired absorption, and antibacterial selective pressure found no passage establishing the claimed chain of effects. (LLM, conf=0.72)
- Partly supportedcites [322] Chokshi, 2008, The role of nitric oxide in intestinal epithelial injury and restitution in neonatal necrotizing enterocolitis, Semin. Perinatol. sourceExperimental — accuracy not yet measured
Split into 2 atoms — 1 confirmed, 1 partially supported, 0 disputed, 0 misattributed, 0 unverifiable. Expand the claim to see per-atom verdicts.
- Partly supportedcites [323] Scales, 2016, A tale of two sites: how inflammation can reshape the microbiomes of the gut and lungs, J. Leukoc. Biol. sourceExperimental — accuracy not yet measured
The Introduction says inflammatory reactive nitrogen species have antimicrobial activity and can give denitrifying bacteria a selective advantage at inflamed mucosal surfaces. It does not address direct effects on enterocytes or mucosal integrity, impaired NO-dependent vascular function, or reduced nitrate and nitrite absorption. It describes bacterial selection chiefly through inflammation-derived nitrate supporting bacterial growth, rather than through augmented antibacterial effects. (LLM, conf=0.87)
- Not checked yetcites [324] Petersson, 2007, Dietary nitrate increases gastric mucosal blood flow and mucosal defense, Am. J. Physiol. Gastrointest. Liver Physiol. source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
The sources with a verdict support this claim; the rest weren’t checked yet, have no full text we could read, or their verdicts aren’t rated yet.
In the paper
“commensal gut bacteria are able to directly produce NO and also modify NO production, potentially influencing regional blood flow, mucosal integrity, microbial diversity, and effective nitrate and nitrite uptake.”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Dysbiosis of the Microbiome in Pulmonary hypertension & Vascular Disease > NO Production
What the sources say
- Not checked yetcites [217] Sobko, 2006, Generation of NO by probiotic bacteria in the gastrointestinal tract, Free Radic. Biol. Med. source
- Supportedcites [233] Tiso, 2015, Nitrate reduction to nitrite, nitric oxide and ammonia by gut bacteria under physiological conditions, PLoS One source
The Abstract reports NO production by bacterial cultures, including nitrite conversion to NO by E. coli. It also describes how bacterial lactic-acid production acidifies the medium and generates NO through non-enzymatic nitrite reduction, supporting the claim that gut bacteria can both produce NO and alter its production. The Discussion (Physiological significance of NO formation by bacterial nitrate reduction; page unavailable) likewise describes NO generated by gut bacteria. (LLM, conf=0.88)
- Not checked yetcites [271] Vermeiren, 2009, Nitric oxide production by the human intestinal microbiota by dissimilatory nitrate reduction to ammonium, J. Biomed. Biotechnol.
- Not checked yetcites [278] Sobko, 2004, Gastrointestinal nitric oxide generation in germ-free and conventional rats, Am. J. Physiol. Gastrointest. Liver Physiol. source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Indeed, members of these genera are among the only probiotics accepted in Canada and Italy as ones with sufficient evidence to market beneficial health claims[400] and achieve GRAS status (“generally recognized as safe”) in the U.S.[399]”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Therapeutic Strategies to Target the Enterosalivary Pathway: Beyond Nitrate Supplementation > Probiotics
What the sources say
- Could not verifycites [400] Hill, 2014, Expert consensus document. The International Scientific Association for Probiotics and Prebiotics consensus statement on the scope and appropriate use of the term probiotic, Nat. Rev. Gastroenterol. Hepatol. sourceExperimental — accuracy not yet measured
Citation [399] is attached to the U.S. GRAS-status portion of the sentence, not the Canada-and-Italy health-claims portion. The Consensus Statements table (p. 6) refers to safe probiotic species and cites the FDA’s GRAS guidance, but our copy does not say that members of Bifidobacterium or Lactobacillus have achieved GRAS status. Searches for those genera together with GRAS found no passage establishing that link. (LLM, conf=0.72)
- Not checked yetcites [399] Gogineni, 2013, Probiotics: history and evolution, J. Anc.
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
- Could not verify
The cited sources support only part of this claim — read each source’s verdict below.
In the paper
“At the genus level, Lactobacilli are common and robust bacteria in the mouth and gut, able to tolerate low pH and to generate NO in culture[74,412].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Therapeutic Strategies to Target the Enterosalivary Pathway: Beyond Nitrate Supplementation > Probiotics
What the sources say
- Not checked yetcites [74] Sobko, 2005, Gastrointestinal bacteria generate nitric oxide from nitrate and nitrite, Nitric Oxide source
- Partly supportedcites [412] Edlund, 2015, Meta-omics uncover temporal regulation of pathways across oral microbiome genera during in vitro sugar metabolism, ISME J. sourceExperimental — accuracy not yet measured
The Results and discussion section, under “Multiple low pH tolerance mechanisms are active in Lactobacillus” (page not provided), describes lactobacilli in oral plaque and reports their acid resistance and activity at low pH, including in vitro. Our copy does not establish that they are common in the gut or that they generate nitric oxide (NO) in culture. (LLM, conf=0.88)
plain- Asserted: passes — The authors put it forward as true.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Deficits in mammalian nitric oxide (NO) signaling have been linked to PH pathogenesis, as well as a host of associated risk factors such as hypertension, obesity, reduced insulin sensitivity and CVD.”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Introduction
plaincorrelational- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper may give no reason why it holds.
In the paper
“Characterization of body site-specific microbial ecosystems has revealed a highly diverse and regional set of microbial community networks that can exert systemic effects on the host through the production of metabolites, shaping the immune response, and influencing host gene expression[1].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Introduction
What the sources say
- Not checked yetcites [1] Takahashi, 2015, Commensal microbiota-derived signals regulate host immune system through epigenetic modifications, Inflamm. Regen. source
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Our discussion centers on the hypothesis that maintenance of pulmonary and systemic vascular health in mammals in part depends on the enzymatic reduction of dietary nitrates by commensal oral bacteria to vasoactive and anti-inflammatory mediators that provide systemic NO-effects critical under conditions of hypoxemia and stress.”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Introduction
hedgedconditional- Asserted: fails — The authors may not put it forward as true.
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Probably not a substantial claim. The authors may not put it forward as true. The paper may give no reason why it holds.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“Changes in these microbial populations have been linked to many ‘non-infectious’ diseases, such as obesity, diabetes, and cardiovascular disease (CVD).”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Introduction
plaincorrelational- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Chiefly, NO acts directly on smooth muscle cells via activation of soluble guanylyl cyclase leading to formation of the second-messenger, cyclic guanosine monophosphate (cGMP), that in turn promotes smooth muscle relaxation and inhibits both platelet function and vascular smooth muscle cell proliferation and migration[19–21].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Dysfunctional Nitric Oxide Signaling underlies Pulmonary Hypertension Pathogenesis > Nitric Oxide Signaling Dysfunction in Pulmonary Hypertension
What the sources say
- Not checked yetcites [19] Lundberg, 2015, Strategies to increase nitric oxide signalling in cardiovascular disease, Nat. Rev. Drug Discov. source
- Not checked yetcites [20] Moncada, 1993, The L-arginine-nitric oxide pathway, N. Engl. J. Med. source
- Not checked yetcites [21] Chatterjee, 2008, Endothelial nitric oxide (NO) and its pathophysiologic regulation, Vasc. Pharmacol. source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“The hallmark feature of PAH and other forms of PH is reduced bioavailability of NO signaling and poor endothelial responsiveness to triggers of vasodilatation[28–34].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Dysfunctional Nitric Oxide Signaling underlies Pulmonary Hypertension Pathogenesis > Nitric Oxide Signaling Dysfunction in Pulmonary Hypertension
What the sources say
- Not checked yetcites [28] Gaston, 1994, The biology of nitrogen oxides in the airways, Am. J. Respir. Crit. Care Med. source
- Not checked yetcites [29] Kaneko, 1998, Biochemical reaction products of nitric oxide as quantitative markers of primary pulmonary hypertension, Am. J. Respir. Crit. Care Med. source
- Not checked yetcites [30] Ozkan, 2001, High levels of nitric oxide in individuals with pulmonary hypertension receiving epoprostenol therapy, Lung source
- Not checked yetcites [31] Champion, 2002, Adenoviral gene transfer of endothelial nitric-oxide synthase (eNOS) partially restores normal pulmonary arterial pressure in eNOS-deficient mice, Proc. Natl. Acad. Sci. source
- Not checked yetcites [32] Hsu, 2007, Hemolysis in sickle cell mice causes pulmonary hypertension due to global impairment in nitric oxide bioavailability, Blood source
- Not checked yetcites [33] Goret, 2008, Acute administration of l-arginine restores nitric oxide-mediated relaxation in isolated pulmonary arteries from pulmonary hypertensive exercise trained rats, Eur. J. Pharmacol. source
- Not checked yetcites [34] Tonelli, 2013, Nitric oxide deficiency in pulmonary hypertension: pathobiology and implications for therapy, Pulm. Circ. source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Classically, the majority of NO is derived from the oxidation of the essential amino acid, L-arginine by a set of 3 isoforms of the enzyme nitric oxide synthase (NOS) in a reaction requiring oxygen, reduced nicotinamide-adenine dinucleotide phosphate (NADPH), tetrahydrobiopterin (BH4) and other cofactors[20,22].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Dysfunctional Nitric Oxide Signaling underlies Pulmonary Hypertension Pathogenesis > Nitric Oxide Signaling Dysfunction in Pulmonary Hypertension
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“As with NOS-derived NO, inorganic nitrite demonstrates robust NO-signaling effects[52,53,57,59] and contributes to basal vascular tone[51,55,60,61], blood pressure[62–66], protection from endothelial dysfunction[67–71] and vascular inflammation[72] under conditions of metabolic and inflammatory stress.”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > The nitrate-nitrite-NO Pathway & Enterosalivary Circulation of Nitrate as ‘Alternate’ Source of NO Signaling
What the sources say
- Not checked yetcites [52] Gladwin, 2005, The emerging biology of the nitrite anion, Nat. Chem. Biol. source
- Not checked yetcites [53] Huang, 2005, Enzymatic function of hemoglobin as a nitrite reductase that produces NO under allosteric control, J. Clin. Investig. source
- Not checked yetcites [57] Bueno, 2013, Nitrite signaling in pulmonary hypertension: mechanisms of bioactivation, signaling, and therapeutics, Antioxid. Redox Signal. source
- Not checked yetcites [59] Gladwin, 2006, Nitrite as a vascular endocrine nitric oxide reservoir that contributes to hypoxic signaling, cytoprotection, and vasodilation, Am. J. Physiol. Heart Circ. Physiol. source
- Not checked yetcites [51] Cosby, 2003, Nitrite reduction to nitric oxide by deoxyhemoglobin vasodilates the human circulation, Nat. Med. source
- Not checked yetcites [55] Dejam, 2007, Nitrite infusion in humans and nonhuman primates: endocrine effects, pharmacokinetics, and tolerance formation, Circulation source
- Not checked yetcites [60] Gladwin, 2000, Role of circulating nitrite and S-nitrosohemoglobin in the regulation of regional blood flow in humans, Proc. Natl. Acad. Sci. source
- Not checked yetcites [61] Lidder, 2013, Vascular effects of dietary nitrate (as found in green leafy vegetables and beetroot) via the nitrate-nitrite-nitric oxide pathway, Br. J. Clin. Pharmacol. source
- Not checked yetcites [62] Classen, 1990, Hypothesis: the effect of oral nitrite on blood pressure in the spontaneously hypertensive rat. Does dietary nitrate mitigate hypertension after conversion to nitrite?, J. Am. Coll. Nutr. source
- Not checked yetcites [63] Beier, 1995, Antihypertensive effect of oral nitrite uptake in the spontaneously hypertensive rat, Arzneimittelforschung
boosteddirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Nitrite is then swallowed where it can undergo a diversity of downstream reactions, including formation of NO and NO-donating species following a) protonation to HNO2 and an array of secondary nitrosating and nitrating species in reactions facilitated by the low pH of the stomach[80,83,89–91], or b) further reduction by enteric bacterial nitrite reductases (NiRs)[74].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > The nitrate-nitrite-NO Pathway & Enterosalivary Circulation of Nitrate as ‘Alternate’ Source of NO Signaling
What the sources say
- Not checked yetcites [80] Licht, 1986, Mechanisms for nitrite loss from the stomach, Carcinogenesis source
- Not checked yetcites [83] McKnight, 1997, Chemical synthesis of nitric oxide in the stomach from dietary nitrate in humans, Gut source
- Not checked yetcites [89] Benjamin, 1994, Stomach NO synthesis, Nature source
- Not checked yetcites [90] Lundberg, 1994, Intragastric nitric oxide production in humans: measurements in expelled air, Gut source
- Not checked yetcites [91] Fukuto, 2012, Small molecule signaling agents: the integrated chemistry and biochemistry of nitrogen oxides, oxides of carbon, dioxygen, hydrogen sulfide, and their derived species, Chem. Res. Toxicol. source
- Not checked yetcites [74] Sobko, 2005, Gastrointestinal bacteria generate nitric oxide from nitrate and nitrite, Nitric Oxide source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“These reactions can beneficially regulate cardio-metabolic function and will be attenuated or abolished by chemical or physical destruction of the oral microbiota[60,75,76,97–99].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > The nitrate-nitrite-NO Pathway & Enterosalivary Circulation of Nitrate as ‘Alternate’ Source of NO Signaling
What the sources say
- Not checked yetcites [60] Gladwin, 2000, Role of circulating nitrite and S-nitrosohemoglobin in the regulation of regional blood flow in humans, Proc. Natl. Acad. Sci. source
- Not checked yetcites [75] Lundberg, 2004, Inorganic nitrate is a possible source for systemic generation of nitric oxide, Free Radic. Biol. Med. source
- Not checked yetcites [76] Govoni, 2008, The increase in plasma nitrite after a dietary nitrate load is markedly attenuated by an antibacterial mouthwash, Nitric Oxide source
- Not checked yetcites [97] Webb, 2008, Acute blood pressure lowering, vasoprotective, and antiplatelet properties of dietary nitrate via bioconversion to nitrite, Hypertension source
- Not checked yetcites [98] Hendgen-Cotta, 2012, Dietary nitrate supplementation improves revascularization in chronic ischemia, Circulation source
- Not checked yetcites [99] Woessner, 2016, A stepwise reduction in plasma and salivary nitrite with increasing strengths of mouthwash following a dietary nitrate load, Nitric Oxide source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“In turn, these reactions and their products can not only instigate salutary NO signaling responses, but also post-translational protein modifications and altered patterns of gene expression.”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > The nitrate-nitrite-NO Pathway & Enterosalivary Circulation of Nitrate as ‘Alternate’ Source of NO Signaling
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Oral supplementation with either nitrite or nitrate increases circulating nitrite levels and prevents and reverses endothelial dysfunction in a dose-dependent manner both in mice[68,69] and in healthy[70,71,97,111,112], hypertensive[113], and obese individuals[114], or in those with hypercholesterolemia[115] and peripheral arterial disease[116].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Microbial Nitrate Reduction to Nitrite and NO is Physiologically Important > Blood Pressure & Endothelial Health
What the sources say
- Not checked yetcites [68] Stokes, 2009, Dietary nitrite prevents hypercholesterolemic microvascular inflammation and reverses endothelial dysfunction, Am. J. Physiol. Heart Circ. Physiol. source
- Not checked yetcites [69] Sindler, 2011, Nitrite supplementation reverses vascular endothelial dysfunction and large elastic artery stiffness with aging, Aging Cell. source
- Not checked yetcites [70] Rodriguez-Mateos, 2015, Interactions between cocoa flavanols and inorganic nitrate: additive effects on endothelial function at achievable dietary amounts, Free Radic. Biol. Med. source
- Not checked yetcites [71] Lara, 2016, Effects of inorganic nitrate and beetroot supplementation on endothelial function: a systematic review and meta-analysis, Eur. J. Nutr. source
- Not checked yetcites [97] Webb, 2008, Acute blood pressure lowering, vasoprotective, and antiplatelet properties of dietary nitrate via bioconversion to nitrite, Hypertension source
- Not checked yetcites [111] Liu, 2013, Effects of a nitrate-rich meal on arterial stiffness and blood pressure in healthy volunteers, Nitric Oxide source
- Not checked yetcites [112] Lee, 2015, Effects of chronic dietary nitrate supplementation on the hemodynamic response to dynamic exercise, Am. J. Physiol. Regul. Integr. Comp. Physiol. source
- Not checked yetcites [113] Kapil, 2015, Dietary nitrate provides sustained blood pressure lowering in hypertensive patients: a randomized, phase 2, double-blind, placebo-controlled study, Hypertension source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Additionally, in the setting of heart failure and cardiomyopathy, dietary nitrate improves left ventricular function in mice[133] and overall cardiac contractility and exercise performance in humans[134–137]”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Microbial Nitrate Reduction to Nitrite and NO is Physiologically Important > Exercise Capacity & Oxygen Utilization
What the sources say
- Not checked yetcites [133] Rammos, 2016, Impact of dietary nitrate on age-related diastolic dysfunction, Eur. J. Heart Fail. source
- Not checked yetcites [134] Coggan, 2015, Acute dietary nitrate intake improves muscle contractile function in patients with heart failure: a, Circ. Heart Fail. source
- Not checked yetcites [135] Coggan, 2016, Dietary Nitrate and Skeletal Muscle Contractile Function in Heart Failure, Curr. Heart Fail Rep. source
- Not checked yetcites [136] Kerley, 2016, Dietary nitrate increases exercise tolerance in patients with non-ischemic, dilated cardiomyopathy-a double-blind, randomized, placebo-controlled, crossover trial, J. Heart Lung Transplant. source
- Not checked yetcites [137] Zamani, 2015, Effect of inorganic nitrate on exercise capacity in heart failure with preserved ejection fraction, Circulation source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“In terms of PH, there have been no human clinical studies testing the effects of oral nitrate or nitrite, though animal model data support a therapeutic role.”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Microbial Nitrate Reduction to Nitrite and NO is Physiologically Important > Pulmonary Hypertension
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Inhaled NO induces vasodilation in PAH and is capable of reversing hypoxic pulmonary vasoconstriction[139–141].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Microbial Nitrate Reduction to Nitrite and NO is Physiologically Important > Pulmonary Hypertension
What the sources say
- Not checked yetcites [139] Frostell, 1991, Inhaled nitric oxide. A selective pulmonary vasodilator reversing hypoxic pulmonary vasoconstriction, Circulation source
- Not checked yetcites [140] Pepke-Zaba, 1991, Inhaled nitric oxide as a cause of selective pulmonary vasodilatation in pulmonary hypertension, Lancet source
- Not checked yetcites [141] Totzeck, 2012, Nitrite regulates hypoxic vasodilation via myoglobin-dependent nitric oxide generation, Circulation source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Yet, despite the importance of these microbial populations, relatively little is known about the identity and function of specific bacteria and their effects on nitrate metabolism.”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Microbial Nitrate Reduction to Nitrite and NO is Physiologically Important > Pulmonary Hypertension
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Delivered via intravenous, inhaled, or oral routes, nitrite reduces pulmonary and right heart pressures and prevents or reverses characteristic vascular remodeling and right ventricular hypertrophy (RVH) in several animal models of PAH[15,117,143,146–149].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Microbial Nitrate Reduction to Nitrite and NO is Physiologically Important > Pulmonary Hypertension
What the sources say
- Not checked yetcites [15] Lai, 2016, SIRT3-AMP-activated protein kinase activation by nitrite and metformin improves hyperglycemia and normalizes pulmonary hypertension associated with heart failure with preserved ejection fraction, Circulation source
- Not checked yetcites [117] Alef, 2011, Nitrite-generated NO circumvents dysregulated arginine/NOS signaling to protect against intimal hyperplasia in Sprague-Dawley rats, J. Clin. Investig. source
- Not checked yetcites [143] Hunter, 2004, Inhaled nebulized nitrite is a hypoxia-sensitive NO-dependent selective pulmonary vasodilator, Nat. Med. source
- Not checked yetcites [146] Casey, 2009, Pulmonary vasodilator responses to sodium nitrite are mediated by an allopurinol-sensitive mechanism in the rat, Am. J. Physiol. Heart Circ. Physiol. source
- Not checked yetcites [147] Pankey, 2012, Effect of chronic sodium nitrite therapy on monocrotaline-induced pulmonary hypertension, Nitric Oxide source
- Not checked yetcites [148] Dias-Junior, 2006, Low-dose intravenous nitrite improves hemodynamics in a canine model of acute pulmonary thromboembolism, Free Radic. Biol. Med. source
- Not checked yetcites [149] Horstman, 1998, Prolonged inhaled NO attenuates hypoxic, but not monocrotaline-induced, pulmonary vascular remodeling in rats, Anesth. Analg. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“For many years, dietary nitrate and nitrite were considered harmful for regular human consumption due to two prominent health concerns, the development of methemoglobinemia and the potential for carcinogenic effects.”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Safety of Inorganic Nitrate and Nitrite
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In the paper
“Methemogobinemia becomes clinically significant when baseline levels of metHgb (1–3%) rise to 5–12%, with cyanosis and fatal toxicity occurring at levels between 30–50%[153].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Safety of Inorganic Nitrate and Nitrite
What the sources say
- Not checked yetcites [153] Cortazzo, 2014, Methemoglobinemia: a review and recommendations for management, J. Cardiothorac. Vasc. Anesth. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Ostensibly, the toxic effects of nitrate and nitrite are driven by the more reactive nitrite after either oral reduction by the enterosalivary pathway or direct consumption.”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Safety of Inorganic Nitrate and Nitrite
hedgeddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Up to 80% of oral bacteria are dominated by about 200 species in the Phyla Firmicutes (esp. Streptococcus, Veillonella, Granulicatella, Gemella spp.) and Proteobacteria (esp. Neisseria, Haemophilus spp.), with contributions from Bacteroidetes, Actinobacteria and Fusobacteria totaling upwards of 95% of all identified oral microbiota (Figure 2)[171–177].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > The Oral Microbiome and Bacterial Nitrate Reduction > Complexity of the Oral Microbiome
What the sources say
- Not checked yetcites [171] Dewhirst, 2010, The human oral microbiome, J. Bacteriol. source
- Not checked yetcites [172] Zaura, 2009, Defining the healthy “core microbiome” of oral microbial communities, BMC Microbiol. source
- Not checked yetcites [173] Segata, 2012, Composition of the adult digestive tract bacterial microbiome based on seven mouth surfaces, tonsils, throat and stool samples, Genome Biol. source
- Not checked yetcites [174] Eren, 2014, Oligotyping analysis of the human oral microbiome, PNAS source
- Not checked yetcites [175] Bik, 2010, Bacterial diversity in the oral cavity of 10 healthy individuals, ISME J. source
- Not checked yetcites [176] Aas, 2005, Defining the normal bacterial flora of the oral cavity, J. Clin. Microbiol. source
- Not checked yetcites [177] Ahn, 2011, Oral microbiome profiles: 16S rRNA pyrosequencing and microarray assay comparison, PLoS One source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Culture-independent sequencing of the bacterial 16S ribosome has suggested an estimated 50–100 billion bacteria in the mouth, comprised of nearly 700 identified bacterial species[170,171].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > The Oral Microbiome and Bacterial Nitrate Reduction > Complexity of the Oral Microbiome
What the sources say
hedged- Asserted: passes — The authors put it forward as true.
