Microbiota Protects Mice Against Acute Alcohol‐Induced Liver Injury

Abstract

Background Chronic alcohol abuse is associated with intestinal bacterial overgrowth, increased intestinal permeability, and translocation of microbial products from the intestine to the portal circulation and liver. Translocated microbial products contribute to experimental alcoholic liver disease. Aim To investigate the physiological relevance of the intestinal microbiota in alcohol-induced liver injury. Methods We subjected germ-free and conventional C57BL/6 mice to a model of acute alcohol exposure that mimics binge drinking. Results Germ-free mice showed significantly greater liver injury and inflammation after oral gavage of ethanol compared with conventional mice. In parallel, germ-free mice exhibited increased hepatic steatosis and upregulated expression of genes involved in fatty acid and triglyceride synthesis compared with conventional mice after acute ethanol administration. The absence of microbiota was also associated with increased hepatic expression of ethanol metabolizing enzymes, which led to faster ethanol elimination from the blood and lower plasma ethanol concentrations. Intestinal levels of ethanol metabolizing genes showed regional expression differences, and were overall higher in germ-free relative to conventional mice. Conclusion Our findings indicate that absence of the intestinal microbiota increases hepatic ethanol metabolism and the susceptibility to binge-like alcohol drinking.

Gut microbiome and liver diseases

“…This fits with recently presented data where Chen et al 57 showed that ALD is aggravated in germ-free mice and in these studies hepatic ethyl alcohol (EtOH) metabolism was enhanced and susceptibility to binge-like alcohol drinking increased. Another exciting research area deals with the key questions how an intact intestinal microbiota is regulated.…”

Changes in the Intestinal Microbiome and Alcoholic and Nonalcoholic Liver Diseases: Causes or Effects?

“…Rodents have also been shown to have increased endotoxemia after binge consumption of ethanol 40 . Interestingly, germ-free mice given an alcohol gavage developed more severe acute alcohol-associated injury than mice with a control microbiome 41 .…”

Critical Roles of Kupffer Cells in the Pathogenesis of Alcoholic Liver Disease: From Basic Science to Clinical Trials

“…To test the roles of gut microbiota in the pathogenesis of acute ALD, the sensitivity to binge drinking (3 g/kg body weight)-induced liver injury was compared between germ-free and conventional C57BL/6 mice (118). Unexpectedly, germ-free mice were found to be more susceptible to binge drinking-induced hepatic fat accumulation, elevation of serum aminotransferase activity, and hepatic inflammation compared with the conventional mice.…”