title: The mucosa-associated microbiota of PSC patients is characterized by low diversity and low abundance of uncultured Clostridiales II.
abstract: BACKGROUND
  Primary sclerosing cholangitis (PSC) is a cholestatic liver disease that is strongly associated with a particular phenotype of inflammatory bowel disease (IBD) with right-sided colonic involvement. In IBD, several studies demonstrated significant aberrancies in the intestinal microbiota in comparison with healthy controls. We aimed to explore the link between IBD and PSC by studying the intestinal mucosa-adherent microbiota in PSC and ulcerative colitis (UC) patients and noninflammatory controls.
  
  
  METHODS
  We included 12 PSC patients, 11 UC patients, and nine noninflammatory controls. The microbiota composition was determined in ileocecal biopsies from each patient by 16S rRNA-based analyses using the human intestinal tract chip.
  
  
  RESULTS
  Profiling of the mucosa-adherent microbiota of PSC patients, UC patients, and noninflammatory controls revealed that these groups did not cluster separately based on microbiota composition. At the genus-like level, the relative abundance of uncultured Clostridiales II was significantly lower (almost 2-fold) in PSC (0.26 ± 0.10%) compared with UC (0.41 ± 0.29%) and controls (0.49 ± 0.25%) (p = 0.02). Diversity and richness in the microbiota composition differed across the groups and were significantly lower in PSC patients compared with noninflammatory controls (p = 0.04 and p = 0.02, respectively). No significant differences were found in evenness.
  
  
  CONCLUSIONS
  Reduced amounts of uncultured Clostridiales II in PSC biopsies in comparison with UC and healthy controls can be considered a signature of a compromised gut, as we have recently observed that this group of as yet uncultured Firmicutes correlates significantly with health.
authors.affiliation: Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands c.y.ponsioen@amc.uva.nl.
authors.forename: Noortje G
authors.initials: NG
authors.lastname: Rossen
authors.affiliation: Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands.
authors.forename: Susana
authors.initials: S
authors.lastname: Fuentes
authors.affiliation: Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Boonstra
authors.affiliation: Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands.
authors.forename: Geert R
authors.initials: GR
authors.lastname: D'Haens
authors.affiliation: Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands.
authors.forename: Hans G
authors.initials: HG
authors.lastname: Heilig
authors.affiliation: Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands.
authors.forename: Erwin G
authors.initials: EG
authors.lastname: Zoetendal
authors.affiliation: Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands Departments of Bacteriology & Immunology and Veterinary Biosciences, University of Helsinki, Finland.
authors.forename: Willem M
authors.initials: WM
authors.lastname: de Vos
authors.affiliation: Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands c.y.ponsioen@amc.uva.nl.
authors.forename: Cyriel Y
authors.initials: CY
authors.lastname: Ponsioen
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D015209:Cholangitis, Sclerosing / Q000175:diagnosis / Q000209:etiology*; D000068016:Eubacteriales / Q000235:genetics / Q000302:isolation & purification*; D003093:Colitis, Ulcerative / Q000150:complications* / Q000175:diagnosis; D003113:Colonoscopy; D003430:Cross-Sectional Studies; D005260:Female; D016908:Gram-Positive Bacterial Infections / Q000150:complications* / Q000382:microbiology; D006801:Humans; D007413:Intestinal Mucosa / Q000382:microbiology* / Q000473:pathology; D008297:Male; D064307:Microbiota; D008875:Middle Aged; D012329:RNA, Bacterial / Q000032:analysis; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D012329:RNA, Bacterial
keywords: Primary sclerosing cholangitis; inflammatory bowel disease; intestinal microbiota