The Role of Gut Microbiome in Patients with Acute Coronary Syndrome

Background. Cardiovascular disease (CVD) is a leading cause of morbidity and mortality worldwide. Current atherosclerosis treatment is based on traditional and modifiable risk factors, but results in only partial success, suggests that many yet unknown factors contribute to atherosclerosis. The human microbiome is involved in a variety of pathophysiological processes, including obesity, inflammatory diseases, metabolic diseases, and aging.

Methods. Stool samples were collected from 159 ACS patients since February 2017, at the Rabin Medical Center and from 659 healthy controls at the Weitzman Institute. After DNA extraction from the samples, we performed a metagenome-wide association study.

Results. The microbiome of ACS patients was enriched for oral bacteria, consistent with a known association between bacterial infection and CVD incidence. Many bacterial genes also differed, including enrichment of trimethylamine (TMA) bacterial pathway genes, in ACS patients that by themselves were predictive of ACS (AUC=0.67). However, we found 7 other pathways that were even more predictive (e.g., bacteria secretion, AUC=0.71), and a total of 67 novel bacterial pathway associations with AUC>0.6. Strikingly, using only microbiome features, we could construct a model that classified held out ACS patients with very high accuracy (AUC=0.89).

Conclusions. Patients with ACS have a unique microbiome pattern. TMA-lyase genes play a role in this pattern, suggesting increased production of TMA-lyase in the gut of patients with ACS. The results of the present study provide a novel insight into the pathophysiology of ACS and may eventually lead to the development of unique ACS prevention strategies.