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.
AI snapshot
Written from the paper’s full text.
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.
Model-written summary. Check it against the paper before relying on it.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
0 of 35 cited sources checked · 0 supported · 0 flagged
- Findingown data
In SHR compared with WKY, microbial evenness was drastically decreased.
“Microbial richness, evenness, and diversity were all found to be drastically decreased in the SHR group when compared with the WKY control (Figure 1A).”
Quote in the paperSubstantial claim - Findingown data
Enrichment of Akkermansia, Bacteroides, Enterorhabdus and Marvinbryantia was observed in Ang II + minocycline treated group.
“Figure 7A shows the enrichment of Akkermansia, Bacteroides, Enterorhabdus and Marvinbryantia in Ang II + minocycline treated group.”
Quote in the paperSubstantial claim - Findingown data
The composition of fecal microbial communities of WKY and SHR were distinct.
“The composition of the fecal microbial communities of the WKY and SHR were found to be distinct, as presented in Figure 1B.”
Quote in the paperSubstantial claim - Findingown data
Uncultured and incertae sedis bacteria genera OTUs (2761 and 3955) belonging to Firmicutes were significantly enriched in SHR.
“The abundance of other uncultured and incertae sedis bacteria genera OTUs (2761 and 3955) that belonged to Firmicutes were significantly enriched in the SHR.”
Quote in the paperSubstantial claim - Findingown data
Oral administration of minocycline resulted in a remarkable increase of both acetate- and butyrate-producing bacteria.
“However, oral administration of minocycline resulted in a remarkable increase of both the acetate- and butyrate-producing bacteria.”
Quote in the paperSubstantial claim
- Findingown data
In SHR compared with WKY, microbial diversity was drastically decreased.
“Microbial richness, evenness, and diversity were all found to be drastically decreased in the SHR group when compared with the WKY control (Figure 1A).”
Quote in the paperSubstantial claim - Findingown data
Two uncultured genera OTUs (109 and 177) belonging to Bacteroidetes were more abundant in WKY.
“Two uncultured genera OTUs (109 and 177) that belonged to the Bacteroidetes phylum were more abundant in WKY.”
Quote in the paperNot a substantial claim - Findingown data
In SHR compared with WKY, microbial richness was drastically decreased.
“Microbial richness, evenness, and diversity were all found to be drastically decreased in the SHR group when compared with the WKY control (Figure 1A).”
Quote in the paperSubstantial claim - Findingown data
Minocycline treatment significantly reduced the F/B ratio in Ang II-infused rats.
“This was significantly reduced by minocycline treatment.”
Quote in the paperSubstantial claim - Findingown data
In patients with high SBP compared with normal SBP, bacterial Chao richness was reduced.
“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).”
Quote in the paperSubstantial claim - Findingown data
Ang II + minocycline rats displayed a significant separation from the other two groups in PCoA.
“However, Ang II + minocycline rats displayed a significant separation from the other two groups, indicating a shift in the gut bacterial composition by the administration of minocycline.”
Quote in the paperSubstantial claim - Findingown data
In patients with high SBP compared with normal SBP, Shannon diversity was reduced.
“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).”
Quote in the paperSubstantial claim - Findingown data
Oral minocycline for 4 weeks significantly lowered mean arterial pressure in Ang II-infused rats (24 hour MAP: 124 ± 2 mmHg vs 168 ± 2 mmHg).
“As expected, oral minocycline for 4 weeks was able to significantly lower mean arterial pressure in Ang II-infused rats (24 hour MAP: 124 ± 2 mmHg vs 168 ± 2 mmHg) (Figure 5A).”
Quote in the paperSubstantial claim - Findingown data
The two patient populations (high and normal SBP) formed separate clusters in PCoA.
“As shown in Figure 4B, the two patient populations formed separate clusters.”
Quote in the paperSubstantial claim - Findingown data
In SHR, acetate-producing bacteria were decreased approximately 3-fold.
“We observed ~3-fold decrease in acetate- and a 2-fold decrease in butyrate-producing bacteria in the SHR (Figure 3B).”
Quote in the paperSubstantial claim - Findingcitation
Minocycline treatment did not result in a further reduction of bacterial load.
“Minocycline treatment did not result in a further reduction of bacterial load.”
Quote in the paperNot a substantial claim - Findingown data
The F/B ratio was considerably increased in Ang II-infused rats compared to control.
“Most importantly, the F/B ratio was considerably increased in the Ang II-infused rats compared to control (Figure 6A).”
Quote in the paperSubstantial claim - Findingown data
The increase in acetate- and butyrate-producing bacteria was associated with a decrease in the abundance of lactate-producing bacteria.
“This was associated with a decrease in the abundance of lactate-producing bacteria.”
Quote in the paperNot a substantial claim - Findingown data
In WKY, butyrate-producing bacteria including Coprococcus and Pseudobutyrivibrio were highly accumulated.
“LEfSe performed at the genus level demonstrated that butyrate-producing bacteria were found to be highly accumulated in WKY, including Coprococcus and Pseudobutyrivibrio (Figure 3A).”
Quote in the paperSubstantial claim - Findingown data
Bifidobacterium was significantly depleted in SHR.
“Remarkably, a significant depletion of Bifidobacterium was found in the SHR, which greatly contributed to the diminished proportion of Actinobacteria and therefore the decreased gut microbiota diversity.”
Quote in the paperSubstantial claim - Findingown data
In SHR compared with WKY, fecal bacterial load was significantly reduced.
“A significant reduction of bacterial load was found in SHR when compared with WKY (Figure 1A).”
Quote in the paperSubstantial claim - Findingown data
A striking bloom of other bacteria phyla (including Verrucomicrobia) beyond Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria and Tenericutes was observed.
“In addition, we observed a striking bloom of other bacteria phyla (including Verrucomicrobia) beyond Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria and Tenericutes, indicating a significant shift of intestinal microbial composition towards diversity.”
Quote in the paperNot a substantial claim - Findingown data
Fecal samples from both WKY and SHR were dominated by Firmicutes and Bacteroidetes, with smaller proportions of Actinobacteria and Proteobacteria.
“Fecal samples from both WKY and SHR were dominated by Firmicutes and Bacteroidetes, and with smaller proportions of Actinobacteria and Proteobacteria (Figure 2B).”
Quote in the paperNot a substantial claim - Findingown data
Significant differences were observed between WKY and SHR in the relative abundances of Actinobacteria, Bacteroidetes and Firmicutes.
“However, significant differences were observed between the groups in terms of the relative abundances of Actinobacteria, Bacteroidetes and Firmicutes.”
Quote in the paperSubstantial claim - Findingown data
Rats infused with Ang II alone demonstrated a lower richness value compared with control.
“Rats infused with Ang II alone demonstrated a lower richness value when compared with control (Figure 5B).”
Quote in the paperSubstantial claim - Findingown data
Oral administration of minocycline was capable of increasing Bacteroidetes in the gut.
“Interestingly, oral administration of minocycline was capable of increasing Bacteroidetes in the gut, which has been reported as a positive sign after successful fecal microbiota transplantation for the treatment of recurrent C. difficile infection induced dysbiosis32.”
Quote in the paperSubstantial claim - Findingown data
Two uncultured genera OTUs (109 and 177) belonging to Bacteroidetes were completely depleted in SHR.
“Interestingly, both of these two genera were completely depleted in the SHR.”
Quote in the paperSubstantial claim - Findingown data
In SHR compared with WKY, the F/B ratio was approximately 5-fold higher.
“The F/B ratio in the SHR was ~5-fold higher compared with WKY (Figure 2A).”
Quote in the paperSubstantial claim - Findingown data
In SHR, the abundance of lactate-producing bacteria was significantly increased.
“In contrast, the abundance of lactate-producing bacteria was significantly increased in the SHR.”
Quote in the paperSubstantial claim - Findingown data
In SHR, lactate-producing bacteria Streptococcus and Turicibacter were in higher quantities.
“In contrast, lactate-producing bacteria, Streptococcus and Turicibacter, were in higher quantities in the SHR.”
Quote in the paperSubstantial claim - Findingown data
In SHR, butyrate-producing bacteria were decreased approximately 2-fold.
“We observed ~3-fold decrease in acetate- and a 2-fold decrease in butyrate-producing bacteria in the SHR (Figure 3B).”
Quote in the paperSubstantial claim - Findingown data
No clear separation was observed between the clusters of Ang II alone and control in PCoA analysis.
“Despite this lower richness value, we did not observe a clear separation between the clusters of these two groups in PCoA analysis, due to the comparable values of evenness and diversity (Figure 5C).”
Quote in the paperNot a substantial claim - Findingown data
The F/B ratio was dramatically increased in both the SHR and Ang II infusion models.
“However, the most important and recognized biomarker, the F/B ratio, was dramatically increased in both the SHR and Ang II infusion models.”
Quote in the paperSubstantial claim - Findingown data
Minocycline treatment resulted in a drastic shift in the microbial environment characterized by a bloom of diverse bacteria in the gut.
“our data show that this treatment resulted in a drastic shift in the microbial environment characterized by a bloom of diverse bacteria in the gut.”
