Document Detail


Deficiency of intestinal mucin-2 ameliorates experimental alcoholic liver disease in mice.
MedLine Citation:
PMID:  23408358     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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. Conclusion: 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:
Phillipp Hartmann; Peng Chen; Hui J Wang; Lirui Wang; Declan F McCole; Katharina Brandl; Peter Stärkel; Clara Belzer; Claus Hellerbrand; Hidekazu Tsukamoto; Samuel B Ho; Bernd Schnabl
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2013-05-27
Journal Detail:
Title:  Hepatology (Baltimore, Md.)     Volume:  58     ISSN:  1527-3350     ISO Abbreviation:  Hepatology     Publication Date:  2013 Jul 
Date Detail:
Created Date:  2013-06-26     Completed Date:  2013-08-30     Revised Date:  2014-07-02    
Medline Journal Info:
Nlm Unique ID:  8302946     Medline TA:  Hepatology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  108-19     Citation Subset:  IM    
Copyright Information:
Copyright © 2013 American Association for the Study of Liver Diseases.
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MeSH Terms
Descriptor/Qualifier:
Alcoholism / pathology
Animals
Disease Models, Animal
Ethanol / metabolism
Fatty Liver / etiology,  genetics
Humans
Intestinal Absorption / genetics
Intestinal Mucosa / pathology
Intestines / microbiology
Lipopolysaccharides / blood
Liver / metabolism
Liver Diseases, Alcoholic / etiology,  genetics*
Male
Mice
Mice, Inbred C57BL
Mucin-2 / deficiency*,  physiology
Grant Support
ID/Acronym/Agency:
DK080506/DK/NIDDK NIH HHS; K08 DK081830/DK/NIDDK NIH HHS; K08 DK081830/DK/NIDDK NIH HHS; P50AA11999/AA/NIAAA NIH HHS; R01 AA020703/AA/NIAAA NIH HHS; R01 AA020703/AA/NIAAA NIH HHS; R24 DK080506/DK/NIDDK NIH HHS; U01 AA021856/AA/NIAAA NIH HHS; UH2 AA019708/AA/NIAAA NIH HHS
Chemical
Reg. No./Substance:
0/Lipopolysaccharides; 0/Mucin-2; 3K9958V90M/Ethanol
Comments/Corrections

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