TMAO is a gut-microbiota-derived metabolite increasingly recognized as a biomarker connecting diet, gut bacteria, and disease risk. Since it’s modifiable through diet, probiotics, and nutraceuticals, understanding its mechanisms opens doors to new preventive and therapeutic strategies for cardiovascular and neurodegenerative disease — conditions that remain leading causes of death and disability worldwide.
This review explains how TMAO is produced (gut bacteria convert dietary choline, carnitine, and betaine into TMA, which the liver enzyme FMO3 oxidizes to TMAO) and details its physiological roles as an osmolyte and protein-stabilizing chaperone. It then covers TMAO’s pathological effects — endothelial dysfunction, NLRP3 inflammasome-driven inflammation, disrupted cholesterol/bile acid metabolism, platelet hyperreactivity, and impaired endothelial progenitor cell function — that drive atherosclerosis, heart failure, hypertension, and peripheral vascular disease. It further reviews TMAO’s role in neurodegeneration (Alzheimer’s, Parkinson’s, ALS) via blood-brain barrier disruption and neuroinflammation. The paper closes with strategies to lower TMAO: dietary changes (reduced red meat, more plant-based foods), probiotics, statins, ACE inhibitors, and polyphenol-based nutraceuticals like Taurisolo®.
Caradonna, E.; Abate, F.; Schiano, E.; Paparella, F.; Ferrara, F.; Vanoli, E.; Difruscolo, R.; Goffredo, V.M.; Amato, B.; Setacci, C.; Setacci, F.; Novellino, E. Trimethylamine-N-Oxide (TMAO) as a Rising-Star Metabolite: Implications for Human Health. Metabolites 2025, 15, 220. https://doi.org/10.3390/metabo15040220
