Targeting the gut microbiome in coronary artery disease

Host-microbiota interactions via numerous inflammatory and metabolic pathways contribute to the pathogenesis of a multitude of diseases such as cardiovascular and metabolic diseases.1 Alterations in the microbial flora generate increased circulating levels of microbiota-dependent metabolites associated with disease risk.2 One such metabolite, trimethylamine N-oxide (TMAO), is formed from the metabolism of phosphatidylcholine or L-carnitine into trimethylamine by bacteria, which is converted to TMAO in the liver by flavin-containing monooxygenases (FMO).3 While TMAO is the most commonly studied gut microbiota-derived metabolite demonstrating associations with heart failure,3 myocardial infarction4 and heart disease,5 precursor metabolites to TMAO have also shown similar associations with cardiovascular disease (CVD) risk such as betaine,6 choline,6 γ-butyrobetaine7 and more recently, acetyl-L-carnitine and L-carnitine.8 Given that TMAO can be generated from two pathways; 1) betaine -> choline -> TMAO and 2) carnitine -> TMAO, this demonstrates that TMAO levels are determined from a multitude of sources including dietary (e.g., carnitine from red meat and choline from eggs), microbial flora, medications (e.g., antibiotics), liver flavin monooxygenase activity, as well as age, gender and ethnicity.9., 10., 11. [Opening paragraph]