Role of Gut Microbiota in Liver Disease.
Role of Gut Microbiota in Liver Disease.
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DOI：
10.1097/mcg.0000000000000391
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发表时间：
2015-11
影响因子：
2.9
通讯作者：
Schnabl B
中科院分区：
文献类型：
--
作者：
Brenner DA;Paik YH;Schnabl B
许多研究已经建立了肠道微生物组与肝病患者之间的关系。例如，肝硬化患者的菌血症增加，脂多糖的血液水平增加，肠通透性增加。肝硬化患者的小肠内有细菌过度生长。抗生素选择性肠道去污对失代偿期肝硬化患者有益。在慢性肝损伤伴纤维化的实验模型中，需要几种Toll样受体（TLR）来使小鼠对肝纤维化敏感。TLR的假定配体是源自肠道微生物组的细菌产物，TLR敲除小鼠对肝脏炎症和纤维化具有抗性。我们和其他人已经表征了小鼠肝脏疾病临床前模型与肠道微生物组中微生物多样性之间的关联。在每种模型中，包括胃内酒精、胆管结扎、慢性四氯化碳（CCl 4）、给药和遗传性肥胖，正常对照小鼠的肠道微生物组有显著变化。然而，没有一种明确的细菌菌株或模式可以将肝损伤小鼠与对照小鼠区分开来。那么肠道微生物群如何影响肝脏疾病呢？我们可以确定至少6种可能导致肝损伤、炎症和/或纤维化的变化。这些包括：（1）饮食热量产生的变化;（2）调节肠道通透性以释放细菌产物;（3）调节胆碱代谢;（4）产生内源性乙醇;（5）调节胆汁酸代谢;和（6）调节脂质代谢。
Many lines of research have established a relationship between the gut microbiome and patients with liver disease. For example, patients with cirrhosis have increased bacteremia, increased blood levels of lipopolysaccharide, and increased intestinal permeability. Patients with cirrhosis have bacterial overgrowth in the small intestine. Selective intestinal decontamination with antibiotics is beneficial for patients with decompensated cirrhosis. In experimental models of chronic liver injury with fibrosis, several toll-like receptors (TLR) are required to make mice sensitive to liver fibrosis. The presumed ligand for the TLRs are bacterial products derived from the gut microbiome, and TLR knockout mice are resistant to liver inflammation and fibrosis. We and others have characterized the association between preclinical models of liver disease in mice with the microbial diversity in their gut microbiome. In each model, including intragastric alcohol, bile duct ligation, chronic carbon tetrachloride (CCl 4), administration, and genetic obesity, there is a significant change in the gut microbiome from normal control mice. However, there is not a single clear bacterial strain or pattern that distinguish mice with liver injury from controlled mice. So how can the gut microbiota affect liver disease? We can identify at least 6 changes that would result in liver injury, inflammation, and/or fibrosis. These include:(1) changes in caloric yield of diet;(2) regulation of gut permeability to release bacterial products;(3) modulation of choline metabolism;(4) production of endogenous ethanol;(5) regulation of bile acid metabolism; and (6) regulation in lipid metabolism.