title: Primary sclerosing cholangitis is characterised by intestinal dysbiosis independent from IBD.
abstract: 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.
  
  
  
  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).
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Leuven, Belgium.
authors.forename: João
authors.initials: J
authors.lastname: Sabino
authors.affiliation: Department of Microbiology and Immunology, Laboratory of Molecular Bacteriology, KU Leuven-University of Leuven, Rega Institute for Medical Research, Leuven, Belgium Center for the Biology of Disease, VIB, Leuven, Belgium.
authors.forename: Sara
authors.initials: S
authors.lastname: Vieira-Silva
authors.affiliation: Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Leuven, Belgium.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Machiels
authors.affiliation: Department of Microbiology and Immunology, Laboratory of Molecular Bacteriology, KU Leuven-University of Leuven, Rega Institute for Medical Research, Leuven, Belgium Center for the Biology of Disease, VIB, Leuven, Belgium Department of Microbiology, VUB, Brussels, Belgium.
authors.forename: Marie
authors.initials: M
authors.lastname: Joossens
authors.affiliation: Department of Microbiology and Immunology, Laboratory of Molecular Bacteriology, KU Leuven-University of Leuven, Rega Institute for Medical Research, Leuven, Belgium Center for the Biology of Disease, VIB, Leuven, Belgium.
authors.forename: Gwen
authors.initials: G
authors.lastname: Falony
authors.affiliation: Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Leuven, Belgium.
authors.forename: Vera
authors.initials: V
authors.lastname: Ballet
authors.affiliation: Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Leuven, Belgium.
authors.forename: Marc
authors.initials: M
authors.lastname: Ferrante
authors.affiliation: Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Leuven, Belgium.
authors.forename: Gert
authors.initials: G
authors.lastname: Van Assche
authors.affiliation: Department of Microbiology and Immunology, Center for the Biology of Disease, REGA institute, KU Leuven-VIB, Leuven, Belgium.
authors.forename: Schalk
authors.initials: S
authors.lastname: Van der Merwe
authors.affiliation: Translational Research Center for Gastrointestinal Disorders (TARGID), University of Leuven, Leuven, Belgium.
authors.forename: Severine
authors.initials: S
authors.lastname: Vermeire
authors.affiliation: Department of Microbiology and Immunology, Laboratory of Molecular Bacteriology, KU Leuven-University of Leuven, Rega Institute for Medical Research, Leuven, Belgium Center for the Biology of Disease, VIB, Leuven, Belgium.
authors.forename: Jeroen
authors.initials: J
authors.lastname: Raes
mesh_terms: D000328:Adult; D000368:Aged; D000469:Alkaline Phosphatase / Q000037:antagonists & inhibitors; D001706:Biopsy; D002756:Cholagogues and Choleretics / Q000627:therapeutic use; D015209:Cholangitis, Sclerosing / Q000188:drug therapy / Q000382:microbiology / Q000473:pathology; D003113:Colonoscopy / Q000379:methods; D064806:Dysbiosis / Q000209:etiology / Q000382:microbiology; D016983:Enterococcus / Q000302:isolation & purification / Q000472:pathogenicity; D005243:Feces / Q000382:microbiology*; D005260:Female; D000069196:Gastrointestinal Microbiome / Q000502:physiology; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000382:microbiology / Q000473:pathology; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D013223:Statistics as Topic; D014580:Ursodeoxycholic Acid / Q000627:therapeutic use*
chemical_list: D002756:Cholagogues and Choleretics; D014580:Ursodeoxycholic Acid; D000469:Alkaline Phosphatase
keywords: INTESTINAL MICROBIOLOGY; PRIMARY SCLEROSING CHOLANGITIS