The DOI matches its Crossref record; 66 of the 67 references it cites were found in a registry or an index; none of the 35 sources its claims cite is checked for support yet.
Gut Dysbiosis Is Linked to Hypertension
Open accessAbstract
Emerging evidence suggests that gut microbiota is critical in the maintenance of physiological homeostasis. This study was designed to test the hypothesis that dysbiosis in gut microbiota is associated with hypertension because genetic, environmental, and dietary factors profoundly influence both gut microbiota and blood pressure. Bacterial DNA from fecal samples of 2 rat models of hypertension and a small cohort of patients was used for bacterial genomic analysis. We observed a significant decrease in microbial richness, diversity, and evenness in the spontaneously hypertensive rat, in addition to an increased Firmicutes/Bacteroidetes ratio. These changes were accompanied by decreases in acetate- and butyrate-producing bacteria. In addition, the microbiota of a small cohort of human hypertensive patients was found to follow a similar dysbiotic pattern, as it was less rich and diverse than that of control subjects. Similar changes in gut microbiota were observed in the chronic angiotensin II infusion rat model, most notably decreased microbial richness and an increased Firmicutes/Bacteroidetes ratio. In this model, we evaluated the efficacy of oral minocycline in restoring gut microbiota. In addition to attenuating high blood pressure, minocycline was able to rebalance the dysbiotic hypertension gut microbiota by reducing the Firmicutes/Bacteroidetes ratio. These observations demonstrate that high blood pressure is associated with gut microbiota dysbiosis, both in animal and human hypertension. They suggest that dietary intervention to correct gut microbiota could be an innovative nutritional therapeutic strategy for hypertension.
Overview
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TL;DR
This study reports that hypertension is associated with gut microbiota dysbiosis in two rat models and a small human cohort, characterized by reduced microbial richness/diversity and an increased Firmicutes-to-Bacteroidetes ratio. Oral minocycline lowered blood pressure in Ang II-infused rats and rebalanced several dysbiotic features of the gut microbiota.
Key findings
- In spontaneously hypertensive rats (SHR; MAP 148 ± 10 mmHg) versus Wistar Kyoto controls (WKY; MAP 108 ± 2 mmHg), microbial richness, evenness, and diversity were decreased, and the Firmicutes/Bacteroidetes ratio was ~5-fold higher.
- SHR showed ~3-fold fewer acetate-producing and ~2-fold fewer butyrate-producing bacteria, with increased lactate-producing bacteria; Bifidobacterium was significantly depleted.
- In a small human cohort, high-systolic-blood-pressure patients (144 ± 9 mmHg; n=7) had lower Chao richness and Shannon diversity than normal-SBP controls (119 ± 2 mmHg; n=10), with a non-significant trend toward lower Pielou evenness.
- In chronic Ang II-infused rats, oral minocycline for 4 weeks lowered 24-hour MAP (124 ± 2 mmHg vs 168 ± 2 mmHg), reduced the elevated Firmicutes/Bacteroidetes ratio, increased Bacteroidetes, and expanded acetate- and butyrate-producing bacteria.
Methods
- Fecal bacterial DNA from two rat hypertension models—SHR versus WKY and chronic Ang II infusion with/without oral minocycline—and from a small human cohort with normal versus high systolic blood pressure was analyzed by 16S rDNA sequencing.
- Microbial communities were assessed using Chao richness, Pielou evenness, Shannon diversity, weighted UniFrac distances with PCoA, phylum-level composition, and LEfSe at the genus level.
- Animal procedures were approved by the University of Florida IACUC; human studies were approved by the University of Florida IRB.
Limitations
- The paper states that the human cohort was small and that larger studies are needed; it also notes that plasma lactate was not measured, that some Ang II findings did not reach significance, and that whether dysbiosis precedes hypertension remains unknown.
- The paper states that minocycline can cross the blood-brain barrier, so it cannot rule out whether its antihypertensive effect is primarily gut-mediated, brain-mediated, or linked.
- Evident from the text: the human data are cross-sectional and associational, with only 17 total subjects, and the two control subjects within the HTN PCoA plot were under anti-hypertensive treatment with suboptimal medication/dosage, limiting causal and subgroup inference.
