Steatohepatitis/Metabolic Liver Disease
Article first published online: 10 DEC 2010
Copyright © 2010 American Association for the Study of Liver Diseases
Volume 53, Issue 1, pages 96–105, January 2011
How to Cite
Yan, A. W., E. Fouts, D., Brandl, J., Stärkel, P., Torralba, M., Schott, E., Tsukamoto, H., E. Nelson, K., A. Brenner, D. and Schnabl, B. (2011), Enteric dysbiosis associated with a mouse model of alcoholic liver disease. Hepatology, 53: 96–105. doi: 10.1002/hep.24018
Supported in part by National Institutes of Health grants K08 DK081830 (to B. S.) and RO1 DK072237 (to D. A. B.). This study was also supported by the Pilot Project Program of the Southern California Research Center for Alcoholic Liver and Pancreatic Diseases and Cirrhosis (P50AA11999) funded by the National Institute on Alcohol Abuse and Alcoholism (to B. S.).
Potential conflict of interest: Nothing to report.
- Issue published online: 12 JAN 2011
- Article first published online: 10 DEC 2010
- Accepted manuscript online: 30 SEP 2010 09:16AM EST
- Manuscript Accepted: 7 SEP 2010
- Manuscript Received: 9 FEB 2010
- National Institutes of Health. Grant Numbers: K08 DK081830, RO1 DK072237
- National Institute on Alcohol Abuse and Alcoholism. Grant Number: P50AA11999
The translocation of bacteria and bacterial products into the circulation contributes to alcoholic liver disease. Intestinal bacterial overgrowth is common in patients with alcoholic liver disease. The aims of our study were to investigate bacterial translocation, changes in the enteric microbiome, and its regulation by mucosal antimicrobial proteins in alcoholic liver disease. We used a mouse model of continuous intragastric feeding of alcohol or an isocaloric diet. Bacterial translocation occurred prior to changes observed in the microbiome. Quantitative changes in the intestinal microflora of these animals were assessed first using conventional culture techniques in the small and large intestine. Although we found no difference after 1 day or 1 week, intestinal bacterial overgrowth was observed in the gastrointestinal tract of mice fed alcohol for 3 weeks compared with control mice fed an isocaloric liquid diet. Because <20% of all gastrointestinal bacteria can be cultured using conventional methodologies, we performed massively parallel pyrosequencing to further assess the qualitative changes in the intestinal microbiome following alcohol exposure. Sequencing of 16S ribosomal RNA genes revealed a relative abundance of Bacteroidetes and Verrucomicrobia bacteria in mice fed alcohol compared with a relative predominance of Firmicutes bacteria in control mice. With respect to the host's transcriptome, alcohol feeding was associated with down-regulation in gene and protein expression of bactericidal c-type lectins Reg3b and Reg3g in the small intestine. Treatment with prebiotics partially restored Reg3g protein levels, reduced bacterial overgrowth, and lessened alcoholic steatohepatitis. Conclusion: Alcohol feeding is associated with intestinal bacterial overgrowth and enteric dysbiosis. Intestinal antimicrobial molecules are dysregulated following chronic alcohol feeding contributing to changes in the enteric microbiome and to alcoholic steatohepatitis. (HEPATOLOGY 2011)