A multi-omic characterization reveals personalized risk factors for coronary artery disease

Coronary artery disease (CAD) is a major cause of morbidity and mortality worldwide. While current treatments for CAD that are based on traditional and modifiable risk factors have been proven effective, they result in only partial success, emphasizing CAD as a complex multifactorial disease, which might be driven by different factors in subgroups of diseased populations. Here, we obtained a comprehensive clinical and multi-omic profiling for 199 patients with acute coronary syndrome (ACS), an acute subcategory of CAD, that we recruited in two major Israeli hospitals. We demonstrate that ACS has distinct serum metabolome and gut microbial signatures, as compared to a healthy control cohort consisting of 474 of individuals. By integrating prior knowledge regarding metabolite’ determinant factors, we found that the metabolic deviations from healthy matched serum profiles are person-specific with respect to their potential origin, and that they correlate with clinical parameters and glycemic status. Furthermore, we show that a metabolomic-based model of body mass index (BMI) that we trained from our healthy cohort, predicts higher BMI when applied to serum metabolomics profiles of patients with ACS, and that the excess BMI predictions independently correlate with both diabetes mellitus (DM) and the severity of CAD, defined by the number of vessels involved. We identified an unknown bacterial species of the Clostridiaceae family that was depleted in our ACS patients, we showed that this bacterial species was associated with the levels of multiple circulating metabolites in healthy participants, several of which were previously linked with an increased risk of CAD, while others are possibly novel CAD targets. Taken together, our results highlight the potential for a precision/personalized medicine approach in normalizing the metabolic disruptions associated with CAD, and suggest concrete targets for metabolic manipulations based on diet, human genetics and microbiome.