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.