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首页> 外文期刊>Cell metabolism >γ-butyrobetaine is a proatherogenic intermediate in gut microbial metabolism of L-carnitine to TMAO
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γ-butyrobetaine is a proatherogenic intermediate in gut microbial metabolism of L-carnitine to TMAO

机译:γ-丁甜菜碱是L-肉碱转化为TMAO的肠道微生物代谢中的促动脉粥样硬化中间体

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摘要

L-carnitine, a nutrient in red meat, was recently reported to accelerate atherosclerosis via a metaorganismal pathway involving gut microbial trimethylamine (TMA) formation and host hepatic conversion into trimethylamine-N-oxide (TMAO). Herein, we show that following L-carnitine ingestion, γ-butyrobetaine (γBB) is produced as an intermediary metabolite by gut microbes at a site anatomically proximal to and at a rate ~1,000-fold higher than the formation of TMA. Moreover, we show that γBB is the major gut microbial metabolite formed from dietary L-carnitine in mice, is converted into TMA and TMAO in a gut microbiota-dependent manner (like dietary L-carnitine), and accelerates atherosclerosis. Gut microbial composition and functional metabolic studies reveal that distinct taxa are associated with the production of γBB or TMA/TMAO from dietary L-carnitine. Moreover, despite their close structural similarity, chronic dietary exposure to L-carnitine or γBB promotes development of functionally distinct microbial communities optimized for the metabolism of L-carnitine or γBB, respectively.
机译:最近报道了左旋肉碱(一种红肉中的营养物)通过涉及肠道微生物三甲胺(TMA)形成和宿主肝转化为三甲胺-N-氧化物(TMAO)的代谢途径加速动脉粥样硬化。在此,我们显示,摄入左旋肉碱后,肠道微生物在解剖学上最接近的部位产生了作为中间代谢产物的γ-丁甜菜碱(γBB),其速率比TMA的形成高约1,000倍。此外,我们表明,γBB是小鼠饮食中的左旋肉碱形成的主要肠道微生物代谢产物,以肠道菌群依赖性的方式(如饮食中的左旋肉碱)转化为TMA和TMAO,并加速了动脉粥样硬化。肠道微生物组成和功能代谢研究表明,不同的分类群与饮食中左旋肉碱产生的γBB或TMA / TMAO有关。此外,尽管它们在结构上相似,但长期饮食中的L-肉碱或γBB分别促进了针对L-肉碱或γBB的代谢而优化的功能独特的微生物群落的发展。

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