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In the paper
“Local variation in site-specific “core” microbial members speaks to the heterogeneity of influences bacterial communities experience, including host factors such as age, diet, geography and oral health[180–182].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > The Oral Microbiome and Bacterial Nitrate Reduction > Complexity of the Oral Microbiome
What the sources say
- Not checked yetcites [180] McLean, 2014, Advancements toward a systems level understanding of the human oral microbiome, Front. Cell. Infect. Microbiol. source
- Not checked yetcites [181] Chen, 2014, Application of high-throughput sequencing in understanding human oral microbiome related with health and disease, Front. Microbiol. source
- Not checked yetcites [182] Kumar, 2016, From focal sepsis to periodontal medicine: a century of exploring the role of the oral microbiome in systemic disease, J. Physiol.
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“For instance, saccharolytic (sugar metabolizing) bacteria such as Streptococcus and Lactobacillus have been associated with dental caries, while proteolytic (protein metabolizing) bacteria such as Prevotella and Porphyromonas have been associated with periodontitis and halitosis[183].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > The Oral Microbiome and Bacterial Nitrate Reduction > Complexity of the Oral Microbiome
What the sources say
- Not checked yetcites [183] Takahashi, 2015, Oral microbiome metabolism: from "Who Are They?" to "What Are They Doing?", J. Dental Res. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“while more recent work has linked Porphyromonas gingivalis to atherosclerosis[185], smoking[186], and several cancers[187].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > The Oral Microbiome and Bacterial Nitrate Reduction > Complexity of the Oral Microbiome
What the sources say
- Not checked yetcites [185] Ford, 2007, Anti-P. gingivalis response correlates with atherosclerosis, J. Dent. Res. source
- Not checked yetcites [186] Morris, 2013, Comparison of the respiratory microbiome in healthy nonsmokers and smokers, Am. J. Respir. Crit. Care Med. source
- Not checked yetcites [187] Atanasova, 2014, Looking in the Porphyromonas gingivalis cabinet of curiosities: the microbium, the host and cancer association, Mol. Oral Microbiol. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Amid this complexity, an ever-growing number of specific microbial taxa have been associated with both oral and systemic diseases[181,182].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > The Oral Microbiome and Bacterial Nitrate Reduction > Complexity of the Oral Microbiome
What the sources say
- Not checked yetcites [181] Chen, 2014, Application of high-throughput sequencing in understanding human oral microbiome related with health and disease, Front. Microbiol. source
- Not checked yetcites [182] Kumar, 2016, From focal sepsis to periodontal medicine: a century of exploring the role of the oral microbiome in systemic disease, J. Physiol.
plaincorrelational- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
In the paper
“Reduction of nitrate to nitrite by molybdenum-dependent nitrate reductases is the initial and rate-limiting step in anaerobic nitrogen metabolism[77].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > The Oral Microbiome and Bacterial Nitrate Reduction > Bacterial Nitrate Reduction
What the sources say
- Not checked yetcites [77] Sparacino-Watkins, 2014, Nitrate and periplasmic nitrate reductases, Chem. Soc. Rev. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Broadly, nitrate reduction is classified into three major pathways (Figure 3)[77,195–197]: 1) Respiratory denitrification, catalyzed by membrane-bound nitrate reductase, nar, or periplasmic nap, is the major electrochemical respiratory pathway for bacterial energy generation under hypoxia via generation of a proton motive force, serving as a two-electron sink in the final step of ATP generation”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > The Oral Microbiome and Bacterial Nitrate Reduction > Bacterial Nitrate Reduction
What the sources say
- Not checked yetcites [77] Sparacino-Watkins, 2014, Nitrate and periplasmic nitrate reductases, Chem. Soc. Rev. source
- Not checked yetcites [195] Kox, 2015, The nitrogen cycle, Princ. Plant-Microbe Interact. source
- Not checked yetcites [196] Brittain, 1992, Bacterial nitrite-reducing enzymes, Eur. J. Biochem. source
- Not checked yetcites [197] Maia, 2014, How biology handles nitrite, Chem. Rev. source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“Indeed, even the nitrate-nitrite-NO pathway is affected by microbial diversity[190] and oral pathology[191–193].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > The Oral Microbiome and Bacterial Nitrate Reduction > Complexity of the Oral Microbiome
What the sources say
- Not checked yetcites [190] Hyde, 2014, Metagenomic analysis of nitrate-reducing bacteria in the oral cavity: implications for nitric oxide homeostasis, PLoS One source
- Not checked yetcites [191] Doel, 2004, Protective effect of salivary nitrate and microbial nitrate reductase activity against caries, Eur. J. Oral Sci. source
- Not checked yetcites [192] Schreiber, 2010, Denitrification in human dental plaque, BMC Biol. source
- Not checked yetcites [193] Sánchez, 2014, Total salivary nitrates and nitrites in oral health and periodontal disease, Nitric Oxide source
plaindirect- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Both the oral virome and mycobiome thus have the potential to alter bacterial nitrate metabolism through alterations in bacterial populations and their metabolism, direct reduction of nitrate and alterations in metabolic substrate, changing local host and environmental conditions such as stimulating inflammation, and propagation of oral and systemic disease.”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > The Oral Microbiome and Bacterial Nitrate Reduction > Local Factors Influence Bacterial Nitrate Reduction
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“Importantly, multiple fungal species, including the ubiquitous Candida, contain a fungal nitrate reductase enzyme and are known nitrate-reducers in the environment[229,230].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > The Oral Microbiome and Bacterial Nitrate Reduction > Local Factors Influence Bacterial Nitrate Reduction
What the sources say
- Not checked yetcites [229] Gorfer, 2011, Community profiling and gene expression of fungal assimilatory nitrate reductases in agricultural soil, ISME J. source
- Not checked yetcites [230] Shoun, 2012, Fungal denitrification and nitric oxide reductase cytochrome P450nor, Philos. Trans. R. Soc. Lond. B Biol. Sci. source
boosteddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Thus, alterations in bacterial communities may be more important than changes in single bacterial species, and due consideration must be paid to functional community networks in the design and implementation of targeted therapies[218,219].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > The Oral Microbiome and Bacterial Nitrate Reduction > Local Factors Influence Bacterial Nitrate Reduction
What the sources say
- Not checked yetcites [218] Bashan, 2016, Universality of human microbial dynamics, Nature source
- Not checked yetcites [219] Lee, 2014, Characterization of microbial associations in human oral microbiome, Biomed. Mater. Eng.
plainconditional- Asserted: passes — The authors put it forward as true.
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The paper states this without a source or data behind it here, so there is nothing to check it against. The quote shows it is in the paper.
