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Gut. 2017 Apr;66(4):611-619. doi: 10.1136/gutjnl-2015-310500. Epub 2016 Feb 17.

The gut microbial profile in patients with primary sclerosing cholangitis is distinct from patients with ulcerative colitis without biliary disease and healthy controls.

Kummen M1,2,3,4, Holm K1,4, Anmarkrud JA1,4, Nygård S5,6,7, Vesterhus M1,8, Høivik ML9, Trøseid M1,2,10, Marschall HU11, Schrumpf E1,3, Moum B3,9, Røsjø H7,12, Aukrust P2,3,4,10, Karlsen TH1,2,3,4,13,14, Hov JR1,2,3,4,14.

Author information

1
Norwegian PSC Research Center, Department of Transplantation Medicine Oslo University Hospital Rikshospitalet, Oslo, Norway.
2
K.G. Jebsen Inflammation Research Centre, University of Oslo, Oslo, Norway.
3
Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
4
Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.
5
Bioinformatics Core Facility, Institute for Medical Informatics, Oslo University Hospital, Oslo, Norway.
6
Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway.
7
K.G. Jebsen Cardiac Research Centre and Center for Heart Failure Research, University of Oslo, Oslo, Norway.
8
National Centre for Ultrasound in Gastroenterology, Department of Medicine Haukeland University Hospital, Bergen, Norway.
9
Department of Gastroenterology, Oslo University Hospital Ullevål, Oslo, Norway.
10
Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Oslo, Norway.
11
Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
12
Division of Medicine, Akershus University Hospital, Lørenskog, Norway.
13
Department of Clinical Medicine, University of Bergen, Bergen, Norway.
14
Section of Gastroenterology, Department of Transplantation Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.

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.

KEYWORDS:

HEPATOBILIARY DISEASE; PRIMARY SCLEROSING CHOLANGITIS

PMID:
26887816
DOI:
10.1136/gutjnl-2015-310500
[Indexed for MEDLINE]

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