The Role of Gut Microbiome in Patients with Acute Coronary Syndrome

Background: The human gut microbiota contribute to a variety of metabolic and immunologic mechanisms in the human body. It has been linked to cardiovascular disease through the production of Trimethylamine (TMA), which is produced by the gut microbiota, mainly from choline and carnitine, and is associated with atherosclerosis. Data regarding the microbiome in patients with acute coronary syndrome (ACS) is lacking.

Aim: To investigate gut microbiota of patients with ACS.

Methods: Stool samples were collected from 140 ACS patients since February 2017, at the Rabin Medical Center and from 659 healthy controls at the Weitzman Institute. After DNA extraction, we performed a metagenome-wide association study on stool samples from 101 individuals with ACS and 659 healthy controls.

Results: Both groups exhibit similar distributions of global metagenome sequencing parameters and similar levels of microbial gene diversities. There was significant difference in the percentages of reads mapping for microbial genes, and higher levels of microbial specie diversities as well as microbiome dissimilarities in ACS patients. Levels of carnitine TMA-lyase genes (CntA/B, YeaX/W and its derivatives CaiT/X in gut bacteria) were significantly higher in ACS patients (MannWhitneyU p-value < 1e-9), however, levels of choline TMA-lyase genes CutC/D were similar. When performing k-fold cross validation using decision tree based algorithms, the area under receiver operating curve (AUC) using microbial specie abundance was 0.83, when using bacterial gene abundance the AUC was 0.90. While using only TMA related gene abundance the AUC was 0.76.

Conclusion: Patients with ACS have a unique microbiome pattern. TMA-lyase genes play a key 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.