Colitis ameliorates cholestatic liver disease via suppression of bile acid synthesis

Autor(en)

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

Abstrakt

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.

Organisation(en)

Department für Ernährungswissenschaften

Externe Organisation(en)

Sahlgrenska University Hospital, University of Oslo, Oslo University Hospital, Universitätsklinikum Aachen, Leibniz-Institut für Arbeitsforschung an der TU Dortmund, Universitätsklinikum Jena, Helmholtz-Zentrum für Infektionsforschung, Tongji University, University of Gothenburg

Journal

Nature Communications

Band

14

ISSN

2041-1723

Publikationsdatum

06-2023

Peer-reviewed

Ja

ÖFOS 2012

303009 Ernährungswissenschaften

ASJC Scopus Sachgebiete

Allgemeine Physik und Astronomie, Allgemeine Chemie, Allgemeine Biochemie, Genetik und Molekularbiologie

Link zum Portal

https://ucrisportal.univie.ac.at/de/publications/8ea3d00a-9d1e-430d-a7f8-56d6fcdb9fca