Altered Gut Microbial Metabolism of Essential Nutrients in Primary Sclerosing Cholangitis.

Adolescent Adult Aged Bacteria / genetics Case-Control Studies Cholangitis, Sclerosing / blood Cross-Sectional Studies Dysbiosis Feces / microbiology Female Gastrointestinal Microbiome Germany Humans Liver Transplantation Male Metabolome Metabolomics Metagenome Metagenomics Middle Aged Norway Phylogeny Progression-Free Survival Young Adult
Branched Chain Amino Acids Microbiome Primary Sclerosing Cholangitis Vitamin B

Journal

Gastroenterology
ISSN: 1528-0012
Titre abrégé: Gastroenterology
Pays: United States
ID NLM: 0374630

Informations de publication

Date de publication:
04 2021
Historique:
received: 19 06 2020
revised: 02 12 2020
accepted: 22 12 2020
pubmed: 3 1 2021
medline: 31 8 2021
entrez: 2 1 2021
Statut: ppublish

Résumé

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 patients with PSC compared with healthy controls (HCs) and patients with inflammatory bowel disease (IBD). Fecal DNA from 2 cohorts (1 Norwegian and 1 German), in total comprising 136 patients with PSC (58% with IBD), 158 HCs, and 93 patients with IBD 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. Patients with PSC had fewer microbial genes compared with HCs (P < .0001). Compared with HCs, patients with PSC showed enrichment and increased prevalence of Clostridium species and a depletion of, for example, 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 synthesis (Q The gut microbiome in patients with PSC exhibits large functional differences compared with that in HCs, 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.

Sections du résumé

BACKGROUND & AIMS
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 patients with PSC compared with healthy controls (HCs) and patients with inflammatory bowel disease (IBD).
METHODS
Fecal DNA from 2 cohorts (1 Norwegian and 1 German), in total comprising 136 patients with PSC (58% with IBD), 158 HCs, and 93 patients with IBD 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.
RESULTS
Patients with PSC had fewer microbial genes compared with HCs (P < .0001). Compared with HCs, patients with PSC showed enrichment and increased prevalence of Clostridium species and a depletion of, for example, 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 synthesis (Q
CONCLUSIONS
The gut microbiome in patients with PSC exhibits large functional differences compared with that in HCs, 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.

Identifiants

DOI: 10.1053/j.gastro.2020.12.058 PMID: 33387530 PMC: PMC7611822
pubmed: 33387530
pii: S0016-5085(20)35622-5
doi: 10.1053/j.gastro.2020.12.058
pmc: PMC7611822
mid: EMS136001
pii:
doi:

Types de publication

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

Langues

eng

Sous-ensembles de citation

IM

Pagination

1784-1798.e0

Subventions

Organisme : European Research Council
ID : 802544
Pays : International

Commentaires et corrections

Type : CommentIn

Informations de copyright

Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.