Quote in the paperSubstantial claim - Findingown data
Oral minocycline treatment results in the attenuation of high BP induced by chronic Ang II infusion.
“Oral minocycline treatment results in the attenuation of high BP induced by chronic Ang II infusion.”
Quote in the paperSubstantial claim - Findingown data
Decreases in butyrate- and acetate-producing bacteria were found in both models of HTN.
“Interestingly, decreases in the butyrate- and acetate-producing bacteria were found in both models of HTN.”
Quote in the paperSubstantial claim - Findingown data
Minocycline did not reduce fecal biomass.
“The first important finding was that minocycline did not reduce fecal biomass”
Quote in the paperSubstantial claim - Findingown data
Lactate-producing bacteria were increased in both animal models of HTN.
“Of particular interest is the finding that lactate-producing bacteria were increased in both animal models of HTN”
Quote in the paperNot a substantial claim - Findingown data
Further analysis of Verrucomicrobia phylum revealed a significant increase in the mucin-degrading bacterium, Akkermansia.
“Further analysis of Verrucomicrobia phylum revealed a significant increase in the mucin-degrading bacterium, Akkermansia.”
Quote in the paperNot a substantial claim - Findingown data
HTN is associated with gut microbiota dysbiosis.
“our study demonstrates that HTN is associated with gut microbiota dysbiosis”
- Also stated in: § Discussion · plain
“these observations support our overall proposal of a microbial dysbiosis linked to HTN.”
Quote in the paperSubstantial claim - Also stated in: § Discussion · plain
- Findingown data
A dramatic increase in Verrucomicrobia phylum bacteria was observed.
“A dramatic increase in Verrucomicrobia phylum bacteria was observed”
Quote in the paperNot a substantial claim - Findingown data
Preliminary data indicate that minocycline treatment was able to reverse the Ang II-induced decrease in cingulin in the colon.
“In addition, preliminary data indicate that minocycline treatment was able to reverse the Ang II-induced decrease in cingulin in the colon.”
Quote in the paperSubstantial claim - Findingown data
The gut microbiota dysbiosis associated with HTN in two rat models is characterized by an increased F/B ratio.
“our study demonstrates that HTN is associated with gut microbiota dysbiosis, characterized by an increased F/B ratio, as well as a drastic decrease in acetate-, butyrate-, and an accumulation of lactate- producing microbial populations in two rat models of HTN.”
Quote in the paperSubstantial claim - Findingown data
This study demonstrates a dysbiotic gut profile in patients with high BP.
“Most importantly, this study does indeed demonstrate a dysbiotic gut profile in patients with high BP.”
Quote in the paperSubstantial claim - Interpretationown data
Ang II + minocycline rats displayed a shift in gut bacterial composition by the administration of minocycline.
“However, Ang II + minocycline rats displayed a significant separation from the other two groups, indicating a shift in the gut bacterial composition by the administration of minocycline.”
Quote in the paperSubstantial claim - Interpretationreasoning
The discrepancy in ecological parameters between SHR and Ang II models can be attributed to differences in pathogenesis in both animal models.
“This discrepancy can be attributed to the differences in pathogenesis in both of these animal models, and may represent an important area of future research focus.”
Quote in the paperNot a substantial claim - Interpretationown data
The human data confirmed the observation made in the animal model that gut dysbiosis is observed between high and normal SBP cohorts.
“The analyzed human data clearly confirmed the observation made in our animal model where gut dysbiosis is observed between the high and normal SBP cohorts.”
Quote in the paperSubstantial claim - Interpretationown data
The bloom of other bacteria phyla indicates a significant shift of intestinal microbial composition towards diversity.
“In addition, we observed a striking bloom of other bacteria phyla (including Verrucomicrobia) beyond Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria and Tenericutes, indicating a significant shift of intestinal microbial composition towards diversity.”
Quote in the paperSubstantial claim - Interpretationreasoning
The signature of gut microbiota dysbiosis in the Ang II model is consistent with that previously shown in the SHR model.
“This signature of gut microbiota dysbiosis is consistent with that previously shown in the SHR model.”
Quote in the paperNot a substantial claim - Interpretationown data
This study provides the first evidence of an association of HTN with altered gut microbiota using two rat models and a small cohort of HTN patients.
“This study provides the first evidence, to our knowledge, of an association of HTN with altered gut microbiota with the use of two different rat models of HTN and a small cohort of HTN patients.”
Quote in the paperSubstantial claim - Interpretationown data
The depletion of Bifidobacterium greatly contributed to the diminished proportion of Actinobacteria and therefore the decreased gut microbiota diversity in SHR.
“Remarkably, a significant depletion of Bifidobacterium was found in the SHR, which greatly contributed to the diminished proportion of Actinobacteria and therefore the decreased gut microbiota diversity.”
Quote in the paperSubstantial claim - Interpretationown data
These findings clearly implicate the role of gut microbiota in the pathophysiology of both animal and human HTN.
“These findings clearly implicate the role of gut microbiota in the pathophysiology of both animal and human HTN.”
Quote in the paperSubstantial claim - Interpretationown data
The changes in specific bacterial genera were the major contributors to the increased F/B ratio in SHR.
“These changes were the major contributors to the increased F/B ratio in the SHR.”
Quote in the paperSubstantial claim - Interpretationown data
Minocycline does not have negative effects on the gut microbiota.
“providing evidence that this antibiotic does not have negative effects on the gut microbiota.”
Quote in the paperSubstantial claim - Interpretationown data
Minocycline produced an intestinal environment that was extremely conducive to nurturing the growth of bacteria of the Verrucomicrobia phylum.
“indicating that minocycline produced an intestinal environment that was extremely conducive to nurturing the growth of bacteria of this phylum.”
Quote in the paperNot a substantial claim - Premisecitation
Cingulin is a tight junction protein whose decreased levels have been associated with gut barrier dysfunction leading to increased inflammation.
“Cingulin is a tight junction protein whose decreased levels have been associated with gut barrier dysfunction leading to increased inflammation50.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [50] Bordin M D’Atri F Guillemot L Citi S Histone deacetylase inhibitors up-regulate the expression of tight junction proteins Mol Cancer Res 2004 2 692 701 15634758 source
Not checked in the free run.
- Interpretationreasoning
These gut specific effects of minocycline appear to be linked with minocycline's beneficial effects on inflammation and HTN.
“Thus, these gut specific effects of minocycline appear to be linked with minocycline’s beneficial effects on inflammation and HTN.”
Quote in the paperSubstantial claim - Premisecitation
A meta-analysis of nine randomized trials showed a significant decrease in both systolic and diastolic BP in patients that consumed a daily dose of 10^9 CFU of probiotics.
“A meta-analysis of nine randomized trials showed a significant decrease in both systolic and diastolic BP in patients that consumed a daily dose of 109 CFU of probiotics17.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [17] Khalesi S Sun J Buys N Jayasinghe R Effect of probiotics on blood pressure: A systematic review and meta-analysis of randomized, controlled trials Hypertension 2014 64 897 903 25047574 source
Not checked in the free run.
- Interpretationreasoning
Microbial diversity plays an important role in HTN.
“Our observations are consistent with these reports and support the important role of microbial diversity in HTN.”
Quote in the paperSubstantial claim - Study design and conductnone given
The two control subjects observed within the HTN PCoA plot distribution were currently under anti-HTN treatment although optimum medication combination and dosage had not been met.
“It is important to mention that the two control subjects observed within the HTN PCoA plot distribution pertain to subjects who were currently under anti-HTN treatment although optimum medication combination and dosage had not been met.”
Quote in the paperNot a substantial claim - Premisecitation
Evidence exists of direct anti-inflammatory effects of minocycline in the brain in many neurodegenerative and neurobehavioral diseases.
“Furthermore, evidence also exists of direct anti-inflammatory effects of minocycline in the brain in many neurodegenerative and neurobehavioral diseases54, 55.”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [54] Galpern WR Singhal AB Neuroprotection: Lessons from a spectrum of neurological disorders Int J Stroke 2006 1 97 99 18706052 source
Not checked in the free run.
- cites [55] Garrido-Mesa N Zarzuelo A Gálvez J Minocycline: Far beyond an antibiotic Br J Pharmacol 2013 169 337 352 23441623 PMC3651660 source
Not checked in the free run.
- Interpretationreasoning
Reversing the gut dysbiosis might be affected by the stability of BP control and the time undergoing such treatment.
“Therefore, this suggests that reversing the gut dysbiosis might be affected by the stability of BP control and the time undergoing such treatment.”
Quote in the paperNot a substantial claim
- May combine two claims. 22
- The quote only partly states this claim. 1
- Classified as probably not a substantial claim. 13
May combine two claims.
Findingown dataIn chronically infused Ang II rats, acetate- and butyrate-producing bacteria genera were depleted, but this finding failed to reach significance.
“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).”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataRats infused with Ang II showed a trend toward lower bacterial load compared with control, but it did not reach significance.
“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).”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataIn Ang II-infused rats compared with control, there was a trend towards relatively higher abundance of Firmicutes and lower abundance of Bacteroidetes, but differences did not reach individual significance.
“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.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataIn patients with high SBP compared with normal SBP, there was a trend towards a decrease in Pielou evenness, but it did not reach statistical significance.
