In 2011, Wang and colleagues published their initial findings linking high plasma trimethylamine-N-oxide (TMAO) with cardiovascular disease (CVD). Since then, TMAO's role in the etiology of cardiometabolic diseases remains a matter of controversy within the scientific community. In the PREDIMED trial, an inverse association between plasma TMAO levels with incident T2D was recently reported. In this symposium, Dr. Christopher Papandreou will present findings in relation to TMAO and cardiometabolic traits. TMAO production involves flavin-containing monoxygenases (FMO), a family of enzymes located in the liver and known to be modulated by different factors. Dr. Cashman will provide information on the FMO gene regulation and how this connects to cardiometabolic outcomes.