Altered gut microbial metabolism of essential nutrients in primary sclerosing cholangitis.

Jan 4, 2021

Contributor: Martin Kummen,Louise B Thingholm,Malte C Rühlemann,Kristian Holm,Simen H Hansen,Lucas Moitinho-Silva,Timur Liwinski,Roman Zenouzi,Christopher Storm-Larsen,Øyvind Midttun,Adrian McCann,Per M Ueland,Marte L Høivik,Mette Vesterhus,Marius Trøseid,Matthias Laudes,Wolfgang Lieb,Tom H Karlsen,Corinna Bang,Christoph Schramm,Andre Franke,Johannes R Hov

Altered gut microbial metabolism of essential nutrients in primary sclerosing cholangitis.

To influence host and disease phenotype, compositional microbiome changes, which have been demonstrated in patients with primary sclerosing cholangitis (PSC), must be accompanied by functional changes. We therefore aimed to characterize the genetic potential of the gut microbiome in PSC compared to healthy controls (HCs) and inflammatory bowel disease (IBD).
Fecal DNA from two cohorts (one Norwegian and one German), in total comprising 136 patients with PSC (58% with IBD), 158 HCs and 93 IBD patients without PSC were subjected to metagenomic shotgun sequencing, generating 17 billion paired end sequences, which were processed using HUMAnN2 and MetaPhlAn2, and analyzed using generalized linear models and random effects meta-analyses.
PSC patients had fewer microbial genes compared to HC (P<.0001). Compared to HC, PSC patients showed enrichment and increased prevalence of Clostridium species, and a depletion of e.g., Eubacterium spp. and Ruminococcus obeum. Patients with PSC showed marked differences in the abundance of genes related to vitamin B6 synthesis and branched chain amino acid (BCAA) synthesis (Q<.05). Targeted metabolomics of plasma from an independent set of PSC patients and controls found reduced concentrations of vitamin B6 and BCAAs in PSC (P<.0001), which strongly associated with reduced liver transplantation-free survival (log-rank P<.001). No taxonomic or functional differences were detected between PSC patients with and without IBD.
The gut microbiome of PSC patients exhibits large functional differences compared to HC, including microbial metabolism of essential nutrients. Alterations in related circulating metabolites associated with disease course, suggesting that microbial functions may be relevant for the disease process in PSC.

Copyright © 2020 AGA Institute. Published by Elsevier Inc. All rights reserved.

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About The Expert

Martin Kummen

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

Louise B Thingholm

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

Malte C Rühlemann

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

Kristian Holm

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

Simen H Hansen

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

Lucas Moitinho-Silva

Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel, Kiel, Germany; Department of Dermatology, Venereology and Allergy, University Hospital Schleswig-Holstein, Campus Kiel, Kiel, Germany.

Timur Liwinski

Institute of Medical Systems Biology, Center for Molecular Neurobiology, Hamburg, Germany; I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Roman Zenouzi

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

Christopher Storm-Larsen

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

Øyvind Midttun

BEVITAL, Bergen, Norway.

Adrian McCann

BEVITAL, Bergen, Norway.

Per M Ueland

BEVITAL, Bergen, Norway.

Marte L Høivik

Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Gastroenterology, Oslo University Hospital Ullevål, Oslo, Norway.

Mette Vesterhus

Norwegian PSC Research Center, Department of Transplantation Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Department of Medicine, Haraldsplass Deaconess Hospital, Bergen, Norway; Department of Clinical Science, University of Bergen, Bergen, Norway.

Marius Trøseid

Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Oslo, Norway.

Matthias Laudes

Division of Endocrinology, Diabetes and Clinical Nutrition, Department of Medicine 1, University of Kiel, Germany.

Wolfgang Lieb

Institute of Epidemiology, Christian-Albrechts-University of Kiel, Kiel, Germany.

Tom H Karlsen

Norwegian PSC Research Center, Department of Transplantation Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Section of Gastroenterology, Department of Transplantation Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway.

Corinna Bang

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

Christoph Schramm

I. Department of Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Martin Zeitz Centre for Rare Diseases, University Medical Center Hamburg-Eppendorf, Hamburg, Germany; Hamburg Center for Translational Immunology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.

Andre Franke

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

Johannes R Hov

Norwegian PSC Research Center, Department of Transplantation Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway; Section of Gastroenterology, Department of Transplantation Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway. Electronic address: j.e.r.hov@medisin.uio.no.

References

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