The Metabolite Trimethylamine-N-Oxide is an Emergent Biomarker of Human Health.

Trimethylamine-N-oxide (TMAO) is a low molecular weight metabolite whose production is dependent on metabolism of its precursors choline, carnitine, creatinine, betaine or lecithin by host gut microbes resulting in the synthesis of trimethylamine (TMA), which is subsequently oxidized to TMAO via hepatic flavin monooxygenase (FMO). TMAO is associated with microbial dysbiosis and is being studied for its linkage with cardiovascular disorders. In addition, dysregulated levels of TMAO have been linked with renal diseases, neurological disorders and cancer. Here we discuss the enzymatic and metabolic landscape that results in TMAO production, and in addition, collate data from numerous clinical studies that have assessed TMAO as a biomarker for various disease conditions. We also summarize the interaction of TMAO with modern and traditional drugs that together affect circulating TMAO levels in the human body.