“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.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataMinocycline treatment improves gut microbial homeostasis during HTN dysbiosis and rebalances the gut acetate-, butyrate-, and lactate-producing bacterial populations.
“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.”
Quote in the paperSubstantial claim- Also stated in: § Discussion · plain
May combine two claims.
InterpretationreasoningThe diminished proportion of Actinobacteria indicates a less diverse microbiota in SHR, consistent with decreased Chao richness and Shannon diversity.
“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.”
Quote in the paperSubstantial claimMay combine two claims. The quote only partly states this claim.
InterpretationreasoningThe decrease in acetate- and butyrate-producing bacteria and increase in lactate-producing bacteria in SHR indicates a dysfunction in both acetogenic and butyrogenic capabilities.
“This indicates a dysfunction in both acetogenic and butyrogenic capabilities.”
Quote in the paperSubstantial claimMay combine two claims.
Interpretationown dataThe dysbiosis in the Ang II model is characterized by both an increase in Firmicutes and a decrease in Bacteroidetes.
“This indicates that the dysbiosis in this model is characterized by both an increase in Firmicutes and a decrease in Bacteroidetes.”
Quote in the paperSubstantial claimMay combine two claims.
InterpretationcitationThe reduction in fecal biomass in SHR and trend toward reduction in Ang II model is consistent with previous reports that dysbiosis is associated with a decrease of bacterial loads.
“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.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [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
Not checked in the free run.
May combine two claims.
Interpretationown dataHTN-associated dysbiosis is characterized as an accumulation of lactate-producing bacteria and a reduction of acetate and butyrate producers.
“Thus, HTN-associated dysbiosis is characterized as an accumulation of lactate-producing bacteria and a reduction of acetate and butyrate producers.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
InterpretationreasoningThe discrepancies between our findings and previous studies may be accounted for by pathophysiological differences between WKY and SHR colonies, lack of housing details, sample size, and model choice.
“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.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim.
PremisecitationOur previous studies have indicated that minocycline influences microglial activation and neuroinflammation in autonomic brain regions.
“Our previous studies have indicated that minocycline influences microglial activation and neuroinflammation in autonomic brain regions27.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [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
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenAll animal procedures were approved by the University of Florida Institutional Animal Care and Use Committee.
“All animal procedures were approved by the University of Florida Institutional Animal Care and Use Committee.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim.
PremisecitationRecent data suggest that gut microbiota may play a role in the development and maintenance of CVD and metabolic disorders such as obesity, diabetes and metabolic syndrome.
“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.”
Quote in the paperSubstantial claim0 of 4 sources checked- cites [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 in the free run.
- cites [12] Tilg H Kaser A Gut microbiome, obesity, and metabolic dysfunction J Clin Invest 2011 121 2126 2132 21633181 PMC3104783
Not checked in the free run.
- cites [13] Everard A Cani PD Diabetes, obesity and gut microbiota Best Pract Res Clin Gastroenterol 2013 27 73 83 23768554
Not checked in the free run.
- cites [14] Howitt MR Garrett WS A complex microworld in the gut: Gut microbiota and cardiovascular disease connectivity Nat Med 2012 18 1188 1189 22869188
Not checked in the free run.
May combine two claims.
PremisecitationPrevious studies failed to identify differences in the gut microbiota between WKY and SHR and L-NAME hypertension.
“Previous studies failed to identify differences in the gut microbiota between WKY and SHR36, and L-NAME hypertension37.”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [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 in the free run.
- cites [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
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationA 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 patients.
“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.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [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
Not checked in the free run.
May combine two claims.
PremisecitationDoxycycline belongs to the same antibiotic class as minocycline but has limited ability to pass through the blood brain barrier, and its effects on BP are inconclusive.
“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.”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [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 in the free run.
- cites [55] Garrido-Mesa N Zarzuelo A Gálvez J Minocycline: Far beyond an antibiotic Br J Pharmacol 2013 169 337 352 23441623 PMC3651660
Not checked in the free run.
May combine two claims.
PremisecitationPrevious studies have indicated that depletion of microbiota required a combination of at least 3 antibiotics for 3-4 weeks, and single antibiotics may not be sufficient to reduce total bacterial load.
“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.”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [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 in the free run.
- cites [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 in the free run.
- cites [31] Million M Lagier JC Yahav D Paul M Gut bacterial microbiota and obesity Clin Microbiol Infect 2013 19 305 313 23452229
Not checked in the free run.
May combine two claims.
PremisecitationMinocycline inhibits expression of pro-inflammatory cytokines and intestinal damage in mouse model of colitis.
“it inhibits expression of pro-inflammatory cytokines and intestinal damage in mouse model of colitis51, 52”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [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 in the free run.
- cites [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
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationMinocycline attenuates gut damage and intestinal mucositis due to cancer chemotherapy.
“it attenuates gut damage and intestinal mucositis due to cancer chemotherapy53”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [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
Not checked in the free run.
May combine two claims.
InterpretationreasoningHTN 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.
“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.”
Quote in the paperSubstantial claimMay combine two claims.
PremisecitationBoth Bacteroides and Marvinbryantia produce acetate as their main fermentation product, and Akkermansia and Enterorhabdus have been found to be inversely associated with obesity and diabetes.
“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.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [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 in the free run.
May combine two claims.
PremisecitationMinocycline is an anti-inflammatory antibiotic that freely crosses the blood-brain barrier and has been shown to produce beneficial effects in combating HTN.
“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.”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [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 in the free run.
- cites [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
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationChanges in gut microbiota have been related to chronic inflammatory diseases such as asthma, allergies, inflammatory bowel disease, and infectious diseases.
“Typically, changes in gut microbiota have been related to chronic inflammatory diseases such as asthma, allergies, inflammatory bowel disease, and infectious diseases10.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [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
Not checked in the free run.
Classified as probably not a substantial claim. May combine two claims.
PremisecitationAn increased F/B ratio is widely considered a signature of gut dysbiosis and has been associated with obesity, diabetes, and CVD.
“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.”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [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 in the free run.
- cites [13] Everard A Cani PD Diabetes, obesity and gut microbiota Best Pract Res Clin Gastroenterol 2013 27 73 83 23768554
Not checked in the free run.
- cites [16] Sanz Y Moya-Perez A Microbiota, inflammation and obesity Adv Exp Med Biol 2014 817 291 317 24997040
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenHuman studies were approved by the University of Florida Institutional Review Board.
“Human studies were approved by the University of Florida Institutional Review Board.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
PremisecitationGut microbiota plays an important role in shaping a robust systemic and intestinal immune system.
“In the periphery, gut microbiota plays an important role in shaping a robust systemic and intestinal immune system6, 7.”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [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 in the free run.
- cites [7] McDermott AJ Huffnagle GB The microbiome and regulation of mucosal immunity Immunology 2014 142 24 31 24329495 PMC3992044
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenWe did not measure plasma lactate in any of our experiments.
“However, we did not measure plasma lactate in any of our experiments, and this remains a future direction.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationThe F/B ratio is well validated in rodent and human samples; its significance in pig models requires further studies.
“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.”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [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 in the free run.
- cites [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
Not checked in the free run.
May combine two claims.
PremisecitationMinocycline has shown an impressive ability to decrease BP, improve HbA1C levels, and weight loss in our pilot study.
“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.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [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
Not checked in the free run.
Classified as probably not a substantial claim.
PremisecitationAn increase in hematopoietic stem cells has been implicated in their extravasation into the brain and establishment of neuroinflammation in many neural diseases.
“This increase in HSCs has been implicated in their extravasation into the brain and establishment of neuroinflammation in many neural diseases57,58.”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [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 in the free run.
- cites [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
Not checked in the free run.
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?
Microbial compositional changes have been reported in patients with cardiovascular disease risk factors including hypertension, dyslipidemia, insulin resistance, and other metabolic phenotypes.
“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]
A significant proportion of SCFAs produced in the distal bowel is reabsorbed from the gut lumen by facilitated apical solute transport via multiple transporters and passive diffusion.
“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]
Elevations in the Firmicutes:Bacteroidetes ratio have been associated with a high-fat diet and obesity, irritable bowel syndrome, hypertension, type 1 diabetes, and HIV.
“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]
Interventions that target the gut microbiota, such as a high-fibre diet, probiotics and antibiotics, have blood-pressure lowering effects in animal models and in patients with hypertension.
“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]
Gut dysbiosis has been reported in animal models and in patients with hypertension.
“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]
Our research group was the first to demonstrate a contribution of the brain-gut-bone-marrow axis to blood pressure elevation.
“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 rats with angiotensin-II-induced hypertension, minocycline administration changes the gut microbiota and lowers blood pressure.
