Trimethylamine N-Oxide (TMAO) and cancer risk: Insights into a possible link

The gut microbiota play a crucial role in cancer pathogenesis, partly through metabolites derived from dietary components or host compounds. Among these, trimethylamine N-oxide (TMAO), a secondary gut microbiota-derived metabolite has gained attention for its potential link to cancer. TMAO is formed when gut microbes convert dietary choline, carnitine, and betaine into trimethylamine (TMA), which is then oxidized in the liver by FMO3. While TMAO has been well studied in cardiovascular, kidney, and metabolic diseases, growing evidence links elevated TMAO levels to increased risks of colorectal cancer (CRC) and hepatocellular carcinoma (HCC). Although the exact mechanisms remain unclear, TMAO appears to contribute to cancer progression by promoting inflammation, oxidative stress, endoplasmic reticulum stress, and insulin resistance. This review discusses the dietary and microbial pathways involved in TMAO synthesis, its role in cancer progression, and critically evaluates the current literature on its potential contribution to cancer. Understanding the role of TMAO could offer new strategies for cancer prevention and therapy that target the gut microbiota and their metabolites.