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Bacteroides vulgatus and Bacteroides dorei Reduce Gut Microbial Lipopolysaccharide Production and Inhibit Atherosclerosis
Abstract
Background: It is increasingly recognized that gut microbiota play a pivotal role in the development of atherosclerotic cardiovascular disease. Previously, we have reported that the abundance of genus Bacteroides is lower in patients with coronary artery disease (CAD) than in patients without CAD with coronary risk factors or in healthy volunteers. However, it remains unclear which and how specific gut bacteria contribute to the progression of atherosclerosis. Methods: We recruited patients with CAD patients and controls without CAD with coronary risk factors. We then compared gut microbial composition using 16S ribosomal RNA gene sequencing in fecal samples to detect species with differential abundance between 2 groups. Subsequently, we used atherosclerosis-prone mice to study the mechanisms underlying the relationship between such species and atherosclerosis. Results: Human fecal 16S ribosomal RNA gene sequencing revealed a significantly lower abundance of Bacteroides vulgatus and Bacteroides dorei in patients with CAD. This significant differential abundance was confirmed by quantitative polymerase chain reaction. Gavage with live B. vulgatus and B. dorei attenuated atherosclerotic lesion formation in atherosclerosis-prone mice, markedly ameliorating endotoxemia followed by decreasing gut microbial lipopolysaccharide production, effectively suppressing proinflammatory immune responses. Furthermore, fecal lipopolysaccharide levels in patients with CAD were significantly higher and negatively correlated with the abundance of B. vulgatus and B. dorei . Conclusions: Our translational research findings identify a previously unknown link between specific gut bacteria and atherosclerosis. Treatment with live B. vulgatus and B. dorei may help prevent CAD. Clinical Trial Registration: URL: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000018051 . Unique identifier: UMIN000015703.
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TL;DR
In patients with coronary artery disease (CAD), gut abundance of *Bacteroides vulgatus* and *Bacteroides dorei* was lower than in controls without CAD, and fecal lipopolysaccharide (LPS) levels were higher. In atherosclerosis-prone mice, oral gavage with live *B. vulgatus* and *B. dorei* reduced fecal and plasma LPS, dampened inflammation, and attenuated atherosclerotic plaque.
Key findings
- In 30 patients with CAD versus 30 age- and sex-matched controls without CAD but with coronary risk factors, 16S rRNA sequencing showed relative depletion of *B. vulgatus* and *B. dorei* in CAD; qPCR confirmed significantly decreased abundance of these species.
- Fecal LPS levels were significantly higher in patients with CAD than controls, and fecal LPS correlated negatively with *B. vulgatus*/*B. dorei* abundance in CAD (r=−0.541, P=0.002); genus *Bacteroides* showed a trend toward negative correlation (r=−0.227, P=0.0838).
- In apolipoprotein E-deficient mice, gavage with live *B. vulgatus* and *B. dorei* (2.5×10⁹ cfu/100 μL, 5 times/week) significantly reduced aortic root and en face atherosclerotic lesion size, macrophage and CD4⁺ T-cell accumulation, plasma LPS, and proatherogenic cytokines, without significant differences in body weight, plasma cholesterol, or plasma glucose.
- Live *Bacteroides* treatment decreased predicted microbial LPS biosynthesis genes *LpxA* and *LpxD* and dramatically lowered fecal LPS; heat-killed *Bacteroides* did not decrease fecal LPS, aortic sinus plaque, or plasma LPS compared with controls (reported P=0.92, P=0.74, and P=0.93, respectively).
Methods
- Human study: 30 patients with CAD and 30 controls without CAD with coronary risk factors were recruited at Kobe University Hospital between October 2014 and July 2015; fecal samples underwent 16S rRNA gene sequencing (V3–V4 region), qPCR, PICRUSt functional prediction, and limulus amebocyte lysate assay for LPS.
- Mouse study: 6-week-old female apolipoprotein E-deficient mice on C57BL/6 background were randomized to control, live *Bacteroides*, or heat-killed *Bacteroides* groups; mice were gavaged 5 times per week for 10 weeks and euthanized at 16 weeks for atherosclerosis, immune, gut permeability, and LPS analyses.
- Statistical analysis used R, JMP, and Prism; Shapiro-Wilk test, Student’s t test or Mann-Whitney U test, Fisher exact or χ² test, Spearman correlation, one-way ANOVA, and Benjamini-Hochberg adjustment for multiple comparisons.
Limitations
- The paper states that 16S rRNA sequencing has low phylogenetic power at the species level and poor discriminatory power for some genera, and that the human CAD gut microbial analysis was a single-center study with a relatively small number of patients.
- The paper states that controls without CAD did not all undergo coronary angiography, so subclinical CAD may have been present; the limulus amebocyte lysate assay could not measure LPS immunogenicity or the impact of *Bacteroides* on LPS structure/function; mechanisms of atherosclerosis protection by lower LPS were not completely elucidated; mouse and human dominant microbiota differ; and only *B. vulgatus* and *B. dorei* were tested, so more effective strains may exist.
- Evident from the text: the human findings are cross-sectional and cannot establish causality, and the causal evidence comes from a mouse gavage model rather than a human intervention.
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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
“immunohistochemical staining followed by morphometric analysis of atherosclerotic lesions in the aortic sinus revealed a marked reduction in macrophage and CD4 + T-cell accumulation in mice gavaged with live Bacteroides compared with controls (Figure 2C and 2D).”
§ Live Bacteroides Treatment Ameliorated Endotoxemia and Systemic Inflammation > Gut Microbial Profile in Patients With CAD
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In the paper
“we observed significantly higher expression levels of ZO-1 (mRNA and protein) in HT29 cells stimulated with fecal supernatant from live Bacteroides-treated mice than in cells stimulated with fecal supernatant from control mice (Figure VD and VE in the online-only Data Supplement).”
§ Live Bacteroides Treatment Ameliorated Endotoxemia and Systemic Inflammation > Live Bacteroides Treatment Strengthened Tight Junction Formation In Vivo and In Vitro
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In the paper
“we found that the abundance of Bacteroides vulgatus and Bacteroides dorei was decreased in patients with CAD.”
- Also stated in: § Gut Microbial Profile in Patients With CAD · plain
“patients with CAD showed a relative depletion of B. vulgatus and B. dorei”
§ Live Bacteroides Treatment Ameliorated Endotoxemia and Systemic Inflammation > Abstract
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In the paper
“The mRNA expression of several proatherogenic immune cell markers and chemokines/ chemokine receptors was decreased in mice gavaged with live Bacteroides (Figure 2E).”
§ Live Bacteroides Treatment Ameliorated Endotoxemia and Systemic Inflammation > Gut Microbial Profile in Patients With CAD
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In the paper
“reflected in higher mean fluorescence intensity of ZO-1 in the colon (Figure VC in the online-only Data Supplement).”
