Animal food such as egg and red meat rich in choline and carnitine (dietary precursors of TMAO), and fish naturally abundant in TMAO, are the main dietary source of TMAO. Dietary nutrients choline and carnitine are converted into TMA by distinctive enzymes encoded by gut microbiota. The gut-derived TMA is then oxidised into TMAO by hepatic FMO3, released into blood, taken up by extrahepatic tissues and excreted in urine. Fish-source TMAO can bypass gut and live metabolism and directly be absorbed into blood. High circulating TMAO increase the risk of multiple diseases including CKD, CVD, type 2 diabetes, neurodegenerative disorders and cancer. In deep sea fish (and other marine organisms), high TMAO is evolutionally adapted as an organic osmolyte and antifreeze to maintain cell volume and protein stability against hydrostatic and thermal pressures.