Coronary artery disease is one of the most prevalent cardiovascular diseases worldwide. The gut microbes-derived metabolites have been suggested to use as markers for major adverse cardiac event, yet the contributions of gut microbes and bacterial metabolites towards atherosclerosis remain largely uncharacterized. We indicated a relationship between the gut microbiome and metabolomics and provided preliminary evidence that gut dysbiosis interacts with metabolic pathways to affect atherosclerosis severity. Our findings point towards a new strategy aimed at reducing cardiovascular risks through restoring the homeostasis of gut microbiota.. Alterations of the gut microbiome and metabolism with progression of coronary artery disease

Alterations of gut microbiota are associated with coronary artery disease(CAD) in different populations. The gut microbes-derived metabolites have been suggested to use as markers for major adverse cardiac event. However, it is remaining to establish the relationship between gut microbiome and the pathophysiological progression of CAD by systematic study. Based on the multi-omics analysis(metagenomics and metabolomics) from 161 CAD patients and 40 healthy controls, we have found that the composition of both gut microbiota and metabolites changed significantly with the severity of CAD. We identified 35 metabolite modules classified separately positive or negative correlated with CAD phenotypes, and bacteria co-abundance group(CAG) with characteristic changes in plaque formation, plaque rupture and myocardial infarction process represented by Roseburia, Klebsiella, Clostridium IV and Ruminococcaceae, respectively. Through multi-omics analysis, we revealed that certain bacteria showed modulational role to affect atherosclerosis by influencing the metabolic pathways such like taurine metabolism, sphingolipids and ceramides, and benzene metabolism. Moreover, a disease classifier based on differential microbiota and metabolites was constructed to discriminate cases from controls even though stable coronary artery disease to acute coronary syndrome accurately. The area under the receiver-operating characteristics curve (AUC) of the disease classifier is 0.737(95% CI, 0.508–0.965) and 0.812(95% CI, 0.626-0.997), respectively. Overall, the composition and functions of the gut microbial community differed from healthy controls to diverse coronary artery disease subtypes. Our study identified novel relationships between the feature of the gut microbiota and circulating metabolites and provides a resource for future studies to understand host–gut microbiota interplay in atherosclerotic pathogenesis.