Intestinal Permeability in Irritable Bowel Syndrome With and Without Comorbid Conditions: Results From the European DISCOvERIE Cohort
Alice Rustichelli, Juan Manuel Garcia‐Illarramendi, Javier Santos, Ana Maria González‐Castro, Magnus Simrén, Irina Midenfjord, Amanda Rodriguez‐Urrutia, Elba Expósito, Beatriz Lobo, Jose Alegre‐Martin, Miriam Almirall, Jesús Castro‐Marrero, Ramon Sanmartin‐Sentañes, Jan Tack, Florencia Carbone, Lukas Van Oudenhove, Maaike Van Den Houte, Liene Bervoets, Sybren Rinckhout, Daisy Jonkers, Michelle Bosman, Maria Raffaella Barbaro, Giovanni Barbara, Istvan Bitter, Eva Jekkel, Andreas Reif, Mareike Aichholzer, Carmen Uckermark, Alejandro Arias Vasquez, Dan Lucian Dumitrascu, Andrei‐Vasile Pop, Kristin Verbeke, Carmen Alonso‐Cotoner, Ricard FarréABSTRACT
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.