Gut microbes can metabolize nutrient with structural formula containing trimethylamine (TMA) moiety, such as
phosphatidylcholine, choline, carnitine and ?-butyrobetaine in diet, to produce TMA and TMA is further oxidized as
trimethylamine N-oxide (TMAO) catalyzed by host hepatic Flavin monooxygenases (FMOs). The TMAO metaorganismal pathway is a universal metabolic pathway, contributing to cardiometabolic disease. TMAO shows multiple pro-atherogenic properties including activating MAPK and NF?B signaling, NLRP3 inflammasome and PERK pathway, leading to atherosclerosis, thrombosis, heart hypertrophy, chronic kidney disease, fatty liver disease and obesity even gallstone formation. TMAO can independently predict future risk for major adverse cardiac events (=non-fatal myocardial infarction, stroke and death). Targeting this metabolic pathway by limiting TMA precursor enriched diet consumption, administration of prebiotic or probiotic to decrease the bacterium abundance which encodes enzymes involved in the conversion of TMA precursors to TMA or inhibitors to TMA lyase and FMOs, can decrease circulating TMAO, therefore ameliorating cardiometabolic disease.
Dr. Zeneng Wang received bachelor’s degree from Fudan University, and master’s degree and PhD from Peking University. Since Jan, 2003, she joined Cleveland Clinic Lerner Research Institute as Postdoctoral Research Fellow, Research Associate, Project Scientist and now Staff Scientist. He was awarded American Heart Association Scientist Development Grant and NIH RO1 grants. Dr Wang reported the association between TMAO metaorganismal pathway and cardiovascular disease the first time. So far, he has published more than 97 papers in high-impact journals, including Nature, Cell, Nature Medicine, European Heart Journal and Cell Metabolism as well.