Nature2014-01-01 12:32 AM

Intestinal microbiota metabolism of L-carnitine, a nutrient in red meat, promotes atherosclerosis 红肉中的营养成分左旋肉碱肠道菌群代谢促进动脉粥样硬化

Abstract Intestinal microbiota metabolism of choline and phosphatidylcholine produces trimethylamine (TMA), which is further metabolized to a proatherogenic species, trimethylamine-N-oxide (TMAO). We demonstrate here that metabolism by intestinal microbiota of dietary L-carnitine, a trimethylamine abundant in red meat, also produces TMAO and accelerates atherosclerosis in mice. Omnivorous human subjects produced more TMAO than did vegans or vegetarians following ingestion of L-carnitine through a microbiota-dependent mechanism. The presence of specific bacterial taxa in human feces was associated with both plasma TMAO concentration and dietary status. Plasma L-carnitine levels in subjects undergoing cardiac evaluation (n = 2,595) predicted increased risks for both prevalent cardiovascular disease (CVD) and incident major adverse cardiac events (myocardial infarction, stroke or death), but only among subjects with concurrently high TMAO levels. Chronic dietary L-carnitine supplementation in mice altered cecal microbial composition, markedly enhanced synthesis of TMA and TMAO, and increased atherosclerosis, but this did not occur if intestinal microbiota was concurrently suppressed. In mice with an intact intestinal microbiota, dietary supplementation with TMAO or either carnitine or choline reduced in vivo reverse cholesterol transport. Intestinal microbiota may thus contribute to the well-established link between high levels of red meat consumption and CVD risk. 论文摘要 胆碱和磷脂酰胆碱肠道菌群代谢会产生三甲胺(TMA),这将进一步代谢成动脉粥样硬化的一个种类,即三甲胺-N-氧化物(TMAO)。我们在这里证实膳食左旋肉碱肠道菌群代谢,即在红肉中含量丰富的某种一甲胺,也能产生TMAO从而加速小鼠动脉粥样硬化。与严格素食者或素食者相比,杂食性受试者通过微生物依赖机制摄入左旋肉碱从而产生更多TMAO。在人类粪便中特定细菌类群的存在与血浆中TMAO浓度和饮食状况有关。接受心脏评估的受试者体内血浆左旋肉碱水平(N = 2,595)预示着流行性心血管疾病(CVD)和主要突发性有害心脏疾病(心肌梗死,卒中或死亡)增长的风险,但只发生在现有高TMAO水平的受测者群体中。在小鼠体内慢性膳食左旋肉碱补给改变了盲肠微生物组成,明显增强了TMA和TMAO的合成,并增加了动脉粥样硬化,但假如肠道菌群同时被抑制,则这种情况不会发生。给具有完整肠道菌群小鼠的每天饮食中添加TMAO或肉(毒)碱或胆碱能减少体内胆固醇的逆向转运。因此肠道菌群可能导致了红肉高消费量和心血管疾病风险之间的紧密关联。

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