Liver tissue microbiota in nonalcoholic liver disease:a change in the paradigm of host-bacterial interactions  

作　　者：Silvia Sookoian Carlos J.Pirola 

机构地区：[1]School of Medicine,Institute of Medical Research A Lanari,University of Buenos Aires,Ciudad Autónoma de Buenos Aires,Argentina [2]Department of Clinical and Molecular Hepatology,Institute of Medical Research(IDIM),National Scientific and Technical Research Council(CONICET),University of Buenos Aires,Ciudad Autónoma de Buenos Aires,Argentina [3]Department of Molecular Genetics and Biology of Complex Diseases,Institute of Medical Research(IDIM),National Scientific and Technical Research Council(CONICET),University of Buenos Aires,Ciudad Autónoma de Buenos Aires,Argentina

出　　处：《Hepatobiliary Surgery and Nutrition》2021年第3期337-349,共13页肝胆外科与营养（英文）

基　　金：This study was partially supported by grants PID-C2012-0061,PICT 2014-0432,PICT 2014-1816,PICT 2015-0551;PICT 2016-0135(Agencia Nacional de Promoción Científica y Tecnológica,FONCyT),CONICET Proyectos Unidades Ejecutoras 2017,PUE 0055.

摘　　要：Nonalcoholic fatty liver disease(NAFLD)pathogenesis is explained by the complex relationship among diet and lifestyle-predisposing factors,the genetic variance of the nuclear and mitochondrial genome,associated phenotypic traits,and the yet not fully explored interactions with epigenetic and other environmental factors,including the microbiome.Despite the wealth of knowledge gained from molecular and genome-wide investigations in patients with NAFLD,the precise mechanisms that explain the variability of the histological phenotypes are not fully understood.Earlier studies of the gut microbiota in patients with NAFLD and nonalcoholic steatohepatitis(NASH)provided clues on the role of the fecal microbiome in the disease pathogenesis.Nevertheless,the composition of the gut microbiota does not fully explain tissue-specific mechanisms associated with the degree of disease severity,including liver inflammation,ballooning of hepatocytes,and fibrosis.The liver acts as a key filtration system of the whole body by receiving blood from the hepatic artery and the portal vein.Therefore,not only microbes would become entrapped in the complex liver anatomy but,more importantly,bacterial derived products that are likely to be potentially powerful stimuli for initiating the inflammatory response.Hence,the study of liver tissue microbiota offers the opportunity of changing the paradigm of host-NAFLD-microbial interactions from a“gut-centric”to a“liver-centric”approach.Here,we highlight the evidence on the role of liver tissue bacterial DNA in the biology of NAFLD and NASH.Besides,we provide evidence of metagenomic findings that can serve as the seed of further hypothesis-raising studies as well as can be leveraged to discover novel therapeutic targets.

关 键 词：Nonalcoholic fatty liver disease(NAFLD) nonalcoholic steatohepatitis(NASH) HSD17B13 MICROBIOTA MICROBIOME PROTEOBACTERIA lipopolysaccharide(LPS) drug prediction 

分 类 号：R57[医药卫生—消化系统]