§ Live Bacteroides Treatment Ameliorated Endotoxemia and Systemic Inflammation > Live Bacteroides Treatment Strengthened Tight Junction Formation In Vivo and In Vitro
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In the paper
“Although the expression of genes related to TMA synthesis (CutC, CutD) had no difference among the groups”
§ Live Bacteroides Treatment Ameliorated Endotoxemia and Systemic Inflammation > Gavage With Live Bacteroides Alters Gut Microbial LPS Production
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In the paper
“We found that the relative abundance of the genus Bacteroides was visibly lower in patients with CAD compared with controls (Figure 1G).”
§ Live Bacteroides Treatment Ameliorated Endotoxemia and Systemic Inflammation > Gut Microbial Profile in Patients With CAD
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In the paper
“The abundance of B. vulgatus and B. dorei was considerably higher in feces from live Bacteroides-gavaged mice (Figure IIIF in the online-only Data Supplement).”
§ Live Bacteroides Treatment Ameliorated Endotoxemia and Systemic Inflammation > Gavage With Live Bacteroides Alters Gut Microbial LPS Production
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In the paper
“the expression of genes involved in LPS biosynthesis, especially LpxA and LpxD, which are involved in lipid A biosynthesis and constitute the essential acyltransferases of the lipid A structure (Figure 3B), 38,39 was significantly decreased in mice gavaged with live Bacteroides (Figure 3A and 3C, Figure IV in the online-only Data Supplement).”
§ Live Bacteroides Treatment Ameliorated Endotoxemia and Systemic Inflammation > Gavage With Live Bacteroides Alters Gut Microbial LPS Production
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In the paper
“We also confirmed the significantly decreased abundance of B. vulgatus and B. dorei in patients with CAD by quantitative polymerase chain reaction (Figure 1J and Table II in the online-only Data Supplement).”
§ Live Bacteroides Treatment Ameliorated Endotoxemia and Systemic Inflammation > Gut Microbial Profile in Patients With CAD
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- It may state two separate claims as one. 29
- Probably not a substantial claim. 21
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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
“mice gavaged with Bacteroides exhibited decreased expression of major histocompatibility complex class II and costimulatory molecule CD86, as well as increased expression of the coinhibitory molecules programmed death ligand-1 and programmed death ligand-2 on splenic CD11c high dendritic cells (Figure IIB in the online-only Data Supplement).”
- Also stated in: § ORIGINAL RESEARCH ARTICLE · plain
“Similar phenotypic changes along with increased expression of PD-L1 and PD-L2 in dendritic cells were observed in the spleen.”
§ Live Bacteroides Treatment Ameliorated Endotoxemia and Systemic Inflammation > ORIGINAL RESEARCH ARTICLE
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- Also stated in: § ORIGINAL RESEARCH ARTICLE · plain
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In the paper
“the samples were clustered into 3 clusters at the genus level”
§ Live Bacteroides Treatment Ameliorated Endotoxemia and Systemic Inflammation > Gut Microbial Profile in Patients With CAD
Strength:plain· not yet calibratedn = 30Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
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In the paper
“mice gavaged with live Bacteroides showed significantly reduced lesion size in the aortic root and en face analysis of thoracoabdominal aortas (Figure 2A and 2B)”
§ Live Bacteroides Treatment Ameliorated Endotoxemia and Systemic Inflammation > Gut Microbial Profile in Patients With CAD
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In the paper
“The controls without CAD were significantly more likely to be categorized into cluster 1, whereas few patients with CAD were categorized into this cluster (Figure 1F).”
§ Live Bacteroides Treatment Ameliorated Endotoxemia and Systemic Inflammation > Gut Microbial Profile in Patients With CAD
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In the paper
“without significant difference in body weight (Figure 2F), plasma cholesterol levels (Figure 2G), or plasma glucose levels (data not shown).”
§ Live Bacteroides Treatment Ameliorated Endotoxemia and Systemic Inflammation > Gut Microbial Profile in Patients With CAD
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In the paper
“Each cluster was characterized by a high abundance of a specific genus as follows: Bacteroides in cluster 1, Prevotella in cluster 2, and Faecalibacterium, Ruminococcus, or Bifidobacterium in cluster 3 (Figure 1E).”
§ Live Bacteroides Treatment Ameliorated Endotoxemia and Systemic Inflammation > Gut Microbial Profile in Patients With CAD
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In the paper
“Mice gavaged with live Bacteroides had lower numbers of effector CD44 high CD62Llow CD4 + T cells and a significantly higher proportion of CD4 + CD25 + Foxp3 + regulatory T cells, with higher levels of intracellular CTLA4 (Figure IID and IIE in the online-only Data Supplement)”
§ Live Bacteroides Treatment Ameliorated Endotoxemia and Systemic Inflammation > ORIGINAL RESEARCH ARTICLE
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In the paper
“patients with CAD showed a relative depletion of B. vulgatus and B. dorei and enrichment in Faecalibacterium prausnitzii and Prevotella copri (Figure 1H).”
§ Live Bacteroides Treatment Ameliorated Endotoxemia and Systemic Inflammation > Gut Microbial Profile in Patients With CAD
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In the paper
“The α diversity, Bacteroidetes/Firmicutes ratio, and Gram-positive to Gramnegative strain ratio did not differ significantly between the 2 groups (Figure 1A and 1C).”
§ Live Bacteroides Treatment Ameliorated Endotoxemia and Systemic Inflammation > Gut Microbial Profile in Patients With CAD
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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
“were the 2 most abundant species within the genus Bacteroides in 16S rRNA gene sequencing analysis (Figure 1I).”
- Also stated in: § DISCUSSION · plain
“B. vulgatus and B. dorei are the dominant species of genus Bacteroides in human gut microbiota.”
§ Live Bacteroides Treatment Ameliorated Endotoxemia and Systemic Inflammation > Gut Microbial Profile in Patients With CAD
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- Also stated in: § DISCUSSION · plain
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In the paper
“The Bacteroidetes/Firmicutes ratio, Gram-positive to Gram-negative strain ratio, and fecal water content did not differ significantly among the 3 groups”
§ Live Bacteroides Treatment Ameliorated Endotoxemia and Systemic Inflammation > Affiliations
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In the paper
“whereas the number of CD4 + T cells and several markers on CD4 + T cells did not significantly change (Figure VIC and VIF in the online-only Data Supplement).”
§ Live Bacteroides Treatment Ameliorated Endotoxemia and Systemic Inflammation > ORIGINAL RESEARCH ARTICLE
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In the paper
“we found that fecal LPS levels were higher in patients with lower abundance of B. vulgatus and B. dorei.”
§ Live Bacteroides Treatment Ameliorated Endotoxemia and Systemic Inflammation > DISCUSSION
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- Rests on an assumption: Fecal lipopolysaccharide levels reflect colon lipopolysaccharide concentrations produced by gut microbiota.