In the paper
“One of the main functions of low gastric pH is to clear pathogenic bacteria before they enter the distal GI tract.”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > The Oral Microbiome and Bacterial Nitrate Reduction > Local Factors Influence Bacterial Nitrate Reduction
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Epidemiologically, H. pylori is linked to peptic ulcer disease, gastric cancer, as well as diabetes, autoimmune disease, chronic inflammation, CVD and endothelial dysfunction[240–245].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > The Oral Microbiome and Bacterial Nitrate Reduction > Local Factors Influence Bacterial Nitrate Reduction
What the sources say
- Not checked yetcites [240] Wang, 2015, Association of Helicobacter pyloriinfection with chronic obstructive pulmonary disease and chronic bronchitis: a meta-analysis of 16 studies, Infect. Dis. source
- Not checked yetcites [241] Franceschi, 2014, Helicobacter pyloriand extragastric diseases, Helicobacter source
- Not checked yetcites [242] Gobert, 2016, The immune Battle against helicobacter pylori infection: NO offense, Trends Microbiol. source
- Not checked yetcites [243] J. Danesh, Coronary Heart Disease, Helicobacter Pylori, Dental Disease, Chlamydia Pneumoniae, and Cytome Galovirus: Meta-Analyses of Prospective Studies, 138, 1999, pp. S434 S437. 〈http://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=10539843&retmode=ref&cmd=prlinks〉. source
- Not checked yetcites [244] Tabata, 2016, Helicobacter pylori-seropositivity along with pro-inflammatory interleukin-1 polymorphisms correlated with myocardial infarction, Ctrsc
- Not checked yetcites [245] Grabczewska, 2006, Endothelial function parameters in patients with unstable angina and infection with Helicobacter pylori and Chlamydia pneumoniae, Eur. J. Intern. Med. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
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In the paper
“This may relate to the paradoxical association between nitrate-reducing oral bacteria and protection from dental caries[191,205,232,238,239].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > The Oral Microbiome and Bacterial Nitrate Reduction > Local Factors Influence Bacterial Nitrate Reduction
What the sources say
- Not checked yetcites [191] Doel, 2004, Protective effect of salivary nitrate and microbial nitrate reductase activity against caries, Eur. J. Oral Sci. source
- Not checked yetcites [205] Koopman, 2016, Nitrate and the origin of saliva influence composition and short chain fatty acid production of oral microcosms, Micro. Ecol. source
- Not checked yetcites [232] Silva Mendez, 1999, Antimicrobial effect of acidified nitrite on cariogenic bacteria, Oral Microbiol. Immunol. source
- Not checked yetcites [238] Nascimento, 2009, Correlations of oral bacterial arginine and urea catabolism with caries experience, Oral Microbiol. Immunol. source
- Not checked yetcites [239] Li, 2007, Salivary nitrate--an ecological factor in reducing oral acidity, Oral Microbiol. Immunol. source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
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In the paper
“Nitrite can exert pH-dependent antimicrobial effects[204,232,233] via formation of reactive secondary nitrogen oxides that can disrupt aerobic respiration[234], inhibit bacterial acid production, and disrupt biofilm formation[235–237].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > The Oral Microbiome and Bacterial Nitrate Reduction > Local Factors Influence Bacterial Nitrate Reduction
What the sources say
- Not checked yetcites [204] Hyde, 2014, Characterization of the rat oral microbiome and the effects of dietary nitrate, Free Radic. Biol. Med. source
- Not checked yetcites [232] Silva Mendez, 1999, Antimicrobial effect of acidified nitrite on cariogenic bacteria, Oral Microbiol. Immunol. source
- Not checked yetcites [233] Tiso, 2015, Nitrate reduction to nitrite, nitric oxide and ammonia by gut bacteria under physiological conditions, PLoS One source
- Not checked yetcites [234] Rowe, 1979, Nitrite inhibition of aerobic bacteria, Curr. Microbiol. source
- Not checked yetcites [235] Schlag, 2007, Inhibition of staphylococcal biofilm formation by nitrite, J. Bacteriol. source
- Not checked yetcites [236] Zemke, 2014, Nitrite modulates bacterial antibiotic susceptibility and biofilm formation in association with airway epithelial cells, Free Radic. Biol. Med. source
- Not checked yetcites [237] Arora, 2015, Nitric oxide regulation of bacterial biofilms, Biochemistry source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Supporting the importance of such mechanisms, a growing body of evidence has linked acid-reducing medications such as proton pump inhibitors and histamine H2 antagonists, with increased risk of enteric infections such as clostridium difficile[248–250] and profound alterations”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > The Oral Microbiome and Bacterial Nitrate Reduction > Local Factors Influence Bacterial Nitrate Reduction
What the sources say
- Not checked yetcites [248] McDonald, 2015, Continuous proton pump inhibitor therapy and the associated risk of recurrent Clostridium difficile infection, JAMA Intern. Med. source
- Not checked yetcites [249] Leonard, 2007, Systematic review of the risk of enteric infection in patients taking acid suppression, Am. J. Gastroenterol. source
- Not checked yetcites [250] Janarthanan, 2012, Clostridium difficile-associated diarrhea and proton pump inhibitor therapy: a meta-analysis, Am. J. Gastroenterol. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
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In the paper
“Second, H. pylori can alter stomach pH via expression of urease that allows for the formation of both ammonia and bicarbonate from urea, thus reducing the acidity of the stomach and potentially reducing the nascent pH-dependent formation of NO from salivary nitrite[242,246,247].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > The Oral Microbiome and Bacterial Nitrate Reduction > Local Factors Influence Bacterial Nitrate Reduction
What the sources say
- Not checked yetcites [242] Gobert, 2016, The immune Battle against helicobacter pylori infection: NO offense, Trends Microbiol. source
- Not checked yetcites [246] Briskey, 2016, Microbiota and the nitrogen cycle: Implications in the development and progression of CVD and CKD, Nitric Oxide source
- Not checked yetcites [247] Kuwahara, 2000, Helicobacter pylori urease suppresses bactericidal activity of peroxynitrite via carbon dioxide production, Infect. Immun. source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“From the standpoint of energetics, facultative anaerobes prefer aerobic respiration, although they maintain the capacity to use anaerobic fermentation for growth in anoxic or low oxygen environments, a mechanism dominated by the respiratory nitrate reductive pathway[77].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > The Oral Microbiome and Bacterial Nitrate Reduction > Local Factors Influence Bacterial Nitrate Reduction
What the sources say
- Not checked yetcites [77] Sparacino-Watkins, 2014, Nitrate and periplasmic nitrate reductases, Chem. Soc. Rev. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“For instance, the respiratory nitrate reductase, nar, expresses two major operons, NarGHI and NarZYW[77,256].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > The Oral Microbiome and Bacterial Nitrate Reduction > Local Factors Influence Bacterial Nitrate Reduction
What the sources say
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
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In the paper
“Conversely, NarZYW is constitutively expressed at low levels in the aerobic setting and only up-regulated in response to high nitrate concentrations, likely aiding in the transition from aerobic to anaerobic respiration [256,259,260].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > The Oral Microbiome and Bacterial Nitrate Reduction > Local Factors Influence Bacterial Nitrate Reduction
What the sources say
- Not checked yetcites [256] Hille, 2014, The mononuclear molybdenum enzymes, Chem. Rev. source
- Not checked yetcites [259] Constantinidou, 2006, A reassessment of the FNR regulon and transcriptomic analysis of the effects of nitrate, nitrite, NarXL, and NarQP as Escherichia coli K12 adapts from aerobic to anaerobic growth, J. Biol. Chem. source
- Not checked yetcites [260] Dong, 2012, two-component system regulates nitrate and nitrite respiration in Shewanella oneidensis, PLoS One source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“Comparatively, while the DNRA nitrate reductase, nap, shares some regulatory elements with nar such as the oxygen-dependent FNR[77,256,261–264]”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > The Oral Microbiome and Bacterial Nitrate Reduction > Local Factors Influence Bacterial Nitrate Reduction
What the sources say
- Not checked yetcites [77] Sparacino-Watkins, 2014, Nitrate and periplasmic nitrate reductases, Chem. Soc. Rev. source
- Not checked yetcites [256] Hille, 2014, The mononuclear molybdenum enzymes, Chem. Rev. source
- Not checked yetcites [261] Stewart, 1994, Regulation of nitrate and nitrite reductase synthesis in enterobacteria, Antonie Van. Leeuwenhoek. source
- Not checked yetcites [262] Stewart, 1993, Nitrate regulation of anaerobic respiratory gene expression in Escherichia coli, Mol. Microbiol. source
- Not checked yetcites [263] Sears, 2000, Control of periplasmic nitrate reductase gene expression (napEDABC) from Paracoccus pantotrophus in response to oxygen and carbon substrates, Microbiology source
- Not checked yetcites [264] Gavira, 2002, Regulation of nap gene expression and periplasmic nitrate reductase activity in the phototrophic bacterium Rhodobacter sphaeroides DSM158, J. Bacteriol. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
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In the paper
“it is notable that nap is maximally expressed under low oxygen and low nitrate conditions, a difference suggested to possibly relate to a selective advantage over nar in the distal GI tract[77,265].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > The Oral Microbiome and Bacterial Nitrate Reduction > Local Factors Influence Bacterial Nitrate Reduction
What the sources say
- Not checked yetcites [77] Sparacino-Watkins, 2014, Nitrate and periplasmic nitrate reductases, Chem. Soc. Rev. source
- Not checked yetcites [265] Potter, 1999, Competition between Escherichia coli strains expressing either a periplasmic or a membrane-bound nitrate reductase: does Nap confer a selective advantage during …, Biochem J. source
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
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In the paper
“The first, NarGHI, is highly oxygen-responsive, under primary transcriptional control via the oxygen sensor fumarate nitrate reductase regulator (FNR), and appears to be the major contributor to respiratory anaerobic activity[256–258].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > The Oral Microbiome and Bacterial Nitrate Reduction > Local Factors Influence Bacterial Nitrate Reduction
What the sources say
- Not checked yetcites [256] Hille, 2014, The mononuclear molybdenum enzymes, Chem. Rev. source
- Not checked yetcites [257] Rabin, 1992, In vivo requirement of integration host factor for nar (nitrate reductase) operon expression in Escherichia coli K-12, Proc. Natl. Acad. Sci. source
- Not checked yetcites [258] Noriega, 2010, Asymmetric cross-regulation between the nitrate-responsive NarX-NarL and NarQ-NarP two-component regulatory systems from Escherichia coli K-12, Mol. Microbiol. source
hedgeddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Longitudinally, oxygen concentrations generally fall, with the highest pO2 in the proximal gut including the gastric fundus (77mmHg; ~10%) and small bowel (30–45mmHg, ~4–6%), and declining through the colon to concentrations of less than 3 mmHg (ρ%) in the sigmoid colon and rectum[267].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > The Oral Microbiome and Bacterial Nitrate Reduction > Local Factors Influence Bacterial Nitrate Reduction
What the sources say
- Not checked yetcites [267] Espey, 2013, Role of oxygen gradients in shaping redox relationships between the human intestine and its microbiota, Free Radic. Biol. Med. source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“In a recent set of experiments using gut facultative anaerobes, Escherichia coli and several Lactobacillus sp., there was an increase in the expression of nitrate reductase enzymes, an increase in nitrite formation, and a clear growth benefit in the setting of adequate nitrate as oxygen concentration decreases below 4% [233].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > The Oral Microbiome and Bacterial Nitrate Reduction > Local Factors Influence Bacterial Nitrate Reduction
What the sources say
- Not checked yetcites [233] Tiso, 2015, Nitrate reduction to nitrite, nitric oxide and ammonia by gut bacteria under physiological conditions, PLoS One source
boosteddirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“Conversely, under conditions of host stress or inflammation, selective pressures on the microbiota change, leading to increased nitrate, nitrite and reactive nitrogen oxides, reduced pH, and a hostile environment”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > The Oral Microbiome and Bacterial Nitrate Reduction > Local Factors Influence Bacterial Nitrate Reduction
What the sources say
- Not checked yetcites [271] Vermeiren, 2009, Nitric oxide production by the human intestinal microbiota by dissimilatory nitrate reduction to ammonium, J. Biomed. Biotechnol.
