Microbiota Protects Mice Against Acute Alcohol-Induced Liver Injury.
Microbiota Protects Mice Against Acute Alcohol-Induced Liver Injury.
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DOI：
10.1111/acer.12900
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发表时间：
2015-12
期刊：
影响因子：
--
通讯作者：
Schnabl B
中科院分区：
文献类型：
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作者：
Chen P;Miyamoto Y;Mazagova M;Lee KC;Eckmann L;Schnabl B
慢性酒精滥用与肠道细菌过度生长、肠道通透性增加以及微生物产物从肠道转移到门脉循环和肝脏有关。移位的微生物产物导致实验性酒精性肝病。探讨肠道微生物区系在酒精性肝损伤中的生理学意义。我们对无菌和常规的C57BL/6小鼠进行了急性酒精暴露的模型，模拟酗酒。与常规小鼠相比，无菌小鼠在口服乙醇后表现出明显更严重的肝脏损伤和炎症。与常规小鼠相比，无菌小鼠在急性酒精注射后，肝脏脂肪变性加重，与脂肪酸和甘油三酯合成相关的基因表达上调。微生物区系的缺乏也与肝脏乙醇代谢酶表达增加有关，这导致血液中乙醇更快地消除，并降低了血浆乙醇浓度。肠道中乙醇代谢基因的表达水平存在区域性差异，无菌小鼠的总体表达水平高于常规小鼠。我们的发现表明，肠道微生物区系的缺失增加了肝脏乙醇代谢，增加了酗酒的易感性。
Chronic alcohol abuse is associated with intestinal bacterial overgrowth, increased intestinal permeability, and translocation of microbial products from the intestine to the portal circulation and liver. Translocated microbial products contribute to experimental alcoholic liver disease. To investigate the physiological relevance of the intestinal microbiota in alcohol-induced liver injury. We subjected germ-free and conventional C57BL/6 mice to a model of acute alcohol exposure that mimics binge drinking. Germ-free mice showed significantly greater liver injury and inflammation after oral gavage of ethanol compared with conventional mice. In parallel, germ-free mice exhibited increased hepatic steatosis and upregulated expression of genes involved in fatty acid and triglyceride synthesis compared with conventional mice after acute ethanol administration. The absence of microbiota was also associated with increased hepatic expression of ethanol metabolizing enzymes, which led to faster ethanol elimination from the blood and lower plasma ethanol concentrations. Intestinal levels of ethanol metabolizing genes showed regional expression differences, and were overall higher in germ-free relative to conventional mice. Our findings indicate that absence of the intestinal microbiota increases hepatic ethanol metabolism and the susceptibility to binge-like alcohol drinking.