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

Lirui Wang, Derrick E. Fouts, Peter Stärkel, Phillipp Hartmann, Peng Chen, Cristina Llorente, Jessica DePew, Kelvin Moncera, Samuel B. Ho, David A. Brenner, Lora V. Hooper, Bernd Schnabl

Research output: Contribution to journalArticle

119 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)227-239
Number of pages13
JournalCell host & microbe
Volume19
Issue number2
DOIs
StatePublished - Feb 10 2016

ASJC Scopus subject areas

  • Molecular Biology
  • Immunology and Microbiology(all)
  • Cancer Research

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    Wang, L., Fouts, D. E., Stärkel, P., Hartmann, P., Chen, P., Llorente, C., DePew, J., Moncera, K., Ho, S. B., Brenner, D. A., Hooper, L. V., & Schnabl, B. (2016). Intestinal REG3 Lectins Protect against Alcoholic Steatohepatitis by Reducing Mucosa-Associated Microbiota and Preventing Bacterial Translocation. Cell host & microbe, 19(2), 227-239. https://doi.org/10.1016/j.chom.2016.01.003