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“it is possible that dysbiosis and systemic inflammation due to periodontal disease and overall oral health may impact or reverse the beneficial effects of physiological enterosalivary nitrate metabolism and promote the development of PH.”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Dysbiosis of the Microbiome in Pulmonary hypertension & Vascular Disease > Microbial Communities & Nitrate Bioactivation are Disrupted in Periodontal Disease & Xerostomia
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“Interestingly, both salivary nitrate and nitrite concentrations and gingival expression of NO-forming NOS have been found to be increased in periodontal disease, which also tend to increase with disease severity and improve with periodontal treatment[99,193,291,292].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Dysbiosis of the Microbiome in Pulmonary hypertension & Vascular Disease > Microbial Communities & Nitrate Bioactivation are Disrupted in Periodontal Disease & Xerostomia
What the sources say
- Not checked yetcites [99] Woessner, 2016, A stepwise reduction in plasma and salivary nitrite with increasing strengths of mouthwash following a dietary nitrate load, Nitric Oxide source
- Not checked yetcites [193] Sánchez, 2014, Total salivary nitrates and nitrites in oral health and periodontal disease, Nitric Oxide source
- Not checked yetcites [291] Parwani, 2012, Salivary nitric oxide levels in inflammatory periodontal disease - a case-control and interventional study, Int J. Dent. Hyg. source
- Not checked yetcites [292] Wadhwa, 2013, Determination of levels of nitric oxide in smoker and nonsmoker patients with chronic periodontitis, J. Periodontal Impant Sci. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“In the setting of salivary gland dysfunction, there is a decrease in salivary nitrate concentration and corollary increase in urinary excretion, thereby reducing total body nitrate content and its enterosalivary circulation[84,193,231,293].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Dysbiosis of the Microbiome in Pulmonary hypertension & Vascular Disease > Microbial Communities & Nitrate Bioactivation are Disrupted in Periodontal Disease & Xerostomia
What the sources say
- Not checked yetcites [84] Xia, 2003, Alterations of nitrate and nitrite content in saliva, serum, and urine in patients with salivary dysfunction, J. Oral Pathol. Med. source
- Not checked yetcites [193] Sánchez, 2014, Total salivary nitrates and nitrites in oral health and periodontal disease, Nitric Oxide source
- Not checked yetcites [231] Lundberg, 2012, Nitrate transport in salivary glands with implications for NO homeostasis, Proc. Natl. Acad. Sci. U.S.A. source
- Not checked yetcites [293] Xia, 2003, Destruction of parotid glands affects nitrate and nitrite metabolism, J. Dent. Res. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Relative to the oral cavity, the gut harbors over 1kg of bacterial biomass and upwards of 1000 different species[307].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Dysbiosis of the Microbiome in Pulmonary hypertension & Vascular Disease > The Gut Microbiome
What the sources say
- Not checked yetcites [307] Nicholson, 2005, Gut microorganisms, mammalian metabolism and personalized health care, Nat. Rev. Microbiol. source
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
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In the paper
“Ecological conditions vary immensely along both the length of the GI tract as well as in cross-section from lumen to the mucosal brush-border[173,267,308,309].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Dysbiosis of the Microbiome in Pulmonary hypertension & Vascular Disease > The Gut Microbiome
What the sources say
- Not checked yetcites [173] Segata, 2012, Composition of the adult digestive tract bacterial microbiome based on seven mouth surfaces, tonsils, throat and stool samples, Genome Biol. source
- Not checked yetcites [267] Espey, 2013, Role of oxygen gradients in shaping redox relationships between the human intestine and its microbiota, Free Radic. Biol. Med. source
- Not checked yetcites [308] Maynard, 2012, Reciprocal interactions of the intestinal microbiota and immune system, Nature source
- Not checked yetcites [309] Yasuda, 2015, Biogeography of the intestinal mucosal and lumenal microbiome in the rhesus macaque, Cell Host Microbe source
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
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In the paper
“Numerous facets of GI microbial community composition and metabolism have been associated with various disease states, including CVD, obesity, diabetes, and features of metabolic syndrome[274,310–313].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Dysbiosis of the Microbiome in Pulmonary hypertension & Vascular Disease > The Gut Microbiome
What the sources say
- Not checked yetcites [274] Turnbaugh, 2009, A core gut microbiome in obese and lean twins, Nature source
- Not checked yetcites [310] Serino, 2009, Intestinal microflora and metabolic diseases, Diabetes Metab. source
- Not checked yetcites [311] Qin, 2012, A metagenome-wide association study of gut microbiota in type 2 diabetes, Nature source
- Not checked yetcites [312] Serino, 2014, Far from the eyes, close to the heart: dysbiosis of gut microbiota and cardiovascular consequences, Curr. Cardiol. Rep. source
- Not checked yetcites [313] Le Chatelier, 2013, Richness of human gut microbiome correlates with metabolic markers, Nature source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
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In the paper
“Elevations in the Firmicutes:Bacteroidetes ratio have been associated with a high-fat diet and obesity[274,328,329], irritable bowel syndrome[330], hypertension[331], type 1 diabetes[276], and HIV[332].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Dysbiosis of the Microbiome in Pulmonary hypertension & Vascular Disease > Inflammation
What the sources say
- Not checked yetcites [274] Turnbaugh, 2009, A core gut microbiome in obese and lean twins, Nature source
- Not checked yetcites [328] Ley, 2006, Microbial ecology: human gut microbes associated with obesity, Nature source
- Not checked yetcites [329] Turnbaugh, 2006, An obesity-associated gut microbiome with increased capacity for energy harvest, Nature source
- Not checked yetcites [330] Kassinen, 2007, The fecal microbiota of irritable bowel syndrome patients differs significantly from that of healthy subjects, Gastroenterology source
- Not checked yetcites [331] Yang, 2015, Gut dysbiosis is linked to hypertension, Hypertension source
- Not checked yetcites [276] Wen, 2008, Innate immunity and intestinal microbiota in the development of Type 1 diabetes, Nature source
- Not checked yetcites [332] Salas, 2014, Microbiome in human immunodeficiency virus infection, Clin. Lab. Med. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
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In the paper
“Consequently, microbial diversity is reduced[325,326] while local and systemic inflammation and decreased NO bioavailability persist, propagating vascular injury and the risk of developing PH.”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Dysbiosis of the Microbiome in Pulmonary hypertension & Vascular Disease > Inflammation
What the sources say
- Not checked yetcites [325] Moilanen, 1995, Nitric oxide in inflammation and immune response, Ann. Med. source
- Not checked yetcites [326] Stuehr, 1989, Activated murine macrophages secrete a metabolite of arginine with the bioactivity of endothelium-derived relaxing factor and the chemical reactivity of nitric oxide, J. Exp. Med. source
plaindirect- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“The typically low-abundance Enterobacteraceae expand in concert with inflammation[336] and degree of dysbiosis of the Firmicutes:Bacteroidetes ratio[333,337,338].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Dysbiosis of the Microbiome in Pulmonary hypertension & Vascular Disease > Inflammation
What the sources say
- Not checked yetcites [336] Biagi, 2010, Through ageing, and beyond: gut microbiota and inflammatory status in seniors and centenarians, PLoS One source
- Not checked yetcites [333] Winter, 2013, Host-derived nitrate boosts growth of E. coli in the inflamed gut, Science source
- Not checked yetcites [337] Vázquez-Torres, 2016, Nitrate, nitrite and nitric oxide reductases: from the last universal common ancestor to modern bacterial pathogens, Curr. Opin. Microbiol. source
- Not checked yetcites [338] Stecher, 2007, Salmonella enterica serovar typhimurium exploits inflammation to compete with the intestinal microbiota, PLoS Biol. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“This alteration in turn can promote chronic inflammation and contribute to the impaired NO signaling and inflammation-rich intravascular environment that is a hallmark PH.”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Dysbiosis of the Microbiome in Pulmonary hypertension & Vascular Disease > Inflammation
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Presumably, in the setting of inflammation, excess nitrite and nitrate are formed along with reactive oxygen radicals and nitrogen oxides through NO oxidation, thereby increasing the amount of substrate available for respiratory denitrification and rapid bacterial growth[323,337].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Dysbiosis of the Microbiome in Pulmonary hypertension & Vascular Disease > Inflammation
What the sources say
- Not checked yetcites [323] Scales, 2016, A tale of two sites: how inflammation can reshape the microbiomes of the gut and lungs, J. Leukoc. Biol. source
- Not checked yetcites [337] Vázquez-Torres, 2016, Nitrate, nitrite and nitric oxide reductases: from the last universal common ancestor to modern bacterial pathogens, Curr. Opin. Microbiol. source
hedgeddirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“H2S is a biologically important thiol that shares significant overlapping signaling activity with NO, reacts with NO-derived reactive species and has been implicated in modulating the pathogenesis of several inflammatory bowel diseases[91,343,344].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Dysbiosis of the Microbiome in Pulmonary hypertension & Vascular Disease > NO Production
What the sources say
- Not checked yetcites [91] Fukuto, 2012, Small molecule signaling agents: the integrated chemistry and biochemistry of nitrogen oxides, oxides of carbon, dioxygen, hydrogen sulfide, and their derived species, Chem. Res. Toxicol. source
- Not checked yetcites [343] Cortese-Krott, 2015, On the chemical biology of the nitrite/sulfide interaction, Nitric Oxide source
- Not checked yetcites [344] Singh, 2015, Hydrogen sulfide in physiology and diseases of the digestive tract, Microorganisms source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“From the standpoint of NO signaling and PH, respiratory denitrification of nitrite and NOS-derived NO likely serve beneficial roles in modifying the local microenvironment, and maintaining adequate blood flow and mucus generation.”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Dysbiosis of the Microbiome in Pulmonary hypertension & Vascular Disease > NO Production
hedgedconditional- Asserted: passes — The authors put it forward as true.
