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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
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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
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In the paper
“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.”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Results > Gut microbial diversity is increased by treatment of minocycline
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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
“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).”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Results > Gut microbial diversity is increased by treatment of minocycline
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In the paper
“As shown in Figure 4B, the two patient populations formed separate clusters.”
§ 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
“We observed ~3-fold decrease in acetate- and a 2-fold decrease in butyrate-producing bacteria in the SHR (Figure 3B).”
§ 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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In the paper
“Minocycline treatment did not result in a further reduction of bacterial load.”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Results > Gut microbial diversity is increased by treatment of minocycline
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In the paper
“Most importantly, the F/B ratio was considerably increased in the Ang II-infused rats compared to control (Figure 6A).”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Results > Gut microbial diversity is increased by treatment of minocycline
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In the paper
“This was associated with a decrease in the abundance of lactate-producing bacteria.”
§ 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
“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).”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Results > Acetate and butyrate fermenters are decreased in the SHR
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In the paper
“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.”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Results > Acetate and butyrate fermenters are decreased in the SHR
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In the paper
“A significant reduction of bacterial load was found in SHR when compared with WKY (Figure 1A).”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Results > HTN is associated with alteration in fecal microbiota composition in the SHR
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In the paper
“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.”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Results > Gut microbial diversity is increased by treatment of minocycline
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In the paper
“Fecal samples from both WKY and SHR were dominated by Firmicutes and Bacteroidetes, and with smaller proportions of Actinobacteria and Proteobacteria (Figure 2B).”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Results > HTN is associated with alteration in fecal microbiota composition in the SHR
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In the paper
“However, significant differences were observed between the groups in terms of the relative abundances of Actinobacteria, Bacteroidetes and Firmicutes.”
§ 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
“Rats infused with Ang II alone demonstrated a lower richness value when compared with control (Figure 5B).”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Results > Gut microbial diversity is increased by treatment of minocycline
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In the paper
“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.”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Results > Gut microbial diversity is increased by treatment of minocycline
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In the paper
“Interestingly, both of these two genera were completely depleted 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
“The F/B ratio in the SHR was ~5-fold higher compared with WKY (Figure 2A).”
§ 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
“In contrast, the abundance of lactate-producing bacteria was significantly increased 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
“In contrast, lactate-producing bacteria, Streptococcus and Turicibacter, were in higher quantities in the SHR.”
§ 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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In the paper
“We observed ~3-fold decrease in acetate- and a 2-fold decrease in butyrate-producing bacteria in the SHR (Figure 3B).”
§ 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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In the paper
“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).”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Results > Gut microbial diversity is increased by treatment of minocycline
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In the paper
“However, the most important and recognized biomarker, the F/B ratio, was dramatically increased in both the SHR and Ang II infusion models.”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Discussion
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In the paper
“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.”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Discussion
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In the paper
“Oral minocycline treatment results in the attenuation of high BP induced by chronic Ang II infusion.”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Discussion
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In the paper
“Interestingly, decreases in the butyrate- and acetate-producing bacteria were found in both models of HTN.”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Discussion
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In the paper
“The first important finding was that minocycline did not reduce fecal biomass”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Discussion
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In the paper
“Of particular interest is the finding that lactate-producing bacteria were increased in both animal models of HTN”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Discussion
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In the paper
“Further analysis of Verrucomicrobia phylum revealed a significant increase in the mucin-degrading bacterium, Akkermansia.”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Discussion
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In the paper
“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.”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Discussion
boostedcorrelationaln = 2- Asserted: passes — The authors put it forward as true.
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- Also stated in: § Discussion · plain
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
“A dramatic increase in Verrucomicrobia phylum bacteria was observed”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Discussion
plain- 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
“In addition, preliminary data indicate that minocycline treatment was able to reverse the Ang II-induced decrease in cingulin in the colon.”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Discussion
hedgeddirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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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
“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.”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Discussion
boostedcorrelationaln = 2- 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
“Most importantly, this study does indeed demonstrate a dysbiotic gut profile in patients with high BP.”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Discussion
boostedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
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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
“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.”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Results > Gut microbial diversity is increased by treatment of minocycline
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 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.”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Discussion
plaindirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
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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 analyzed human data clearly confirmed the observation made in our animal model where gut dysbiosis is observed between the high and normal SBP cohorts.”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Results > Lower richness and diversity of gut microbiota in HTN patients
boostedcorrelationaln = 7- 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.
