A review on the beneficial and detrimental roles of gut microbiota-derived trimethylamine-N-oxide (TMAO)

In recent years, increasing attention has focused on the role of the gut microbiome in converting dietary substances into bioactive metabolites implicated in the etiology of various diseases. Among these metabolites, trimethylamine-N-oxide (TMAO), a gut microbial metabolite derived from choline, carnitine, and betaine, has emerged as a novel molecule of interest as an alternative messenger with multiple, tissue-specific effects on human physiology. Once considered a benign osmolyte in marine organisms, TMAO is now implicated in human health risks through mechanisms involving oxidative stress, inflammation, and metabolic regulation. While elevated TMAO levels are associated with cardiovascular disease, chronic kidney disease, and neurodegeneration, evidence also highlights its cytoprotective properties, including protein stabilization and osmoprotection. This review provides a comprehensive analysis of TMAO's dual role in oxidative stress, inflammation, and endothelial mechanisms, clarifying its context-dependent effects and therapeutic implications.