Choline Diet and Its Gut Microbe-Derived Metabolite, Trimethylamine N-Oxide, Exacerbate Pressure Overload-Induced Heart Failure.
Choline Diet and Its Gut Microbe-Derived Metabolite, Trimethylamine N-Oxide, Exacerbate Pressure Overload-Induced Heart Failure.
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DOI：
10.1161/circheartfailure.115.002314
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发表时间：
2016-01
期刊：
影响因子：
--
通讯作者：
Lefer DJ
中科院分区：
文献类型：
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作者：
Organ CL;Otsuka H;Bhushan S;Wang Z;Bradley J;Trivedi R;Polhemus DJ;Tang WH;Wu Y;Hazen SL;Lefer DJ
N-氧化三甲胺（TMAO）是膳食胆碱和其他含有营养素的三甲胺的肠道微生物依赖性代谢物，其在患有心力衰竭（HF）的患者的循环中升高并且预示着更差的总体预后。在动物研究中，饮食胆碱或TMAO显著加速ApoE缺陷小鼠中动脉粥样硬化病变的发展，并且TMAO水平的降低抑制LDL受体敲除小鼠中动脉粥样硬化的发展。在手术TAC前3周开始，给C57 BL 6/J小鼠喂食对照饮食、含有胆碱（1.2%）的饮食或含有TMAO（0.12%）的饮食。小鼠在TAC后研究12周。每隔3周用超声心动图监测心功能和左心室结构。TAC后12周收集心肌组织以评估心脏和血管纤维化，并评估血液样品的心脏BNP、胆碱和TMAO水平。与对照饮食相比，喂食TMAO或胆碱补充饮食的小鼠的肺水肿、心脏扩大和左心室射血分数（LVEF）显著（p < 0.05，各）更差。此外，TMAO和胆碱组的心肌纤维化也显著高于对照组（p < 0.01）。在喂食补充胆碱或肠道微生物依赖性代谢物TMAO的饮食的小鼠中，心力衰竭的严重程度显著增强。目前的结果表明，有必要进一步研究肠道微生物群和饮食胆碱-> TMAO途径是否有助于增加心力衰竭的易感性。
Trimethylamine N-oxide (TMAO), a gut microbe dependent metabolite of dietary choline and other trimethylamine containing nutrients, is both elevated in the circulation of patients suffering from heart failure (HF) and heralds worse overall prognosis. In animal studies, dietary choline or TMAO significantly accelerate atherosclerotic lesion development in ApoE deficient mice, and reduction in TMAO levels inhibits atherosclerosis development in the LDL receptor knockout mouse. C57BL6/J mice were fed either a control diet, a diet containing choline (1.2%) or a diet containing TMAO (0.12%) starting 3 weeks prior to surgical TAC. Mice were studied for 12 weeks following TAC. Cardiac function and left ventricular structure were monitored at 3-week intervals using echocardiography. Twelve weeks post-TAC myocardial tissues were collected to evaluate cardiac and vascular fibrosis, and blood samples were evaluated for cardiac BNP, choline, and TMAO levels. Pulmonary edema, cardiac enlargement, and left ventricular ejection fraction (LVEF) were significantly (p < 0.05, each) worse in mice fed either TMAO or choline supplemented diets compared to the control diet. In addition, myocardial fibrosis was also significantly greater (p < 0.01, each) in the TMAO and choline groups relative to controls. Heart failure severity is significantly enhanced in mice fed diets supplemented in either choline or the gut microbe-dependent metabolite TMAO. The present results suggest that further studies are warranted examining whether gut microbiota and the dietary choline -> TMAO pathway contribute to increased heart failure susceptibility.