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Gut-liver axis and sterile signals in the development of alcoholic liver disease.

ABSTRACT: Innate immunity plays a critical role in the development of alcohol-induced liver inflammation. Understanding the inter-relationship of signals from within and outside of the liver that trigger liver inflammation is pivotal for development of novel therapeutic targets of alcoholic liver disease (ALD).The aim of this paper is to review recent advances in the field of alcohol-induced liver inflammation.A detailed literature review was performed using the PubMed database published between January 1980 and December 2016.We provide an update on the role of intestinal microbiome, metabolome and the gut-liver axis in ALD, discuss the growing body of evidence on the diversity of liver macrophages and their differential contribution to alcohol-induced liver inflammation, and highlight the crucial role of inflammasomes in integration of inflammatory signals in ALD. Studies to date have identified a multitude of new therapeutic targets, some of which are currently being tested in patients with severe alcoholic hepatitis. These treatments aim to strengthen the intestinal barrier, ameliorate liver inflammation and augment hepatocyte regeneration.Given the complexity of inflammation in ALD, multiple pathobiological mechanisms may need to be targeted at the same time as it seems unlikely that there is a single dominant pathogenic pathway in ALD that would be easily targeted using a single target drug approach.Here, we focus on recent advances in immunopathogenesis of alcoholic liver disease (ALD), including gut-liver axis, hepatic macrophage activation, sterile inflammation and synergy between bacterial and sterile signals. We propose a multiple parallel hit model of inflammation in ALD and discuss its implications for clinical trials in alcoholic hepatitis.

SUBMITTER: Szabo G

PROVIDER: S-EPMC5860369 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Gut-liver axis and sterile signals in the development of alcoholic liver disease.

Szabo Gyongyi G Petrasek Jan J

Alcohol and alcoholism (Oxford, Oxfordshire) 20170701 4

<h4>Background</h4>Innate immunity plays a critical role in the development of alcohol-induced liver inflammation. Understanding the inter-relationship of signals from within and outside of the liver that trigger liver inflammation is pivotal for development of novel therapeutic targets of alcoholic liver disease (ALD).<h4>Aim</h4>The aim of this paper is to review recent advances in the field of alcohol-induced liver inflammation.<h4>Methods</h4>A detailed literature review was performed using ...[more]

PMID: 28482064

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Project description:IntroductionNon-alcoholic fatty liver disease (NAFLD) with obesity seriously threats public health. Our previous studies showed that dark tea had more potential on regulating lipid metabolism than other teas, and theabrownin (TB) was considered to be a main contributor to the bioactivity of dark tea.ObjectivesThis in vivo study aims to reveal the effects and molecular mechanisms of TB on NAFLD and obesity, and the role of the gut-liver axis is explored.MethodsThe histopathological examinations, biochemical tests, and nuclear magnetic resonance were applied to evaluate the effects of TB on NAFLD and obesity. The untargeted metabolomics was used to find the key molecule for further exploration of molecular mechanisms. The 16S rRNA gene sequencing was used to assess the changes in gut microbiota. The antibiotic cocktail and fecal microbiota transplant were used to clarify the role of gut microbiota.ResultsTB markedly reduced body weight gain (67.01%), body fat rate (62.81%), and hepatic TG level (51.35%) in the preventive experiment. Especially, TB decreased body weight (32.16%), body fat rate (42.56%), and hepatic TG level (42.86%) in the therapeutic experiment. The mechanisms of action could be the improvement of fatty acid oxidation, lipolysis, and oxidative stress via the regulation of serotonin-related signaling pathways. Also, TB increased the abundance of serotonin-related gut microbiota, such as Akkermansia, Bacteroides and Parabacteroides. Antibiotics-induced gut bacterial dysbiosis disrupted the regulation of TB on serotonin-related signaling pathways in liver, whereas the beneficial regulation of TB on target proteins was regained with the restoration of gut microbiota.ConclusionWe find that TB has markedly preventive and therapeutic effects on NAFLD and obesity by regulating serotonin level and related signaling pathways through gut microbiota. Furthermore, gut microbiota and TB co-contribute to alleviating NAFLD and obesity. TB could be a promising medicine for NAFLD and obesity.

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Gut-liver axis and sterile signals in the development of alcoholic liver disease.

Publications

Gut-liver axis and sterile signals in the development of alcoholic liver disease.

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