title: The gut microbial profile in patients with primary sclerosing cholangitis is distinct from patients with ulcerative colitis without biliary disease and healthy controls.
abstract: Gut microbiota could influence gut, as well as hepatic and biliary immune responses. We therefore thoroughly characterised the gut microbiota in primary sclerosing cholangitis (PSC) compared with healthy controls (HC) and patients with ulcerative colitis without liver disease.
  
  
  
  We prospectively collected 543 stool samples. After a stringent exclusion process, bacterial DNA was submitted for 16S rRNA gene sequencing. PSC and HC were randomised to an exploration panel or a validation panel, and only significant results (p<0.05, QFDR<0.20) in both panels were reported, followed by a combined comparison of all samples against UC.
  
  
  
  Patients with PSC (N=85) had markedly reduced bacterial diversity compared with HC (N=263, p<0.0001), and a different global microbial composition compared with both HC (p<0.001) and UC (N=36, p<0.01). The microbiota of patients with PSC with and without IBD was similar. Twelve genera separated PSC and HC, out of which 11 were reduced in PSC. However, theVeillonellagenus showed a marked increase in PSC compared with both HC (p<0.0001) and UC (p<0.02). Using receiver operating characteristic analysis,Veillonellaabundance yielded an area under the curve (AUC) of 0.64 to discriminate PSC from HC, while a combination of PSC-associated genera yielded an AUC of 0.78.
  
  
  
  Patients with PSC exhibited a gut microbial signature distinct from both HC and UC without liver disease, but similar in PSC with and without IBD. TheVeillonellagenus, which is also associated with other chronic inflammatory and fibrotic conditions, was enriched in PSC.
authors.affiliation: Norwegian PSC Research Center, Department of Transplantation Medicine Oslo University Hospital Rikshospitalet, Oslo, Norway.|K.G. Jebsen Inflammation Research Centre, University of Oslo, Oslo, Norway.|Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.
authors.forename: Martin
authors.initials: M
authors.lastname: Kummen
authors.affiliation: Norwegian PSC Research Center, Department of Transplantation Medicine Oslo University Hospital Rikshospitalet, Oslo, Norway.|Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.
authors.forename: Kristian
authors.initials: K
authors.lastname: Holm
authors.affiliation: Norwegian PSC Research Center, Department of Transplantation Medicine Oslo University Hospital Rikshospitalet, Oslo, Norway.|Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.
authors.forename: Jarl Andreas
authors.initials: JA
authors.lastname: Anmarkrud
authors.affiliation: Bioinformatics Core Facility, Institute for Medical Informatics, Oslo University Hospital, Oslo, Norway.|Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway.|K.G. Jebsen Cardiac Research Centre and Center for Heart Failure Research, University of Oslo, Oslo, Norway.
authors.forename: Ståle
authors.initials: S
authors.lastname: Nygård
authors.affiliation: Norwegian PSC Research Center, Department of Transplantation Medicine Oslo University Hospital Rikshospitalet, Oslo, Norway.|National Centre for Ultrasound in Gastroenterology, Department of Medicine Haukeland University Hospital, Bergen, Norway.
authors.forename: Mette
authors.initials: M
authors.lastname: Vesterhus
authors.affiliation: Department of Gastroenterology, Oslo University Hospital Ullevål, Oslo, Norway.
authors.forename: Marte L
authors.initials: ML
authors.lastname: Høivik
authors.affiliation: Norwegian PSC Research Center, Department of Transplantation Medicine Oslo University Hospital Rikshospitalet, Oslo, Norway.|K.G. Jebsen Inflammation Research Centre, University of Oslo, Oslo, Norway.|Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Oslo, Norway.
authors.forename: Marius
authors.initials: M
authors.lastname: Trøseid
authors.affiliation: Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
authors.forename: Hanns-Ulrich
authors.initials: HU
authors.lastname: Marschall
authors.affiliation: Norwegian PSC Research Center, Department of Transplantation Medicine Oslo University Hospital Rikshospitalet, Oslo, Norway.|Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
authors.forename: Erik
authors.initials: E
authors.lastname: Schrumpf
authors.affiliation: Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|Department of Gastroenterology, Oslo University Hospital Ullevål, Oslo, Norway.
authors.forename: Bjørn
authors.initials: B
authors.lastname: Moum
authors.affiliation: K.G. Jebsen Cardiac Research Centre and Center for Heart Failure Research, University of Oslo, Oslo, Norway.|Division of Medicine, Akershus University Hospital, Lørenskog, Norway.
authors.forename: Helge
authors.initials: H
authors.lastname: Røsjø
authors.affiliation: K.G. Jebsen Inflammation Research Centre, University of Oslo, Oslo, Norway.|Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.|Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Oslo, Norway.
authors.forename: Pål
authors.initials: P
authors.lastname: Aukrust
authors.affiliation: Norwegian PSC Research Center, Department of Transplantation Medicine Oslo University Hospital Rikshospitalet, Oslo, Norway.|K.G. Jebsen Inflammation Research Centre, University of Oslo, Oslo, Norway.|Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.|Department of Clinical Medicine, University of Bergen, Bergen, Norway.|Section of Gastroenterology, Department of Transplantation Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.
authors.forename: Tom H
authors.initials: TH
authors.lastname: Karlsen
authors.affiliation: Norwegian PSC Research Center, Department of Transplantation Medicine Oslo University Hospital Rikshospitalet, Oslo, Norway.|K.G. Jebsen Inflammation Research Centre, University of Oslo, Oslo, Norway.|Institute of Clinical Medicine, University of Oslo, Oslo, Norway.|Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.|Section of Gastroenterology, Department of Transplantation Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.
authors.forename: Johannes R
authors.initials: JR
authors.lastname: Hov
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D016022:Case-Control Studies; D015209:Cholangitis, Sclerosing / Q000150:complications / Q000188:drug therapy / Q000382:microbiology*; D003093:Colitis, Ulcerative / Q000150:complications / Q000382:microbiology*; D003430:Cross-Sectional Studies; D005243:Feces / Q000382:microbiology; D005260:Female; D000069196:Gastrointestinal Microbiome; D064368:Healthy Volunteers; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012336:RNA, Ribosomal, 16S / Q000032:analysis*; D012372:ROC Curve; D012720:Severity of Illness Index; D014678:Veillonella / Q000302:isolation & purification*; D055815:Young Adult
chemical_list: D012336:RNA, Ribosomal, 16S
keywords: HEPATOBILIARY DISEASE; PRIMARY SCLEROSING CHOLANGITIS