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48 Own result · 21 Not checked yet · 20 Own interpretation · 4 Own method
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Microbial richness, evenness, and diversity were all found to be drastically decreased in the SHR group when compared with the WKY control (Figure 1A).”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Results > HTN is associated with alteration in fecal microbiota composition in the SHR
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Figure 7A shows the enrichment of Akkermansia, Bacteroides, Enterorhabdus and Marvinbryantia in Ang II + minocycline treated group.”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Results > Acetate- and butyrate-producing bacteria are expanded by minocycline treatment
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“The composition of the fecal microbial communities of the WKY and SHR were found to be distinct, as presented in Figure 1B.”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Results > HTN is associated with alteration in fecal microbiota composition in the SHR
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“The abundance of other uncultured and incertae sedis bacteria genera OTUs (2761 and 3955) that belonged to Firmicutes were significantly enriched in the SHR.”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Results > Acetate and butyrate fermenters are decreased in the SHR
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In the paper
“However, oral administration of minocycline resulted in a remarkable increase of both the acetate- and butyrate-producing bacteria.”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Results > Acetate- and butyrate-producing bacteria are expanded by minocycline treatment
boosteddirect- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Microbial richness, evenness, and diversity were all found to be drastically decreased in the SHR group when compared with the WKY control (Figure 1A).”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Results > HTN is associated with alteration in fecal microbiota composition in the SHR
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Two uncultured genera OTUs (109 and 177) that belonged to the Bacteroidetes phylum were more abundant in WKY.”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Results > Acetate and butyrate fermenters are decreased in the SHR
plaincorrelational- Asserted: passes — The authors put it forward as true.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Microbial richness, evenness, and diversity were all found to be drastically decreased in the SHR group when compared with the WKY control (Figure 1A).”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Results > HTN is associated with alteration in fecal microbiota composition in the SHR
plaincorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“This was significantly reduced by minocycline treatment.”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Results > Gut microbial diversity is increased by treatment of minocycline
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“We observed a reduction in bacterial Chao richness and Shannon diversity in the patients with high SBP when compared with control patients with normal SBP (Figure 4A).”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Results > Lower richness and diversity of gut microbiota in HTN patients
plaincorrelationaln = 7- Asserted: passes — The authors put it forward as true.
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In the paper
“Similar to the SHR, the acetate- and butyrate-producing bacteria genera were also depleted in chronically infused Ang II rats, although this finding failed to reach significance (Figure 7B).”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Results > Acetate- and butyrate-producing bacteria are expanded by minocycline treatment
hedged- Asserted: passes — The authors put it forward as true.
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In the paper
“Consistent with the SHR, rats infused with Ang II showed a trend toward lower bacterial load, although this finding did not reach significance (Figure 5B).”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Results > Gut microbial diversity is increased by treatment of minocycline
hedged- Asserted: passes — The authors put it forward as true.
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In the paper
“Additionally, the pie charts that represent the composition of microbiota at the phylum level show a trend towards relative higher abundance of Firmicutes and a lower abundance of Bacteroidetes in Ang II-infused rats when compared with control (Figure 6B), though the differences between those two groups did not reach individual significance.”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Results > Gut microbial diversity is increased by treatment of minocycline
hedged- Asserted: passes — The authors put it forward as true.
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In the paper
“There was a trend towards a decrease in Pielou evenness as well, but it did not reach statistical significance with this limited number of patients.”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Results > Lower richness and diversity of gut microbiota in HTN patients
hedgedn = 7- Asserted: passes — The authors put it forward as true.
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In the paper
“our data show it improves gut microbial homeostasis during HTN dysbiosis and is able to rebalance the gut acetate-, butyrate-, and lactate-producing bacterial populations.”