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None of the sources cited for this claim have been checked yet.
In the paper
“while on the other, increased H2S formation by SRB can promote oxidant formation, impair colonic epithelial H2S detoxification and induce cytotoxicity and disruption of intestinal barrier integrity, thereby driving local and systemic inflammation[344,347,352,353].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Dysbiosis of the Microbiome in Pulmonary hypertension & Vascular Disease > NO Production
What the sources say
- Not checked yetcites [344] Singh, 2015, Hydrogen sulfide in physiology and diseases of the digestive tract, Microorganisms source
- Not checked yetcites [347] Guo, 2016, Emerging roles of hydrogen sulfide in inflammatory and neoplastic colonic diseases, Front. Physiol. source
- Not checked yetcites [352] Arijs, 2013, Decreased mucosal sulfide detoxification capacity in patients with Crohn's disease, Inflamm. Bowel Dis. source
- Not checked yetcites [353] De Preter, 2012, Decreased mucosal sulfide detoxification is related to an impaired butyrate oxidation in ulcerative colitis, Inflamm. Bowel Dis. source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“H2S directly interfaces with nitrogen oxide reduction and the generation of intestinal NO by serving as an electron donor during nitrite reduction to NO by nitrite reductase, or by reacting with the nitrogen oxide S-nitrosothiol[91,102,346].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Dysbiosis of the Microbiome in Pulmonary hypertension & Vascular Disease > NO Production
What the sources say
- Not checked yetcites [91] Fukuto, 2012, Small molecule signaling agents: the integrated chemistry and biochemistry of nitrogen oxides, oxides of carbon, dioxygen, hydrogen sulfide, and their derived species, Chem. Res. Toxicol. source
- Not checked yetcites [102] Vitturi, 2015, Convergence of biological nitration and nitrosation via symmetrical nitrous anhydride, Nat. Chem. Biol. source
- Not checked yetcites [346] Vermeiren, 2012, Sulfide- and nitrite-dependent nitric oxide production in the intestinal tract, Microb. Biotechnol. source
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Notably, H2S is required for both efficient nitrite reduction to NO in the gut and in NO formation from nitrite in hypoxic systemic tissues[343,346].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Dysbiosis of the Microbiome in Pulmonary hypertension & Vascular Disease > NO Production
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Indeed, there remains conflicting evidence regarding the precise role of H2S in the gut[344,347].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Dysbiosis of the Microbiome in Pulmonary hypertension & Vascular Disease > NO Production
What the sources say
plain- Asserted: passes — The authors put it forward as true.
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- Load-bearing: fails — The paper’s conclusions may not depend on it.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
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In the paper
“Major epidemiological studies have consistently identified that vegetable- and fruit-rich diets improve every major risk factor for PH and CVD, including blood pressure[361,363,364], ischemic stroke[365], ischemic heart disease[366], obesity, insulin resistance and diabetes[367], and metabolic syndrome[365,366,368,369].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Therapeutic Strategies to Target the Enterosalivary Pathway: Beyond Nitrate Supplementation > Prebiotic therapy: Dietary Interventions
What the sources say
- Not checked yetcites [361] Appel, 1997, A clinical trial of the effects of dietary patterns on blood pressure. DASH Collaborative Research Group, N. Engl. J. Med. source
- Not checked yetcites [363] Rouse, 1983, Blood-pressure-lowering effect of a vegetarian diet: controlled trial in normotensive subjects, Lancet source
- Not checked yetcites [364] Lindahl, 1984, A vegan regimen with reduced medication in the treatment of hypertension, Br. J. Nutr. source
- Not checked yetcites [365] Joshipura, 1999, Fruit and vegetable intake in relation to risk of ischemic stroke, JAMA source
- Not checked yetcites [366] Hung, 2004, Fruit and vegetable intake and risk of major chronic disease, J. Natl. Cancer Inst. source
- Not checked yetcites [367] Carter, 2010, Fruit and vegetable intake and incidence of type 2 diabetes mellitus: systematic review and meta-analysis, BMJ source
- Not checked yetcites [368] Wang, 2014, Fruit and vegetable consumption and mortality from all causes, cardiovascular disease, and cancer: systematic review and dose-response meta-analysis of prospective cohort studies, BMJ source
- Not checked yetcites [369] Joshipura, 2001, The effect of fruit and vegetable intake on risk for coronary heart disease, Ann. Intern. Med. source
boosteddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Current dietary investigations have found these fatty acids and dietary nitrate to be concentrated in the traditional Mediterranean diet, a diet with beneficial effects on the development of CVD and its risk factors[362,375–377].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Therapeutic Strategies to Target the Enterosalivary Pathway: Beyond Nitrate Supplementation > Prebiotic therapy: Dietary Interventions
What the sources say
- Not checked yetcites [362] de Lorgeril, 2013, Mediterranean diet and cardiovascular disease: historical perspective and latest evidence, Curr. Atheroscler. Rep. source
- Not checked yetcites [375] Charles, 2014, Protection from hypertension in mice by the Mediterranean diet is mediated by nitro fatty acid inhibition of soluble epoxide hydrolase, Proc. Natl. Acad. Sci. USA source
- Not checked yetcites [376] Martinez-Gonzalez, 2009, Mediterranean food pattern and the primary prevention of chronic disease: recent developments, Nutr. Rev. source
- Not checked yetcites [377] Estruch, 2013, Primary prevention of cardiovascular disease with a Mediterranean diet, N. Engl. J. Med. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Comparing this level of consumption to a study of the high vegetable-containing, traditional Japanese diet, a population with historically low rates of cardiovascular disease, Sobko et al. found the average daily nitrate consumption in Japan to be >1100mg/day for a 60kg person, and associated with increased circulating nitrate and nitrite and with reduced blood pressure[373].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Therapeutic Strategies to Target the Enterosalivary Pathway: Beyond Nitrate Supplementation > Prebiotic therapy: Dietary Interventions
What the sources say
- Not checked yetcites [373] Sobko, 2010, Dietary nitrate in Japanese traditional foods lowers diastolic blood pressure in healthy volunteers, Nitric Oxide source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Unsurprisingly, estimates of average daily nitrate consumption in the U.S. and Europe, regions with high rates of CVD and vascular disease, reach only 40–100mg and 30–180mg, respectively[157,161,372].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Therapeutic Strategies to Target the Enterosalivary Pathway: Beyond Nitrate Supplementation > Prebiotic therapy: Dietary Interventions
What the sources say
- Not checked yetcites [157] Rathod, 2016, A “green” diet-based approach to cardiovascular health? Is inorganic nitrate the answer?, Mol. Nutr. Food Res. source
- Not checked yetcites [161] Hord, 2009, Food sources of nitrates and nitrites: the physiologic context for potential health benefits, Am. J. Clin. Nutr. source
- Not checked yetcites [372] Gangolli, 1994, Nitrate, nitrite and N-nitroso compounds, Eur. J. Pharmacol.
hedged- Asserted: passes — The authors put it forward as true.
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In the paper
“In contrast to the high-nitrate diet of Japan, the Seven Countries Study[378] found lower rates of CVD and cancer with the traditional Mediterranean diet, despite 37% of total daily energy coming from fat, versus only 11% in the traditional Japanese diet[378,379].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Therapeutic Strategies to Target the Enterosalivary Pathway: Beyond Nitrate Supplementation > Prebiotic therapy: Dietary Interventions
What the sources say
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Comparatively, U.S. consumption of total polyunsaturated fatty acids and ALA are around 6–7% and 0.6–0.7% of total energy intake, respectively[382,383].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Therapeutic Strategies to Target the Enterosalivary Pathway: Beyond Nitrate Supplementation > Prebiotic therapy: Dietary Interventions
What the sources say
- Not checked yetcites [382] Kris-Etherton, 2000, Polyunsaturated fatty acids in the food chain in the United States, Am. J. Clin. Nutr. source
- Not checked yetcites [383] Gebauer, 2006, n-3 fatty acid dietary recommendations and food sources to achieve essentiality and cardiovascular benefits, Am. J. Clin. Nutr. source
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“NO2-FAs exert pleiotropic post-translational, anti-oxidant and anti-inflammatory effects[105,321,385] that include inhibition of vascular smooth muscle proliferation and neointima formation after injury, cardioprotection, improved endothelial function[94,386–390], and activation of downstream NO signaling pathways[385,389,391–394].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Therapeutic Strategies to Target the Enterosalivary Pathway: Beyond Nitrate Supplementation > Prebiotic therapy: Dietary Interventions
What the sources say
- Not checked yetcites [94] Schopfer, 2011, Formation and signaling actions of electrophilic lipids, Chem. Rev. source
- Not checked yetcites [386] Nadtochiy, 2015, Nitroalkenes confer acute Cardioprot. via Aden. Nucleotide translocase
- Not checked yetcites [387] Cole, 2009, Nitro-fatty acid inhibition of neointima formation after endoluminal vessel injury, Circ. Res. source
- Not checked yetcites [388] Rudolph, 2010, Endogenous generation and protective effects of nitro-fatty acids in a murine model of focal cardiac ischaemia and reperfusion, Cardiovasc. Res. source
- Not checked yetcites [389] Kansanen, 2011, Electrophilic nitro-fatty acids activate NRF2 by a KEAP1 cysteine 151-independent mechanism, J. Biol. Chem. source
- Not checked yetcites [390] Kelley, 2008, Nitro-oleic acid, a novel and irreversible inhibitor of xanthine oxidoreductase, J. Biol. Chem. source
- Not checked yetcites [391] Kelley, 2014, Fatty acid nitroalkenes ameliorate glucose intolerance and pulmonary hypertension in high-fat diet-induced obesity, Cardiovasc. Res. source
- Not checked yetcites [392] Khoo, 2010, Activation of vascular endothelial nitric oxide synthase and heme oxygenase-1 expression by electrophilic nitro-fatty acids, Free Radic. Biol. Med. source
- Not checked yetcites [393] Cui, 2006, Nitrated fatty acids: Endogenous anti-inflammatory signaling mediators, J. Biol. Chem. source
- Not checked yetcites [394] Narala, 2014, The role of nitrated fatty acids and peroxisome proliferator-activated receptor gamma in modulating inflammation, Int. Immunopharmacol. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“These numbers, along with the relative incidence of CVD and vascular risk factors support the hypothesis of a possible synergistic, diet-mediated NO-effect between inorganic nitrates and unsaturated fatty acids[19].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Therapeutic Strategies to Target the Enterosalivary Pathway: Beyond Nitrate Supplementation > Prebiotic therapy: Dietary Interventions
What the sources say
- Not checked yetcites [19] Lundberg, 2015, Strategies to increase nitric oxide signalling in cardiovascular disease, Nat. Rev. Drug Discov. source
hedgedconditional- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
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In the paper
“In subsequent years, there has been an explosion of work demonstrating clinical benefit of probiotics in modifying cardiovascular risk, inflammatory and infectious bowel disorders, and even ventilator-associated pneumonia (reviewed in:[399,403]).”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Therapeutic Strategies to Target the Enterosalivary Pathway: Beyond Nitrate Supplementation > Probiotics
What the sources say
- Not checked yetcites [399] Gogineni, 2013, Probiotics: history and evolution, J. Anc.
