Department of Pathophysiology and Transplantation, Università degli Studi di Milano, 20122 Milano, Italy.
General Medicine and Metabolic Diseases, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, 20122 Milan, Italy.
Int J Mol Sci. 2019 Sep 14;20(18):4568. doi: 10.3390/ijms20184568.
Alcoholic liver disease (ALD), a disorder caused by excessive alcohol intake represents a global health care burden. ALD encompasses a broad spectrum of hepatic injuries including asymptomatic steatosis, alcoholic steatohepatitis (ASH), fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). The susceptibility of alcoholic patients to develop ALD is highly variable and its progression to more advanced stages is strongly influenced by several hits (i.e., amount and duration of alcohol abuse). Among them, the intestinal microbiota and its metabolites have been recently identified as paramount in ALD pathophysiology. Ethanol abuse triggers qualitative and quantitative modifications in intestinal flora taxonomic composition, mucosal inflammation, and intestinal barrier derangement. Intestinal hypermeability results in the translocation of viable pathogenic bacteria, Gram-negative microbial products, and pro-inflammatory luminal metabolites into the bloodstream, further corroborating the alcohol-induced liver damage. Thus, the premise of this review is to discuss the beneficial effect of gut microbiota modulation as a novel therapeutic approach in ALD management.
酒精性肝病(ALD)是由过量饮酒引起的一种疾病,是全球医疗保健的负担。ALD 包括一系列广泛的肝损伤,包括无症状性脂肪变性、酒精性肝炎(ASH)、纤维化、肝硬化和肝细胞癌(HCC)。酒精性患者发生 ALD 的易感性差异很大,其向更高级阶段的进展受到多种因素的强烈影响(即,酒精滥用的数量和持续时间)。其中,肠道微生物群及其代谢物最近被确定为 ALD 病理生理学中的关键因素。乙醇滥用会导致肠道菌群分类组成、黏膜炎症和肠道屏障紊乱的定性和定量改变。肠道通透性增加导致有活力的致病性细菌、革兰氏阴性微生物产物和促炎腔代谢物易位进入血液,进一步证实了酒精引起的肝损伤。因此,本综述的前提是讨论肠道微生物群调节作为 ALD 管理的一种新的治疗方法的有益效果。