“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]
Cites
2 retracted
Million, M., Maraninchi, M., Henry, M., Armougom, F., Richet, H., Carrieri, P., Valéro, R., Raccah, D., Vialettes, B., & Raoult, D. (2011) · International Journal of Obesity · doi:10.1038/ijo.2011.153 · Cited by 660 · see citing works
RetractedDuca, F. A., Sakar, Y., Lepage, P., Devime, F., Goustard, B., Dore, J. M., & Covașă, M. (2014) · Diabetes · doi:10.2337/db13-1526 · Cited by 162 · see citing works
RetractedQIIME allows analysis of high-throughput community sequencing data
Caporaso, J. G., Kuczynski, J., Stombaugh, J., Bittinger, K., Bushman, F. D., Costello, E. K., Fierer, N., Peña, A. G., Goodrich, J. K., Gordon, J. I., et al. (2010) · Nature Methods · doi:10.1038/nmeth.f.303 · Cited by 34,887 · see citing works
Changes of Intestinal Functions in Liver Cirrhosis
Fukui, H., & Wiest, R. (2016) · Inflammatory Intestinal Diseases · doi:10.1159/000444436 · Cited by 6,820 · see citing works
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 · see citing works
Self-citationTurnbaugh, P. J., Ley, R. E., Hamady, M., Fraser-Liggett, C. M., Knight, R., & Gordon, J. I. (2007) · Nature · doi:10.1038/nature06244 · Cited by 6,091 · see citing works
Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells
Furusawa, Y., Obata, Y., Fukuda, S., Endo, T. A., Nakato, G., Takahashi, D., Nakanishi, Y., Uetake, C., Kato, K., Kato, T., et al. (2013) · Nature · doi:10.1038/nature12721 · Cited by 5,549 · see citing works
Everard, A., Belzer, C., Geurts, L., Ouwerkerk, J. P., Druart, C., Bindels, L. B., Guiot, Y., Derrien, M., Muccioli, G. G., Delzenne, N. M., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1219451110 · Cited by 4,511 · see citing works
Recognition of Commensal Microflora by Toll-Like Receptors Is Required for Intestinal Homeostasis
Rakoff-Nahoum, S., Paglino, J., Eslami-Varzaneh, F., Edberg, S., & Medzhitov, R. (2004) · Cell · doi:10.1016/j.cell.2004.07.002 · Cited by 4,251 · see citing works
Gut microbiota in health and disease
Sekirov, I., Russell, S. L., Antunes, L. C. M., & Finlay, B. B. (2010) · Physiological Reviews · doi:10.1152/physrev.00045.2009 · Cited by 4,182 · see citing works
Intestinal microbial metabolism of phosphatidylcholine and cardiovascular risk
Tang, W. H. W., Wang, Z., Levison, B. S., Koeth, R. A., Britt, E. B., Fu, X., Wu, Y., & Hazen, S. L. (2013) · New England Journal of Medicine · doi:10.1056/nejmoa1109400 · Cited by 3,402 · see citing works
Butyrate improves insulin sensitivity and increases energy expenditure in mice
Gao, Z., Yin, J., Zhang, J., Ward, R. E., Martin, R. J., Lefevre, M., Cefalu, W. T., & Ye, J. (2009) · Diabetes · doi:10.2337/db08-1637 · Cited by 2,204 · see citing works
The Firmicutes/Bacteroidetes ratio of the human microbiota changes with age
Mariat, D., Firmesse, O., Levenez, F., Guimarăes, V., Sokol, H., Doré, J., Corthier, G., & Furet, J.-P. (2009) · BMC Microbiology · doi:10.1186/1471-2180-9-123 · Cited by 1,755 · see citing works
Regulation of inflammation by short chain fatty acids
Vinolo, M. A. R., Rodrigues, H. G., Nachbar, R. T., & Curi, R. (2011) · Nutrients · doi:10.3390/nu3100858 · Cited by 1,724 · see citing works
Potential beneficial effects of butyrate in intestinal and extraintestinal diseases
Canani, R. B. (2011) · World Journal of Gastroenterology · doi:10.3748/wjg.v17.i12.1519 · Cited by 1,381 · see citing works
Lin, H. V., Frassetto, A., Kowalik Jr, E. J., Nawrocki, A. R., Lu, M. M., Kosinski, J. R., Hubert, J. A., Szeto, D., Yao, X., Forrest, G., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0035240 · Cited by 1,378 · see citing works
Potential beneficial effects of butyrate in intestinal and extraintestinal diseases.
Canani, R., Costanzo, M. D., Leone, L., Pedata, M., Meli, R., & Calignano, A. (2011) · World Journal of Gastroenterology · doi:10.3748/wjg.v17.i12 · Cited by 1,316
Pluznick, J. L., Protzko, R. J., Gevorgyan, H., Peterlin, Z., Sipos, A., Han, J., Brunet, I., Wan, L.-X., Rey, F., Wang, T., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1215927110 · Cited by 1,191 · see citing works
Leclercq, S., Matamoros, S., Cani, P. D., Neyrinck, A. M., Jamar, F., Stärkel, P., Windey, K., Tremaroli, V., Bäckhed, F., Verbeke, K., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1415174111 · Cited by 972 · see citing works
Minocycline: Far beyond an Antibiotic
Garrido‐Mesa, N., Zarzuelo, A., & Gálvez, J. (2013) · British Journal of Pharmacology · doi:10.1111/bph.12139 · Cited by 935 · see citing works
Gut microbiome, obesity, and metabolic dysfunction
Tilg, H., & Kaser, A. (2011) · Journal of Clinical Investigation · doi:10.1172/jci58109 · Cited by 860 · see citing works
Anderson, E. A., Sinkey, C. A., Lawton, W. J., & Mark, A. L. (1989) · Hypertension · doi:10.1161/01.hyp.14.2.177 · Cited by 632 · see citing works
Diabetes, obesity and gut microbiota
Everard, A., & Cani, P. D. (2013) · Best Practice & Research Clinical Gastroenterology · doi:10.1016/j.bpg.2013.03.007 · Cited by 546 · see citing works
Depletion of Murine Intestinal Microbiota: Effects on Gut Mucosa and Epithelial Gene Expression
Reikvam, D. H., Erofeev, A. S., Sandvik, A., Grcic, V., Jahnsen, F. L., Gaustad, P., McCoy, K. D., Macpherson, A. J., Meza‐Zepeda, L. A., & Johansen, F. (2011) · PLoS ONE · doi:10.1371/journal.pone.0017996 · Cited by 531 · see citing works
Khalesi, S., Sun, J., Buys, N., & Jayasinghe, R. (2014) · Hypertension · doi:10.1161/hypertensionaha.114.03469 · Cited by 516 · see citing works
Sympathetic Augmentation in Hypertension
Schlaich, M. P., Lambert, É., Kaye, D. M., Krozowski, Z. S., Campbell, D. J., Lambert, G. W., Hastings, J., Aggarwal, A., & Esler, M. (2003) · Hypertension · doi:10.1161/01.hyp.0000103160.35395.9e · Cited by 509 · see citing works
Gut Bacteria Products Prevent AKI Induced by Ischemia-Reperfusion
Andrade‐Oliveira, V., Amano, M. T., Corrêa-Costa, M., Castoldi, Â., Felizardo, R. J. F., de Almeida, D. C., Bassi, Ê. J., Moraes‐Vieira, P. M., Hiyane, M. I., Rodas, A. C. D., et al. (2015) · Journal of the American Society of Nephrology · doi:10.1681/asn.2014030288 · Cited by 507 · see citing works
Contribution of acetate to butyrate formation by human faecal bacteria
Duncan, S. H., Holtrop, G., Lobley, G. E., Calder, A. G., Stewart, C. S., & Flint, H. J. (2004) · British Journal Of Nutrition · doi:10.1079/bjn20041150 · Cited by 494 · see citing works
Antharam, V. C., Li, E. C., Ishmael, A., Sharma, A., Mai, V., Rand, K. H., & Wang, G. P. (2013) · Journal of Clinical Microbiology · doi:10.1128/jcm.00845-13 · Cited by 485 · see citing works
Self-citationHost–Bacterial Symbiosis in Health and Disease
Chow, J., Lee, S. M., Shen, Y. L., Khosravi, A., & Mazmanian, S. K. (2010) · Advances in immunology · doi:10.1016/b978-0-12-381300-8.00008-3 · Cited by 467 · see citing works
The epigenetic effects of butyrate: potential therapeutic implications for clinical practice
Berni Canani, R., Di Costanzo, M., & Leone, L. (2012) · Clinical Epigenetics · doi:10.1186/1868-7083-4-4 · Cited by 431 · see citing works
Brain Microglial Cytokines in Neurogenic Hypertension
Shi, P. D., Díez-Freire, C., Jun, J. Y., Qi, Y., Katovich, M. J., Li, Q., Sriramula, S., Francis, J., Sumners, C., & Raizada, M. K. (2010) · Hypertension · doi:10.1161/hypertensionaha.110.150409 · Cited by 384 · see citing works
Self-citationThe microbiome and regulation of mucosal immunity
McDermott, A. J., & Huffnagle, G. B. (2013) · Immunology · doi:10.1111/imm.12231 · Cited by 335 · see citing works
Recovery of the Gut Microbiome following Fecal Microbiota Transplantation
Seekatz, A. M., Aas, J., Gessert, C. E., Rubin, T. A., Saman, D. M., Bakken, J., & Young, V. B. (2014) · mBio · doi:10.1128/mbio.00893-14 · Cited by 331 · see citing works
Gut bacterial microbiota and obesity
Million, M., Lagier, J., Yahav, D., & Paul, M. (2013) · Clinical Microbiology and Infection · doi:10.1111/1469-0691.12172 · Cited by 297 · see citing works
Exercise induction of gut microbiota modifications in obese, non-obese and hypertensive rats
Petriz, B. A., Castro, A. P., Almeida, J. A., Gomes, C. P., Fernandes, G. R., Kruger, R. H., Pereira, R. W., & Franco, O. L. (2014) · BMC Genomics · doi:10.1186/1471-2164-15-511 · Cited by 293 · see citing works
Vieira, E. L. M., Leonel, A. J., Sad, A. P., Beltrão, N. R. M., Costa, T. F., Ferreira, T. M. R., Gomes-Santos, A. C., Faria, A. M. C., Peluzio, M. C. G., Cara, D. C., et al. (2012) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2011.01.007 · Cited by 290 · see citing works