- Also stated in: § Discussion · plain
“Treatment with oral minocycline dose that attenuates HTN also produces beneficial effects on dysbiosis.”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Discussion
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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 diminished proportion of Actinobacteria indicates a less diverse microbiota in the SHR, which is consistent with the decrease in Chao richness and Shannon diversity.”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Results > HTN is associated with alteration in fecal microbiota composition in the SHR
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“This indicates a dysfunction in both acetogenic and butyrogenic capabilities.”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Results > Acetate and butyrate fermenters are decreased in the SHR
hedgeddirect- 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
“This indicates that the dysbiosis in this model is characterized by both an increase in Firmicutes and a decrease in Bacteroidetes.”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Results > Gut microbial diversity is increased by treatment of minocycline
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Finally, we found a reduction in the fecal biomass in the SHR, as well as a trend toward reduction in the Ang II infusion model. This is consistent with the previous reports that dysbiosis is associated with a decrease of bacterial loads35.”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Discussion
What the sources say
- Not checked yetcites [35] Leclercq S Matamoros S Cani PD Neyrinck AM Jamar F Starkel P Windey K Tremaroli V Backhed F Verbeke K de Timary P Delzenne NM Intestinal permeability, gut-bacterial dysbiosis, and behavioral markers of alcohol-dependence severity Proc Natl Acad Sci U S A 2014 111 E4485 4493 25288760 PMC4210345 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
“Thus, HTN-associated dysbiosis is characterized as an accumulation of lactate-producing bacteria and a reduction of acetate and butyrate producers.”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Results > Acetate and butyrate fermenters are decreased in the SHR
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
“However, the discrepancies may be accounted for by: (1) significant pathophysiological differences between WKY and SHR colonies depending on origin, breeding, and maintenance protocols; (2) lack of details regarding animal housing or pathogen-free facilities; (3) utilizing large enough number of rats necessary to detect a differences; (4) choosing the best models available for human HTN.”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Discussion
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. It may state two separate claims as one.
In the paper
“Our previous studies have indicated that minocycline influences microglial activation and neuroinflammation in autonomic brain regions27.”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Discussion
What the sources say
- Not checked yetcites [27] Shi P Diez-Freire C Jun JY Qi Y Katovich MJ Li Q Sriramula S Francis J Sumners C Raizada MK Brain microglial cytokines in neurogenic hypertension Hypertension 2010 56 297 303 20547972 PMC2929640
hedgeddirect- Asserted: passes — The authors put it forward as true.
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Probably not a substantial claim.
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In the paper
“All animal procedures were approved by the University of Florida Institutional Animal Care and Use Committee.”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Methods
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
“However, recent data suggest that it may also play a role in the development and maintenance of CVD and metabolic disorders such as obesity, diabetes and metabolic syndrome11–14.”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Introduction
What the sources say
- Not checked yetcites [11] Tang WH Wang Z Levison BS Koeth RA Britt EB Fu X Wu Y Hazen SL Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk N Engl J Med 2013 368 1575 1584 23614584 PMC3701945 source
- Not checked yetcites [12] Tilg H Kaser A Gut microbiome, obesity, and metabolic dysfunction J Clin Invest 2011 121 2126 2132 21633181 PMC3104783
- Not checked yetcites [13] Everard A Cani PD Diabetes, obesity and gut microbiota Best Pract Res Clin Gastroenterol 2013 27 73 83 23768554
- Not checked yetcites [14] Howitt MR Garrett WS A complex microworld in the gut: Gut microbiota and cardiovascular disease connectivity Nat Med 2012 18 1188 1189 22869188
hedgedconditional- 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
“Previous studies failed to identify differences in the gut microbiota between WKY and SHR36, and L-NAME hypertension37.”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Discussion
What the sources say
- Not checked yetcites [36] Petriz BA Castro AP Almeida JA Gomes CP Fernandes GR Kruger RH Pereira RW Franco OL Exercise induction of gut microbiota modifications in obese, non-obese and hypertensive rats BMC Genomics 2014 15 511 24952588 PMC4082611 source
- Not checked yetcites [37] Xu J Ahren IL Prykhodko O Olsson C Ahrne S Molin G Intake of blueberry fermented by lactobacillus plantarum affects the gut microbiota of l-name treated rats Evid Based Complement Alternat Med 2013 2013 809128 23690854 PMC3638594
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“It is pertinent to point out that a decrease in Akkermansia has been associated with obesity and diabetes, and introduction of Akkermansia could reverse the metabolic disorder and improve inflammation in diabetic and obese patients49.”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Discussion
What the sources say
- Not checked yetcites [49] Everard A Belzer C Geurts L Ouwerkerk JP Druart C Bindels LB Guiot Y Derrien M Muccioli GG Delzenne NM de Vos WM Cani PD Cross-talk between akkermansia muciniphila and intestinal epithelium controls diet-induced obesity Proc Natl Acad Sci U S A 2013 110 9066 9071 23671105 PMC3670398 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. It may state two separate claims as one.
