Intestinal Permeability in Irritable Bowel Syndrome With and Without Comorbid Conditions: Results From the European DISCOvERIE Cohort.
21 affiliations
- 1Department of Chronic Diseases and Metabolism (CHROMETA), Translational Research Centre for Gastrointestinal Disorders (TARGID), KU Leuven, Leuven, Belgium.
- 2Laboratory of Neuro-Immuno-Gastroenterology, Digestive System Research Unit, Vall d'Hebron Institut de Recerca (VHIR), Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain.
- 3Department of Gastroenterology, Vall d'Hebron Hospital Universitari, Vall d'Hebron Barcelona Hospital Campus, Barcelona, Spain.
- 4Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Instituto de Salud Carlos III, Madrid, Spain.
- 5Facultat de Medicina, Universitat Autònoma de Barcelona, Bellaterra, Spain.
- 6Department of Molecular and Clinical Medicine, Institute of Medicine, University of Gothenburg, Gothenburg, Sweden.
- 7Group of Psychiatry, Mental Health and Addictions, Vall d'Hebron Research Institute (VHIR), Barcelona, Spain.
- 8Department of Psychiatry and Forensic Medicine, Universitat Autònoma de Barcelona, Barcelona, Spain.
- 9Mental Health Department, Treatment-Resistant Depression Programme, The Brain-Inmune-Gut Unit, Vall d'Hebron Hospital Campus, Barcelona, Spain.
- 10Centro de Investigación Biomédica en Red, Salud Mental (CIBERSAM), Instituto de Salud Carlos III, Madrid, Spain.
- 11Division of Rheumatology Research, Vall d'Hebron Research Institute, Universitat Autònoma de Barcelona, Barcelona, Spain.
- 12Division of Rheumatology, Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain.
- 13Department of Gastroenterology-Hepatology, NUTRIM Institute of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center+, Maastricht, the Netherlands.
- 14Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy.
- 15IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy.
- 16Università di Bologna, Bologna, Italy.
- 17Department of Psychiatry and Psychotherapy, Semmelweis University, Budapest, Hungary.
- 18Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt-Goethe University, Frankfurt, Germany.
- 19Departments of Psychiatry and Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, the Netherlands.
- 20Universitatea De Medicina Si Farmacie Iuliu Hatieganu, Cluj-Napoca, Romania.
- 21Department of Chronic Diseases and Metabolism (CHROMETA), Epithelial Physiology and Organ Interaction (EPIC) Lab, Translational Research Centre for Gastrointestinal Disorders (TARGID), KU Leuven, Leuven, Belgium.
Abstract
Background
Irritable bowel syndrome (IBS) is a disorder of gut-brain interaction often accompanied by psychiatric and/or somatic comorbidities. Intestinal-barrier dysfunction has been implicated in IBS pathophysiology. However, the contribution of psychiatric and somatic comorbidities to intestinal permeability remains unclear. We aimed to assess intestinal permeability in a large multicentric cohort of IBS patients with and without psychiatric and/or somatic comorbidities, compared with disease controls, and healthy subjects.Methods
IBS patients and disease controls were recruited across nine European centres. Small intestinal and colonic permeabilities were assessed using the lactulose-mannitol-sucralose urinary excretion test. Urinary sugar concentrations were quantified by gas chromatography-mass spectrometry. Analyses were adjusted for relevant clinical and lifestyle confounders.Results
The lactulose/mannitol (L/M) ratio, but not the percentage of sucralose (%S), was significantly increased in IBS patients (N = 418) compared with disease controls (N = 200), regardless of IBS subtype or sex. Notably, the increased L/M in IBS patients was primarly driven by a significant decrease in mannitol excretion. IBS patients with psychiatric or combined psychiatric and somatic comorbidities showed a higher L/M than their corresponding disease control groups. However, L/M values did not differ between IBS patients with and without comorbidities. Substantial between-centre variability in L/M ratios awas observed.Discussion
Small intestinal, but not colonic, permeability, as reflected by an elevated L/M ratio, is increased in IBS patients. These alterations seem to be related to the presence of IBS per se rather than to comorbid conditions. Interestingly, substantial geographic variability was observed, which may reflect environmental or population-related factors influencing barrier function. Further investigations are needed to better understand the clinical relevance of these findings.