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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
“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.”
§ 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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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 signature of gut microbiota dysbiosis is consistent with that previously shown in the SHR model.”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Results > Gut microbial diversity is increased by treatment of minocycline
plaincorrelational- Asserted: passes — The authors put it forward as true.
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- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Discussion
hedgedcorrelational- 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
“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.”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Results > Acetate and butyrate fermenters are decreased in the SHR
boosteddirect- Asserted: passes — The authors put it forward as true.
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A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“These findings clearly implicate the role of gut microbiota in the pathophysiology of both animal and human HTN.”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Discussion
boosteddirect- Asserted: passes — The authors put it forward as true.
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- Load-bearing: passes — The paper’s conclusions depend on it.
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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
“These changes were the major contributors to the increased F/B ratio in the SHR.”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Results > Acetate and butyrate fermenters are decreased in the SHR
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“providing evidence that this antibiotic does not have negative effects on the gut microbiota.”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Discussion
hedged- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“indicating that minocycline produced an intestinal environment that was extremely conducive to nurturing the growth of bacteria of this phylum.”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Discussion
hedgeddirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“Cingulin is a tight junction protein whose decreased levels have been associated with gut barrier dysfunction leading to increased inflammation50.”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Discussion
What the sources say
- Not checked yetcites [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
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Thus, these gut specific effects of minocycline appear to be linked with minocycline’s beneficial effects on inflammation and HTN.”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Discussion
hedgedcorrelational- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
In the paper
“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.”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Introduction
What the sources say
- Not checked yetcites [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
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Our observations are consistent with these reports and support the important role of microbial diversity in HTN.”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Discussion
plaincorrelational- 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.
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
“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.”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Discussion
plainn = 2- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
None of the sources cited for this claim have been checked yet.
In the paper
“Furthermore, evidence also exists of direct anti-inflammatory effects of minocycline in the brain in many neurodegenerative and neurobehavioral diseases54, 55.”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Discussion
What the sources say
- Not checked yetcites [54] Galpern WR Singhal AB Neuroprotection: Lessons from a spectrum of neurological disorders Int J Stroke 2006 1 97 99 18706052 source
- 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 source
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: unclear — It is unclear whether the paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
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, this suggests that reversing the gut dysbiosis might be affected by the stability of BP control and the time undergoing such treatment.”
§ GUT MICROBIOTA DYSBIOSIS IS LINKED TO HYPERTENSION > Discussion
hedgedconditionaln = 2- 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. 22
- The quote only partly states this claim. 1
- Probably not a substantial claim. 13
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
“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.
- 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.
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
“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.
- 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.
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
“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.
- 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.
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
“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.
- 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.
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
“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
plaindirect- Asserted: passes — The authors put it forward as true.
- Checkable: passes — It can be checked against evidence.
- Load-bearing: passes — The paper’s conclusions depend on it.
- Based: passes — The paper gives a reason why it holds.
It may state two separate claims as one.
- Also stated in: § Discussion · plain
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.
- 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.
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 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.
- 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. The quote only partly states this claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“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.
- 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.
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.
- 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.
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.
- 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.
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.
- 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
“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.
- 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.
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
“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.
- 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
“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.
- 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.
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.
- 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.
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.
- 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.
None of the sources cited for this claim have been checked yet.
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.
- 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 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.
- 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
“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.
- 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.
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.
- 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.
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.
- 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.
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.
- 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.
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]
Citations
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 684
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 169
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
Changes of Intestinal Functions in Liver Cirrhosis
Fukui, H., & Wiest, R. (2016) · Inflammatory Intestinal Diseases · doi:10.1159/000444436 · Cited by 6,820
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
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
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
Cross-talk between Akkermansia muciniphila and intestinal epithelium controls diet-induced obesity
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
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
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
Cited by
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The microbiome and innate immunity
Thaiss, C. A., Zmora, N., Levy, M., & Elinav, E. (2016) · Nature · doi:10.1038/nature18847 · Cited by 2,012
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
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
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
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 1,397
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
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.
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