Vol. 7, Issue 2, Part E (2025)

Trimethylamine N-oxide (TMAO) is a metabolite of the gut microbiota that originates from dietary sources of nutrients such as choline, L-carnitine, and phosphatidylcholine. Microbial metabolism of these precursors yields trimethylamine (TMA) which is then oxidized to TMAO through hepatic flavin monooxygenase-3 (FMO3). Elevated circulating levels of TMAO have been linked to several cardiometabolic diseases including atherosclerosis, type 2 diabetes mellitus, obesity, non-alcoholic fatty liver disease (NAFLD), and chronic kidney disease. Suggested pathways linking TMAO to disease and disrupted cardiometabolic health include impaired cholesterol transport, increased platelet reactivity, endothelial dysfunction, and activation of pro-inflammatory pathways. Recently, studies have also implicated TMAO in cancer and metabolic syndrome. TMAO levels can be modulated by gut microbiota, and dietary interventions, prebiotics, probiotics, and synbiotics have been studied as food-based approaches to modulate TMAO levels. While strong associations have been made between TMAO and disease, precise mechanisms connecting TMAO to disease are unclear. Understanding these associations gives a necessity to review TMAO as a biomarker and therapeutic target in cardiometabolic disease and health.