Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease.
Gut flora metabolism of phosphatidylcholine promotes cardiovascular disease.
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磷脂酰胆碱的肠道菌群代谢促进心血管疾病。
DOI：
10.1038/nature09922
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发表时间：
2011-04-07
期刊：
影响因子：
64.8
通讯作者：
Hazen, Stanley L.
中科院分区：
文献类型：
--
作者：
Wang, Zeneng;Klipfell, Elizabeth;Bennett, Brian J.;Koeth, Robert;Levison, Bruce S.;Dugar, Brandon;Feldstein, Ariel E.;Britt, Earl B.;Fu, Xiaoming;Chung, Yoon-Mi;Wu, Yuping;Schauer, Phil;Smith, Jonathan D.;Allayee, Hooman;Tang, W. H. Wilson;DiDonato, Joseph A.;Lusis, Aldons J.;Hazen, Stanley L.
代谢组学研究有望发现与疾病过程相关的途径。心血管疾病（CVD）是全球死亡和发病的主要原因。代谢组学方法用于产生预测CVD风险的血浆中无偏倚的小分子代谢谱。膳食脂质磷脂酰胆碱的三种代谢物，即胆碱，三甲胺N-氧化物（TMAO）和甜菜碱，被确定，然后在一个独立的大型临床队列中显示预测CVD的风险。饮食补充胆碱，TMAO或甜菜碱的小鼠促进与动脉粥样硬化相关的多个巨噬细胞清道夫受体的上调，补充胆碱或TMAO促进动脉粥样硬化。使用无菌小鼠的研究证实了饮食胆碱和肠道植物群在TMAO产生、增加巨噬细胞胆固醇积累和泡沫细胞形成中的关键作用。抑制易患动脉粥样硬化的小鼠肠道菌群可抑制饮食胆碱增强的动脉粥样硬化。控制黄素单加氧酶（FMOs）表达的遗传变异，TMAO的酶源，与高脂血症小鼠动脉粥样硬化分离。膳食磷脂酰胆碱的肠道菌群依赖性代谢与CVD发病机制之间的关系的发现为开发动脉粥样硬化性心脏病的新诊断测试和治疗方法提供了机会。
Metabolomics studies hold promise for discovery of pathways linked to disease processes. Cardiovascular disease (CVD) represents the leading cause of death and morbidity worldwide. A metabolomics approach was used to generate unbiased small molecule metabolic profiles in plasma that predict risk for CVD. Three metabolites of the dietary lipid phosphatidylcholine, namely 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 up-regulation 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 (FMOs), an enzymatic source of TMAO, segregated with atherosclerosis in hyperlipidemic mice. Discovery of a relationship between gut flora-dependent metabolism of dietary phosphatidylcholine and CVD pathogenesis provides opportunities for development of both novel diagnostic tests and therapeutic approaches for atherosclerotic heart disease.
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影响因子：
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