title: Deficiency of intestinal mucin-2 ameliorates experimental alcoholic liver disease in mice.
abstract: The intestinal mucus layer protects the epithelium from noxious agents, viruses, and pathogenic bacteria present in the gastrointestinal tract. It is composed of mucins, predominantly mucin (Muc) 2, secreted by goblet cells of the intestine. Experimental alcoholic liver disease requires translocation of bacterial products across the intestinal barrier into the systemic circulation, which induces an inflammatory response in the liver and contributes to steatohepatitis. We investigated the roles of the intestinal mucus layer, and in particular Muc2, in development of experimental alcohol-associated liver disease in mice. We studied experimental alcohol-induced liver disease, induced by the Tsukamoto-French method (which involves continuous intragastric feeding of an isocaloric diet or alcohol) in wild-type and Muc2(-/-) mice. Muc2(-/-) mice showed less alcohol-induced liver injury and steatosis than developed in wild-type mice. Most notably, Muc2(-/-) mice had significantly lower plasma levels of lipopolysaccharide than wild-type mice after alcohol feeding. In contrast to wild-type mice, Muc2(-/-) mice were protected from alcohol-associated microbiome changes that are dependent on intestinal mucins. The antimicrobial proteins regenerating islet-derived 3 beta and gamma were expressed at significantly higher levels in the jejunum of Muc2(-/-) mice fed the isocaloric diet or alcohol compared with wild-type mice. Consequently, Muc2(-/-) mice showed increased killing of commensal bacteria and prevented intestinal bacterial overgrowth.
  
  
  CONCLUSIONS
  Muc2(-/-) mice are protected from intestinal bacterial overgrowth and dysbiosis in response to alcohol feeding. Subsequently, lower amounts of bacterial products such as endotoxin translocate into the systemic circulation, decreasing liver disease.
authors: Department of Medicine, University of California San Diego, La Jolla, CA, USA.
authors: Phillipp
authors: P
authors: Hartmann
authors: Peng
authors: P
authors: Chen
authors: Hui J
authors: HJ
authors: Wang
authors: Lirui
authors: L
authors: Wang
authors: Declan F
authors: DF
authors: McCole
authors: Katharina
authors: K
authors: Brandl
authors: Peter
authors: P
authors: Stärkel
authors: Clara
authors: C
authors: Belzer
authors: Claus
authors: C
authors: Hellerbrand
authors: Hidekazu
authors: H
authors: Tsukamoto
authors: Samuel B
authors: SB
authors: Ho
authors: Bernd
authors: B
authors: Schnabl
mesh_terms: D000437:Alcoholism / Q000473:pathology; D000818:Animals; D004195:Disease Models, Animal; D000431:Ethanol / Q000378:metabolism; D005234:Fatty Liver / Q000209:etiology / Q000235:genetics; D006801:Humans; D007408:Intestinal Absorption / Q000235:genetics; D007413:Intestinal Mucosa / Q000473:pathology; D007422:Intestines / Q000382:microbiology; D008070:Lipopolysaccharides / Q000097:blood; D008099:Liver / Q000378:metabolism; D008108:Liver Diseases, Alcoholic / Q000209:etiology / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D055262:Mucin-2 / Q000172:deficiency* / Q000502:physiology
chemical_list: D008070:Lipopolysaccharides; D055262:Mucin-2; D000431:Ethanol