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In the paper
“Trimethylamine (TMA) and TMA N-oxide, which are gut microbiota metabolites of dietary phosphatidylcholine, are known to be associated with cardiovascular disease and with the atherosclerosis process in particular.3,4”
§ Live Bacteroides Treatment Ameliorated Endotoxemia and Systemic Inflammation > Abstract
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In the paper
“CAD remains the leading cause of morbidity and mortality worldwide, despite the widespread use of statin therapy in the last decade.12”
§ Live Bacteroides Treatment Ameliorated Endotoxemia and Systemic Inflammation > Abstract
What the sources say
- Not checked yetcites [12] source
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In the paper
“Endotoxemia is known to cause systemic inflammation leading to the disruption of innate and adaptive immunity and the development of atherosclerosis.[34][35][36]”
§ Live Bacteroides Treatment Ameliorated Endotoxemia and Systemic Inflammation > Gut Microbial Profile in Patients With CAD
What the sources say
- Not checked yetcites [34]
- Not checked yetcites [35] source
- Not checked yetcites [36]
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In the paper
“a recent clinical trial has shown contradictory results indicating that fish consumption drastically increases circulating TMA N-oxide levels”
§ Live Bacteroides Treatment Ameliorated Endotoxemia and Systemic Inflammation > Abstract
What the sources say
- Not checked yetcites [6] source
Strength:hedged· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
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In the paper
“This study was approved by the Ethics Committee of Kobe University (approval No. 1595) and registered with the University hospital Medical Information Network Clinical Trials Registry (trial registration No. UMIN000015703).”
§ Live Bacteroides Treatment Ameliorated Endotoxemia and Systemic Inflammation > Recruitment of Patients With CAD and Controls
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In the paper
“The success of the heat treatment was confirmed by the absence of growth of plated heat-killed bacteria.”
§ Live Bacteroides Treatment Ameliorated Endotoxemia and Systemic Inflammation > Animals
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In the paper
“All participants provided written informed consent on enrollment, and the study was conducted according to the guidelines of the Declaration of Helsinki.”
§ Live Bacteroides Treatment Ameliorated Endotoxemia and Systemic Inflammation > Recruitment of Patients With CAD and Controls
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In the paper
“All experiments were performed according to the Guidelines for Animal Experiments in effect at Kobe University School of Medicine (guideline No. P160701).”
§ Live Bacteroides Treatment Ameliorated Endotoxemia and Systemic Inflammation > Animals
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In the paper
“However, it remains unclear which specific Bacteroides species are involved and what their exact role is in CAD.11”
§ Live Bacteroides Treatment Ameliorated Endotoxemia and Systemic Inflammation > Abstract
What the sources say
- Not checked yetcites [11]
Load-bearingStrength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may state two separate claims as one.
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In the paper
“Six-week-old mice were randomly divided into 3 treatment groups”
§ Live Bacteroides Treatment Ameliorated Endotoxemia and Systemic Inflammation > Animals
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In the paper
“Because these 2 species share similar 16S rRNA sequencing patterns, 32 we were not able to distinguish them using our methodology.”
§ Live Bacteroides Treatment Ameliorated Endotoxemia and Systemic Inflammation > Gut Microbial Profile in Patients With CAD
What the sources say
- Not checked yetcites [32]
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In the paper
“The sample size was calculated using R software (power=0.9,significance level=0.05,mean difference=6, SD=7; n=30 per group.).”
§ Live Bacteroides Treatment Ameliorated Endotoxemia and Systemic Inflammation > Recruitment of Patients With CAD and Controls
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In the paper
“The genus Bacteroides includes some of the predominant gut bacteria in humans and is known to have an important role in maintaining a healthy gut ecosystem.7”
§ Live Bacteroides Treatment Ameliorated Endotoxemia and Systemic Inflammation > Abstract
What the sources say
- Not checked yetcites [7]
Strength:boosted· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“Because LPS stimulates cells through TLR4 and upregulates costimulatory molecules on antigen-presenting cells, 37”
§ Live Bacteroides Treatment Ameliorated Endotoxemia and Systemic Inflammation > Gut Microbial Profile in Patients With CAD
What the sources say
- Not checked yetcites [37]
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. 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
“These results suggested that replenishment of live B. vulgatus and B. dorei by oral gavage reduced plaque inflammation, attenuating atherosclerotic lesion formation.”
§ Live Bacteroides Treatment Ameliorated Endotoxemia and Systemic Inflammation > Gut Microbial Profile in Patients With CAD
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- Rests on an assumption: The effects of live B. vulgatus and B. dorei on atherosclerosis in apolipoprotein E-deficient mice are representative of human coronary artery disease.
None of the sources cited for this claim have been checked yet.
In the paper
“Although LPS from E. coli increases intestinal permeability in a TLR4-dependent manner, 40,41”
§ Live Bacteroides Treatment Ameliorated Endotoxemia and Systemic Inflammation > ORIGINAL RESEARCH ARTICLE
What the sources say
- Not checked yetcites [40]
- Not checked yetcites [41]
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably 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
“because we did not perform coronary angiography for all the controls without CAD, there might have been individuals with subclinical CAD in the control group”
§ Live Bacteroides Treatment Ameliorated Endotoxemia and Systemic Inflammation > ORIGINAL RESEARCH ARTICLE
Strength:hedged· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. 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
“These limitations imply that we did not fully elucidate the characteristics of gut microbial composition in CAD”
§ Live Bacteroides Treatment Ameliorated Endotoxemia and Systemic Inflammation > ORIGINAL RESEARCH ARTICLE
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
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In the paper
“16S rRNA sequencing analysis helped to seek candidate and translate to animal experiments”
§ Live Bacteroides Treatment Ameliorated Endotoxemia and Systemic Inflammation > ORIGINAL RESEARCH ARTICLE
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In the paper
“Given that gut microbiota-derived LPS and systemic endotoxemia are involved in the onset and progression of not only atherosclerosis but also many prevalent disorders, such as inflammatory bowel disease, obesity and related metabolic diseases, and nonalcoholic steatohepatitis, [47][48][49]”
§ Live Bacteroides Treatment Ameliorated Endotoxemia and Systemic Inflammation > ORIGINAL RESEARCH ARTICLE
What the sources say
- Not checked yetcites [47][48][49]
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
“the gut microbial analysis in patients with CAD was a single-center study with a relatively small number of patients”
§ Live Bacteroides Treatment Ameliorated Endotoxemia and Systemic Inflammation > ORIGINAL RESEARCH ARTICLE
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. 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
“used a mouse model to clarify the causal relationship between B. vulgatus and B. dorei and atherosclerosis”
§ Live Bacteroides Treatment Ameliorated Endotoxemia and Systemic Inflammation > ORIGINAL RESEARCH ARTICLE
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“the LPS compounds penta-and tetraacylated lipid A of these Bacteroides species are structur-ally distinct from the hexa-acylated LPS of E.scherichia coli and elicit reduced TLR4 responses.33”
§ Live Bacteroides Treatment Ameliorated Endotoxemia and Systemic Inflammation > DISCUSSION
What the sources say
- Not checked yetcites [33] source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
“These results strongly support the idea that B. vulgatus and B. dorei regulate gut microbial production of LPS and that their activity can influence the progression of atherosclerosis in patients with CAD.”