Related
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BibTeX
@article{rustichelli2026intestinal,
title = {{Intestinal Permeability in Irritable Bowel Syndrome With and Without Comorbid Conditions: Results From the European DISCOvERIE Cohort.}},
author = {Alice Rustichelli and Juan Manuel Garcia-Illarramendi and Javier Santos and Ana Maria González-Castro and Magnus Simrén and Irina Midenfjord and Amanda Rodriguez-Urrutia and Elba Expósito and Beatriz Lobo and Jose Alegre-Martin and Miriam Almirall and Jesús Castro-Marrero and Ramon Sanmartin-Sentañes and Jan Tack and Florencia Carbone and Lukas Van Oudenhove and Maaike Van Den Houte and Liene Bervoets and Sybren Rinckhout and Daisy Jonkers and Michelle Bosman and Maria Raffaella Barbaro and Giovanni Barbara and Istvan Bitter and Eva Jekkel and Andreas Reif and Mareike Aichholzer and Carmen Uckermark and Alejandro Arias Vasquez and Dan Lucian Dumitrascu and Andrei-Vasile Pop and Kristin Verbeke and Carmen Alonso-Cotoner and Ricard Farré},
journal = {United European gastroenterology journal},
year = {2026},
month = nov,
doi = {10.1002/ueg2.70301},
url = {https://europepmc.org/article/MED/42973115},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Intestinal Permeability in Irritable Bowel Syndrome With and Without Comorbid Conditions: Results From the European DISCOvERIE Cohort.
AU - Alice Rustichelli
AU - Juan Manuel Garcia-Illarramendi
AU - Javier Santos
AU - Ana Maria González-Castro
AU - Magnus Simrén
AU - Irina Midenfjord
AU - Amanda Rodriguez-Urrutia
AU - Elba Expósito
AU - Beatriz Lobo
AU - Jose Alegre-Martin
AU - Miriam Almirall
AU - Jesús Castro-Marrero
AU - Ramon Sanmartin-Sentañes
AU - Jan Tack
AU - Florencia Carbone
AU - Lukas Van Oudenhove
AU - Maaike Van Den Houte
AU - Liene Bervoets
AU - Sybren Rinckhout
AU - Daisy Jonkers
AU - Michelle Bosman
AU - Maria Raffaella Barbaro
AU - Giovanni Barbara
AU - Istvan Bitter
AU - Eva Jekkel
AU - Andreas Reif
AU - Mareike Aichholzer
AU - Carmen Uckermark
AU - Alejandro Arias Vasquez
AU - Dan Lucian Dumitrascu
AU - Andrei-Vasile Pop
AU - Kristin Verbeke
AU - Carmen Alonso-Cotoner
AU - Ricard Farré
PY - 2026
DA - 2026/11/01
JO - United European gastroenterology journal
DO - 10.1002/ueg2.70301
UR - https://europepmc.org/article/MED/42973115
AB - Background Irritable bowel syndrome (IBS) is a disorder of gut-brain interaction often accompanied by psychiatric and/or somatic comorbidities. Intestinal-barrier dysfunction has been implicated in IBS pathophysiology. However, the contribution of psychiatric and somatic comorbidities to intestinal permeability remains unclear. We aimed to assess intestinal permeability in a large multicentric cohort of IBS patients with and without psychiatric and/or somatic comorbidities, compared with disease controls, and healthy subjects.Methods IBS patients and disease controls were recruited across nine European centres. Small intestinal and colonic permeabilities were assessed using the lactulose-mannitol-sucralose urinary excretion test. Urinary sugar concentrations were quantified by gas chromatography-mass spectrometry. Analyses were adjusted for relevant clinical and lifestyle confounders.Results The lactulose/mannitol (L/M) ratio, but not the percentage of sucralose (%S), was significantly increased in IBS patients (N = 418) compared with disease controls (N = 200), regardless of IBS subtype or sex. Notably, the increased L/M in IBS patients was primarly driven by a significant decrease in mannitol excretion. IBS patients with psychiatric or combined psychiatric and somatic comorbidities showed a higher L/M than their corresponding disease control groups. However, L/M values did not differ between IBS patients with and without comorbidities. Substantial between-centre variability in L/M ratios awas observed.Discussion Small intestinal, but not colonic, permeability, as reflected by an elevated L/M ratio, is increased in IBS patients. These alterations seem to be related to the presence of IBS per se rather than to comorbid conditions. Interestingly, substantial geographic variability was observed, which may reflect environmental or population-related factors influencing barrier function. Further investigations are needed to better understand the clinical relevance of these findings.
SN - 2050-6406
SN - 2050-6414
ER -