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In the paper
“Doxycycline belongs to the same antibiotic class but has limited ability to pass through the blood brain barrier, and its effects on BP are inconclusive as there are multiple conflicting reports25,55.”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Discussion
What the sources say
- Not checked yetcites [25] Duncan SH Holtrop G Lobley GE Calder AG Stewart CS Flint HJ Contribution of acetate to butyrate formation by human faecal bacteria Br J Nutr 2004 91 915 923 15182395
- Not checked yetcites [55] Garrido-Mesa N Zarzuelo A Gálvez J Minocycline: Far beyond an antibiotic Br J Pharmacol 2013 169 337 352 23441623 PMC3651660
plain- Asserted: passes — The authors put it forward as true.
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In the paper
“This is not surprising, as previous studies have indicated that the depletion of microbiota required a combination of at least of 3 antibiotics for 3–4 weeks29, 30, and single antibiotics may not be sufficient to reduce the total bacterial load31.”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Results > Gut microbial diversity is increased by treatment of minocycline
What the sources say
- Not checked yetcites [29] Rakoff-Nahoum S Paglino J Eslami-Varzaneh F Edberg S Medzhitov R Recognition of commensal microflora by toll-like receptors is required for intestinal homeostasis Cell 2004 118 229 241 15260992 source
- Not checked yetcites [30] Reikvam DH Erofeev A Sandvik A Grcic V Jahnsen FL Gaustad P McCoy KD Macpherson AJ Meza-Zepeda LA Johansen FE Depletion of murine intestinal microbiota: Effects on gut mucosa and epithelial gene expression PLoS One 2011 6 e17996 21445311 PMC3061881
- Not checked yetcites [31] Million M Lagier JC Yahav D Paul M Gut bacterial microbiota and obesity Clin Microbiol Infect 2013 19 305 313 23452229
hedgedconditional- Asserted: passes — The authors put it forward as true.
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In the paper
“it inhibits expression of pro-inflammatory cytokines and intestinal damage in mouse model of colitis51, 52”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Discussion
What the sources say
- Not checked yetcites [51] Garrido-Mesa N Camuesco D Arribas B Comalada M Bailón E Cueto-Sola M Utrilla P Nieto A Zarzuelo A Rodríguez-Cabezas ME Gálvez J The intestinal anti-inflammatory effect of minocycline in experimental colitis involves both its immunomodulatory and antimicrobial properties Pharmacol Res 2011 63 308 319 21193045
- Not checked yetcites [52] Garrido-Mesa N Utrilla P Comalada M Zorrilla P Garrido-Mesa J Zarzuelo A Rodríguez-Cabezas ME Gálvez J The association of minocycline and the probiotic escherichia coli nissle 1917 results in an additive beneficial effect in a dss model of reactivated colitis in mice Biochem Pharmacol 2011 82 1891 1900 21930116
plaindirect- Asserted: passes — The authors put it forward as true.
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In the paper
“it attenuates gut damage and intestinal mucositis due to cancer chemotherapy53”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Discussion
What the sources say
- Not checked yetcites [53] Huang TY Chu HC Lin YL Ho WH Hou HS Chao YC Liao CL Minocycline attenuates 5-fluorouracil-induced small intestinal mucositis in mouse model Biochem Biophys Res Commun 2009 389 634 639 19765544
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
“Therefore, we can conclude that the HTN gut dysbiosis is characterized by an imbalance in specific microbial populations and their corresponding metabolites, specifically decreased acetate and butyrate-producing bacteria and increased lactate-producing bacteria.”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Discussion
boostedcorrelational- Asserted: passes — The authors put it forward as true.