§ Live Bacteroides Treatment Ameliorated Endotoxemia and Systemic Inflammation > ORIGINAL RESEARCH ARTICLE
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Rests on an assumption: Fecal lipopolysaccharide levels reflect colon lipopolysaccharide concentrations produced by gut microbiota.
- Rests on an assumption: The effects of live B. vulgatus and B. dorei on atherosclerosis in apolipoprotein E-deficient mice are representative of human coronary artery disease.
None of the sources cited for this claim have been checked yet.
In the paper
“we considered that augmentation of these tolerogenic dendritic cells' phenotype in MLNs or spleen was suspected to migrate into the blood and was closely associated with attenuated atherosclerotic lesion formation as previously reported.42,43,46”
§ Live Bacteroides Treatment Ameliorated Endotoxemia and Systemic Inflammation > ORIGINAL RESEARCH ARTICLE
What the sources say
- Not checked yetcites [42]
- Not checked yetcites [43]
- Not checked yetcites [46]
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- The authors state this as an assumption: Decreased circulating lipopolysaccharide levels after live Bacteroides treatment may reduce expression of TLR4, CCR7, CCL17, and CCL21 in the aorta, resulting in less macrophage and CD4+ T cell accumulation in atherosclerotic plaque.
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
“we performed gavage only with B. vulgatus and B. dorei”
§ Live Bacteroides Treatment Ameliorated Endotoxemia and Systemic Inflammation > ORIGINAL RESEARCH ARTICLE
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
A conclusion the paper draws from its own results — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“we believe that B. vulgatus and B. dorei might improve the enteric environment, providing gut bacteria with good living conditions and having a beneficial effect on bacterial LPS production.”
§ Live Bacteroides Treatment Ameliorated Endotoxemia and Systemic Inflammation > DISCUSSION
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt 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
“we did not completely elucidate the mechanisms of atherosclerosis protection by lower LPS concentrations in mice”
§ Live Bacteroides Treatment Ameliorated Endotoxemia and Systemic Inflammation > ORIGINAL RESEARCH ARTICLE
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably 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
“it could not measure LPS immunogenicity and the impact of Bacteroides on the structure and function of LPS”
§ Live Bacteroides Treatment Ameliorated Endotoxemia and Systemic Inflammation > ORIGINAL RESEARCH ARTICLE
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
The authors state this as an assumption.
Decreased circulating lipopolysaccharide levels after live Bacteroides treatment may reduce expression of TLR4, CCR7, CCL17, and CCL21 in the aorta, resulting in less macrophage and CD4+ T cell accumulation in atherosclerotic plaque.
“it is intriguing to assume that decreased circulating LPS levels after live Bacteroides treatment may reduce the expression of TLR4, CCR7, CCL17, and CCL21 in the aorta, resulting in less macrophage and CD4 + T cell accumulation in atherosclerotic plaque.”
The paper relies on this without support.
Fecal lipopolysaccharide levels reflect colon lipopolysaccharide concentrations produced by gut microbiota.
“we measured fecal LPS levels as an indicator of colon LPS concentrations pro-duced by gut microbiota.”
The paper relies on this without support.
The effects of live B. vulgatus and B. dorei on atherosclerosis in apolipoprotein E-deficient mice are representative of human coronary artery disease.
“Bacteroides treatment may serve as a novel and attractive therapeutic strategy for suppressing lipopolysaccharide-induced inflammatory response in CAD.”
The paper relies on this without support.
The hospital diet consumed by participants did not confound the gut microbiome or fecal lipopolysaccharide measurements.
“Fecal samples were collected while participants were hospitalized and thus consuming a hospital diet for >1 day.”
The paper relies on this without support.
The impact of colon lipopolysaccharide concentrations on intestinal permeability has not been fully investigated to date.
“the impact of colon LPS concentrations on intestinal permeability has not been fully investigated to date.”
The paper relies on this without support.
A specific gut microbiota-based target to prevent coronary artery disease has yet to emerge.
“a specific gut microbiota-based target to prevent CAD has yet to emerge.”
The paper relies on this without support.
Gut microbial profiles depend on age, sex, local food or lifestyle, and many other factors, making it difficult to define dysbiosis in atherosclerosis.
“it is difficult to conclude the definition of dysbiosis in atherosclerosis because each gut microbial profile depends on age, sex, local food or lifestyle, and many other factors”
The paper relies on this without support.
16S rRNA sequencing analysis has low phylogenetic power at the species level and poor discriminatory power for some genera.
“It has low phylogenetic power at the species level and poor discriminatory power for some genera”
The paper relies on this without support.
The relative abundances of most of the dominant gut microbiota in mice and humans are quite different.
“the relative abundances of most of the dominant gut microbiota in mice and human are quite different”
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?
In the citing paper
“For instance, gavage with the gram-negative Bacteroides (vulgatus and dorei) that produce penta- and tetra-acylated lipid A – in contrast to the hexa-acylated lipid A of e. coli, reduced colonic inflammation, endotoxemia, and atherosclerosis in ApoE−/− mice31.”
From Gut microbiota and cardiovascular disease. (2020) · cites this paper as [31]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Two different articles are assigned the same DOI
MinorReferences 31 and 33 give the identical DOI for articles with different titles, journals, and page ranges. At least one DOI is incorrect.
“Variation in microbiome LPS immunogenicity contributes to autoim- munity in humans. Cell. 2016;165:842-853. doi: 10.1002/art.39783”
“Dysbio- sis contributes to arthritis development via activation of autoreactive T cells in the intestine. Arthritis Rheumatol. 2016;68:2646-2661. doi: 10.1002/art.39783”
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Role of gut microbiota in type 2 diabetes pathophysiology
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BackgroundGut microbiota, intestinal permeability, and systemic inflammation: a narrative review
Di Vincenzo, F., Del Gaudio, A., Petito, V., Lopetuso, L. R., & Scaldaferri, F. (2024) · Internal and Emergency Medicine · doi:10.1007/s11739-023-03374-w · Cited by 1,498
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BackgroundResultThe intestinal microbiota fuelling metabolic inflammation
Tilg, H., Zmora, N., Adolph, T. E., & Elinav, E. (2020) · Nature Reviews Immunology · doi:10.1038/s41577-019-0198-4 · Cited by 1,089
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The Gut Microbiota and Unhealthy Aging: Disentangling Cause from Consequence
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“…that gavage with live Bacteroides vulgates and Bacteroides dorei attenuate atherosclerotic lesion formation in AS-prone mice, markedly ameliorating endotoxemia followed by decreasing gut microbial LPS production, effectively suppressing proinflammatory immune responses (Yoshida et al. 2018).”
