Impaired intestinal barrier integrity in the colon of patients with irritable bowel syndrome: involvement of soluble mediators
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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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Intestinal microbiota may be an active participant in mucosal immune activation through stimulation of the immune system, likely in the subgroup of subjects showing increased epithelial permeability which could expose the immune system to an abnormal microbial antigenic load.
“Intestinal microbiota may well be an active participant in this scenario through stimulation of the immune system,153 likely in the subgroup of subjects showing increased epithelial permeability which could154 expose the immune system to an abnormal microbial antigenic load.”
From Intestinal microbiota in functional bowel disorders: a Rome foundation report (2013) · cites this paper as [154]
Several in vivo studies in children and adults with IBS and in vitro studies of mucosal samples from IBS patients demonstrated increased intestinal permeability in IBS compared with healthy controls.
“Several in vivo studies in children and adults with IBS (56, 128, 162) and in vitro studies of mucosal samples from IBS patients (132) demonstrated increased intestinal permeability in IBS compared with healthy controls.”
From Intestinal microbiota and immune function in the pathogenesis of irritable bowel syndrome (2013) · cites this paper as [132]
When fecal supernatants from IBS patients were applied to colonic mucosa from mice or to Caco-2 cells, expression of zonula occludens-1 decreased and permeability increased.
“When fecal supernatants from IBS patients were applied to colonic mucosa from mice (67) or to Caco-2 cells (132), the expression of ZO-1 decreased and permeability increased.”
From Intestinal microbiota and immune function in the pathogenesis of irritable bowel syndrome (2013) · cites this paper as [132]
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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
- Venue
- Gut
- Publisher
- BMJ
- Published
- 2008-09-29
- Volume
- 58
- Issue
- 2
- Pages
- 196-201
- ISSN
- 0017-5749 (ISSN-L)
- 1468-3288
- 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
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › 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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