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In the paper
“Functionally, both Bacteroides and Marvinbryantia produce acetate as their main fermentation product, and Akkermansia and Enterorhabdus have been found to be inversely associated with obesity and diabetes33.”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Results > Acetate- and butyrate-producing bacteria are expanded by minocycline treatment
What the sources say
- Not checked yetcites [33] Duca FA Sakar Y Lepage P Devime F Langelier B Dore J Covasa M Replication of obesity and associated signaling pathways through transfer of microbiota from obese-prone rats Diabetes 2014 63 1624 1636 24430437
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.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Minocycline is an anti-inflammatory antibiotic that freely crosses the blood-brain barrier and has been shown to produce beneficial effects in combating HTN26, 27.”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Results > Gut microbial diversity is increased by treatment of minocycline
What the sources say
- Not checked yetcites [26] Liao TV Forehand CC Hess DC Fagan SC Minocycline repurposing in critical illness: Focus on stroke Curr Top Med Chem 2013 13 2283 2290 24059465
- Not checked yetcites [27] Shi P Diez-Freire C Jun JY Qi Y Katovich MJ Li Q Sriramula S Francis J Sumners C Raizada MK Brain microglial cytokines in neurogenic hypertension Hypertension 2010 56 297 303 20547972 PMC2929640
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
“Typically, changes in gut microbiota have been related to chronic inflammatory diseases such as asthma, allergies, inflammatory bowel disease, and infectious diseases10.”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Introduction
What the sources say
- Not checked yetcites [10] Collado MC Rautava S Isolauri E Salminen S Gut microbiota: A source of novel tools to reduce the risk of human disease? Pediatr Res 2015 77 182 188 25335085 source
plaincorrelational- 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.
- Based: passes — The paper gives a reason why it holds.
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
“An increased F/B ratio, caused by an expansion of Firmicutes and/or a contraction of Bacteroidetes, has been widely considered a signature of gut dysbiosis and has been associated with obesity, diabetes, and CVD8, 13, 16.”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Discussion
What the sources say
- Not checked yetcites [8] Mariat D Firmesse O Levenez F Guimaraes V Sokol H Dore J Corthier G Furet JP The firmicutes/bacteroidetes ratio of the human microbiota changes with age BMC Microbiol 2009 9 123 19508720 PMC2702274 source
- Not checked yetcites [13] Everard A Cani PD Diabetes, obesity and gut microbiota Best Pract Res Clin Gastroenterol 2013 27 73 83 23768554
- Not checked yetcites [16] Sanz Y Moya-Perez A Microbiota, inflammation and obesity Adv Exp Med Biol 2014 817 291 317 24997040
boostedcorrelational- 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. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Human studies were approved by the University of Florida Institutional Review Board.”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Methods
plain- 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.
- Based: passes — The paper gives a reason why it holds.
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
“In the periphery, gut microbiota plays an important role in shaping a robust systemic and intestinal immune system6, 7.”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Introduction
What the sources say
- Not checked yetcites [6] Chow J Lee SM Shen Y Khosravi A Mazmanian SK Host-bacterial symbiosis in health and disease Adv Immunol 2010 107 243 274 21034976 PMC3152488
- Not checked yetcites [7] McDermott AJ Huffnagle GB The microbiome and regulation of mucosal immunity Immunology 2014 142 24 31 24329495 PMC3992044
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.
- Based: passes — The paper gives a reason why it holds.
Probably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“However, we did not measure plasma lactate in any of our experiments, and this remains a future direction.”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Discussion
plain- 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.
- Based: passes — The paper gives a reason why it holds.
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
“It is important to note that the F/B ratio is well validated in rodent and human samples; however its significance in pig models requires further studies33, 34.”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Discussion
What the sources say
- Not checked yetcites [33] Duca FA Sakar Y Lepage P Devime F Langelier B Dore J Covasa M Replication of obesity and associated signaling pathways through transfer of microbiota from obese-prone rats Diabetes 2014 63 1624 1636 24430437
- Not checked yetcites [34] Pedersen R Andersen AD Molbak L Stagsted J Boye M Changes in the gut microbiota of cloned and non-cloned control pigs during development of obesity: Gut microbiota during development of obesity in cloned pigs BMC Microbiol 2013 13 30 23391125 PMC3610253
boosted- 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.
- Based: passes — The paper gives a reason why it holds.
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
“Additionally, minocycline is the drug approved in our patient studies (NCT#02133872 and 02133885) which has shown an impressive ability to decrease BP, improve HbA1C levels, and weight loss in our pilot study28.”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Results > Gut microbial diversity is increased by treatment of minocycline
What the sources say
- Not checked yetcites [28] Hu P Thinschmidt JS Yan Y Hazra S Bhatwadekar A Caballero S Salazar T Miyan JA Li W Derbenev A Zsombok A Tikhonenko M Dominguez JM 2nd McGorray SP Saban DR Boulton ME Busik JV Raizada MK Chan-Ling T Grant MB Cns inflammation and bone marrow neuropathy in type 1 diabetes Am J Pathol 2013 183 1608 1620 24160325 PMC3814523
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.