BackgroundGut Microbiota and Intestinal Trans-Epithelial Permeability
Allam‐Ndoul, B., Castonguay-Paradis, S., & Veilleux, A. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21176402 · Cited by 371
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BackgroundLai, H., Lin, T., Chen, T.-W., Kuo, Y.-L., Chang, C., Wu, T.-R., Shu, C.-C., Tsai, Y.-H., Swift, S., & Lu, C. (2021) · Gut · doi:10.1136/gutjnl-2020-322599 · Cited by 341
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Bacteroides utilization for dietary polysaccharides and their beneficial effects on gut health
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Gut microbiota in the pathogenesis and therapeutic approaches of diabetes
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“11 Akkermansia muciniphila has been shown to stimulate mucin production in mice, thereby contributing to strengthening the intestinal epithelial barrier, and thickening of the colonic mucus, increasing the physical distance between the intestinal epithelium and pathogens.”
BackgroundGut microbiota and metabolic syndrome
Wang, P.-X., Deng, X., Zhang, C., & Yuan, H. (2020) · Chinese Medical Journal · doi:10.1097/cm9.0000000000000696 · Cited by 266
“The imbalance of the gut microbiota caused by diet, diarrhea, heredity, and other factors may increase the expression of lipopolysaccharide (LPS), drive Tolllike receptor signaling, degrade the mucous layer, cause endotoxemia, produce pro-atherogenic trimethylamine (TMA) or use other pathways that ultimately cause the…”
BackgroundIntestinal microbiome and fitness in kidney disease
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“In particular, Bacteroides supplementation in atherosclerosis-prone mice reduces LPS production, and successfully ameliorates endotoxemia, suppressing pro-inflammatory immune responses [139].”
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“vulgatus has been reported to lead to increased gut microbial production of lipopolysaccharide (LPS), which impairs immune function (28).”
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BackgroundLeonard, M. M., Karathia, H., Pujolassos, M., Troisi, J., Valitutti, F., Subramanian, P., Camhi, S. S., Kenyon, V., Colucci, A., Serena, G., et al. (2020) · Microbiome · doi:10.1186/s40168-020-00906-w · Cited by 145
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“vulgatus suppresses these inflammatory processes.(120) In more recent research, Akkermansia and its species A.”
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“The roles of different Bacteroides species in alleviating diseases have been demonstrated in a series of studies, including inhibiting tumor [13], protecting against colitis [14], alleviating obesity [15], preventing atherosclerosis [16], etc.”
BackgroundReciprocal Interactions between Epigallocatechin-3-gallate (EGCG) and Human Gut Microbiota In Vitro
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Bacteroides spp. promotes branched-chain amino acid catabolism in brown fat and inhibits obesity
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“…depleted in individuals with obesity (Liu et al., 2017), have an important role in maintaining a healthy gut ecosystem, play a protective role against atherosclerosis, and decrease fecal lipopolysaccharide activity, as we have previously reported (Emoto et al., 2016; Yoshida et al., 2018, 2020b).”
BackgroundResultInfluentialSelf-citationCoronary artery disease is associated with an altered gut microbiome composition
Toya, T., Corban, M., Marietta, E. V., Horwath, I. E., Lerman, L. O., Murray, J. A., & Lerman, A. (2020) · PLoS ONE · doi:10.1371/journal.pone.0227147 · Cited by 131
Gut Microbiome Alterations in COVID-19
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“Amongst these Bacteroidetes species, Bacteroides dorei was previously shown to inhibit colonic ACE2 expression [57] and to calibrate host immune response [58,59].”
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“50-647U; Lonza Inc) according to the manufacturer’s instructions.(45) The plasma was diluted 10-fold, and the fecal supernatant was diluted 10,000-fold in pyrogen-free water and inactivated for 15 min at 90°C.”
MethodGut commensal Christensenella minuta modulates host metabolism via acylated secondary bile acids
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Multi-omic integration of microbiome data for identifying disease-associated modules
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Management of Type 2 Diabetes: Current Strategies, Unfocussed Aspects, Challenges, and Alternatives
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Altered intestinal microbiome and metabolome correspond to the clinical outcome of sepsis
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Daily, J. W., & Park, S. (2022) · Cells · doi:10.3390/cells11030338 · Cited by 115
Gut microbiota impacts bone via Bacteroides vulgatus-valeric acid-related pathways
Lin, X., Xiao, H.-M., Liu, H.-M., Lv, W.-Q., Greenbaum, J., Gong, R., Zhang, Q., Chen, Y.-C., Peng, C., Xu, X.-J., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-42005-y · Cited by 101
“For the statistical analysis, as in previous study 61 , non-parametric one-way analysis of variance (ANOVA, Kruskal-Wallis test) was performed to identify the differences of relative abundance of B. vulgatus and VA-producing bacteria ( Megasphaera elsdenii and Oscillibacter valericigenes )/VA…”
MethodGut Microbiota and Atherosclerosis—Focusing on the Plaque Stability
Shen, X., Li, L., Sun, Z., Zang, G., Zhang, L., Shao, C., & Wang, Z. (2021) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2021.668532 · Cited by 103
“As a result, this downstream effect can lead to the formation of oxidized LDL, proving that LPS is a molecule that promotes oxidative stress at the site of atherosclerotic plaque (Figure 2), which may lead to the rupture of the plaque (93).”
BackgroundKynurenine Pathway in Diabetes Mellitus—Novel Pharmacological Target?
Kozieł, K., & Urbańska, E. M. (2023) · Cells · doi:10.3390/cells12030460 · Cited by 104
“Gut microbes may affect DMT2 in a few ways: by modulation of inflammation [86,87], by influencing gut permeability [88,89], by influencing glucose metabolism and IR [90] and by influencing fatty acid oxidation and energy expenditure [91].”
BackgroundTsai, C.-Y., Lu, H.-C., Chou, Y.-H., Liu, P., Chen, H., Huang, M., Lin, C.-H., & Tsai, C. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.814770 · Cited by 100
“Bacteroides dorei upregulated expression of tight junction genes in the colon and reduced microbial lipopolysaccharide production, thereby reducing gut permeability, and ameliorating endotoxemia (45).”
BackgroundThe microbiome-driven impact of western diet in the development of noncommunicable chronic disorders
Severino, A., Tohumcu, E., Tamai, L., D’Argenio, P., Porcari, S., Rondinella, D., Venturini, I., Maida, M. F., Gasbarrini, A., Cammarota, G., et al. (2024) · Best Practice & Research Clinical Gastroenterology · doi:10.1016/j.bpg.2024.101923 · Cited by 102
Xu, M., Lan, R., Qiao, L., Lin, X., Hu, D., Zhang, S., Yang, H. J., Zhou, J., Ren, Z., Li, X., et al. (2023) · Microbiology Spectrum · doi:10.1128/spectrum.02517-22 · Cited by 89
“In this study, levels of proinflammatory cytokines as well as endotoxin were significantly reduced in the BV group, which was consistent with previous results (23), suggesting that the immune regulation role of B.”
