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Original article
The gut microbial profile in patients with primary sclerosing cholangitis is distinct from patients with ulcerative colitis without biliary disease and healthy controls
  1. Martin Kummen1,2,3,4,
  2. Kristian Holm1,4,
  3. Jarl Andreas Anmarkrud1,4,
  4. Ståle Nygård5,6,7,
  5. Mette Vesterhus1,8,
  6. Marte L Høivik9,
  7. Marius Trøseid1,2,10,
  8. Hanns-Ulrich Marschall11,
  9. Erik Schrumpf1,3,
  10. Bjørn Moum3,9,
  11. Helge Røsjø7,12,
  12. Pål Aukrust2,3,4,10,
  13. Tom H Karlsen1,2,3,4,13,14,
  14. Johannes R Hov1,2,3,4,14
  1. 1Norwegian PSC Research Center, Department of Transplantation Medicine Oslo University Hospital Rikshospitalet, Oslo, Norway
  2. 2K.G. Jebsen Inflammation Research Centre, University of Oslo, Oslo, Norway
  3. 3Institute of Clinical Medicine, University of Oslo, Oslo, Norway
  4. 4Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway
  5. 5Bioinformatics Core Facility, Institute for Medical Informatics, Oslo University Hospital, Oslo, Norway
  6. 6Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway
  7. 7K.G. Jebsen Cardiac Research Centre and Center for Heart Failure Research, University of Oslo, Oslo, Norway
  8. 8National Centre for Ultrasound in Gastroenterology, Department of Medicine Haukeland University Hospital, Bergen, Norway
  9. 9Department of Gastroenterology, Oslo University Hospital Ullevål, Oslo, Norway
  10. 10Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Oslo, Norway
  11. 11Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
  12. 12Division of Medicine, Akershus University Hospital, Lørenskog, Norway
  13. 13Department of Clinical Medicine, University of Bergen, Bergen, Norway
  14. 14Section of Gastroenterology, Department of Transplantation Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway
  1. Correspondence to Dr Johannes R Hov, Division for Cancer Medicine, Surgery and Transplantation, Norwegian PSC Research Center, Oslo University Hospital Rikshospitalet, Pb 4950 Nydalen, Oslo N-0424, Norway; j.e.r.hov{at}medisin.uio.no

Abstract

Objective 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.

Design 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.

Results 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, the Veillonella genus showed a marked increase in PSC compared with both HC (p<0.0001) and UC (p<0.02). Using receiver operating characteristic analysis, Veillonella abundance 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.

Conclusions 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. The Veillonella genus, which is also associated with other chronic inflammatory and fibrotic conditions, was enriched in PSC.

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