It may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“This increase in HSCs has been implicated in their extravasation into the brain and establishment of neuroinflammation in many neural diseases57,58.”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Discussion
What the sources say
- Not checked yetcites [57] Santisteban MM Zubcevic J Kim S Marulanda-Carvajal J Zingler M Joseph J Raizada MK Iba1+ microglia/macrophages in the rat hypothalamic paraventricular nucleus are both resident and bone marrow-derived in ang ii induced hypertension the faseb journal 2014 28 1
- Not checked yetcites [58] Katsumoto A Lu H Miranda AS Ransohoff RM Ontogeny and functions of central nervous system macrophages J Immunol 2014 193 2615 2621 25193935 PMC4157312
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.
The paper relies on this without support.
The chronic Ang II infusion rat model is a well-validated and established model of human hypertension.
“For this purpose, we used the chronic Ang II infusion model, which is a well-validated and established model of HTN.”
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
“microbial compositional changes have been reported in patients with numerous CVD risk factors including hypertension, dyslipidemia, insulin resistance, and other metabolic phenotypes10, 11.”
From Gut microbiota and cardiovascular disease. (2020) · cites this paper as [10]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Gut dysbiosis has been reported in animal models87–89 and in patients with hypertension87,90 (Table 1).”
From The gut microbiota and the brain–gut–kidney axis in hypertension and chronic kidney disease (2018) · cites this paper as [87]
In the citing paper
“A significant proportion of the SCFAs produced in the distal bowel is reabsorbed from the gut lumen by facilitated apical solute transport via multiple different transporters114–117 as well as via passive (concentration-dependent) diffusion118.”
From Dietary metabolism, the gut microbiome, and heart failure (2019) · cites this paper as [116]
In the citing 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].”
From Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health (2017) · cites this paper as [331]
In the citing paper
“Finally, studies in animal models and in patients with hypertension have reported that interventions that target the gut microbiota, such as a high-fibre diet, probiotics and antibiotics, have blood-pressure lowering effects87,92–99.”
From The gut microbiota and the brain–gut–kidney axis in hypertension and chronic kidney disease (2018) · cites this paper as [87]
In the citing paper
“Our research group was the first to demonstrate a contribution of the brain-gut-bone-marrow axis to blood pressure elevation15,87,91,154–159.”
From The gut microbiota and the brain–gut–kidney axis in hypertension and chronic kidney disease (2018) · cites this paper as [87]
In the citing paper
“For example, in rats with angiotensin-II-induced hypertension, minocycline administration changed the gut micro-biota and lowered blood pressure87.”
From The gut microbiota and the brain–gut–kidney axis in hypertension and chronic kidney disease (2018) · cites this paper as [87]
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Guidelines for Transparency on Gut Microbiome Studies in Essential and Experimental Hypertension
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Yang, G., Jiang, Y., Yang, W., Du, F., Yao, Y., Shi, C., & Wang, C. (2015) · Microbial Cell Factories · doi:10.1186/s12934-015-0394-2 · Cited by 77
Homeostasis in the Gut Microbiota in Chronic Kidney Disease
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Weber, G. J., Pushpakumar, S. B., Tyagi, S. C., & Sen, U. (2016) · Pharmacological Research · doi:10.1016/j.phrs.2016.09.002 · Cited by 76
The Influence of Diet on MicroRNAs that Impact Cardiovascular Disease
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How Dietary Fibre, Acting via the Gut Microbiome, Lowers Blood Pressure
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Sayec, M. L., Xu, Y., Laiola, M., Gallego, F. A., Katsikioti, D., Durbidge, C., Kivisild, U., Armes, S., Lecomte, M., Fança‐Berthon, P., et al. (2022) · Clinical Nutrition · doi:10.1016/j.clnu.2022.08.024 · Cited by 80