BackgroundResultChanges of gut microbiota reflect the severity of major depressive disorder: a cross sectional study
Hu, X., Li, Y., Wu, J., Zhang, H., Huang, Y., Tan, X., Wen, L., Zhou, X., Xie, P., Olasunkanmi, O. I., et al. (2023) · Translational Psychiatry · doi:10.1038/s41398-023-02436-z · Cited by 93
A systematic review on gut microbiota in type 2 diabetes mellitus
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Farsi, Y., Tahvildari, A., Arbabi, M., Vazife, F., Sechi, L. A., Bonjar, A. H. S., Jamshidi, P. K., Nasiri, M. J., & Mirsaeidi, M. S. (2022) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2022.804644 · Cited by 81
“This species is associated with IL-6 and IL-8 and downregulation of the ACE-2 receptor (Yoshida et al., 2018; Yeoh et al., 2021).”
BackgroundAnhê, F. F., Zlitni, S., Zhang, S., Choi, B. S.-Y., Chen, C. Y., Foley, K. P., Barra, N. G., Surette, M. G., Biertho, L. D., Richard, D., et al. (2022) · Gut · doi:10.1136/gutjnl-2022-328185 · Cited by 82
Martemucci, G., Fracchiolla, G., Muraglia, M., Tardugno, R., Dibenedetto, R. S., & D‘Alessandro, A. G. (2023) · Antioxidants · doi:10.3390/antiox12122091 · Cited by 89
“Bacteroides vulgatus and B. dorei have been shown to control the expression of tight junction genes in the colon, reducing intestinal permeability, LPS production and endotoxaemia [288].”
Van den Abbeele, P., Verstrepen, L., Ghyselinck, J., Albers, R., Marzorati, M., & Mercenier, A. (2020) · Nutrients · doi:10.3390/nu12071917 · Cited by 73
“dorei reduced plaque inflammation and decreased intestinal epithelial permeability and systemic endotoxemia [68].”
BackgroundThe gut microbiota and aging: interactions, implications, and interventions
Gyriki, D., Nikolaidis, C. G., Bezirtzoglou, E., Voidarou, C. C., Stavropoulou, E., & Tsigalou, C. (2025) · Frontiers in Aging · doi:10.3389/fragi.2025.1452917 · Cited by 80
Yoshida, N., Yamashita, T., Kishino, S., Watanabe, H., Sasaki, K., Sasaki, D., Tabata, T., Sugiyama, Y., Kitamura, N., Saito, Y., et al. (2020) · Scientific Reports · doi:10.1038/s41598-020-69983-z · Cited by 71
Self-citationShort-chain fatty acids: Important components of the gut-brain axis against AD
Huang, Y., Wang, Y. F., Miao, J., Zheng, R. F., & Li, J. Y. (2024) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2024.116601 · Cited by 70
Luo, D., Zhao, W.-B., Lin, Z., Wu, J., Lin, H., Li, Y., Song, J., Zhang, J., & Peng, H. (2021) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2021.579386 · Cited by 73
Kim, E. S., Yoon, B. H., Lee, S. M., CHOI, M. H., Kim, E. H., Lee, B.-W., Kim, S., Pack, C., Sung, Y. H., Baek, I., et al. (2022) · Experimental & Molecular Medicine · doi:10.1038/s12276-022-00728-w · Cited by 67
Flavonifractor plautii Protects Against Elevated Arterial Stiffness
Luo, S., Zhao, Y., Zhu, S., Liu, L., Cheng, K., Ye, B., Han, Y., Fan, J., & Xia, M. (2022) · Circulation Research · doi:10.1161/circresaha.122.321975 · Cited by 73
Gut Microbiota-Associated Activation of TLR5 Induces Apolipoprotein A1 Production in the Liver
Yiu, J. H. C., Chan, K.-S., Cheung, J., Li, J., Liu, Y., Wang, Y., Fung, W. W. L., Cai, J., Cheung, S. W. M., Dorweiler, B., et al. (2020) · Circulation Research · doi:10.1161/circresaha.120.317362 · Cited by 67
Zhang, K., Qin, X., Qiu, J., Sun, T. H., Qu, K., Din, A. U., Yan, W., Li, T., Chen, Y., Gu, W., et al. (2021) · Genes & Diseases · doi:10.1016/j.gendis.2021.09.007 · Cited by 67
“Lipopolysaccharide (LPS) levels in serum, and mesenteric adipose tissue were measured with LAL assay according to a previously described protocol.(6) For glucose tolerance assay, the mice were injected with glucose (2 g kg 1 body weight) intraperitoneally after fasting overnight.”
MethodXiao, C., Wang, J., Su, C., Miao, Z., Tang, J., Ouyang, Y., Yan, Y., Jiang, Z., Fu, Y., Shuai, M., et al. (2022) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/nqac178 · Cited by 67
“vulgatus has been found to protect against coronary artery disease (35).”
BackgroundWei, J., Zheng, Z., Hou, X., Jia, F., Yuan, Y., Yuan, F., He, F., Hu, L., & Zhao, L. (2023) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2023.116866 · Cited by 65
Gu, S., Zaidi, S., Hassan, M. I., Mohammad, T., Malta, T. M., Noushmehr, H., Nguyen, B., Crandall, K. A., Srivastav, J., Obias, V., et al. (2020) · Gastroenterology · doi:10.1053/j.gastro.2019.09.023 · Cited by 63
Forlano, R., Martínez-Gili, L., Takis, P. G., Blanco, J. M., Liu, T., Triantafyllou, E., Skinner, C., Loomba, R. S., Thursz, M. R., Marchesi, J. R., et al. (2024) · Gut Microbes · doi:10.1080/19490976.2024.2304157 · Cited by 70
“32 Overall, it has been demonstrated that small intestinal permeability increases with the degree of hepatic steatosis, while the association with severity of liver disease remains unexplored.”
BackgroundJin, S., Chen, P., Yang, J., Li, D., Liu, X., Zhang, Y., Xia, Q., Li, Y., Chen, G., Li, Y., et al. (2024) · Gut Microbes · doi:10.1080/19490976.2024.2309683 · Cited by 69
“39 Some studies have shown that Phocaeicola can alleviate atherosclerosis 40 and colitis, 41 but its underlying mechanism remains obscure.”
BackgroundKoopen, A. M., Almeida, E. L., Attaye, I., Witjes, J. J., Rampanelli, E., Majait, S., Kemper, M., Levels, J. H. M., Schimmel, A. W. M., Herrema, H., et al. (2021) · Frontiers in Microbiology · doi:10.3389/fmicb.2021.662159 · Cited by 64
“…demonstrated that the effect of a FMT is controlled by the baseline microbiota composition (Li et al., 2016; Kootte et al., 2017) and that subjects with a low baseline diversity have greater metabolic improvement upon interventions (Cotillard et al., 2013; Kootte et al., 2017; Yu et al., 2020).”
