肠道微生物这么热，不得不看呀

文章题目: Non-lethal Inhibition of Gut Microbial Trimethylamine Production for the Treatment of Atherosclerosis

摘要：Trimethylamine (TMA) N-oxide (TMAO), a gut-microbiota-dependent metabolite, both enhances atherosclerosis in animal models and is associated with cardiovascular risks in clinical studies. Here, we
investigate the impact of targeted inhibition of the first step in TMAO generation, commensal microbial TMA production, on diet-induced atherosclerosis. A structural analog of choline, 3,3-dimethyl-1-butanol
(DMB), is shown to non-lethally inhibit TMA formation from cultured microbes, to inhibit distinct microbial TMA lyases, and to both inhibit TMA production
from physiologic polymicrobial cultures (e.g., intestinal contents, humanfeces) and reduce TMAO levels in mice fed a high-choline or L-carnitine diet. DMB
inhibited choline diet-enhanced endogenous macrophage foam cell formation and atherosclerotic lesion development in apolipoprotein e/ mice without
alterations in circulating cholesterol levels. The present studies suggest that targeting gut microbial production of TMA specifically and non-lethal microbial inhibitors in general may serve as a potential therapeutic approach for the treatment of cardiometabolic diseases.

三甲胺（TMA）N-氧化物（TMAO）是一种肠道微生物依赖性代谢物，在动物模型中均可增强动脉粥样硬化，并与临床研究中的心血管风险相关。在这里，我们研究了TMAO生成的第一步靶向抑制对共生微生物TMA产生对饮食诱导的动脉粥样硬化的影响。胆碱3,3-二甲基-1-丁醇（DMB）的结构类似物显示出非致死性地抑制培养微生物的TMA形成，抑制不同的微生物TMA裂解酶，并抑制生理多微生物培养物中TMA的产生（例如，加入高胆碱或左旋肉碱饮食的小鼠的内部含量，人类感受和降低TMAO水平。 DMB抑制胆碱饮食增强的内源性巨噬细胞泡沫细胞形成和载脂蛋白e的动脉粥样硬化病变发展。没有改变循环胆固醇水平的小鼠。先前的研究表明，针对TMA特异性和非致死性微生物抑制剂的肠道微生物生产可以作为治疗心脏代谢疾病的潜在治疗方法。