title: Characterization of Intestinal Microbiota in Ulcerative Colitis Patients with and without Primary Sclerosing Cholangitis.
abstract: OBJECTIVE
  There is an unexplained association between ulcerative colitis [UC] and primary sclerosing cholangitis [PSC], with the intestinal microbiota implicated as an important factor. The study aim was to compare the structure of the intestinal microbiota of patients with UC with and without PSC.
  
  
  METHODS
  UC patients with PSC [PSC-UC] and without PSC [UC] were identified from biobanks at Oslo University Hospital, Foothills Hospital Calgary and Mount Sinai Hospital Toronto. Microbial DNA was extracted from colonic tissue and sequencing performed of the V4 region of the 16S rRNA gene on Illumina MiSeq. Sequences were assigned to operational taxonomic units [OTUs] using Quantitative Insights Into Microbial Ecology [QIIME]. Microbial alpha diversity, beta diversity, and relative abundance were compared between PSC-UC and UC phenotypes.
  
  
  RESULTS
  In all, 31 PSC-UC patients and 56 UC patients were included. Principal coordinate analysis [PCoA] demonstrated that city of sample collection was the strongest determinant of taxonomic profile. In the Oslo cohort, Chao 1 index was modestly decreased in PSC-UC compared with UC [p = 0.04] but did not differ significantly in the Calgary cohort. No clustering by PSC phenotype was observed using beta diversity measures. For multiple microbial genera there were nominally significant differences between UC and PSC-UC, but results were not robust to false-discovery rate correction.
  
  
  CONCLUSIONS
  No strong PSC-specific microbial associations in UC patients consistent across different cohorts were identified. Recruitment centre had a strong effect on microbial composition. Future studies should include larger cohorts to increase power and the ability to control for confounding factors.
authors.affiliation: Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital IBD Group, Toronto, ON, Canada Division of Gastroenterology, Department of Medicine, University of Toronto, Toronto, ON, Canada.
authors.forename: D
authors.initials: D
authors.lastname: Kevans
authors.affiliation: Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital IBD Group, Toronto, ON, Canada.
authors.forename: A D
authors.initials: AD
authors.lastname: Tyler
authors.affiliation: Norwegian PSC Research Center, Oslo University Hospital, Oslo, Norway.
authors.forename: K
authors.initials: K
authors.lastname: Holm
authors.affiliation: Norwegian PSC Research Center, Oslo University Hospital, Oslo, Norway Department of Gastroenterology, Akershus University Hospital, Lørenskog, Norway.
authors.forename: K K
authors.initials: KK
authors.lastname: Jørgensen
authors.affiliation: Institute of Clinical Epidemiology and Molecular Biology [EpiGen], University of Oslo, Oslo, Norway K. G. Jebsen Inflammation Research Centre, University of Oslo, Oslo, Norway.
authors.forename: M H
authors.initials: MH
authors.lastname: Vatn
authors.affiliation: Norwegian PSC Research Center, Oslo University Hospital, Oslo, Norway Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway.
authors.forename: T H
authors.initials: TH
authors.lastname: Karlsen
authors.affiliation: Department of Medicine, University of Calgary, Calgary, AB, Canada.
authors.forename: G G
authors.initials: GG
authors.lastname: Kaplan
authors.affiliation: Department of Medicine, University of Calgary, Calgary, AB, Canada.
authors.forename: B
authors.initials: B
authors.lastname: Eksteen
authors.affiliation: Broad Institute of MIT and Harvard, Cambridge, MA, USA.
authors.forename: D
authors.initials: D
authors.lastname: Gevers
authors.affiliation: Norwegian PSC Research Center, Oslo University Hospital, Oslo, Norway Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway.
authors.forename: J R
authors.initials: JR
authors.lastname: Hov
authors.affiliation: Zane Cohen Centre for Digestive Diseases, Mount Sinai Hospital IBD Group, Toronto, ON, Canada Division of Gastroenterology, Department of Medicine, University of Toronto, Toronto, ON, Canada msilverberg@mtsinai.on.ca.
authors.forename: M S
authors.initials: MS
authors.lastname: Silverberg
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D044822:Biodiversity; D016022:Case-Control Studies; D002648:Child; D015209:Cholangitis, Sclerosing / Q000150:complications / Q000382:microbiology*; D003093:Colitis, Ulcerative / Q000150:complications / Q000382:microbiology*; D005260:Female; D000069196:Gastrointestinal Microbiome; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D025341:Principal Component Analysis; D055815:Young Adult
keywords: PSC; intestinal microbiota; next generation sequencing