Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India.
Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India.
J Hepatol. 2019 Feb;70(2):260-272. doi: 10.1016/j.jhep.2018.10.019.
Alcohol-related liver disease is associated with significant changes in gut microbial composition. The transmissibility of ethanol-induced liver disease has been demonstrated using faecal microbiota transfer in preclinical models. This technique has also led to improved survival in patients with severe alcoholic hepatitis, suggesting that changes in the composition and function of the gut microbiota are causatively linked to alcohol-related liver disease. A major mechanism by which gut microbiota influence the development of alcohol-related liver disease is through a leaky intestinal barrier. This permits translocation of viable bacteria and microbial products to the liver, where they induce and promote inflammation, as well as contribute to hepatocyte death and the fibrotic response. In addition, gut dysbiosis is associated with changes in the metabolic function of the intestinal microbiota, bile acid composition and circulation, immune dysregulation during onset and progression of alcohol-related liver disease. Findings from preclinical and human studies will be used to demonstrate how alcohol causes intestinal pathology and contributes to alcohol-related liver disease and how the latter is self-perpetuating. Additionally, we summarise the effects of untargeted treatment approaches on the gut microbiota, such as diet, probiotics, antibiotics and faecal microbial transplantation in alcohol-related liver disease. We further discuss how targeted approaches can restore intestinal homeostasis and improve alcohol-related liver disease. These approaches are likely to add to the therapeutic options for alcohol-related liver disease independently or in conjunction with steroids.
酒精性肝病与肠道微生物组成的显著变化有关。使用临床前模型中的粪便微生物转移已经证明了乙醇诱导的肝病具有传染性。这项技术还提高了严重酒精性肝炎患者的存活率，表明肠道微生物组成和功能的变化与酒精性肝病有因果关系。肠道微生物影响酒精性肝病发展的一个主要机制是通过肠漏。这允许活细菌和微生物产物易位到肝脏，在肝脏中它们诱导和促进炎症，以及导致肝细胞死亡和纤维化反应。此外，肠道菌群失调与酒精性肝病发生和进展期间肠道微生物代谢功能、胆汁酸组成和循环、免疫失调的变化有关。临床前和人体研究的结果将用于证明酒精如何导致肠道病理学，并导致酒精性肝病，以及后者如何自我延续。此外，我们总结了非靶向治疗方法（如饮食、益生菌、抗生素和粪便微生物移植）对肠道微生物群的影响在酒精性肝病中的作用。我们进一步讨论了靶向方法如何恢复肠道内稳态并改善酒精性肝病。这些方法可能会增加酒精性肝病的治疗选择，无论是独立使用还是与类固醇联合使用。