Grönlund, M., Gueimonde, M., Laitinen, K., Kociubinski, G., Grönroos, T., Salminen, S., & Isolauri, E. (2007) · Clinical & Experimental Allergy · doi:10.1111/j.1365-2222.2007.02849.x · Cited by 277 · see citing works
The immune system in hypertension
Trott, D. W., & Harrison, D. G. (2014) · AJP Advances in Physiology Education · doi:10.1152/advan.00063.2013 · Cited by 190 · see citing works
The immune system and hypertension
Singh, M. V., Chapleau, M. W., Harwani, S. C., & Abboud, F. M. (2014) · Immunologic Research · doi:10.1007/s12026-014-8548-6 · Cited by 176 · see citing works
Henagan, T. M., Stefañska, B., Fang, Z., Navard, A. M., Ye, J., Lenard, N. R., & Devarshi, P. P. (2015) · British Journal of Pharmacology · doi:10.1111/bph.13058 · Cited by 172 · see citing works
Histone Deacetylase Inhibitors Up-Regulate the Expression of Tight Junction Proteins
Bordin, M., D'Atri, F., Guillemot, L., & Citi, S. (2004) · Molecular Cancer Research · doi:10.1158/1541-7786.692.2.12 · Cited by 168 · see citing works
Microbiota, Inflammation and Obesity
Sanz, Y., & Moya-Pérez, Á. (2014) · Advances in experimental medicine and biology · doi:10.1007/978-1-4939-0897-4_14 · Cited by 148 · see citing works
Ontogeny and Functions of Central Nervous System Macrophages
Katsumoto, A., Lu, H., Miranda, A. S., & Ransohoff, R. M. (2014) · The Journal of Immunology · doi:10.4049/jimmunol.1400716 · Cited by 124 · see citing works
Lê, K., Li, Y., Xu, X., Yang, W., Liu, T., Zhao, X., Tang, Y. G., Cai, D., Go, V. L. W., Pandol, S., et al. (2013) · Frontiers in Physiology · doi:10.3389/fphys.2012.00496 · Cited by 113 · see citing works
Zubcevic, J., Jun, J. Y., Kim, S., Perez, P. D., Afzal, A., Shan, Z., Li, W., Santisteban, M. M., Yuan, W., Febo, M., et al. (2014) · Hypertension · doi:10.1161/hypertensionaha.113.02722 · Cited by 104 · see citing works
Self-citationHypertension in Metabolic Syndrome: Vascular Pathophysiology
Mendizábal, Y., Llorens, S., & Nava, E. (2013) · International Journal of Hypertension · doi:10.1155/2013/230868 · Cited by 103 · see citing works
Jansson, Larsson, & LÖnnroth (1998) · European Journal of Clinical Investigation · doi:10.1046/j.1365-2362.1998.00360.x · Cited by 102 · see citing works
Gut microbiota: a source of novel tools to reduce the risk of human disease?
Collado, M. C., Rautava, S., Isolauri, E., & Salminen, S. (2015) · Pediatric Research · doi:10.1038/pr.2014.173 · Cited by 93 · see citing works
The immune system in hypertension.
Harrison, D. G. (2014) · Europe PMC (PubMed Central) · Cited by 85 · see citing works
A complex microworld in the gut: Gut microbiota and cardiovascular disease connectivity
Howitt, M. R., & Garrett, W. S. (2012) · Nature Medicine · doi:10.1038/nm.2895 · Cited by 77 · see citing works
Pedersen, R., Andersen, A. D., Mølbak, L., Stagsted, J., & Boyé, M. (2013) · BMC Microbiology · doi:10.1186/1471-2180-13-30 · Cited by 63 · see citing works
Garrido‐Mesa, N., Camuesco, D., Arribas, B., Comalada, M., Bailón, E., Cueto-Sola, M., Utrilla, P., Nieto, A., Zarzuelo, A., Rodríguez‐Cabezas, M. E., et al. (2010) · Pharmacological Research · doi:10.1016/j.phrs.2010.12.011 · Cited by 62 · see citing works
Garrido‐Mesa, N., Utrilla, P., Comalada, M., Zorrilla, P., Garrido‐Mesa, J., Zarzuelo, A., Rodríguez‐Cabezas, M. E., & Gálvez, J. (2011) · Biochemical Pharmacology · doi:10.1016/j.bcp.2011.09.004 · Cited by 62 · see citing works
CNS inflammation and bone marrow neuropathy in type 1 diabetes.
Hu, P., Thinschmidt, J., Yan, Y., Hazra, S., Bhatwadekar, A., Caballero, S., Salazar, T. E., Miyan, J., Li, W.-C., Derbenev, A., et al. (2013) · American Journal of Pathology · doi:10.1016/j.ajpath.2013.07.009 · Cited by 62 · see citing works
Self-citationBrain-Mediated Dysregulation of the Bone Marrow Activity in Angiotensin II–Induced Hypertension
Jun, J. Y., Zubcevic, J. A., Qi, Y., Afzal, A., Carvajal, J. M., Thinschmidt, J. S., Grant, M. B., Mocco, J., & Raizada, M. K. (2012) · Hypertension · doi:10.1161/hypertensionaha.112.199547 · Cited by 60 · see citing works
Self-citationMinocycline attenuates 5-fluorouracil-induced small intestinal mucositis in mouse model
Huang, T.-Y., Chu, H.-C., Lin, Y.-L., Ho, W.-H., Hou, H.-S., Chao, Y.-C., & Liao, C.-L. (2009) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2009.09.041 · Cited by 59 · see citing works
Plasma Lactate and Incident Hypertension in the Atherosclerosis Risk in Communities Study
Juraschek, S. P., Bower, J. K., Selvin, E., Shantha, G. P. S., Hoogeveen, R. C., Ballantyne, C. M., & Young, J. H. (2014) · American Journal of Hypertension · doi:10.1093/ajh/hpu117 · Cited by 57 · see citing works
Minocycline Repurposing in Critical Illness: Focus on Stroke
Liao, T., Forehand, C. C., Hess, D. C., & Fagan, S. C. (2013) · Current Topics in Medicinal Chemistry · doi:10.2174/15680266113136660160 · Cited by 28 · see citing works
Letters to the Editor: Cardiomyocyte‐secreted acetylcholine
Pappano, A. J. (2014) · The FASEB Journal · doi:10.1096/fj.14-0101lte · Cited by 27 · see citing works
Xu, J., Ahrén, I. L., Prykhodko, O., Olsson, C., Ahrné, S., & Molin, G. (2013) · Evidence-based Complementary and Alternative Medicine · doi:10.1155/2013/809128 · Cited by 25 · see citing works
Lightfoot, Y. L., Yang, T., Sahay, B., Zadeh, M., Cheng, S. X., Wang, G. P., Owen, J. L., & Mohamadzadeh, M. (2014) · PLoS ONE · doi:10.1371/journal.pone.0100532 · Cited by 18 · see citing works
Self-citationMinocycline with Aspirin: An Approach to Attenuate Diabetic Nephropathy in Rats
Bhatt, L. K., & Addepalli, V. (2011) · Renal Failure · doi:10.3109/0886022x.2010.528117 · Cited by 16 · see citing works
Bifidobacteria and subsets of dendritic cells: friendly players in immune regulation!: Figure 1
Grangette, C. (2011) · Gut · doi:10.1136/gutjnl-2011-301476 · Cited by 15 · see citing works
Neuroprotection: Lessons from a Spectrum of Neurological Disorders
Galpern, W. R., & Singhal, A. B. (2006) · International Journal of Stroke · doi:10.1111/j.1747-4949.2006.00023.x · Cited by 4 · see citing works
Zena, L. A., Fonseca, E. M., Santin, J. M., Bícego, K. C., Gargaglioni, L. H., & Hartzler, L. K. (2014) · The FASEB Journal · doi:10.1096/fasebj.28.1_supplement.879.13 · Cited by 3 · see citing works
Santisteban, M. M., Zubcevic, J. A., Kim, S., Marulanda‐Carvajal, J., Zingler, M., Joseph, J., & Raizada, M. K. (2014) · The FASEB Journal · doi:10.1096/fasebj.28.1_supplement.875.5 · Cited by 2 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
The microbiome and innate immunity
Thaiss, C. A., Zmora, N., Levy, M., & Elinav, E. (2016) · Nature · doi:10.1038/nature18847 · Cited by 2,012 · see citing works
Gut microbiota dysbiosis contributes to the development of hypertension
Li, J., Zhao, F., Wang, Y., Chen, J., Tao, J., Tian, G., Wu, S., Liu, W., Cui, Q., Geng, B., et al. (2017) · Microbiome · doi:10.1186/s40168-016-0222-x · Cited by 1,685 · see citing works
Gut microbiota in cardiovascular health and disease
Tang, W. H. W., Kitai, T., & Hazen, S. L. (2017) · Circulation Research · doi:10.1161/circresaha.117.309715 · Cited by 1,670 · see citing works
Alterations in Gut Microbiota of Patients With COVID-19 During Time of Hospitalization
Zuo, T., Zhang, F., Lui, G. C. Y., Yeoh, Y. K., Li, A. Y. L., Zhan, H., Wan, Y., Chung, A. C. K., Cheung, C. P., Chen, N., et al. (2020) · Gastroenterology · doi:10.1053/j.gastro.2020.05.048 · Cited by 1,537 · see citing works
Short-Chain Fatty-Acid-Producing Bacteria: Key Components of the Human Gut Microbiota
Fusco, W. G., Bernabeu, M., Cintoni, M., Porcari, S., Rinninella, E., Kaitsas, F., Lener, E., Mele, M. C., Gasbarrini, A., Collado, M. C., et al. (2023) · Nutrients · doi:10.3390/nu15092211 · Cited by 1,318 · see citing works
The Human Gut Microbiome – A Potential Controller of Wellness and Disease
Kho, Z. Y., & Lal, S. K. (2018) · Frontiers in Microbiology · doi:10.3389/fmicb.2018.01835 · Cited by 1,116 · see citing works
Angiotensin II Signal Transduction: An Update on Mechanisms of Physiology and Pathophysiology
Forrester, S. J., Booz, G. W., Sigmund, C. D., Coffman, T. M., Kawai, T., Rizzo, V., Scalia, R. G., & Eguchi, S. (2018) · Physiological Reviews · doi:10.1152/physrev.00038.2017 · Cited by 1,135 · see citing works
Marques, F. Z., Nelson, E., Chu, P.-Y., Horlock, D., Fiedler, A., Ziemann, M., Tan, J. K., Kuruppu, S., Rajapakse, N. W., El-Osta, A., et al. (2017) · Circulation · doi:10.1161/circulationaha.116.024545 · Cited by 1,065 · see citing works
Gut microbiota and cardiovascular disease.
