Cited by 540Gastrointestinal motility and disordersGut microbiota and healthInflammatory Bowel Disease

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Impaired intestinal barrier integrity in the colon of patients with irritable bowel syndrome: involvement of soluble mediators

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Piche, T, Barbara, G, Aubert, P, Bruley des Varannes, S, Dainese, R, Nano, J L, Cremon, C, Stanghellini, V, De Giorgio, R, Galmiche, J P, Neunlist, M·2009·Gut

DOI 10.1136/gut.2007.140806

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Abstract

Background: Growing evidence suggests that patients with irritable bowel syndrome (IBS) have increased intestinal permeability. In addition, mucosal soluble mediators are involved in the pathophysiology of pain in IBS. We aimed to investigate (1) paracellular permeability in colonic biopsies of patients with IBS; and (2) the ability of soluble factors from colonic biopsies to reproduce these alterations in vitro. Methods: Paracellular permeability in colonic biopsies of healthy subjects and patients with IBS was measured by mounting the biopsies in Ussing chambers. Cleared supernatant (SUP) of the culture from colonic biopsies was collected and applied to Caco-2 cells for 48 h. Paracellular permeability and transepithelial resistance (TER) were evaluated. mRNA expression of the tight junction proteins, zonula occludens (ZO)-1 and occludin, was assessed in colonic biopsies. Abdominal pain was assessed using a validated questionnaire. Results: Permeability of colonic biopsies was significantly higher in patients with IBS compared to healthy subjects. These changes were associated with significantly lower expression of ZO-1 mRNA in biopsies of IBS as compared to healthy subjects. Compared to healthy subjects, SUP of IBS markedly reduced TER and significantly increased permeability in Caco-2 cells. SUP of IBS patients induced a significant decrease of ZO-1 mRNA in Caco-2 as compared to healthy subjects. SUP-induced increased paracellular permeability correlated with the severity of abdominal pain. Conclusions: Our study shows that colonic soluble mediators are able to reproduce functional (permeability) and molecular (ZO-1 mRNA expression) alterations observed in IBS patients. These findings might pave the way both to identify novel biomarkers as well as new therapeutic targets in IBS.

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Authors: Piche, T., Barbara, G., Aubert, P., Bruley des Varannes, S., Dainese, R., Nano, J. L., Cremon, C., Stanghellini, V, De Giorgio, R., Galmiche, J. P., & Neunlist, M.
Affiliations: Inserm (FR)
University of Bologna (IT)
Corresponding author: Neunlist, M
ORCID: Barbara, G
Aubert, P
Cremon, C
Stanghellini, V
Neunlist, M
Venue: Gut
Publisher: BMJ
Published: 2008-09-29
Volume: 58
Issue: 2
Pages: 196-201
ISSN: 0017-5749 (ISSN-L)
1468-3288
DOI: 10.1136/gut.2007.140806
OpenAlex: W2161238054
Cited by: 540
References: 33
Citations by year: 2026: 18 · 2025: 20 · 2024: 26 · 2023: 23 · 2022: 40 · 2021: 32 · 2020: 31 · 2019: 31 · 2018: 24 · 2017: 39 · 2016: 36 · 2015: 26 · 2014: 46 · 2013: 34 · 2012: 38
FWCI: 25.00
Type: journal article
Language: en
Open access: green
inserm.hal.science
Licence: other-oa
Locations: Gut (publishedVersion)
PubMed (publishedVersion)
HAL (submittedVersion, other-oa)
Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion)
HighWire Press Open Archive (submittedVersion)
Institutional Research Information System University of Ferrara (University of Ferrara) (submittedVersion)
Funders: Sanofi
Ministero dell’Istruzione, dell’Università e della Ricerca (2002052573)
Università di Bologna
Topics: Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
Health Sciences › Medicine › Gastroenterology › Inflammatory Bowel Disease
Keywords: irritable bowel syndrome, intestinal permeability, paracellular permeability, intestinal barrier integrity, colonic mucosa, soluble mediators, ZO-1, occludin, tight junction proteins, transepithelial electrical resistance, abdominal pain, Caco-2 cells, biomarkers
MeSH terms: Adult, Aged, Analysis of Variance, Biopsy, Cell Membrane, Cell Membrane Permeability, Colon, Female, Humans, Intestinal Mucosa, Male, Membrane Proteins, Middle Aged, Phosphoproteins, RNA, Messenger, Case-Control Studies, Electric Impedance, Statistics, Nonparametric, Caco-2 Cells, Reverse Transcriptase Polymerase Chain Reaction, Irritable Bowel Syndrome, Young Adult, Occludin, Zonula Occludens-1 Protein

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Impaired intestinal barrier integrity in the colon of patients with irritable bowel syndrome: involvement of soluble mediators

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