Gut butyrate-producers confer post-infarction cardiac protection
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Gut–Brain Axis in Regulation of Blood Pressure
Yang, T., & Zubcevic, J. (2017) · Frontiers in Physiology · doi:10.3389/fphys.2017.00845 · Cited by 74
Self-citationMetabolites and Hypertension: Insights into Hypertension as a Metabolic Disorder
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Self-citationProbiotics: Protecting Our Health from the Gut
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Role of the Gut Microbiome in the Development of Atherosclerotic Cardiovascular Disease
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Gut dysbiosis in patients with chronic pain: a systematic review and meta-analysis
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Sharma, R. K., Oliveira, A. C. D. S., Yang, T., Karas, M. M., Li, J., Lobaton, G. O., Aquino, V. P., Robles‐Vera, I., de Kloet, A. D., Krause, E. G., et al. (2020) · Hypertension · doi:10.1161/hypertensionaha.120.14931 · Cited by 74
Self-citationMicrobiota Introduced to Germ-Free Rats Restores Vascular Contractility and Blood Pressure
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The gut microbiota and aging: interactions, implications, and interventions
Gyriki, D., Nikolaidis, C. G., Bezirtzoglou, E., Voidarou, C. C., Stavropoulou, E., & Tsigalou, C. (2025) · Frontiers in Aging · doi:10.3389/fragi.2025.1452917 · Cited by 80
Farré, N., Farré, R., & Gozal, D. (2018) · CHEST Journal · doi:10.1016/j.chest.2018.03.001 · Cited by 71
Early Programming of Adult Systemic Essential Hypertension
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The role of the gut microbiome in sex differences in arterial pressure
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Zuo, K., Li, J., Wang, P., Liu, Y., Liu, Z., Yin, X., Liu, X., & Yang, X. (2019) · mSystems · doi:10.1128/msystems.00422-19 · Cited by 71
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Gut Microbiota Dysbiosis in Human Hypertension: A Systematic Review of Observational Studies
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Dietary fibre and the gut–brain axis: microbiota-dependent and independent mechanisms of action
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Zou, X., Wang, L., Xiao, L., Wang, S., & Zhang, L. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.975921 · Cited by 71
Plant-Based Diets and Hypertension
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Maksymiuk, K. M., Radkowski, M., Grochowska, M., Perlejewski, K., Huć, T., Jaworska, K., Motooka, D., Nakamura, S., & Ufnal, M. (2018) · Nutrition · doi:10.1016/j.nut.2018.03.004 · Cited by 69
Raizada, M. K., Joe, B., Bryan, N. S., Chang, E. B., Dewhirst, F. E., Borisy, G. G., Galis, Z. S., Henderson, W. A., José, P. A., Ketchum, C. J., et al. (2017) · Hypertension · doi:10.1161/hypertensionaha.117.09699 · Cited by 66
Self-citationVignesh, R., Swathirajan, C. R., Tun, Z. H., Rameshkumar, M. R., Solomon, S. S., & Balakrishnan, P. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2020.607734 · Cited by 66
Gut Microbiome in Chronic Kidney Disease
Armani, R. G., Ramezani, A., Yasir, A., Sharama, S., Canziani, M. E., & Raj, D. S. (2017) · Current Hypertension Reports · doi:10.1007/s11906-017-0727-0 · Cited by 68
Flux, M. C., & Lowry, C. A. (2019) · Neurobiology of Disease · doi:10.1016/j.nbd.2019.104578 · Cited by 70
The Microbiome and Atopic Dermatitis: A Review
Pothmann, A., Illing, T., Wiegand, C., HARTMANN, A. A., & Elsner, P. U. (2019) · American Journal of Clinical Dermatology · doi:10.1007/s40257-019-00467-1 · Cited by 65
Hsu, C., Chang‐Chien, G., Lin, S., Hou, C., Lu, P., & Tain, Y. (2020) · Journal of Clinical Medicine · doi:10.3390/jcm9020336 · Cited by 66
Mushtaq, N., Hussain, S., Zhang, S., Lü, Y., Li, H., Ullah, S., Wang, Y., & Xu, J. (2019) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2019.4235 · Cited by 65
Gut hormones and gut microbiota: implications for kidney function and hypertension
