Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis.
Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis.
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DOI：
10.1038/nm.3145
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发表时间：
2013-05
期刊：
影响因子：
82.9
通讯作者：
Hazen SL
中科院分区：
文献类型：
--
作者：
Koeth RA;Wang Z;Levison BS;Buffa JA;Org E;Sheehy BT;Britt EB;Fu X;Wu Y;Li L;Smith JD;DiDonato JA;Chen J;Li H;Wu GD;Lewis JD;Warrier M;Brown JM;Krauss RM;Tang WH;Bushman FD;Lusis AJ;Hazen SL
肠道微生物代谢胆碱/磷脂酰胆碱产生三甲胺（TMA），其进一步代谢为促动脉粥样硬化物质三甲胺- n -氧化物（TMAO）。本文表明，膳食中的左旋肉碱（一种富含红肉的三甲胺）的肠道微生物代谢也会产生氧化三甲胺并加速动脉粥样硬化。杂食性受试者通过微生物依赖的机制摄入左旋肉碱后，产生的氧化三甲胺明显多于纯素食者。人类粪便中的特定细菌分类被证明与血浆TMAO和饮食状况有关。接受心脏评估的受试者（n = 2595）血浆左旋肉碱水平预测流行心血管疾病（CVD）和发生主要不良心脏事件（心肌梗死、中风或死亡）的风险增加，但仅在TMAO水平较高的受试者中。在小鼠中长期补充左旋肉碱会显著改变盲肠微生物组成，显著增强TMA/TMAO的合成，并增加动脉粥样硬化，但不会抑制肠道微生物群。在肠道菌群完好的小鼠中，通过膳食补充氧化三甲胺、肉碱或胆碱，可显著降低体内胆固醇的逆向转运。因此，肠道微生物群可能参与了红肉摄入量增加与心血管疾病风险之间的既定联系。
Intestinal microbiota metabolism of choline/phosphatidylcholine produces trimethylamine (TMA), which is further metabolized to a proatherogenic species, trimethylamine-N-oxide (TMAO). Herein we demonstrate that intestinal microbiota metabolism of dietary L-carnitine, a trimethylamine abundant in red meat, also produces TMAO and accelerates atherosclerosis. Omnivorous subjects are shown to produce significantly more TMAO than vegans/vegetarians following ingestion of L-carnitine through a microbiota-dependent mechanism. Specific bacterial taxa in human feces are shown to associate with both plasma TMAO and dietary status. Plasma L-carnitine levels in subjects undergoing cardiac evaluation (n = 2,595) predict increased risks for both prevalent cardiovascular disease (CVD) and incident major adverse cardiac events (MI, stroke or death), but only among subjects with concurrently high TMAO levels. Chronic dietary L-carnitine supplementation in mice significantly altered cecal microbial composition, markedly enhanced synthesis of TMA/TMAO, and increased atherosclerosis, but not following suppression of intestinal microbiota. Dietary supplementation of TMAO, or either carnitine or choline in mice with intact intestinal microbiota, significantly reduced reverse cholesterol transport in vivo. Intestinal microbiota may thus participate in the well-established link between increased red meat consumption and CVD risk.
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影响因子：
15.9
作者：
Febbraio, M;Podrez, EA;Silverstein, RL
通讯作者：
Silverstein, RL
DOI：
10.1073/pnas.0504978102
发表时间：
2005-08-02
影响因子：
11.1
作者：
Ley, RE;Bäckhed, F;Gordon, JI
通讯作者：
Gordon, JI
DOI：
10.1056/nejmoa0907355
发表时间：
2010-02-18
期刊：
The New England journal of medicine
影响因子：
--
作者：
Bibbins-Domingo K;Chertow GM;Coxson PG;Moran A;Lightwood JM;Pletcher MJ;Goldman L
通讯作者：
Goldman L
影响因子：
37.8
作者：
Bernstein AM;Sun Q;Hu FB;Stampfer MJ;Manson JE;Willett WC
通讯作者：
Willett WC
影响因子：
56.9
作者：
Altmann, SW;Davis, HR;Graziano, MP
通讯作者：
Graziano, MP