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Microbiome-liver crosstalk:A multihit therapeutic target for liver disease

World Journal of Gastroenterology 2023年第11期29卷 1651-1668页

作者： Jorum Kirundi Sheida Moghadamrad Camilla Urbaniak Department of Biomedical Research University of BernBern 3014Switzerland Department of Gastroenterology/Hepatology Laboratories for Translational ResearchEnte Ospedaliero CantonaleBellinzona and Faculty of Biomedical SciencesUniversitàdella Svizzera italianaLugano 6900Switzerland Biotechnology and Planetary Protection Group NASA Jet Propulsion LaboratoryPasadenaCA 91011United States ZIN Technologies Middleburg HeightsOH 44130United States

Liver disease has become a leading cause of death,particularly in the West,where it is attributed to more than two million deaths annually.The correlation between gut microbiota and liver disease is still not fully understood.However,it is well known that gut dysbiosis accompanied by a leaky gut causes an increase in lipopolysaccharides in circulation,which in turn evoke massive hepatic inflammation promoting liver cirrhosis.Microbial dysbiosis also leads to poor bile acid metabolism and low short-chain fatty acids,all of which exacerbate the inflammatory response of liver cells.Gut microbial homeostasis is maintained through intricate processes that ensure that commensal microbes adapt to the low oxygen potential of the gut and that they rapidly occupy all the intestinal niches,thus outcompeting any potential pathogens for available nutrients.The crosstalk between the gut microbiota and its metabolites also guarantee an intact gut barrier.These processes that protect against destabilization of gut microbes by potential entry of pathogenic bacteria are collectively called colonization resistance and are equally essential for liver health.In this review,we shall investigate how the mechanisms of colonization resistance influence the liver in health and disease and the microbial-liver crosstalk potential as therapeutic target areas.

关键词： Microbiome Nonalcoholic fatty liver disease Nonalcoholic steatohepatitis Liver disease Microbiome-host crosstalk Gut homeostasis Microbial metabolites

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