- Not checked yetcites [403] Ettinger, 2014, The influence of the human microbiome and probiotics on cardiovascular health, Gut Microbes source
boosteddirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Given, however, that probiotic therapy exerts a beneficial effect on dental caries, periodontitis, and pharyngitis in the oral cavity[408–411], as well as on obesity, hypertension, insulin resistance, and heart failure via the gut(reviewed:[399,403])”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Therapeutic Strategies to Target the Enterosalivary Pathway: Beyond Nitrate Supplementation > Probiotics
What the sources say
- Not checked yetcites [408] Toiviainen, 2015, Impact of orally administered lozenges with Lactobacillus rhamnosus GG and Bifidobacterium animalis subsp. lactis BB-12 on the number of salivary mutans streptococci, amount of plaque, gingival inflammation and the oral microbiome in healthy adults, Clin. Oral Investig. source
- Not checked yetcites [409] Romani Vestman, 2015, Oral microbiota shift after 12-week supplementation with Lactobacillus reuteri DSM 17938 and PTA 5289; a randomized control trial, PLoS One source
- Not checked yetcites [410] Terai, 2015, Screening of probiotic candidates in human oral bacteria for the prevention of dental disease, PLoS One source
- Not checked yetcites [411] Anusha, 2015, The magic of magic bugs in oral cavity: probiotics, J. Adv. Pharm. Technol. Res. source
- Not checked yetcites [399] Gogineni, 2013, Probiotics: history and evolution, J. Anc.
- Not checked yetcites [403] Ettinger, 2014, The influence of the human microbiome and probiotics on cardiovascular health, Gut Microbes source
boosteddirect- Asserted: passes — The authors put it forward as true.
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In the paper
“to generate and isomerize cLA and exert anti-obesity effects in diet-induced obese mice in a cLA-dependent manner[279,403,415,416]”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Therapeutic Strategies to Target the Enterosalivary Pathway: Beyond Nitrate Supplementation > Probiotics
What the sources say
- Not checked yetcites [279] Kishino, 2013, Polyunsaturated fatty acid saturation by gut lactic acid bacteria affecting host lipid composition, Proc. Natl. Acad. Sci. U.S.A. source
- Not checked yetcites [403] Ettinger, 2014, The influence of the human microbiome and probiotics on cardiovascular health, Gut Microbes source
- Not checked yetcites [415] Lee, 2007, Antiobesity effect of trans-10,cis-12-conjugated linoleic acid-producing Lactobacillus plantarum PL62 on diet-induced obese mice, J. Appl. Microbiol. source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“In polymicrobial environments, Lactobacilli engage in advantageous, mutualistic interactions with other bacteria to survive under hypoxia and alter NO generation[217,413]”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Therapeutic Strategies to Target the Enterosalivary Pathway: Beyond Nitrate Supplementation > Probiotics
What the sources say
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
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In the paper
“as well as improve inflammation associated with inflammatory bowel conditions and reduce blood pressure in pre-hypertensive and hypertensive patients[401,403,414].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Therapeutic Strategies to Target the Enterosalivary Pathway: Beyond Nitrate Supplementation > Probiotics
What the sources say
- Not checked yetcites [401] McFarland, 2015, From yaks to yogurt: the history, development, and current use of probiotics, Clin. Infect. Dis. source
- Not checked yetcites [403] Ettinger, 2014, The influence of the human microbiome and probiotics on cardiovascular health, Gut Microbes source
- Not checked yetcites [414] Dong, 2013, Effect of probiotic fermented milk on blood pressure: a meta-analysis of randomised controlled trials, Br. J. Nutr. source
plaindirect- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“the U.S. Food and Drug Administration has now banned the public sale of certain antibacterial soaps[423].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Therapeutic Strategies to Target the Enterosalivary Pathway: Beyond Nitrate Supplementation > Antibiotic & Antimicrobial Agents
What the sources say
- Not checked yetcites [423] O.O.T. Commissioner, Press Announcements - FDA Issues Final Rule on Safety and Effectiveness of Antibacterial Soaps. 〈http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm517478.htm〉, 2016. source
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Functionally, L. rhamnosus mediates physiological effects in the mouth and has good adherence to saliva-coated surfaces[408,417].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Therapeutic Strategies to Target the Enterosalivary Pathway: Beyond Nitrate Supplementation > Probiotics
What the sources say
- Not checked yetcites [408] Toiviainen, 2015, Impact of orally administered lozenges with Lactobacillus rhamnosus GG and Bifidobacterium animalis subsp. lactis BB-12 on the number of salivary mutans streptococci, amount of plaque, gingival inflammation and the oral microbiome in healthy adults, Clin. Oral Investig. source
- Not checked yetcites [417] Meurman, 2009, Effect of amine fluoride-stannous fluoride preparations on oral yeasts in the elderly: a randomised placebo-controlled trial, Gerodontology source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“Overuse and antibiotic resistance have proliferated[422]”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Therapeutic Strategies to Target the Enterosalivary Pathway: Beyond Nitrate Supplementation > Antibiotic & Antimicrobial Agents
What the sources say
- Not checked yetcites [422] Neu, 1992, The crisis in antibiotic resistance, Science source
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“It has also been linked to weight reduction, prevention of ischemia-reperfusion injury, and attenuation of cardiac hypertrophy and post-infarction heart failure in rodents[403,418,419]”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Therapeutic Strategies to Target the Enterosalivary Pathway: Beyond Nitrate Supplementation > Probiotics
What the sources say
- Not checked yetcites [403] Ettinger, 2014, The influence of the human microbiome and probiotics on cardiovascular health, Gut Microbes source
- Not checked yetcites [418] Gan, 2014, Probiotic administration attenuates myocardial hypertrophy and heart failure after myocardial infarction in the rat, Circ. Heart Fail. source
- Not checked yetcites [419] Zhao, 2012, Carboxy terminus of heat shock protein (HSP) 70-interacting protein (CHIP) inhibits HSP70 in the heart, J. Physiol. Biochem. source
plaincorrelational- Asserted: passes — The authors put it forward as true.
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It may state two separate claims as one.
In the paper
“In current use, antibiotics are blunt tools of mass microbial destruction that can permanently alter the microbiome and predispose to numerous diseases such as obesity and diabetes[421].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Therapeutic Strategies to Target the Enterosalivary Pathway: Beyond Nitrate Supplementation > Antibiotic & Antimicrobial Agents
What the sources say
- Not checked yetcites [421] Blaser, 2016, Antibiotic use and its consequences for the normal microbiome, Science source
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Recent ecological findings show that even low levels of common antibiotics contaminate groundwater and soil and can disrupt bacterial denitrification[424–426]”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Therapeutic Strategies to Target the Enterosalivary Pathway: Beyond Nitrate Supplementation > Antibiotic & Antimicrobial Agents
What the sources say
- Not checked yetcites [424] DeVries, 2015, The effect of ultralow-dose antibiotics exposure on soil nitrate and N2O flux, Sci. Rep. source
- Not checked yetcites [425] Yan, 2013, The effect of environmental and therapeutic concentrations of antibiotics on nitrate reduction rates in river sediment, Water Res. source
- Not checked yetcites [426] Ahmad, 2014, Inhibitory effect of veterinary antibiotics on denitrification in groundwater: a microcosm approach, Sci. World J. source
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Recently, a Streptococcus mutans-specific peptide was developed and tested in a model of human saliva, where selective depletion of S. mutans triggered community-wide shifts in major nitrate-reducing and non-nitrate-reducing populations[439].”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Therapeutic Strategies to Target the Enterosalivary Pathway: Beyond Nitrate Supplementation > Antibiotic & Antimicrobial Agents
What the sources say
- Not checked yetcites [439] Guo, 2015, Precision-guided antimicrobial peptide as a targeted modulator of human microbial ecology, Proc. Natl. Acad. Sci. USA source
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“After publication by Ahluwalia et al. that 7 days of chlorhexidine mouthwash significantly raises resting blood pressures in healthy volunteers[106]”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Therapeutic Strategies to Target the Enterosalivary Pathway: Beyond Nitrate Supplementation > Antibiotic & Antimicrobial Agents
What the sources say
- Not checked yetcites [106] Kapil, 2013, Physiological role for nitrate-reducing oral bacteria in blood pressure control, Free Radic. Biol. Med. source
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
None of the sources cited for this claim have been checked yet.
