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

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 fecal microbiota and metabolites associated with IBS and to delineate specific phenotypes of IBS that re...

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Main Authors: Zlatan Mujagic, Melpomeni Kasapi, Daisy MAE Jonkers, Isabel Garcia-Perez, Lisa Vork, Zsa Zsa R.M. Weerts, Jose Ivan Serrano-Contreras, Alexandra Zhernakova, Alexander Kurilshikov, Jamie Scotcher, Elaine Holmes, Cisca Wijmenga, Daniel Keszthelyi, Jeremy K Nicholson, Joram M Posma, Ad AM Masclee
Format: Article
Language:English
Published: Taylor & Francis Group 2022-12-01
Series:Gut Microbes
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Online Access:https://www.tandfonline.com/doi/10.1080/19490976.2022.2063016
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author Zlatan Mujagic
Melpomeni Kasapi
Daisy MAE Jonkers
Isabel Garcia-Perez
Lisa Vork
Zsa Zsa R.M. Weerts
Jose Ivan Serrano-Contreras
Alexandra Zhernakova
Alexander Kurilshikov
Jamie Scotcher
Elaine Holmes
Cisca Wijmenga
Daniel Keszthelyi
Jeremy K Nicholson
Joram M Posma
Ad AM Masclee
author_facet Zlatan Mujagic
Melpomeni Kasapi
Daisy MAE Jonkers
Isabel Garcia-Perez
Lisa Vork
Zsa Zsa R.M. Weerts
Jose Ivan Serrano-Contreras
Alexandra Zhernakova
Alexander Kurilshikov
Jamie Scotcher
Elaine Holmes
Cisca Wijmenga
Daniel Keszthelyi
Jeremy K Nicholson
Joram M Posma
Ad AM Masclee
author_sort Zlatan Mujagic
collection DOAJ
description 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 fecal microbiota and metabolites associated with IBS and to delineate specific phenotypes of IBS that represent potential pathophysiological mechanisms. Fecal 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 (HCs) with extensive clinical, biological and phenotype information. Data were analyzed 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 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 fecal microbiome–metabolome data. These clusters could be related plasma levels of serotonin and its metabolite 5-hydroxyindoleacetate, effects of psychological stress on gastrointestinal (GI) 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 unfavorable stress response related to GI symptoms, support the microbiota-gut-brain link in the pathogenesis of IBS.
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spelling doaj-art-e79d1f03f017403cb6d067e98bd9b4582025-08-20T03:12:50ZengTaylor & Francis GroupGut Microbes1949-09761949-09842022-12-0114110.1080/19490976.2022.2063016Integrated fecal microbiome–metabolome signatures reflect stress and serotonin metabolism in irritable bowel syndromeZlatan Mujagic0Melpomeni Kasapi1Daisy MAE Jonkers2Isabel Garcia-Perez3Lisa Vork4Zsa Zsa R.M. Weerts5Jose Ivan Serrano-Contreras6Alexandra Zhernakova7Alexander Kurilshikov8Jamie Scotcher9Elaine Holmes10Cisca Wijmenga11Daniel Keszthelyi12Jeremy K Nicholson13Joram M Posma14Ad AM Masclee15Division Gastroenterology-Hepatology, Maastricht University Medical Center+, Maastricht, The NetherlandsDivision of Systems Medicine, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, South Kensington Campus, Imperial College London, London, UKDivision Gastroenterology-Hepatology, Maastricht University Medical Center+, Maastricht, The NetherlandsDivision of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Hammersmith Campus, Imperial College London, London, UKDivision Gastroenterology-Hepatology, Maastricht University Medical Center+, Maastricht, The NetherlandsDivision Gastroenterology-Hepatology, Maastricht University Medical Center+, Maastricht, The NetherlandsDivision of Systems Medicine, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, South Kensington Campus, Imperial College London, London, UKDepartment of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The NetherlandsDepartment of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The NetherlandsDivision of Systems Medicine, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, South Kensington Campus, Imperial College London, London, UKDivision of Digestive Diseases, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Hammersmith Campus, Imperial College London, London, UKDepartment of Genetics, University of Groningen, University Medical Center Groningen, Groningen, The NetherlandsDivision Gastroenterology-Hepatology, Maastricht University Medical Center+, Maastricht, The NetherlandsThe Australian National Phenome Center, Harry Perkins Institute, Murdoch University, Perth, AustraliaDivision of Systems Medicine, Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, South Kensington Campus, Imperial College London, London, UKDivision Gastroenterology-Hepatology, Maastricht University Medical Center+, Maastricht, The NetherlandsTo 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 fecal microbiota and metabolites associated with IBS and to delineate specific phenotypes of IBS that represent potential pathophysiological mechanisms. Fecal 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 (HCs) with extensive clinical, biological and phenotype information. Data were analyzed 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 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 fecal microbiome–metabolome data. These clusters could be related plasma levels of serotonin and its metabolite 5-hydroxyindoleacetate, effects of psychological stress on gastrointestinal (GI) 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 unfavorable stress response related to GI symptoms, support the microbiota-gut-brain link in the pathogenesis of IBS.https://www.tandfonline.com/doi/10.1080/19490976.2022.2063016Irritable bowel syndromegut microbiotamicrobiomegut metabolomefecal metabolomestress
spellingShingle Zlatan Mujagic
Melpomeni Kasapi
Daisy MAE Jonkers
Isabel Garcia-Perez
Lisa Vork
Zsa Zsa R.M. Weerts
Jose Ivan Serrano-Contreras
Alexandra Zhernakova
Alexander Kurilshikov
Jamie Scotcher
Elaine Holmes
Cisca Wijmenga
Daniel Keszthelyi
Jeremy K Nicholson
Joram M Posma
Ad AM Masclee
Integrated fecal microbiome–metabolome signatures reflect stress and serotonin metabolism in irritable bowel syndrome
Gut Microbes
Irritable bowel syndrome
gut microbiota
microbiome
gut metabolome
fecal metabolome
stress
title Integrated fecal microbiome–metabolome signatures reflect stress and serotonin metabolism in irritable bowel syndrome
title_full Integrated fecal microbiome–metabolome signatures reflect stress and serotonin metabolism in irritable bowel syndrome
title_fullStr Integrated fecal microbiome–metabolome signatures reflect stress and serotonin metabolism in irritable bowel syndrome
title_full_unstemmed Integrated fecal microbiome–metabolome signatures reflect stress and serotonin metabolism in irritable bowel syndrome
title_short Integrated fecal microbiome–metabolome signatures reflect stress and serotonin metabolism in irritable bowel syndrome
title_sort integrated fecal microbiome metabolome signatures reflect stress and serotonin metabolism in irritable bowel syndrome
topic Irritable bowel syndrome
gut microbiota
microbiome
gut metabolome
fecal metabolome
stress
url https://www.tandfonline.com/doi/10.1080/19490976.2022.2063016
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