Colitis ameliorates cholestatic liver disease via suppression of bile acid synthesis

Wengfang Gui, Mikal Jacob Hole, Antonio Molinaro, Karolina Edlund, Kristin K Jørgensen, Huan Su, Brigitte Begher-Tibbe, Nikolaus Gaßler, Carolin V Schneider, Uthayakumar Muthukumarasamy, Antje Mohs, Lijun Liao, Julius Jaeger, Christian J Mertens, Ina Bergheim, Till Strowig, Jan G Hengstler, Johannes R Hov, Hanns-Ulrich Marschall, Christian Trautwein, Kai Markus Schneider

Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease characterized by chronic inflammation and progressive fibrosis of the biliary tree. The majority of PSC patients suffer from concomitant inflammatory bowel disease (IBD), which has been suggested to promote disease development and progression. However, the molecular mechanisms by which intestinal inflammation may aggravate cholestatic liver disease remain incompletely understood. Here, we employ an IBD-PSC mouse model to investigate the impact of colitis on bile acid metabolism and cholestatic liver injury. Unexpectedly, intestinal inflammation and barrier impairment improve acute cholestatic liver injury and result in reduced liver fibrosis in a chronic colitis model. This phenotype is independent of colitis-induced alterations of microbial bile acid metabolism but mediated via hepatocellular NF-κB activation by lipopolysaccharide (LPS), which suppresses bile acid metabolism in-vitro and in-vivo. This study identifies a colitis-triggered protective circuit suppressing cholestatic liver disease and encourages multi-organ treatment strategies for PSC.

Department für Ernährungswissenschaften
Externe Organisation(en)
Sahlgrenska University Hospital, University of Oslo (UiO), Oslo University Hospital, Universitätsklinikum Aachen, Leibniz-Institut für Arbeitsforschung an der TU Dortmund, Universitätsklinikum Jena, Helmholtz-Zentrum für Infektionsforschung, Tongji University, University of Gothenburg
Nature Communications
ÖFOS 2012
303009 Ernährungswissenschaften
ASJC Scopus Sachgebiete
Physics and Astronomy(all), Chemistry(all), Biochemistry, Genetics and Molecular Biology(all)
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