Witkowski, M., Weeks, T. L., & Hazen, S. L. (2020) · Circulation Research · doi:10.1161/circresaha.120.316242 · Cited by 1,051 · see citing works
Estrogen–gut microbiome axis: Physiological and clinical implications
Baker, J. M., Al‐Nakkash, L., & Herbst‐Kralovetz, M. M. (2017) · Maturitas · doi:10.1016/j.maturitas.2017.06.025 · Cited by 1,024 · see citing works
Interaction between the gut microbiome and mucosal immune system
Shi, N., Li, N., Duan, X., & Niu, H. (2017) · Military Medical Research · doi:10.1186/s40779-017-0122-9 · Cited by 940 · see citing works
Short-Chain Fatty Acid Propionate Protects From Hypertensive Cardiovascular Damage
Bartolomaeus, H., Balogh, A., Yakoub, M., Homann, S., Markó, L., Höges, S., Tsvetkov, D., Krannich, A., Wundersitz, S., Avery, E. G., et al. (2019) · Circulation · doi:10.1161/circulationaha.118.036652 · Cited by 822 · see citing works
Health and disease markers correlate with gut microbiome composition across thousands of people
Manor, O., Dai, C. L., Kornilov, S. A., Smith, B., Price, N. D., Lovejoy, J. C., Gibbons, S. M., & Magis, A. T. (2020) · Nature Communications · doi:10.1038/s41467-020-18871-1 · Cited by 839 · see citing works
Dietary metabolism, the gut microbiome, and heart failure
Tang, W. H. W., Li, D. Y., & Hazen, S. L. (2019) · Nature Reviews Cardiology · doi:10.1038/s41569-018-0108-7 · Cited by 789 · see citing works
The gut microbiota and the brain–gut–kidney axis in hypertension and chronic kidney disease
Yang, T., Richards, E. M., Pepine, C. J., & Raizada, M. K. (2018) · Nature Reviews Nephrology · doi:10.1038/s41581-018-0018-2 · Cited by 753 · see citing works
Self-citationRole and Mechanism of Gut Microbiota in Human Disease
Chen, Y., Zhou, J., & Wang, L. (2021) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2021.625913 · Cited by 643 · see citing works
Inflammasome signaling affects anxiety- and depressive-like behavior and gut microbiome composition
Wong, M.-L., Inserra, A., Lewis, M. D., Mastronardi, C. A., Leong, L., Choo, J., Kentish, S., Xie, P., Morrison, M., Wesselingh, S. L., et al. (2016) · Molecular Psychiatry · doi:10.1038/mp.2016.46 · Cited by 568 · see citing works
Kim, S., Goel, R., Kumar, A., Qi, Y., Lobaton, G. O., Hosaka, K., Mohammed, M., Handberg, E. M., Richards, E. M., Pepine, C. J., et al. (2018) · Clinical Science · doi:10.1042/cs20180087 · Cited by 545 · see citing works
Self-citationHypertension-Linked Pathophysiological Alterations in the Gut
Santisteban, M. M., Qi, Y., Zubcevic, J., Kim, S., Yang, T., Shenoy, V., Cole-Jeffrey, C. T., Lobaton, G. O., Stewart, D. C., Rubiano, A., et al. (2017) · Circulation Research · doi:10.1161/circresaha.116.309006 · Cited by 525 · see citing works
Self-citationAlterations of the Gut Microbiome in Hypertension
Yan, Q., Gu, Y., Li, X., Yang, W. Q., Jia, L., Chen, C., Han, X., Huang, Y., Zhao, L., Li, P., et al. (2017) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2017.00381 · Cited by 496 · see citing works
Gut microbiota derived metabolites in cardiovascular health and disease
Wang, Z., & Zhao, Y. (2018) · Protein & Cell · doi:10.1007/s13238-018-0549-0 · Cited by 475 · see citing works
Wang, M., Pan, W., Xu, Y., Zhang, J., Wan, J., & Jiang, H. (2022) · Journal of Inflammation Research · doi:10.2147/jir.s350109 · Cited by 461 · see citing works
Dysbiosis of gut microbiota and microbial metabolites in Parkinson's disease
Sun, M.-F., & Shen, Y.-Q. (2018) · Ageing Research Reviews · doi:10.1016/j.arr.2018.04.004 · Cited by 445 · see citing works
Microbiome–metabolome reveals the contribution of gut–kidney axis on kidney disease
Chen, Y., Chen, D., Chen, L., Liu, J., Vaziri, N. D., Guo, Y. P., & Zhao, Y. (2019) · Journal of Translational Medicine · doi:10.1186/s12967-018-1756-4 · Cited by 430 · see citing works
Immune mechanisms of hypertension
Drummond, G. R., Vinh, A., Guzik, T. J., & Sobey, C. G. (2019) · Nature reviews. Immunology · doi:10.1038/s41577-019-0160-5 · Cited by 436 · see citing works
Microbiota and metabolic diseases
Pascale, A., Marchesi, N., Marelli, C., Coppola, A., Luzi, L., Govoni, S., Giustina, A., & Gazzaruso, C. (2018) · Endocrine · doi:10.1007/s12020-018-1605-5 · Cited by 423 · see citing works
Gut Microbiota in Hypertension and Atherosclerosis: A Review
Verhaar, B. J. H., Prodan, A., Nieuwdorp, M., & Muller, M. (2020) · Nutrients · doi:10.3390/nu12102982 · Cited by 411 · see citing works
The immunology of hypertension
Norlander, A. E., Madhur, M. S., & Harrison, D. G. (2017) · The Journal of Experimental Medicine · doi:10.1084/jem.20171773 · Cited by 403 · see citing works
Beyond gut feelings: how the gut microbiota regulates blood pressure
Marques, F. Z., Mackay, C. R., & Kaye, D. M. (2017) · Nature Reviews Cardiology · doi:10.1038/nrcardio.2017.120 · Cited by 400 · see citing works
Role of the Immune System in Hypertension
Rodríguez‐Iturbe, B., Pons, H., & Johnson, R. J. (2017) · Physiological Reviews · doi:10.1152/physrev.00031.2016 · Cited by 398 · see citing works
Gut microbiota and cardiovascular disease: opportunities and challenges
Kazemian, N., Mahmoudi, M., Halperin, F. A., Wu, J. C., & Pakpour, S. (2020) · Microbiome · doi:10.1186/s40168-020-00821-0 · Cited by 401 · see citing works
Zhang, Z., Zhao, L. Q., Zhou, X., Meng, X., & Zhou, X. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1098725 · Cited by 387 · see citing works
Gómez-Arango, L. F., Barrett, H. L., McIntyre, D. H., Callaway, L. K., Morrison, M., & Nitert, M. D. (2016) · Hypertension · doi:10.1161/hypertensionaha.116.07910 · Cited by 384 · see citing works
Alterations in the gut microbiota can elicit hypertension in rats
Adnan, S., Nelson, J. W., Ajami, N. J., Venna, V. R., Petrosino, J. F., Bryan, R. M., & Durgan, D. J. (2016) · Physiological Genomics · doi:10.1152/physiolgenomics.00081.2016 · Cited by 380 · see citing works
Thirty Years of Lactobacillus rhamnosus GG
Capurso, L. (2019) · Journal of Clinical Gastroenterology · doi:10.1097/mcg.0000000000001170 · Cited by 394 · see citing works
Gut Microbiota Promote Angiotensin II–Induced Arterial Hypertension and Vascular Dysfunction
Karbach, S. H., Schönfelder, T., Brandão, I., Wilms, E., Hörmann, N., Jäckel, S., Schüler, R., Finger, S., Knorr, M., Lagrange, J., et al. (2016) · Journal of the American Heart Association · doi:10.1161/jaha.116.003698 · Cited by 378 · see citing works
Pathophysiology of Hypertension
Harrison, D. G., Coffman, T. M., & Wilcox, C. S. (2021) · Circulation Research · doi:10.1161/circresaha.121.318082 · Cited by 405 · see citing works
Alzheimer’s disease and gut microbiota
Hu, X., Wang, T., & Jin, F. (2016) · Science China Life Sciences · doi:10.1007/s11427-016-5083-9 · Cited by 371 · see citing works
Whole Fruits and Fruit Fiber Emerging Health Effects
Dreher, M. L. (2018) · Nutrients · doi:10.3390/nu10121833 · Cited by 378 · see citing works
Animal Models of Hypertension: A Scientific Statement From the American Heart Association
