Colitis ameliorates cholestatic liver disease via suppression of bile acid synthesis

Wenfang 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 () and Kai Markus Schneider ()
Additional contact information
Wenfang Gui: University Hospital RWTH Aachen
Mikal Jacob Hole: Oslo University Hospital and University of Oslo
Antonio Molinaro: Sahlgrenska University Hospital
Karolina Edlund: Technical University Dortmund
Kristin K. Jørgensen: Oslo University Hospital, Rikshospitalet
Huan Su: University Hospital RWTH Aachen
Brigitte Begher-Tibbe: Technical University Dortmund
Nikolaus Gaßler: University Hospital
Carolin V. Schneider: University Hospital RWTH Aachen
Uthayakumar Muthukumarasamy: Helmholtz Centre for Infection Research, Braunschweig, Germany and Centre for Individualised Infection Medicine (CiiM), a joint venture between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH)
Antje Mohs: University Hospital RWTH Aachen
Lijun Liao: University Hospital RWTH Aachen
Julius Jaeger: University Hospital RWTH Aachen
Christian J. Mertens: University Hospital RWTH Aachen
Ina Bergheim: University of Vienna
Till Strowig: Helmholtz Centre for Infection Research, Braunschweig, Germany and Centre for Individualised Infection Medicine (CiiM), a joint venture between the Helmholtz-Centre for Infection Research (HZI) and the Hannover Medical School (MHH)
Jan G. Hengstler: Technical University Dortmund
Johannes R. Hov: Oslo University Hospital and University of Oslo
Hanns-Ulrich Marschall: University of Gothenburg
Christian Trautwein: University Hospital RWTH Aachen
Kai Markus Schneider: University Hospital RWTH Aachen

Nature Communications, 2023, vol. 14, issue 1, 1-17

Abstract: Abstract 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.

Date: 2023
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-023-38840-8 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38840-8

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-023-38840-8

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().