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Integrated fecal microbiome–metabolome signatures reflect stress and serotonin metabolism in irritable bowel syndrome

Title: Integrated fecal microbiome–metabolome signatures reflect stress and serotonin metabolism in irritable bowel syndrome
Authors: Mujagic, Z
Kasapi, M
Jonkers, DMAE
Garcia Perez, I
Vork, L
Weerts, ZZRM
Serrano Contreras, JI
Zhernakova, A
Kurilshikov, A
Scotcher, J
Holmes, E
Wijmenga, C
Keszthelyi, D
Nicholson, J
Posma, JM
Masclee, AAM
Item Type: Journal Article
Abstract: To gain insight into the complex microbiome-gut-brain axis in irritable bowel syndrome (IBS) several modalities of biological and clinical data must be combined. We aimed to identify profiles of faecal microbiota and metabolites associated with IBS and to delineate specific phenotypes of IBS that represent potential pathophysiological mechanisms. Faecal metabolites were measured using proton Nuclear Magnetic Resonance (1H-NMR) spectroscopy and gut microbiome using Shotgun Metagenomic Sequencing (MGS) in a combined dataset of 142 IBS patients and 120 healthy controls (HC) with extensive clinical, biological and phenotype information. Data were analysed using support vector classification and regression and kernel t-SNE. Microbiome and metabolome profiles could distinguish IBS and HC with an area-under-the-receiver-operator-curve (AUC) of 77.3% and 79.5%, respectively, but this could be improved by combining microbiota and metabolites to 83.6%. No significant differences in predictive ability of the microbiome-metabolome data were observed between the three classical, stool pattern-based, IBS subtypes. However, unsupervised clustering showed distinct subsets of IBS patients based on faecal microbiome-metabolome data. These clusters could be related plasma levels of serotonin and its metabolite 5-hydroxyindoleacetate, effects of psychological stress on gastrointestinal symptoms, onset of IBS after stressful events, medical history of previous abdominal surgery, dietary caloric intake and IBS symptom duration. Furthermore, pathways in metabolic reaction networks were integrated with microbiota data, that reflect the host-microbiome interactions in IBS. The identified microbiome-metabolome signatures for IBS, associated with altered serotonin metabolism and unfavourable stress-response related to gastrointestinal symptoms, support the microbiota-gut-brain link in the pathogenesis of IBS.
Issue Date: 21-Apr-2022
Date of Acceptance: 30-Mar-2022
URI: http://hdl.handle.net/10044/1/96377
DOI: 10.1080/19490976.2022.2063016
ISSN: 1949-0976
Publisher: Taylor & Francis Open Access
Start Page: 1
End Page: 20
Journal / Book Title: Gut Microbes
Volume: 14
Issue: 1
Copyright Statement: © 2022 The Author(s). Published with license by Taylor & Francis Group, LLC. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Sponsor/Funder: Wellcome Trust
Medical Research Council (MRC)
Medical Research Council
Imperial College Healthcare NHS Trust- BRC Funding
Funder's Grant Number: 108908/B/15/Z
MR/S004033/1
MR/S004033/1
RDA27
Keywords: Science & Technology
Life Sciences & Biomedicine
Gastroenterology & Hepatology
Clinical Neurology
Neurosciences
Neurosciences & Neurology
Irritable bowel syndrome
fecal metabolome
gut metabolome
gut microbiota
gut-brain
host-microbiome interaction
microbiome
serotonin
stress
Irritable Bowel Syndrome
Microbiota
Metabolomics
Stress, Physiological
Serotonin
1103 Clinical Sciences
1109 Neurosciences
1116 Medical Physiology
Gastroenterology & Hepatology
Publication Status: Published
Article Number: 2063016
Online Publication Date: 2022-04-21
Appears in Collections:Department of Metabolism, Digestion and Reproduction
Faculty of Natural Sciences



This item is licensed under a Creative Commons License Creative Commons