Afsar, B., Vaziri, N. D., Aslan, G., Tarim, K., & Kanbay, M. (2016) · Journal of the American Society of Hypertension · doi:10.1016/j.jash.2016.10.007 · Cited by 63
Gut Microbiota and Short Chain Fatty Acids: Influence on the Autonomic Nervous System
Bruning, J. R., Chapp, A. D., Kaurala, G. A., Wang, R., Techtmann, S. M., & Chen, Q. (2019) · Neuroscience Bulletin · doi:10.1007/s12264-019-00410-8 · Cited by 67
From obesity through gut microbiota to cardiovascular diseases: a dangerous journey
Marzullo, P., Renzo, L. D., Pugliese, G., Siena, M. D., Barrea, L., Muscogiuri, G., Colao, A., & Savastano, S. (2020) · International Journal of Obesity Supplements · doi:10.1038/s41367-020-0017-1 · Cited by 64
Constipation and risk of cardiovascular diseases: a Danish population-based matched cohort study
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The role of the gut microbiota and microbial metabolites in neuroinflammation
Haase, S., Wilck, N., Haghikia, A., Gold, R., Mueller, D. N., & Linker, R. A. (2020) · European Journal of Immunology · doi:10.1002/eji.201847807 · Cited by 65
Glucocorticoids and gut bacteria: “The GALF Hypothesis” in the metagenomic era
Morris, D. J., & Ridlon, J. M. (2017) · Steroids · doi:10.1016/j.steroids.2017.06.002 · Cited by 63
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Functional Foods: An Approach to Modulate Molecular Mechanisms of Alzheimer’s Disease
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New drug targets for hypertension: A literature review
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Gut Microbiome Dysbiosis in Alcoholism: Consequences for Health and Recovery
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The gut microbiota and blood pressure in experimental models
Jama, H. A., Kaye, D. M., & Marques, F. Z. (2018) · Current Opinion in Nephrology & Hypertension · doi:10.1097/mnh.0000000000000476 · Cited by 63
Metadata
- Authors
- Yang, T., Santisteban, M. M., Rodriguez, V., Li, E., Ahmari, N., Carvajal, J. M., Zadeh, M., Gong, M., Qi, Y., Zubcevic, J., Sahay, B., Pepine, C. J., Raizada, M. K., & Mohamadzadeh, M.
- Affiliations
- From the Department of Infectious Diseases and Pathology, College of Veterinary Medicine (T.Y., M.Z., M.G., B.S., M.M.), Division of Gastroenterology, Hematology and Nutrition, Department of Medicine (T.Y., M.Z., M.G., B.S., M.M.), Department of Physiology and Functional Genomics (M.M.S., V.R., J.M.C., M.K.R.), College of Medicine, Division of Cardiovascular Medicine, Department of Medicine (V.R., Y.Q., C.J.P.), Division of Infectious Diseases and Global Medicine, Department of Medicine (E.L.), and...
- Corresponding author
- Yang, Tao
- Santisteban, Monica M.
- ORCID
- Venue
- Hypertension
- Published
- 2015-06
- Volume
- 65
- Issue
- 6
- Pages
- 1331-1340
- ISSN
- 0194-911X (ISSN-L)
- 1524-4563
- PMC
- PMC4433416
- OpenAlex
- W2136344314
- Semantic Scholar
- 2f4fc7ed71095f8622624390622f7074ee0529d3
- Cited by
- 1,478
- References
- 66
- Citations by year
- 2026: 70 · 2025: 144 · 2024: 171 · 2023: 180 · 2022: 207 · 2021: 208 · 2020: 176 · 2019: 126 · 2018: 83 · 2017: 56 · 2016: 40 · 2015: 16
- FWCI
- 28.24
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Hypertension (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- American Heart Association
- National Institutes of Health (UL1TR001427, UL1TR000064)
- National Heart, Lung, and Blood Institute (HL33610, R01HL033610, UM1HL087366, R37HL033610)
- National Institute of Allergy and Infectious Diseases (AI093370, R01AI093370)
- National Center for Advancing Translational Sciences
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Keywords
- gut dysbiosis, gut microbiota, spontaneously hypertensive rats, angiotensin II infusion, Firmicutes/Bacteroidetes ratio, microbial diversity, butyrate-producing bacteria, minocycline, dietary intervention, blood pressure regulation
- MeSH terms
- Animals, Disease Models, Animal, DNA, Bacterial, Feces, Humans, Hypertension, Minocycline, Random Allocation, Rats, Inbred SHR, Rats, Inbred WKY, Species Specificity, Cohort Studies, Comorbidity, Treatment Outcome, Risk Assessment, Gastrointestinal Tract, Rats, Microbiota, Dysbiosis
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