Références

Rapid Commun Mass Spectrom. 2009 May;23(9):1371-9
pubmed: 19337982
Front Genet. 2015 Apr 20;6:148
pubmed: 25941533
J Hepatol. 2017 Feb;66(2):382-389
pubmed: 27720803
Hepatology. 2015 Jul;62(1):188-97
pubmed: 25833813
J Lipid Res. 2015 May;56(5):1034-42
pubmed: 25713100
Gut. 2017 Apr;66(4):611-619
pubmed: 26887816
Gut. 1982 May;23(5):362-70
pubmed: 7076013
J Crohns Colitis. 2017 Jun 1;11(6):649-670
pubmed: 28158501
Nat Microbiol. 2019 Mar;4(3):492-503
pubmed: 30643240
Scand J Gastroenterol Suppl. 1989;170:2-6; discussion 16-9
pubmed: 2617184
Gastroenterology. 2014 May;146(6):1470-6
pubmed: 24631493
Gut. 2016 Oct;65(10):1681-9
pubmed: 27207975
Nature. 2014 May 15;509(7500):361-5
pubmed: 24695216
Semin Liver Dis. 2019 Nov;39(4):432-441
pubmed: 31315136
Biochem J. 2007 Oct 1;407(1):1-13
pubmed: 17822383
Aliment Pharmacol Ther. 2019 Sep;50(5):580-589
pubmed: 31250469
J Hepatol. 2017 Dec;67(6):1298-1323
pubmed: 28802875
Gut. 2020 Jan;69(1):92-102
pubmed: 31003979
Mayo Clin Proc. 2000 Jul;75(7):688-94
pubmed: 10907383
Annu Rev Nutr. 2015;35:33-70
pubmed: 25974692
Gut. 2018 Oct;67(10):1864-1869
pubmed: 28739581
Front Nutr. 2019 Apr 17;6:48
pubmed: 31058161
J Hepatol. 2009 Aug;51(2):237-67
pubmed: 19501929
Hepatology. 1986 May-Jun;6(3):464-71
pubmed: 3710434
Nat Genet. 2016 Nov;48(11):1396-1406
pubmed: 27723756
Liver Int. 2019 Jul;39(7):1186-1196
pubmed: 31125502
United European Gastroenterol J. 2017 Jun;5(4):532-541
pubmed: 28588885
Anal Chem. 2016 Nov 1;88(21):10427-10436
pubmed: 27715010
Nat Med. 2018 Oct;24(10):1532-1535
pubmed: 30150716
Community Genet. 2006;9(1):55-61
pubmed: 16490960
Gut. 2017 Jul;66(7):1344-1346
pubmed: 27670376
Nature. 2019 Nov;575(7783):505-511
pubmed: 31723265
Nat Methods. 2015 Oct;12(10):902-3
pubmed: 26418763
BMC Gastroenterol. 2005 Mar 24;5:11
pubmed: 15790420
Hepatology. 2016 Jan;63(1):185-96
pubmed: 26044703
Nutrition. 2017 Sep;41:80-85
pubmed: 28760433
Am J Clin Nutr. 2012 May;95(5):1072-8
pubmed: 22492365
Am J Gastroenterol. 2019 Jul;114(7):1071-1079
pubmed: 30730351
Am J Gastroenterol. 2015 May;110(5):646-59; quiz 660
pubmed: 25869391
Clin Nutr. 2020 Sep;39(9):2824-2831
pubmed: 31883613
Nat Methods. 2018 Nov;15(11):962-968
pubmed: 30377376
World J Gastroenterol. 2017 Jul 7;23(25):4548-4558
pubmed: 28740343
Nature. 2011 Apr 7;472(7341):57-63
pubmed: 21475195
Nat Chem Biol. 2008 Jul;4(7):425-30
pubmed: 18516049
Nature. 2016 Jul 21;535(7612):376-81
pubmed: 27409811
Nat Rev Gastroenterol Hepatol. 2016 Feb;13(2):88-110
pubmed: 26758786
Eur J Immunol. 2018 Dec;48(12):1997-2004
pubmed: 30252934

Auteurs

Martin Kummen (M)

Norwegian Primary Sclerosing Cholangitis 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 (LB)

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

Malte C Rühlemann (MC)

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

Kristian Holm (K)

Norwegian Primary Sclerosing Cholangitis 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 (SH)

Norwegian Primary Sclerosing Cholangitis 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 (L)

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

Timur Liwinski (T)

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

Roman Zenouzi (R)

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

Christopher Storm-Larsen (C)

Norwegian Primary Sclerosing Cholangitis 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 (Ø)

Bevital, Bergen, Norway.

Adrian McCann (A)

Bevital, Bergen, Norway.

Per M Ueland (PM)

Bevital, Bergen, Norway.

Marte L Høivik (ML)

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

Mette Vesterhus (M)

Norwegian Primary Sclerosing Cholangitis 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 (M)

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

Matthias Laudes (M)

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

Wolfgang Lieb (W)

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

Tom H Karlsen (TH)

Norwegian Primary Sclerosing Cholangitis 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 (C)

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

Christoph Schramm (C)

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 (A)

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

Johannes R Hov (JR)

Norwegian Primary Sclerosing Cholangitis 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.

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Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Adolescent › Altered Gut Microbial Metabolism of Essential...
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questionsmedicales.fr › Maladies de l'appareil digestif › Maladie des voies biliaires › Maladies des canaux biliaires › Angiocholite › Angiocholite sclérosante › Altered Gut Microbial Metabolism of Essential...
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