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Original article
Primary sclerosing cholangitis is characterised by intestinal dysbiosis independent from IBD
  1. João Sabino1,
  2. Sara Vieira-Silva2,3,
  3. Kathleen Machiels1,
  4. Marie Joossens2,3,4,
  5. Gwen Falony2,3,
  6. Vera Ballet1,
  7. Marc Ferrante1,
  8. Gert Van Assche1,
  9. Schalk Van der Merwe5,
  10. Severine Vermeire1,
  11. Jeroen Raes2,3
    1. 1Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Leuven, Belgium
    2. 2Department of Microbiology and Immunology, Laboratory of Molecular Bacteriology, KU Leuven—University of Leuven, Rega Institute for Medical Research, Leuven, Belgium
    3. 3Center for the Biology of Disease, VIB, Leuven, Belgium
    4. 4Department of Microbiology, VUB, Brussels, Belgium
    5. 5Department of Microbiology and Immunology, Center for the Biology of Disease, REGA institute, KU Leuven—VIB, Leuven, Belgium
    6. 6Department of Hepatology, KU Leuven, Leuven, Belgium
    1. Correspondence to Jeroen Raes, Laboratorium Moleculaire Bacteriologie (Rega Instituut), O&N I Herestraat 49—bus 1028, Leuven 3000, Belgium; jeroen.raes{at}


    Objective Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease often leading to end-stage liver disease. Its pathogenesis remains largely unknown, although frequent concomitant IBD hints towards common factors underlying gut and bile duct inflammation. Considering the mounting evidence on the involvement of the intestinal microbiota in initiating and determining IBD phenotype, we investigated intestinal microbiota composition in patients with PSC.

    Design Stool samples were collected from 147 individuals (52 patients with PSC, 52 age, gender and body mass index-matched healthy volunteers, 13 UC and 30 patients with Crohn's disease). An independent validation cohort of 14 PSC and 14 matched controls was recruited. 16S rDNA sequencing of faecal DNA was performed (Illumina MiSeq).

    Results The microbiota of patients with PSC was characterised by decreased microbiota diversity, and a significant overrepresentation of Enterococcus (p=3.76e-05), Fusobacterium (p=3.76e-05) and Lactobacillus (p=0.0002) genera. This dysbiosis was present in patients with PSC with and without concomitant IBD and was distinct from IBD, and independent of treatment with ursodeoxycholic acid. A decision tree based on abundances of these three genera allowed reliable classification in the validation cohort. In particular, one operational taxonomic unit belonging to the Enterococcus genus was associated with increased levels of serum alkaline phosphatase (p=0.048), a marker of disease severity.

    Conclusions We here present the first report of PSC-associated faecal dysbiosis, independent from IBD signatures, suggesting the intestinal microbiota could be a contributing factor in PSC pathogenesis. Further studies are needed to confirm these findings and assess causality.


    This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:

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