Lerman, L. O., Kurtz, T. W., Touyz, R. M., Ellison, D. H., Chade, A., Crowley, S. D., Mattson, D. L., Mullins, J. J., Osborn, J. L., Eirin, A., et al. (2019) · Hypertension · doi:10.1161/hyp.0000000000000090 · Cited by 332 · see citing works
Role of the Gut Microbiome in Obstructive Sleep Apnea–Induced Hypertension
Durgan, D. J., Ganesh, B. P., Cope, J. L., Ajami, N. J., Phillips, S. C., Petrosino, J. F., Hollister, E. B., & Bryan, R. M. (2016) · Hypertension · doi:10.1161/hypertensionaha.115.06672 · Cited by 327 · see citing works
Immune and inflammatory mechanisms in hypertension
Guzik, T. J., Nosalski, R., Maffia, P., & Drummond, G. R. (2024) · Nature Reviews Cardiology · doi:10.1038/s41569-023-00964-1 · Cited by 347 · see citing works
Fecal microbiota transplantation in metabolic syndrome: History, present and future
de Groot, P. F., Frissen, M. N., de Clercq, N. C., & Nieuwdorp, M. (2017) · Gut Microbes · doi:10.1080/19490976.2017.1293224 · Cited by 322 · see citing works
Shou, Y., Huang, Y., Zhu, X., Liu, C., Hu, Y., & Wang, H. (2019) · Ecotoxicology and Environmental Safety · doi:10.1016/j.ecoenv.2019.02.086 · Cited by 303 · see citing works
Microbial Short-Chain Fatty Acids and Blood Pressure Regulation
Pluznick, J. L. (2017) · Current Hypertension Reports · doi:10.1007/s11906-017-0722-5 · Cited by 301 · see citing works
Mutlu, E., Comba, I. Y., Cho, T., Engen, P. A., Yazıcı, C., Soberanes, S., Hamanaka, R. B., Niğdelioğlu, R., Meliton, A. Y., Ghio, A. J., et al. (2018) · Environmental Pollution · doi:10.1016/j.envpol.2018.04.130 · Cited by 298 · see citing works
Chakaroun, R., Massier, L., & Kovacs, P. L. (2020) · Nutrients · doi:10.3390/nu12041082 · Cited by 297 · see citing works
Dietary polyphenols to combat the metabolic diseases via altering gut microbiota
Gowd, V., Karim, N., Shishir, M. R. I., Xie, L., & Chen, W. (2019) · Trends in Food Science & Technology · doi:10.1016/j.tifs.2019.09.005 · Cited by 294 · see citing works
The gut microbiome and hypertension
O’Donnell, J. A., Zheng, T., Méric, G., & Marques, F. Z. (2023) · Nature Reviews Nephrology · doi:10.1038/s41581-022-00654-0 · Cited by 294 · see citing works
Gut Microbiota Composition and Blood Pressure
Sun, S., Lulla, A., Sioda, M., Winglee, K., Wu, M. C., Jacobs, D. R., Shikany, J. M., Lloyd‐Jones, D. M., Launer, L. J., Fodor, A. A., et al. (2019) · Hypertension · doi:10.1161/hypertensionaha.118.12109 · Cited by 281 · see citing works
The metabolic syndrome – What is it and how should it be managed?
Nilsson, P. M., Tuomilehto, J. O., & Rydén, L. (2019) · European Journal of Preventive Cardiology · doi:10.1177/2047487319886404 · Cited by 272 · see citing works
Revisit gut microbiota and its impact on human health and disease
Ding, R., Goh, W.-R., Wu, R., Yue, X., Luo, X. G., Khine, W. W. T., Wu, J., & Lee, Y. K. (2019) · Journal of Food and Drug Analysis · doi:10.1016/j.jfda.2018.12.012 · Cited by 269 · see citing works
Kamo, T., Akazawa, H., Suda, W., Saga-Kamo, A., Shimizu, Y., Yagi, H., Liu, Q., Nomura, S., Naito, A. T., Takeda, N., et al. (2017) · PLoS ONE · doi:10.1371/journal.pone.0174099 · Cited by 265 · see citing works
The Gut Microbiota (Microbiome) in Cardiovascular Disease and Its Therapeutic Regulation
Rahman, M. M., Islam, F., Harun-Or-Rashid, M., Mamun, A. A., Rahaman, M. S., Islam, M. M., Meem, A. F. K., Sutradhar, P. R., Mitra, S., Mimi, A. A., et al. (2022) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2022.903570 · Cited by 272 · see citing works
Gut microbiota and metabolic syndrome
Wang, P.-X., Deng, X., Zhang, C., & Yuan, H. (2020) · Chinese Medical Journal · doi:10.1097/cm9.0000000000000696 · Cited by 250 · see citing works
Dietary Fibers from Fruits and Vegetables and Their Health Benefits via Modulation of Gut Microbiota
Cui, J., Lian, Y., Zhao, C., Du, H., Han, Y., Gao, W. Y., Xiao, H., & Zheng, J. (2019) · Comprehensive Reviews in Food Science and Food Safety · doi:10.1111/1541-4337.12489 · Cited by 243 · see citing works
Yan, X., Jin, J., Su, X., Yin, X., Gao, J., Wang, X., Zhang, S., Bu, P., Wang, M., Zhang, Y., et al. (2020) · Circulation Research · doi:10.1161/circresaha.119.316394 · Cited by 235 · see citing works
Gut microbiota dependent trimethylamine N-oxide aggravates angiotensin II–induced hypertension
Jiang, S., Shui, Y., Cui, Y., Tang, C., Wang, X., Qiu, X., Hu, W., Fei, L., Li, Y., Zhang, S., et al. (2021) · Redox Biology · doi:10.1016/j.redox.2021.102115 · Cited by 237 · see citing works
The role of intestinal microbiota in cardiovascular disease
Jin, M., Qian, Z., Yin, J., Xu, W., & Zhou, X. (2019) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.14195 · Cited by 236 · see citing works
Short-Chain Fatty Acids, Maternal Microbiota and Metabolism in Pregnancy
Ziętek, M., Celewicz, Z., & Szczuko, M. (2021) · Nutrients · doi:10.3390/nu13041244 · Cited by 238 · see citing works
The gut microbial metabolite trimethylamine N-oxide and cardiovascular diseases
Zhen, J., Zhou, Z., He, M., Han, H.-X., Lv, E., Wen, P., Liu, X., Wang, Y., Cai, X., Tian, J., et al. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1085041 · Cited by 241 · see citing works
Gut microbiota: Implications in Parkinson's disease
Parashar, A., & Malairaman, U. (2017) · Parkinsonism & Related Disorders · doi:10.1016/j.parkreldis.2017.02.002 · Cited by 231 · see citing works
The potential role of vitamin D supplementation as a gut microbiota modifier in healthy individuals
Singh, P., Rawat, A., Alwakeel, M., Sharif, E., & Khodor, S. A. (2020) · Scientific Reports · doi:10.1038/s41598-020-77806-4 · Cited by 237 · see citing works
Duttaroy, A. K. (2021) · Nutrients · doi:10.3390/nu13010144 · Cited by 232 · see citing works
The Role of Gut Microbiota in Atherosclerosis and Hypertension
Ma, J., & Li, H. (2018) · Frontiers in Pharmacology · doi:10.3389/fphar.2018.01082 · Cited by 226 · see citing works
Intestinal microbiome and fitness in kidney disease
Meijers, B. K. I., Evenepoel, P., & Anders, H. (2019) · Nature Reviews Nephrology · doi:10.1038/s41581-019-0172-1 · Cited by 223 · see citing works
Gut metagenomic and short chain fatty acids signature in hypertension: a cross-sectional study
Calderón-Pérez, L., Gosalbes, M. J., Yuste, S., Valls, R. M., Pedret, A., Llauradó, E., Jiménez‐Hernández, N., Artacho, A., Pla‐Pagà, L., Companys, J., et al. (2020) · Scientific Reports · doi:10.1038/s41598-020-63475-w · Cited by 224 · see citing works
Konopelski, P., & Mogilnicka, I. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23031222 · Cited by 218 · see citing works
Toral, M., Robles‐Vera, I., de la Visitación, N., Romero, M., Yang, T., Sánchez, M., Gómez‐Guzmán, M., Jiménez, R., Raizada, M. K., & Duarte, J. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2019.00231 · Cited by 223 · see citing works
Self-citationTan, C., Wu, Q., Wang, H., Gao, X., Xu, R., Cui, Z., Zhu, J., Zeng, X., Zhou, H., He, Y., et al. (2020) · Journal of Parenteral and Enteral Nutrition · doi:10.1002/jpen.1861 · Cited by 231 · see citing works
