Gut microbiota, fatty liver disease, and hepatocellular carcinoma.
Gut microbiota, fatty liver disease, and hepatocellular carcinoma.
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DOI：
10.1016/j.livres.2017.11.005
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发表时间：
2018-03
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：
Chu H;Williams B;Schnabl B
肠道细菌参与了非酒精性脂肪性肝病(NAFLD)的发病机制。最近开发的微生物图谱技术开始揭示伴随NAFLD和非酒精性脂肪性肝炎(NASH)的肠道微生物区系变化的本质。本文就肠道微生物区系在非酒精性脂肪肝、非酒精性脂肪肝和肝细胞癌发生发展中的作用作一综述。我们重点介绍了肠道微生物区系对NAFLD/NASH的作用机制，包括通过改变肠上皮通透性、胆碱代谢、内源性酒精产生、炎性细胞因子的释放、肝脏Toll样受体(TLR)的调节以及胆汁酸代谢。此外，我们还分析了增强肝癌发生的可能机制，包括胆汁酸代谢的改变、炎性细胞因子的释放和TLR-4的表达。最后，我们描述了NAFLD/NASH的治疗方法和肝癌的预防策略，包括调节肠道微生物区系或受影响的宿主路径。虽然最近的研究已经提供了有用的信息，但需要进行大规模的前瞻性研究，以更好地表征肠道微生物区系和代谢组，以证明肠道微生物区系的变化在NAFLD/NASH病因中的致病作用，寻找新的治疗NAFLD/NASH的策略，并开发更有效的预防肝癌的方法。
Intestinal bacteria contribute to the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Recently developed microbial profiling techniques are beginning to shed light on the nature of the changes in the gut microbiota that accompany NAFLD and non-alcoholic steatohepatitis (NASH). In this review, we summarize the role of gut microbiota in the development of NAFLD, NASH, and hepatocellular carcinoma (HCC). We highlight the mechanisms by which gut microbiota contribute to NAFLD/NASH, including through alterations in gut epithelial permeability, choline metabolism, endogenous alcohol production, release of inflammatory cytokines, regulation of hepatic Toll-like receptor (TLR), and bile acid metabolism. In addition, we analyze possible mechanisms for enhanced hepatic carcinogenesis, including alterations in bile acid metabolism, release of inflammatory cytokines, and expression of TLR-4. Finally, we describe therapeutic approaches for NAFLD/NASH and preventive strategies for HCC involving modulation of the intestinal microbiota or affected host pathways. Although recent studies have provided useful information, large-scale prospective studies are required to better characterize the intestinal microbiota and metabolome, in order to demonstrate a causative role for changes in the gut microbiota in the etiology of NAFLD/NASH, to identify new therapeutic strategies for NAFLD/NASH, and to develop more effective methods of preventing HCC.