Faecal metabolome and its determinants in inflammatory bowel disease.


Journal

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

Informations de publication

Date de publication:
Aug 2023
Historique:
received: 14 06 2022
accepted: 05 03 2023
medline: 10 7 2023
pubmed: 24 3 2023
entrez: 23 3 2023
Statut: ppublish

Résumé

Inflammatory bowel disease (IBD) is a multifactorial immune-mediated inflammatory disease of the intestine, comprising Crohn's disease and ulcerative colitis. By characterising metabolites in faeces, combined with faecal metagenomics, host genetics and clinical characteristics, we aimed to unravel metabolic alterations in IBD. We measured 1684 different faecal metabolites and 8 short-chain and branched-chain fatty acids in stool samples of 424 patients with IBD and 255 non-IBD controls. Regression analyses were used to compare concentrations of metabolites between cases and controls and determine the relationship between metabolites and each participant's lifestyle, clinical characteristics and gut microbiota composition. Moreover, genome-wide association analysis was conducted on faecal metabolite levels. We identified over 300 molecules that were differentially abundant in the faeces of patients with IBD. The ratio between a sphingolipid and L-urobilin could discriminate between IBD and non-IBD samples (AUC=0.85). We found changes in the bile acid pool in patients with dysbiotic microbial communities and a strong association between faecal metabolome and gut microbiota. For example, the abundance of In this large-scale analysis, we identified alterations in the metabolome of patients with IBD that are independent of commonly overlooked confounders such as diet and surgical history. Considering the influence of the microbiome on faecal metabolites, our results pave the way for future interventions targeting intestinal inflammation.

Identifiants

pubmed: 36958817
pii: gutjnl-2022-328048
doi: 10.1136/gutjnl-2022-328048
pmc: PMC10359577
doi:

Substances chimiques

NAT2 protein, human EC 2.3.1.5
Arylamine N-Acetyltransferase EC 2.3.1.5

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

1472-1485

Informations de copyright

© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Déclaration de conflit d'intérêts

Competing interests: This study was funded by Takeda Development Center Americas. RKW acted as a consultant for Takeda and received unrestricted research grants from Takeda and Johnson and Johnson pharmaceuticals and speaker fees from AbbVie, MSD, Olympus and AstraZeneca. GA-A, CG, JS, JP and AAG are or were employees of Takeda Pharmaceuticals at the time this study was conducted.No disclosures: All other authors have nothing to disclose.

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Auteurs

Arnau Vich Vila (A)

Department of Genetics, University Medical Centre, Groningen, The Netherlands r.k.weersma@umcg.nl arnauvich@gmail.com.
Department of Pediatrics, University Medical Centre, Groningen, The Netherlands.

Shixian Hu (S)

Department of Genetics, University Medical Centre, Groningen, The Netherlands.
Department of Pediatrics, University Medical Centre, Groningen, The Netherlands.

Sergio Andreu-Sánchez (S)

Department of Pediatrics, University Medical Centre, Groningen, The Netherlands.
Department of Gastroenterology and Hepatology, University Medical Centre, Groningen, The Netherlands.

Valerie Collij (V)

Department of Genetics, University Medical Centre, Groningen, The Netherlands.
Department of Pediatrics, University Medical Centre, Groningen, The Netherlands.

Bernadien H Jansen (BH)

Department of Genetics, University Medical Centre, Groningen, The Netherlands.

Hannah E Augustijn (HE)

Department of Pediatrics, University Medical Centre, Groningen, The Netherlands.

Laura A Bolte (LA)

Department of Genetics, University Medical Centre, Groningen, The Netherlands.

Renate A A A Ruigrok (RAAA)

Department of Genetics, University Medical Centre, Groningen, The Netherlands.
Department of Pediatrics, University Medical Centre, Groningen, The Netherlands.

Galeb Abu-Ali (G)

Gastroenterology Drug Discovery Unit, Takeda Pharmaceutical, Cambridge, Massachusetts, USA.

Cosmas Giallourakis (C)

Gastroenterology Drug Discovery Unit, Takeda Pharmaceutical, Cambridge, Massachusetts, USA.

Jessica Schneider (J)

Gastroenterology Drug Discovery Unit, Takeda Pharmaceutical, Cambridge, Massachusetts, USA.

John Parkinson (J)

Gastroenterology Drug Discovery Unit, Takeda Pharmaceutical, Cambridge, Massachusetts, USA.

Amal Al-Garawi (A)

Gastroenterology Drug Discovery Unit, Takeda Pharmaceutical, Cambridge, Massachusetts, USA.

Alexandra Zhernakova (A)

Department of Pediatrics, University Medical Centre, Groningen, The Netherlands.

Ranko Gacesa (R)

Department of Genetics, University Medical Centre, Groningen, The Netherlands.
Department of Pediatrics, University Medical Centre, Groningen, The Netherlands.

Jingyuan Fu (J)

Department of Pediatrics, University Medical Centre, Groningen, The Netherlands.
Department of Gastroenterology and Hepatology, University Medical Centre, Groningen, The Netherlands.

Rinse K Weersma (RK)

Department of Genetics, University Medical Centre, Groningen, The Netherlands r.k.weersma@umcg.nl arnauvich@gmail.com.

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Classifications MeSH