In the paper
“Two studies have since shown increased blood pressures after chlorhexidine-containing mouthwash treatment in a population of hypertensive men on antihypertensive therapy[428] and during exercise in healthy volunteers[429]”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Therapeutic Strategies to Target the Enterosalivary Pathway: Beyond Nitrate Supplementation > Antibiotic & Antimicrobial Agents
What the sources say
- Not checked yetcites [428] Bondonno, 2015, Antibacterial mouthwash blunts oral nitrate reduction and increases blood pressure in treated hypertensive men and women, Am. J. Hypertens. source
- Not checked yetcites [429] McDonagh, 2015, The effects of chronic nitrate supplementation and the use of strong and weak antibacterial agents on plasma nitrite concentration and exercise blood pressure, Int J. Sports Med. source
plaindirect- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The study of probiotics has identified specific bacterial strains and their combinations that are capable of inducing pre-clinical and clinical effects.”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Conclusions
plaindirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper may give no reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Despite these complexities, a rich fund of knowledge already exists in the form of effective PH therapies targeting NO signaling and ongoing clinical testing of inhaled and oral formulations of inorganic nitrate and nitrite, as well as synthetic nitro-fatty acids.”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Conclusions
plain- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. The paper’s conclusions may not depend on it. The paper may give no reason why it holds. It may state two separate claims as one.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“and augmentation of key bacteria or bacterial functions may improve efficacy of therapies with fewer side effects.”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Conclusions
hedgedconditional- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. It may be too vague to check against evidence. The paper may give no reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The breadth of signaling responses instigated by nitrate, nitrite, NO and downstream products of nitrogen oxide reactions uniquely exists at the nexus of NO biology and the human-microbe interface.”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Conclusions
plaincorrelational- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim. It may be too vague to check against evidence. The paper may give no reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“but they could influence response to drug therapy”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Conclusions
hedgedconditional- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Whether changes to resident microbiota are beneficial or harmful in PH is unknown”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Conclusions
plain- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“but represent a novel testable and modifiable factor in disease pathogenesis.”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Conclusions
plainconditional- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim.
- Rests on an assumption: Relationships of the microbiome to PH have never been directly examined.
The paper relies on this without support.
Animal model findings of nitrate/nitrite benefit in pulmonary hypertension are predictive of human pulmonary hypertension.
“though animal model data support a therapeutic role”
The paper relies on this without support.
The enterosalivary nitrate-nitrite-NO pathway operates similarly in humans and rodents.
“Studies in Sprague-Dawley rats[78] and normal human volunteers[106] showed that depletion of oral bacterial nitrate reductases by chlorhexidine mouthwash correlated with a 90% decrease in oral nitrite levels (p<0.001) in humans”
The paper relies on this without support.
The oral microbiome's nitrate-reducing capacity is critical for systemic NO bioavailability in humans.
“These data also support the concept that an intricate and dependent relationship exists between mammals and commensal, oral, nitrate-reducing microbiota in maintaining adequate NO signaling.”
The paper relies on this without support.
The vast majority of oral and GI nitrate reducers are facultative anaerobes.
“The vast majority of oral and GI nitrate reducers are facultative anaerobes.”
The paper relies on this without support.
Nitrite is the common early intermediate in all bacterial nitrate-reductive pathways.
“Nitrite is the common early intermediate in all bacterial nitrate-reductive pathways, but it is unlikely that all three mechanisms contribute in equal amounts.”
The authors state this as an assumption.
In a healthy mouth, ATP-generating respiration would predominate.
“The logical assumption would be that in a healthy mouth, ATP-generating respiration would predominate.”
The paper relies on this without support.
To date, there are no studies that directly link microbial community features of the oral and gut microbiome, nitrate bioavailability, and the development of PH.
“To date, there are no studies that directly link microbial community features of the oral and gut microbiome, nitrate bioavailability, and the development of PH.”
The paper relies on this without support.
There are no studies that directly investigate an association between the gut microbiome, nitrate, and PH.
“There are no studies that directly investigate an association between the gut microbiome, nitrate, and PH.”
The paper relies on this without support.
There is no conclusive link between dysregulated salivary flow, altered oral microbial populations, and PH.
“While there is no conclusive link between these factors, these associations offer a potentially novel line of investigation.”
The paper relies on this without support.
Relationships of the microbiome to PH have never been directly examined.
“Relationships of the microbiome to PH have never been directly examined, but represent a novel testable and modifiable factor in disease pathogenesis.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“The enterosalivary cycle, in which approximately 25% of circulating nitrate is concentrated in saliva and converted to nitrite, represents a critical regulatory step that may become less efficient with age [17,231].”
From Dietary Nitrate-Rich Vegetables as Natural Modulators of Health: Mechanisms and Benefits in Ageing Populations (2026) · cites this paper as [231]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Although the balance of evidence indicates that NO3- represents an potent dietary means for reducing systemic BP [22], [25], [27], [40], [6]”
From Nitrate-responsive oral microbiome modulates nitric oxide homeostasis and blood pressure in humans (2018) · cites this paper as [25]
The cited source says what the claim attributes to it.
In the citing paper
“approximately 25% of circulating nitrate is concentrated in saliva and converted to nitrite”
From Dietary Nitrate-Rich Vegetables as Natural Modulators of Health: Mechanisms and Benefits in Ageing Populations (2026) · cites this paper as [231]
In the citing paper
“Dysfunction of nitric oxide signaling is associated with pulmonary hypertension, obesity, and cardiovascular disease.171”
From The oral microbiome: Role of key organisms and complex networks in oral health and disease (2021) · cites this paper as [171]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Rated minor: it would not touch a result — a value no result rests on, a p-value that stays on the same side of the significance level, or a conflict that is clerical, resolved elsewhere in the paper, or outside its own findings.
In the paper
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > Therapeutic Strategies to Target the Enterosalivary Pathway: Beyond Nitrate Supplementation > Antibiotic & Antimicrobial Agents
“Two studies have since shown increased blood pressures after chlorhexidine-containing mouthwash treatment in a population of hypertensive men on antihypertensive therapy[428]”
§ Enterosalivary nitrate metabolism and the microbiome: intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health > References
“428. Bondonno CP Liu AH Croft KD Considine MJ Puddey IB Woodman RJ Antibacterial mouthwash blunts oral nitrate reduction and increases blood pressure in treated hypertensive men and women Am. J. Hypertens 2015 28 572 575 25359409”
Citations
Cites
2 retracted
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RetractedEstruch, R., Ros, E., Salas-Salvadó, J., Covas, M.-I., Corella, D., Arós, F., Gómez-Gracia, E., Ruiz-Gutiérrez, V., Fiol, M., Lapetra, J., et al. (2018) · New England Journal of Medicine · doi:10.1056/nejmc1806491 · Cited by 1,008
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Gibson, G. R., & Roberfroid, M. B. (1995) · Journal of Nutrition · doi:10.1093/jn/125.6.1401 · Cited by 7,659
2015 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension
Galiè, N., Humbert, M., Vachiery, J.-L., Gibbs, S., Lang, I., Torbicki, A., Simonneau, G., Peacock, A., Vonk Noordegraaf, A., Beghetti, M., et al. (2016) · European Heart Journal · doi:10.1093/eurheartj/ehv317 · Cited by 6,931
A metagenome-wide association study of gut microbiota in type 2 diabetes
Qin, J., Li, Y., Cai, Z., Li, S., Zhu, J., Zhang, F., Liang, S., Zhang, W., Guan, Y., Shen, D., et al. (2012) · Nature · doi:10.1038/nature11450 · Cited by 6,762
The L-Arginine-Nitric Oxide Pathway
Epstein, F. H., Moncada, S., & Higgs, A. (1993) · New England Journal of Medicine · doi:10.1056/nejm199312303292706 · Cited by 6,678
Research works printed but not linked: 3
- Gilbert, 1889, Arterites infectieuses experimentales, C. R. Hebd. Des. Séances Mémoires De. La Soc. Biol., 6, 583
- Sun, 2016, The role of intestinal microflora and its possible mechanisms in hypertension, Lipid Cardiovasc. Res.
- Nadtochiy, 2015, Nitroalkenes confer acute Cardioprot. via Aden. Nucleotide translocase, 1
Cited by
Sorted by citations
The oral microbiome: Role of key organisms and complex networks in oral health and disease
Sedghi, L., DiMassa, V., Harrington, A., Lynch, S. V., & Kapila, Y. L. (2021) · Periodontology 2000 · doi:10.1111/prd.12393 · Cited by 755
Nitric Oxide and Endothelial Dysfunction
Cyr, A. R., Huckaby, L. V., Shiva, S. S., & Zuckerbraun, B. S. (2020) · Critical Care Clinics · doi:10.1016/j.ccc.2019.12.009 · Cited by 712
Functional effects of the microbiota in chronic respiratory disease
Budden, K. F., Shukla, S. D., Rehman, S. F., Bowerman, K. L., Keely, S., Hugenholtz, P., Armstrong-James, D. P. H., Adcock, I. M., Chotirmall, S. H., Chung, K. F., et al. (2019) · The Lancet Respiratory Medicine · doi:10.1016/s2213-2600(18)30510-1 · Cited by 453
Nitrate-responsive oral microbiome modulates nitric oxide homeostasis and blood pressure in humans
Vanhatalo, A., Blackwell, J. R., L’Heureux, J. E., Williams, D. W., Smith, A., van der Giezen, M., Winyard, P. G., Kelly, J., & Jones, A. M. (2018) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2018.05.078 · Cited by 256
The Role of Nitroglycerin and Other Nitrogen Oxides in Cardiovascular Therapeutics
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Metadata
- Authors
- Koch, C. D., Gladwin, M. T., Freeman, B. A., Lundberg, J. O., Weitzberg, E., & Morris, A.
- Affiliations
- University of Pittsburgh Medical Center (US)
- University of Pittsburgh (US)
- Karolinska Institutet (SE)
- Corresponding author
- Koch, Carl D.
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2017-04
- Volume
- 105
- Pages
- 48-67
- ISSN
- 0891-5849 (ISSN-L)
- PMC
- PMC5401802
- OpenAlex
- W2563427802
- Semantic Scholar
- cc25eaf8a902182222770fb2a314cfc869ea60db
- Cited by
- 186
- References
- 460
- Citations by year
- 2026: 18 · 2025: 17 · 2024: 24 · 2023: 23 · 2022: 27 · 2021: 19 · 2020: 20 · 2019: 20 · 2018: 9 · 2017: 9
- FWCI
- 1.49
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Free Radical Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Heart, Lung, and Blood Institute
- Swedish Heart and Lung Foundation
- Topics
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Keywords
- dietary nitrate, nitrite, oral microbiota, gut microbiota, nitric oxide signaling, pulmonary hypertension, cardiovascular disease, hypertension, obesity, nitrate reductase, endothelial dysfunction, ischemia-reperfusion injury, inorganic nitrate supplementation, hypoxia, cardiovascular therapeutics
- MeSH terms
- Animals, Cardiovascular Diseases, Fatty Acids, Humans, Mouth, Nitrates, Nitric Oxide, Pulmonary Circulation, Signal Transduction, Microbiota
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-09, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-09 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Cited sources are checked with a language model’s help (gpt-6-sol).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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