BackgroundTousoulis, D., Guzik, T. J., Padró, T., Duncker, D. J., Luca, G. D., Eringa, E. C., Vavlukis, M., Antonopoulos, A. S., Katsimichas, T., Cenko, E., et al. (2022) · Cardiovascular Research · doi:10.1093/cvr/cvac057 · Cited by 67
“105 Consumption of L. acidophilus preparations may have a greater effect in lowering cholesterol than other probiotics.”
BackgroundDai, H., Hou, T., Wang, Q., Hou, Y., Wang, T., Zheng, J., Lin, H., Zhao, Z., Li, M., Wang, S., et al. (2023) · European Journal of Preventive Cardiology · doi:10.1093/eurjpc/zwad171 · Cited by 65
Zhang, Y., Xu, J., Wang, X., Ren, X., & Liu, Y. (2019) · BMC Genomics · doi:10.1186/s12864-019-6251-7 · Cited by 63
Effect of Gut Microbiota on Blood Cholesterol: A Review on Mechanisms
Deng, C., Pan, J., Zhu, H., & Chen, Z. (2023) · Foods · doi:10.3390/foods12234308 · Cited by 70
“Notably, alpha-linolenic acid (ALA), gamma-linolenic acid (GLA), linoleic acid (LA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) are deemed beneficial for health [172].”
BackgroundInfluentialGut microbial composition in patients with atrial fibrillation: effects of diet and drugs
Tabata, T., Yamashita, T., Hosomi, K., Park, J., Hayashi, T., Yoshida, N., Saito, Y., Fukuzawa, K., Konishi, K., Murakami, H., et al. (2020) · Heart and Vessels · doi:10.1007/s00380-020-01669-y · Cited by 63
Self-citationZhang, Y., Zhang, P., Shang, X., Lu, Y., & Li, Y. (2020) · Comparative Biochemistry and Physiology Part C Toxicology & Pharmacology · doi:10.1016/j.cbpc.2020.108877 · Cited by 61
Autoimmunity and COVID-19 – The microbiotal connection
Katz-Agranov, N. S., & Zandman‐Goddard, G. (2021) · Autoimmunity Reviews · doi:10.1016/j.autrev.2021.102865 · Cited by 64
“positively correlated with disease severity, including the genus Coprobacillus, the species Clostridium ramosum and Clostridium hathewayi, data that might be explained by the diverse role of the Firmicutes bacteria in regulation of ACE-2 expression in the murine gut [88,134].”
BackgroundThe emerging role of gut microbial metabolism on cardiovascular disease
Kasahara, K., & Rey, F. E. (2019) · Current Opinion in Microbiology · doi:10.1016/j.mib.2019.09.007 · Cited by 59
Sequence meets function—microbiota and cardiovascular disease
Kim, M., Huda, M. N., & Bennett, B. J. (2021) · Cardiovascular Research · doi:10.1093/cvr/cvab030 · Cited by 62
“On the other hand, transplants with Bacteroides vulgatus and Bacteroides dorei attenuated atherosclerotic lesions and decreased plasma tumor necrosis factor-a (TNFa) level.(67) Similarly, Lactobacillus plantarum ATCC 14917 supplementation inhibited atherosclerotic lesion formation by decreasing serum oxidized LDL (OxL…”
BackgroundZhu, J., & He, L. (2024) · Microorganisms · doi:10.3390/microorganisms12040642 · Cited by 60
Rodriguez, R. M., Hernandez, B. Y., Menor, M., Deng, Y., & Khadka, V. S. (2020) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2020.03.003 · Cited by 57
“Bacteroides vulgatus is known to be one of the most numerically dominant species of the colonic microflora and thought to have beneficial pro-inflammatory immune response suppression effects [42].”
BackgroundHuman Gut Microbiota in Coronary Artery Disease: A Systematic Review and Meta-Analysis
Choroszy, M., Litwinowicz, K., Bednarz, R., Roleder, T., Lerman, A., Toya, T., Kamiński, K. A., Sawicka, E., Niemira, M., & Sobieszczańska, B. (2022) · Metabolites · doi:10.3390/metabo12121165 · Cited by 65
Gut microbiome and its meta-omics perspectives: profound implications for cardiovascular diseases
Xu, J., & Yang, Y. (2021) · Gut Microbes · doi:10.1080/19490976.2021.1936379 · Cited by 61
Vulnerable Atherosclerotic Plaque: Is There a Molecular Signature?
Chiorescu, R. M., Mocan, M., Inceu, A.-I., Buda, A. P., Blendea, D. C., & Vlaicu, S. I. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232113638 · Cited by 59
The gut microbiota–bile acid–TGR5 axis orchestrates platelet activation and atherothrombosis
Qi, Z., Zhang, W., Zhang, P., Qu, Y., Zhong, H., Zhou, L., Zhou, W., Yang, W., Xu, H., Zhao, X., et al. (2025) · Nature Cardiovascular Research · doi:10.1038/s44161-025-00637-x · Cited by 65
“In accordance with our findings, Yoshida et al. 52 showed that B. vulgatus abundance is lower in the gut microbiome of patients with CAD and that oral gavage with live B. vulgatus can decrease the concentration of plasma lipopolysaccharide and protect mice against atherosclerosis.”
The Role of the Gut Microbiome and Trimethylamine Oxide in Atherosclerosis and Age-Related Disease
Hage, R. E., Al-Arawe, N., & Hinterseher, I. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24032399 · Cited by 56
“2018 [188] Oral gavage of Bacteroides vulgatus and Bacteroides dorei in 6-week-old female ApoE−/− mice 5 times per week for 10 weeks.”
MethodAltered gut microbiota of obesity subjects promotes colorectal carcinogenesis in mice
Kang, X., Ng, S.-K., Liu, C., Lin, Y., Zhou, Y., Kwong, T. N. Y., Ni, Y., Lam, T. Y. T., Wu, W. K. K., Wei, H., et al. (2023) · EBioMedicine · doi:10.1016/j.ebiom.2023.104670 · Cited by 56
Pan, L., Ren, Z., Yang, J., Li, B., Huang, Y., Song, D.-X., Li, X., Xu, J., Bhatia, M., Zou, D., et al. (2023) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2023.08.002 · Cited by 53
Faecalibacterium prausnitzii as a potential Antiatherosclerotic microbe
Yang, H., Jiang, Z., Yang, Y., Wu, T., Zheng, Y., Ma, Y., & Xie, X. (2024) · Cell Communication and Signaling · doi:10.1186/s12964-023-01464-y · Cited by 54
“There is increasing evidence that the gut microbiota plays a key role in the development of atherosclerosis [8, 29].”
