Transmission of Atherosclerosis Susceptibility with Gut Microbial Transplantation
Transmission of Atherosclerosis Susceptibility with Gut Microbial Transplantation
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DOI：
10.1074/jbc.m114.618249
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发表时间：
2015-02-27
影响因子：
4.8
通讯作者：
Hazen, Stanley L.
中科院分区：
文献类型：
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作者：
Gregory, Jill C.;Buffa, Jennifer A.;Hazen, Stanley L.
最近的研究表明，动脉粥样硬化性心脏病和肠道微生物代谢某些饮食营养素产生的三甲胺N-氧化物（TMAO）之间的临床和机制的联系。在这里，我们测试的假设，肠道微生物移植可以传递胆碱饮食诱导的TMAO生产和动脉粥样硬化的易感性。首先，在小鼠多样性组中，动脉粥样硬化斑块和血浆TMAO水平之间存在强相关性（n = 22株，r = 0.38;p = 0.0001）。选择易患动脉粥样硬化和高TMAO产生的菌株C57 BL/6 J和抗动脉粥样硬化和低TMAO产生的菌株NZW/LacJ作为盲肠微生物移植到载脂蛋白e基因敲除小鼠中的供体，其中首先用抗生素抑制肠道微生物。在接受来自C57 B1/6 J近交系小鼠的盲肠微生物的胆碱饮食的接受者中，三甲胺（TMA）和TmAo水平最初较高;然而，TMA/TMAO水平的胆碱饮食依赖性差异的持久性没有维持到研究结束。与接受NZW/LacJ微生物的小鼠相比，接受C57 BL/6 J盲肠微生物的小鼠表现出胆碱饮食依赖性的动脉粥样硬化斑块负荷增强。粪便和盲肠中的微生物DNA分析显示，供体微生物群落特征移植到受体中，供体菌株之间的分类群比例存在差异，这些菌株可传播给受体，并且倾向于显示与TMA（）水平一致的比例。还鉴定了与供体和受体中的血浆TmAo水平以及与受体中的动脉粥样硬化病变面积相关的特定分类群的比例。动脉粥样硬化易感性可能通过肠道微生物群的移植传播。因此，肠道微生物可能是一种新的治疗靶点，用于调节动脉粥样硬化的易感性。
Recent studies indicate both clinical and mechanistic links between atherosclerotic heart disease and intestinal microbial metabolism of certain dietary nutrients producing trimethylamine N-oxide (TMAO). Here we test the hypothesis that gut microbial transplantation can transmit choline diet-induced TMAO production and atherosclerosis susceptibility. First, a strong association was noted between atherosclerotic plaque and plasma TMAO levels in a mouse diversity panel (n = 22 strains, r = 0.38;p = 0.0001). An atherosclerosis-prone and high TMAO-producing strain, C57BL/6J, and an atherosclerosis-resistant and low TMAO-producing strain, NZW/LacJ, were selected as donors for cecal microbial transplantation into apolipoprotein e null mice in which resident intestinal microbes were first suppressed with antibiotics. Trimethylamine (TMA) and TmAo levels were initially higher in recipients on choline diet that received cecal microbes from C57B1/6J inbred mice; however, durability of choline diet-dependent differences in TMA/TMAO levels was not maintained to the end of the study. Mice receiving C57BL/6J cecal microbes demonstrated choline diet-dependent enhancement in atherosclerotic plaque burden as compared with recipients of NZW/LacJ microbes. Microbial DNA analyses in feces and cecum revealed transplantation of donor microbial community features into recipients with differences in taxa proportions between donor strains that were transmissible to recipients and that tended to show coincident proportions with TMA() levels. Proportions of specific taxa were also identified that correlated with plasma TmAo levels in donors and recipients and with atherosclerotic lesion area in recipients. Atherosclerosis susceptibility may be transmitted via transplantation of gut microbiota. Gut microbes may thus represent a novel therapeutic target for modulating atherosclerosis susceptibility.