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Impaired intestinal barrier integrity in the colon of patients with irritable bowel syndrome: involvement of soluble mediators.
Gut. 2009 Feb; 58(2):196-201.Gut

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.

Authors+Show Affiliations

INSERM U913, Nantes, France.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18824556

Citation

Piche, T, et al. "Impaired Intestinal Barrier Integrity in the Colon of Patients With Irritable Bowel Syndrome: Involvement of Soluble Mediators." Gut, vol. 58, no. 2, 2009, pp. 196-201.
Piche T, Barbara G, Aubert P, et al. Impaired intestinal barrier integrity in the colon of patients with irritable bowel syndrome: involvement of soluble mediators. Gut. 2009;58(2):196-201.
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). Impaired intestinal barrier integrity in the colon of patients with irritable bowel syndrome: involvement of soluble mediators. Gut, 58(2), 196-201. https://doi.org/10.1136/gut.2007.140806
Piche T, et al. Impaired Intestinal Barrier Integrity in the Colon of Patients With Irritable Bowel Syndrome: Involvement of Soluble Mediators. Gut. 2009;58(2):196-201. PubMed PMID: 18824556.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Impaired intestinal barrier integrity in the colon of patients with irritable bowel syndrome: involvement of soluble mediators. AU - Piche,T, AU - Barbara,G, AU - Aubert,P, AU - Bruley des Varannes,S, AU - Dainese,R, AU - Nano,J L, AU - Cremon,C, AU - Stanghellini,V, AU - De Giorgio,R, AU - Galmiche,J P, AU - Neunlist,M, Y1 - 2008/09/29/ PY - 2008/10/1/pubmed PY - 2009/2/12/medline PY - 2008/10/1/entrez SP - 196 EP - 201 JF - Gut JO - Gut VL - 58 IS - 2 N2 - 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. SN - 1468-3288 UR - https://www.unboundmedicine.com/medline/citation/18824556/Impaired_intestinal_barrier_integrity_in_the_colon_of_patients_with_irritable_bowel_syndrome:_involvement_of_soluble_mediators_ DB - PRIME DP - Unbound Medicine ER -