BackgroundChandrarathna, H. P. S. U., Liyanage, T. D., Edirisinghe, S. L., Dananjaya, S. H. S., Jayathilaka, E. H. T. T., Nikapitiya, C., Oh, C., Kang, D.-H., & Zoysa, M. D. (2020) · Marine Drugs · doi:10.3390/md18030175 · Cited by 53
Huang, K., Liu, C., Peng, M., Su, Q., Liu, R.-M., Guo, Z., Chen, S., Li, Z., & Chang, G. (2021) · Journal of the American Heart Association · doi:10.1161/jaha.120.019820 · Cited by 56
Yntema, T., Koonen, D. P. Y., & Kuipers, F. (2023) · Nutrients · doi:10.3390/nu15081850 · Cited by 58
“However, others have demonstrated that alpha diversity was either not different or increased in atherosclerosis patients compared with the controls [63,66,67,69,71].”
BackgroundResultChoi, K. J., Yoon, M. Y., Kim, J.-E., & Yoon, S. S. (2023) · Scientific Reports · doi:10.1038/s41598-023-41160-y · Cited by 51
Jiangu granule ameliorated OVX rats bone loss by modulating gut microbiota-SCFAs-Treg/Th17 axis
Sun, P., Zhang, C., Huang, Y., Yang, J., Zhou, F., Zeng, J., & Lin, Y. (2022) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2022.112975 · Cited by 53
The Post-amyloid Era in Alzheimer's Disease: Trust Your Gut Feeling
Osorio, C. P., Kanukuntla, T., Diaz, E. L., Jafri, N., Cummings, M., & Sfera, A. (2019) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2019.00143 · Cited by 50
Alterations of Gut Microbiome in Tibetan Patients With Coronary Heart Disease
Liu, F., Fan, C., Zhang, L., Li, Y., Hou, H., Ma, Y., Fan, J., Tan, Y., Wu, T., Jia, S., et al. (2020) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2020.00373 · Cited by 51
“The results of this Tibetan patient study are consistent with a previous report of higher fecal LPS levels in Japanese patients with coronary atherosclerosis compared to healthy individuals (Yoshida et al., 2018).”
BackgroundResultFernández, J., de la Fuente, V. G., García, M. T. F., Sánchez, J. G., Redondo, B. I., Villar, C. J., & Lombó, F. (2020) · Lipids in Health and Disease · doi:10.1186/s12944-020-01205-x · Cited by 49
Effects of Sevoflurane Inhalation Anesthesia on the Intestinal Microbiome in Mice
Han, C., Zhang, Z., Guo, N., Li, X., Yang, M., Peng, Y., Ma, X., Yu, K., & Wang, C. (2021) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2021.633527 · Cited by 49
“The administration of live Bacteroides by gavage can decrease plaque inflammation, reduce the formation of atherosclerotic lesions, improve endotoxemia, reduce the production of intestinal microbial lipopolysaccharides, and effectively inhibit the proinflammatory immune response (Yoshida et al., 2018).”
BackgroundAlisma orientalis Beverage Treats Atherosclerosis by Regulating Gut Microbiota in ApoE-/- Mice
Zhu, B., Zhai, Y., Ji, M., Wei, Y., Wu, J., Xue, W., Tao, W. W., & Wu, H. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.570555 · Cited by 48
“org 14 metabolic endotoxins, inflammation, and the risk of AS, while Bacteroidetes does the opposite (Poppleton et al., 2017; Rom et al., 2017; Yoshida et al., 2018; Dong et al., 2019).”
BackgroundSheng, S., Su, Y., Chen, J., Zhang, Y., Wang, Y., Qin, Q., Li, W., Li, T., Huang, M., Ding, S., et al. (2022) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2022.946757 · Cited by 52
“dorei may help prevent coronary artery disease (Yoshida et al., 2018) and treat obesity (Yoshida et al.”
BackgroundForlano, R., Mullish, B. H., Roberts, L. A., Thursz, M. R., & Manousou, P. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23020662 · Cited by 52
“have been shown to increase the expression of zonulin and improve epithelial barrier function [80].”
BackgroundNew insights into lipopolysaccharide inactivation mechanisms in sepsis
Pérez-Hernández, E. G., Delgado-Coello, B., Luna-Reyes, I., & Mas-Oliva, J. (2021) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2021.111890 · Cited by 56
Chattopadhyay, I., & Shankar, E. M. (2021) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2021.590874 · Cited by 46
“The predominant involvement of the respiratory system in COVID-19 pathogenesis mainly stems from the mode of entry of the virus into the host, i.e., respiratory tract, and also owing to the high expression of angiotensin-converting enzyme 2 (ACE2), the classical receptor to which the viral spike protein ligand can eng…”
BackgroundInfluentialGut Microbiota Characterization in Patients with Asymptomatic Hyperuricemia: probiotics increased
Yang, H.-T., Xiu, W., Liu, J., Yang, Y., Hou, X., Zheng, Y., Wu, T., Wu, C.-X., & Xie, X. (2021) · Bioengineered · doi:10.1080/21655979.2021.1976897 · Cited by 47
“This conclusion was consistent with existing studies, and this approach was adopted by many scholars in the past [16,17].”
ResultAloo, S. O., & Oh, D. (2022) · Antioxidants · doi:10.3390/antiox11020333 · Cited by 48
Metadata
- Authors
- Yoshida, N., Emoto, T., Yamashita, T., Watanabe, H., Hayashi, T., Tabata, T., Hoshi, N., Hatano, N., Ozawa, G., Sasaki, N., Mizoguchi, T., Amin, H. Z., Hirota, Y., Ogawa, W., Yamada, T., & Hirata, K.-I.
- Affiliations
- Kobe University (JP)
- Tokyo Institute of Technology (JP)
- Technosuruga Laboratory Co., Ltd. (Japan) (JP)
- University of Indonesia (ID)
- Corresponding author
- Yoshida, Naofumi
- Emoto, Takuo
- ORCID
- Venue
- Circulation
- Published
- 2018-11-27
- Volume
- 138
- Issue
- 22
- Pages
- 2486-2498
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2886282415
- Cited by
- 619
- References
- 50
- Citations by year
- 2026: 52 · 2025: 105 · 2024: 112 · 2023: 113 · 2022: 101 · 2021: 75 · 2020: 47 · 2019: 13 · 2018: 1
- FWCI
- 12.54
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Kobe University Repository Kernel (Kobe University) (submittedVersion)
- Funders
- Japan Society for the Promotion of Science (16H06279)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Keywords
- Bacteroides vulgatus, Bacteroides dorei, gut microbiota, atherosclerosis, coronary artery disease, lipopolysaccharide, endotoxemia, pro-inflammatory response, fecal microbiota transplantation, gut-heart axis
- MeSH terms
- Gastrointestinal Microbiome, Aged, Animals, Bacteroides, Feces, Female, Humans, Intestines, Lipopolysaccharides, Male, Mice, Inbred C57BL, Middle Aged, Risk Factors, RNA, Ribosomal, 16S, Sequence Analysis, RNA, Mice, Knockout, Immunity, Mucosal, Tight Junctions, Atherosclerosis, Mice
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