Microbiota Protects Mice Against Acute Alcohol-Induced Liver Injury

Alcohol Clin Exp Res. 2015 Dec;39(12):2313-23. doi: 10.1111/acer.12900. Epub 2015 Nov 11.


Background: Our aim is to investigate the physiological relevance of the intestinal microbiota in alcohol-induced liver injury. 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.

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 (EtOH) compared with conventional mice. In parallel, germ-free mice exhibited increased hepatic steatosis and up-regulated expression of genes involved in fatty acid and triglyceride synthesis compared with conventional mice after acute EtOH administration. The absence of microbiota was also associated with increased hepatic expression of EtOH-metabolizing enzymes, which led to faster EtOH elimination from the blood and lower plasma EtOH concentrations. Intestinal levels of EtOH-metabolizing genes showed regional expression differences and were overall higher in germ-free mice relative to conventional mice.

Conclusions: Our findings indicate that absence of the intestinal microbiota increases hepatic EtOH metabolism and the susceptibility to binge-like alcohol drinking.

Keywords: Alcoholic Liver Disease; Endotoxin; Microbiome; Microbiota; Steatohepatitis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Binge Drinking / complications
  • Binge Drinking / microbiology
  • Ethanol / toxicity*
  • Female
  • Germ-Free Life / drug effects
  • Germ-Free Life / physiology*
  • Liver Diseases, Alcoholic / etiology
  • Liver Diseases, Alcoholic / microbiology*
  • Liver Diseases, Alcoholic / prevention & control*
  • Mice
  • Mice, Inbred C57BL
  • Microbiota / drug effects
  • Microbiota / physiology*


  • Ethanol