Abstract 10273: BacteroidesProtect Against Atherosclerosis by Regulating Gut Microbial Lipopolysaccharide Production

Introduction:Increasing evidence has suggested that a strong correlation exists between the gut microbiota and development of coronary artery disease (CAD). However, how specific gut bacteria contribute to CAD and how we can manipulate their abundance remains to be determined. Here, we aimed to identify the gut bacterial species involved in CAD and determine whether resistant starch (RS) could prevent CAD by acting on gut microbiota.Methods:We recruited 30 CAD patients and 30 non-CAD controls with coronary risk factors and compared the gut microbiota composition in fecal samples to identify bacterial species with differential abundance between the groups. We then used mouse models of atherosclerosis to study the mechanisms underlying the relationship between these differentially expressed bacterial species and atherosclerosis. Finally, we investigated whether RS could manipulate the gut microbiota composition using a single-batch fermentation system.Results:A significantly lower abundance of Bacteroides vulgatusand B. doreiwas observed in CAD patients (9.5% [range, 3.8?16.5%] vs. 3.7% [range, 1.9?11.1%]; p < 0.05). Gavage with B. vulgatusand B. doreiattenuated atherosclerotic lesion formation in atherosclerosis-prone mice, and markedly ameliorated endotoxemia. These mice also showed decreased lipopolysaccharide (LPS) production by the gut microbiota, which effectively suppressed pro-inflammatory immune responses. Furthermore, significantly higher gut microbial LPS production was observed in CAD patients (1.8 ? 105[range, 1.0?3.6 ? 105] endotoxin unit (EU)/g vs. 3.4 ? 105[range, 1.9?6.6 ? 105] EU/g; p < 0.05). Fecal LPS levels in CAD patients were significantly and negatively correlated with the abundance of two species of Bacteroides(r = -0.29; p < 0.05). Finally, RS significantly increased the absolute number of B. vulgatusand B. doreiamong gut bacteria in the fermentation system.Conclusions:We identified two species of Bacteroidesthat may serve as novel, inexpensive therapeutic targets to prevent CAD. RS enhanced their growth in the human gut microbiota, suggesting that this treatment could be used in CAD patients to restore the gut microbiota composition to symbiotic state.