Table 5.
In vitro effects of soluble factors on barrier function and tissue expression in studies including noninflammatory disease
| Reference | Year | Method | IBS Group, n | Permeability | Comments |
|---|---|---|---|---|---|
| Gecse et al. (73) | 2008 | FSN applied to murine colonic strips mounted in Ussing chambers; FITC-dextran transfer | 52 All IBS subtypes and 25 controls | Increased with IBS-D supernatants, no difference with IBS-C | FSN also rapidly increased phosphorylation of myosin light chain and delayed redistribution of ZO-1 in colonocytes |
| Piche et al. (167) | 2009 | Colonic biopsies mounted in Ussing chambers; fluorescein-5-(and-6)-sulfonic acid as probe and ZO-1 and occludin expression | 51 IBS, all subtypes, and 14 controls | Increased FITC paracellular permeability in all IBS subtypes; reduced ZO-1 expression | No difference in occludin expression; increase in FITC-dextran in Caco-2 cell monolayer, which correlated with abdominal pain score |
| Lee et al. (123) | 2010 | Colonic biopsies in Ussing chambers; horseradish peroxidase as probe | 20 IBS-D and 30 controls | Increased in IBS-D compared with controls | Increased permeability decreased with the mast cell tryptase inhibitor nafamostat |
| Bertiaux-Vandaële et al. (16) | 2011 | Colonic mucosal biopsies and ZO-1, occludin, and claudin-1 expression | 50 IBS (-C, -D, -A, or -U) and 31 controls | Occludin and claudin-1 expression decreased in IBS-D but not in IBS-C/A | Occludin (r = 0.40) and claudin-1 (r = 0.46) expression significantly correlated with duration of symptoms |
| Vivinus-Nébot et al. (217) | 2012 | Colonic biopsies mounted in Ussing chambers; fluorescein-5-(and-6)-sulfonic acid | 34 IBS, all subtypes, and 15 controls | Increased in all IBS subtypes | Also higher number of mast cells, and spontaneous release of tryptase; worse in IBS with allergic factors |
| Vivinus-Nébot et al. (218) | 2014 | Cecal biopsies: Ussing chambers, FITC-sulfonic acid as probe, and mRNA expression of TJ proteins (ZO-1, α-catenin, and occludin) | 49 inactive IBD (IBS), 51 IBS, and 27 controls | Increased permeability and lower expression of ZO-1 and α-catenin in both inactive IBD and IBS | Persistent increase in TNF-α in colonic mucosa may contribute to the epithelial barrier defects in quiescent (inactive) IBD but not in IBS |
| Peters et al. (165) | 2017 | TMR and FITC-dextran flux (4 kDa) | 19 IBS-C and 18 controls | No differences | Results consistent with in vivo permeability measurements |
| Wu et al. (232) | 2017 | H&E and semiquantitative immunohistochemistry for phosphorylated MLC, MLC kinase, and claudins-2, -8, and -15 | 27 IBS-D ±gluten diet | Increased MLC phosphorylation and colonocyte expression of the paracellular Na+ channel claudin-15 by GCD | Small intestine MLC phosphorylation increased by GCD correlated with increased intestinal permeability |
Here, n = no. of subjects. FITC, fluorescein isothiocyanate; FSN, fecal supernatant; GCD, gluten-containing diet; H&E, hematoxylin-eosin; IBD, inflammatory bowel disease; IBS, irritable bowel syndrome; IBS-A, IBS with alternating constipation and diarrhea; IBS-C, IBS with constipation; IBS-D, IBS with diarrhea; IBS-U, unsubtyped IBS; MLC, myosin II regulatory light chain; TJ, tight junction; TMR, transmucosal resistance; ZO-1, zonula occludens-1.