Ganesan, K., Chung, S. K., Vanamala, J., & Xu, B. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19123720 · Cited by 221 · see citing works
Robles‐Vera, I., Toral, M., de la Visitación, N., Sánchez, M., Gómez‐Guzmán, M., Romero, M., Yang, T., Izquierdo-García, J. L., Jiménez, R., Ruı́z-Cabello, J., et al. (2020) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201900616 · Cited by 217 · see citing works
Self-citationSánchez-Rodríguez, E., Egea-Zorrilla, A., Plaza‐Díaz, J., Aragón‐Vela, J., Muñoz‐Quezada, S., Tercedor‐Sánchez, L., & Abadía‐Molina, F. (2020) · Nutrients · doi:10.3390/nu12030605 · Cited by 220 · see citing works
Antihypertensive effects of probiotics Lactobacillus strains in spontaneously hypertensive rats
Gómez‐Guzmán, M., Toral, M., Romero, M., Jiménez, R., Galindo, P., Sánchez, M., Zarzuelo-Romero, M. J., Olivares, M. M., Gálvez, J., & Duarte, J. (2015) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201500290 · Cited by 211 · see citing works
Legrand, T. P. R. A., Catalano, S. R., Wos‐Oxley, M. L., Stephens, F., Landos, M., Bansemer, M. S., Stone, D. A. J., Qin, J. G., & Oxley, A. P. A. (2018) · Frontiers in Microbiology · doi:10.3389/fmicb.2017.02664 · Cited by 201 · see citing works
Chidambaram, S. B., Essa, M. M., Rathipriya, A. G., Bishir, M., Ray, B., Mahalakshmi, A. M., Tousif, A. H., Sakharkar, M. K., Kashyap, R. S., Friedland, R. P., et al. (2022) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2021.107988 · Cited by 204 · see citing works
Gut microbiota in atherosclerosis: focus on trimethylamine N‐oxide
Zhu, Y., Li, Q., & Jiang, H. (2020) · Apmis · doi:10.1111/apm.13038 · Cited by 204 · see citing works
Ganesh, B. P., Nelson, J. W., Eskew, J. R., Ganesan, A., Ajami, N. J., Petrosino, J. F., Bryan, R. M., & Durgan, D. J. (2018) · Hypertension · doi:10.1161/hypertensionaha.118.11695 · Cited by 190 · see citing works
Hypertension in HIV-Infected Adults
Fahme, S. A., Bloomfield, G. S., & Peck, R. N. (2018) · Hypertension · doi:10.1161/hypertensionaha.118.10893 · Cited by 193 · see citing works
Gut microbiome and kidney disease: a bidirectional relationship
Al Khodor, S., & Shatat, I. F. (2017) · Pediatric Nephrology · doi:10.1007/s00467-016-3392-7 · Cited by 191 · see citing works
Gut microbiota in hypertension
José, P. A., & Raj, D. S. (2015) · Current Opinion in Nephrology & Hypertension · doi:10.1097/mnh.0000000000000149 · Cited by 187 · see citing works
Koch, C. D., Gladwin, M. T., Freeman, B. A., Lundberg, J. O., Weitzberg, E., & Morris, A. (2017) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.12.015 · Cited by 186 · see citing works
Gut microbiome and its role in cardiovascular diseases
Ahmadmehrabi, S., & Tang, W. H. W. (2017) · Current Opinion in Cardiology · doi:10.1097/hco.0000000000000445 · Cited by 185 · see citing works
The gut microbiota and its interactions with cardiovascular disease
Xu, H., Wang, X., Feng, W., Liu, Q., Zhou, S., Liu, Q., & Cai, L. (2020) · Microbial Biotechnology · doi:10.1111/1751-7915.13524 · Cited by 192 · see citing works
Short-chain fatty acid, acylation and cardiovascular diseases
Chen, X., Chen, X., & Tang, X. (2020) · Clinical Science · doi:10.1042/cs20200128 · Cited by 186 · see citing works
Endometriosis induces gut microbiota alterations in mice
Yuan, M., Li, D., Zhang, Z., Sun, H., An, M., & Wang, G. (2017) · Human Reproduction · doi:10.1093/humrep/dex372 · Cited by 181 · see citing works
Wang, L., Zhu, Q., Lu, A., Liu, X., Zhang, L., Xu, C., Liu, X., Li, H., & Yang, T. (2017) · Journal of Hypertension · doi:10.1097/hjh.0000000000001378 · Cited by 182 · see citing works
Self-citationThe gut microbiota as a novel regulator of cardiovascular function and disease
Battson, M. L., Lee, D. M., Weir, T. L., & Gentile, C. L. (2017) · The Journal of Nutritional Biochemistry · doi:10.1016/j.jnutbio.2017.12.010 · Cited by 189 · see citing works
High dietary salt–induced DC activation underlies microbial dysbiosis-associated hypertension
Ferguson, J. F., Aden, L. A., Barbaro, N. R., Beusecum, J. P. V., Xiao, L., Simmons, A. J., Warden, C., Pasic, L., Himmel, L. E., Washington, M. K., et al. (2019) · JCI Insight · doi:10.1172/jci.insight.126241 · Cited by 182 · see citing works
Gut microbiota and metabolic health among overweight and obese individuals
Kim, M.-H., Yun, K. E., Kim, J., Park, E., Chang, Y., Ryu, S., Kim, H., & Kim, H. (2020) · Scientific Reports · doi:10.1038/s41598-020-76474-8 · Cited by 175 · see citing works
Mediterranean diet and faecal microbiota: a transversal study
Gutiérrez-Díaz, I., Fernández-Navarro, T., Sánchez, B., Margolles, A., & González, S. (2016) · Food & Function · doi:10.1039/c6fo00105j · Cited by 176 · see citing works
Hypertension as an autoimmune and inflammatory disease
Solak, Y., Afşar, B., Vaziri, N. D., Aslan, G., Yalçın, C. E., Covic, A. C., & Kanbay, M. (2016) · Hypertension Research · doi:10.1038/hr.2016.35 · Cited by 176 · see citing works
Felizardo, R. J. F., Watanabe, I. K. M., Dardi, P., Rossoni, L. V., & Câmara, N. O. S. (2019) · Pharmacological Research · doi:10.1016/j.phrs.2019.01.019 · Cited by 181 · see citing works
Interaction between gut microbiome and cardiovascular disease
Peng, J., Xiao, X., Hu, M., & Zhang, X. (2018) · Life Sciences · doi:10.1016/j.lfs.2018.10.063 · Cited by 175 · see citing works
Intestinal barrier dysfunction as a therapeutic target for cardiovascular disease
Lewis, C., & Taylor, W. R. (2020) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00612.2020 · Cited by 174 · see citing works
Yang, X., Qian, Y., Xu, S., Song, Y., & Xiao, Q. (2018) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2017.00441 · Cited by 173 · see citing works
“While, our 16S rRNA gene sequencing results found lower α-diversity in the model group (3 weeks) than the normal initial status (0 week) which can be seen in other animal model of diseases, including colorectal cancer and hypertension (Zhu et al., 2014; Yang et al., 2015).”
ResultThe impact of gut microbiota on kidney function and pathogenesis
Mahmoodpoor, F., Saadat, Y. R., Barzegari, A., Ardalan, M., & Vahed, S. Z. (2017) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2017.06.066 · Cited by 171 · see citing works
The Role of the Gut Microbiome in Diabetes and Obesity-Related Kidney Disease
Zaky, A. A., Glastras, S. J., Wong, M. Y. W., Pollock, C. A., & Saad, S. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22179641 · Cited by 174 · see citing works
Parkinson’s Disease and the Gastrointestinal Microbiome
Lubomski, M., Tan, A. H., Lim, S.-Y., Holmes, A. J., Davis, R. L., & Sue, C. M. (2020) · Journal of Neurology · doi:10.1007/s00415-019-09320-1 · Cited by 172 · see citing works
- 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
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.
Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-09.
Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-09.
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 ›
Are you an author, or do you see a problem with this page? Request a review
