Dr. Wei-Kai Wu, Dr. Lee-Yan Sheen and Dr. Ming-Shiang Wu, from National Taiwan University Hospital, Institute of Food Science and Technology, and College of Medicine, have established a gut microbiota trimethylamine N-oxide (TMAO) production functional test to investigate the “Gut Feeling” in identifying the risk of cardiovascular disease. This research may facilitate precision medicine by proposing a gut microbiota-directed personalized nutrition. The results were patented and published in Gut on October 30, 2018.
The cardiometabolic disease is one of the most important worldwide threats to human health and economics. Recently, the link between gut microbiota and cardiovascular disease is gaining scientist’s attention. A notable gut-microbiota-generated metabolite called TMAO was found as an important causal risk for cardiovascular disease. The formation of TMAO in human body mainly comes from the carnitine (in red meat) and choline (in eggs) in our diet. If excessive carnitine or choline were consumed, it could be utilized by the bacteria in the gut and produce trimethylamine (TMA). The TMA is then oxidized by flavin monooxygenase in the liver and formed TMAO into the circulation. Long-term high concentration plasma TMAO has been proved to cause cardiovascular disease by enhancing vascular plaque formation and platelet aggregation. These findings were also supported by epidemiologic studies and the researches in this field are directing to clinical applications.
Prof. Ming-Shiang Wu, from National Taiwan University College of Medicine teamed up with Prof. Lee-Yan Sheen, from Institute of Food Science in the same school and performed multidisciplinary collaborations under financial supports from Ministry of Science and Technology (MOST). These works have come up with several highlights, including the development of a gut microbiota TMAO-producing capacity measurement study called “Oral Carnitine Challenge Test (OCCT)” as well as utilization of garlic bioactive compound as a measure in regulating gut microbiota to prevent or improve cardiovascular disease.
The team firstly performed a pharmacokinetic study to investigate the timing and efficiency of carnitine being transformed into TMAO in human body and simplified the exam for clinical application. Healthy volunteers including vegetarians and omnivores were recruited for the study and the team found the OCCT is robust in measuring TMAO formation capacity for each individual. The omnivores were found to have a 10-fold odd ratio to be TMAO high producers as compared with vegetarians. The researchers also reconstruct the TMAO-producing gut microbiota in mice by transplanting human feces into germ-free mice. Moreover, the team found the TMAO levels in blood and urine were highly correlated and could further strengthen the clinical feasibility of this test. In the future, the team plan to use the results of OCCT as a novel indicator for cardiovascular risk assessment as well as providing a guidance for medical and dietary intervention. Hopefully, we may move forward towards precision medicine and personalized nutrition by applying a gut microbiota-directed functional approach into clinical scenario.
Dr. Jung-Tsun Chien
Department of Life Sciences, Ministry of Science and Technology