Format

Send to

Choose Destination
Cell Host Microbe. 2016 Feb 10;19(2):227-39. doi: 10.1016/j.chom.2016.01.003.

Intestinal REG3 Lectins Protect against Alcoholic Steatohepatitis by Reducing Mucosa-Associated Microbiota and Preventing Bacterial Translocation.

Author information

1
Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA; Department of Medicine, VA San Diego Healthcare System, San Diego, CA 92161, USA.
2
J. Craig Venter Institute, Rockville, MD 20850, USA.
3
St. Luc University Hospital, Université Catholique de Louvain, Brussels 1200, Belgium.
4
Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA.
5
Howard Hughes Medical Institute; Department of Immunology, The University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
6
Department of Medicine, University of California San Diego, La Jolla, CA 92093, USA; Department of Medicine, VA San Diego Healthcare System, San Diego, CA 92161, USA. Electronic address: beschnabl@ucsd.edu.

Abstract

Approximately half of all deaths from liver cirrhosis, the tenth leading cause of mortality in the United States, are related to alcohol use. Chronic alcohol consumption is accompanied by intestinal dysbiosis and bacterial overgrowth, yet little is known about the factors that alter the microbial composition or their contribution to liver disease. We previously associated chronic alcohol consumption with lower intestinal levels of the antimicrobial-regenerating islet-derived (REG)-3 lectins. Here, we demonstrate that intestinal deficiency in REG3B or REG3G increases numbers of mucosa-associated bacteria and enhances bacterial translocation to the mesenteric lymph nodes and liver, promoting the progression of ethanol-induced fatty liver disease toward steatohepatitis. Overexpression of Reg3g in intestinal epithelial cells restricts bacterial colonization of mucosal surfaces, reduces bacterial translocation, and protects mice from alcohol-induced steatohepatitis. Thus, alcohol appears to impair control of the mucosa-associated microbiota, and subsequent breach of the mucosal barrier facilitates progression of alcoholic liver disease.

PMID:
26867181
PMCID:
PMC4786170
DOI:
10.1016/j.chom.2016.01.003
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center