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.

Changes of intestinal bacterial microbiota in coronary heart disease complicated with nonalcoholic fatty liver disease

“…Correlation analysis found that the abundance of Bacteroides dorei negatively correlated with ALT and AST. Recent studies reported that Bacteroides dorei might inhibit atherosclerosis by reducing the production of intestinal microbial lipopolysaccharide [33]. A Japanese study reported that its abundance in CHD patients was reduced [34], but the sample size was relatively small (11 patients).…”

Effect of cinnamon essential oil on gut microbiota in the mouse model of dextran sodium sulfate‐induced colitis

“…To our knowledge, Bacteroides contain both probiotic and potentially pathogenic species . On the one hand, Bacteroides with beneficial effects, such as B. vulgatus and B. dorei , could suppress the proinflammatory response by ameliorating endotoxemia and gut microbiota lipopolysaccharide levels in atherosclerosis‐prone mice . On the other hand, some potentially harmful strains of Bacteroides, such as B. fragilis , were reported to escape immune system attack in the mucosal surface and to have greater infection potential under abnormal intestinal microbiota .…”

Coronary artery disease is associated with an altered gut microbiome composition

“…Plasma level of TMAO is strongly correlated with the severity of coronary artery disease (CAD), suggestive that gut microbiome may be manipulated to reduce cardiovascular disease burden [4]. In fact, some prebiotic and probiotic treatment successfully showed cardiovascular benefit in mice [5][6][7][8]. However, the application of experimental animal data to CAD in human requires caution and further evaluation, given major differences in gut microbiome between mice and humans.…”