Gutflorametabolismofphosphatidylcholinepromotescardiovasculardisease.docVIP

Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease. Nature.?2011 Apr 7;472(7341):57-63. doi: 10.1038/nature09922. Gut?flora?metabolism?of?phosphatidylcholine?promotes?cardiovascular?disease. Wang Z1,?Klipfell E,?Bennett BJ,?Koeth R,?Levison BS,?Dugar B,?Feldstein AE,?Britt EB,?Fu X,?Chung YM,?Wu Y,?Schauer P,?Smith JD,?Allayee H,?Tang WH,DiDonato JA,?Lusis AJ,?Hazen SL. Author information Abstract Metabolomics studies hold promise for the discovery of pathways linked to?disease?processes.?Cardiovascular?disease?(CVD) represents the leading cause of death and morbidity worldwide. Here we used a metabolomics approach to generate unbiased small-molecule metabolic profiles in plasma that predict risk for CVD. Three metabolites of the dietary lipid?phosphatidylcholine--choline, trimethylamine N-oxide (TMAO) and betaine--were identified and then shown to predict risk for CVD in an independent large clinical cohort. Dietary supplementation of mice with choline, TMAO or betaine promoted upregulation of multiple macrophage scavenger receptors linked to atherosclerosis, and supplementation with choline or TMAO promoted atherosclerosis. Studies using germ-free mice confirmed a critical role for dietary choline and?gut?flora?in TMAO production, augmented macrophage cholesterol accumulation and foam cell formation. Suppression of intestinal microflora in atherosclerosis-prone mice inhibited dietary-choline-enhanced atherosclerosis. Genetic variations controlling expression of flavin monooxygenases, an enzymatic source of TMAO, segregated with atherosclerosis in hyperlipidaemic mice. Discovery of a relationship between?gut-flora-dependent?metabolism?of dietary?phosphatidylcholine?and CVD pathogenesis provides opportunities for the development of new diagnostic tests and therapeutic approaches for atherosclerotic heart?disease. 代谢组学研究的途径与疾病的进程发现承诺。心血管疾病（CVD）是导致的死亡和发病率在世界范围内。在这里，我们使用了代谢组学的方法来产生无偏小分子血浆中的代谢特征，预测心血管疾病的风险。三种代谢物的饮食脂质的磷脂酰胆碱——胆碱，三甲胺N-氧化物（TMAO）和甜菜碱