Alterations of the bile microbiome in primary sclerosing cholangitis.


Journal

Gut
ISSN: 1468-3288
Titre abrégé: Gut
Pays: England
ID NLM: 2985108R

Informations de publication

Date de publication:
04 2020
Historique:
received: 31 01 2019
revised: 03 06 2019
accepted: 06 06 2019
pubmed: 28 6 2019
medline: 24 10 2020
entrez: 28 6 2019
Statut: ppublish

Résumé

Patients with primary sclerosing cholangitis (PSC) display an altered colonic microbiome compared with healthy controls. However, little is known on the bile duct microbiome and its interplay with bile acid metabolism in PSC. Patients with PSC (n=43) and controls without sclerosing cholangitis (n=22) requiring endoscopic retrograde cholangiography were included prospectively. Leading indications in controls were sporadic choledocholithiasis and papillary adenoma. A total of 260 biospecimens were collected from the oral cavity, duodenal fluid and mucosa and ductal bile. Microbiomes of the upper alimentary tract and ductal bile were profiled by sequencing the 16S-rRNA-encoding gene (V1-V2). Bile fluid bile acid composition was measured by high-performance liquid chromatography mass spectrometry and validated in an external cohort (n=20). The bile fluid harboured a diverse microbiome that was distinct from the oral cavity, the duodenal fluid and duodenal mucosa communities. The upper alimentary tract microbiome differed between PSC patients and controls. However, the strongest differences between PSC patients and controls were observed in the ductal bile fluid, including reduced biodiversity (Shannon entropy, p=0.0127) and increase of pathogen PSC is characterised by an altered microbiome of the upper alimentary tract and bile ducts. Biliary dysbiosis is linked with increased concentrations of the proinflammatory and potentially cancerogenic agent taurolithocholic acid.

Sections du résumé

BACKGROUND
Patients with primary sclerosing cholangitis (PSC) display an altered colonic microbiome compared with healthy controls. However, little is known on the bile duct microbiome and its interplay with bile acid metabolism in PSC.
METHODS
Patients with PSC (n=43) and controls without sclerosing cholangitis (n=22) requiring endoscopic retrograde cholangiography were included prospectively. Leading indications in controls were sporadic choledocholithiasis and papillary adenoma. A total of 260 biospecimens were collected from the oral cavity, duodenal fluid and mucosa and ductal bile. Microbiomes of the upper alimentary tract and ductal bile were profiled by sequencing the 16S-rRNA-encoding gene (V1-V2). Bile fluid bile acid composition was measured by high-performance liquid chromatography mass spectrometry and validated in an external cohort (n=20).
RESULTS
The bile fluid harboured a diverse microbiome that was distinct from the oral cavity, the duodenal fluid and duodenal mucosa communities. The upper alimentary tract microbiome differed between PSC patients and controls. However, the strongest differences between PSC patients and controls were observed in the ductal bile fluid, including reduced biodiversity (Shannon entropy, p=0.0127) and increase of pathogen
CONCLUSION
PSC is characterised by an altered microbiome of the upper alimentary tract and bile ducts. Biliary dysbiosis is linked with increased concentrations of the proinflammatory and potentially cancerogenic agent taurolithocholic acid.

Identifiants

pubmed: 31243055
pii: gutjnl-2019-318416
doi: 10.1136/gutjnl-2019-318416
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

665-672

Informations de copyright

© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.

Déclaration de conflit d'intérêts

Competing interests: None declared.

Auteurs

Timur Liwinski (T)

1st Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Roman Zenouzi (R)

1st Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Clara John (C)

Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Hanno Ehlken (H)

Department of Interdisciplinary Endoscopy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Malte C Rühlemann (MC)

Christian-Albrechts-Universität zu Kiel, Institute of Clinical Molecular Biology, Kiel, Germany.

Corinna Bang (C)

Institute for Clinical Molecular Biology, Christian Albrechts University of Kiel, Kiel, Germany.

Stefan Groth (S)

Department of Interdisciplinary Endoscopy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Wolfgang Lieb (W)

Institute of Epidemiology and Biobank PopGen, Christian-Albrechts-University of Kiel, Kiel, Germany.

Marcus Kantowski (M)

Department of Interdisciplinary Endoscopy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Nils Andersen (N)

University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Guido Schachschal (G)

Department of Interdisciplinary Endoscopy, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Tom H Karlsen (TH)

Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway.
Institute of Clinical Medicine, University of Oslo, Oslo, Norway.

Johannes R Hov (JR)

Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
Norwegian PSC Research Center, Department of Transplantation Medicine, Oslo University Hospital, Oslo, Norway.

Thomas Rösch (T)

University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Ansgar W Lohse (AW)

University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Joerg Heeren (J)

Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Andre Franke (A)

Institute for Clinical Molecular Biology, Christian Albrechts University of Kiel, Kiel, Germany.

Christoph Schramm (C)

1st Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Martin Zeitz Center for Rare Diseases, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

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