New study on Zonulin

New study out this month about Zonulin and NCGS (Non-celiac gluten sensitivity).  Here is the news report on the study.  The study was presented at a conference as an oral presentation.  The notes from the presentation are below.

I'll comment later.  For now I just wanted to save this link.
___________________________________________________________________________

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4669990/

OP269 THE ROLE OF ZONULIN IN NON-CELIAC GLUTEN SENSITIVITY AND IRRITABLE BOWEL SYNDROME

M. R. Barbaro¹, C. Cremon¹, G. Caio¹, L. Bellacosa¹, R. De Giorgio¹, U. Volta¹, V. Stanghellini¹, G. Barbara¹

¹Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy

Contact E-mail Address: ti.obinu@2orabrab.airam

Introduction: Zonulin, the human homolog of the zonula occludens toxin secreted by Vibrio cholera, is the only known endogenous modulator of epithelial tight junctions (TJs) and intestinal permeability. Intestinal bacterial infections and gluten evoke zonulin release in the intestinal milieu and in the bloodstream. A role for zonulin has been demonstrated in different diseases such as celiac disease (CD). Increased intestinal permeability has been reported in Non-Celiac Gluten Sensitivity (NCGS) and Irritable Bowel Syndrome (IBS) although the mechanisms involved are not clear. Zonulin serum levels and its diagnostic value in NCGS and IBS remain undetermined

Aims & Methods: In the present study, we aimed at characterizing zonulin serum levels in patients with NCGS (n=27) and IBS-D (n=15) compared with CD (n=15; positive control) and healthy controls (n=15; HC, negative control). ELISA assay was used to evaluate zonulin serum levels; qPCR was used to evaluate zonulin gene expression in the colonic mucosa. Clinical data, abdominal symptoms and bowel habit were recorded and analysis of HLA alleles was performed. Zonulin serum levels were evaluated in a subgroup of NCGS patients during gluten containing diet (GCD) and gluten free diet (GFD).

Results: CD patients showed significantly higher zonulin serum levels compared to HC (0.033± 0.004 vs 0.007 ± 0.001 ng/mg total proteins, p < 0.0001) and to IBS-D patients (0.012 ± 0.002 ng/mg total proteins, p < 0.001). NCGS showed significantly higher zonulin serum levels compared to HC (0.030 ± 0.006 vs 0.007 ± 0.001, p < 0.05) and IBS-D (p < 0.05). IBS-D patients showed higher zonulin serum levels and colonic mRNA expression compared to HC. Zonulin levels were positively correlated with the titer of anti-TTG antibodies (r:0.6; p < 0.05) and anti-DGP antibodies (r:0.6; p < 0.05). A decrease in zonulin serum levels was observed during GFD compared to GCD (p=0.06) and a comparable decrease was observed for AGA IgG levels (p=0.06). Only HLA-DQ2-positive patients showed a significant decrease in zonulin serum levels during GFD compared to GCD (p < 0.05). A significant difference was observed in zonulin serum levels during GFD between HLA-DQ2-positive patients and HLA-DQ2/DQ8 negative ones (p < 0.05).

Conclusion: Zonulin serum levels are increased in IBS-D and NCGS, in addition to CD. A positive and significant correlation was found between zonulin serum levels and both anti-DGP and anti-TTG antibody titers. A comparable decrease of AGA IgG and zonulin serum levels was observed during GFD. Interestingly, only HLA-DQ2-positive patients showed a significant decrease of zonulin serum levels during GFD compared to GCD. Our data suggest that a zonulin-dependent TJ dysfunction may play a role in the pathophysiology of IBS and NCGS, particularly in a subset of patients.

Disclosure of Interest: None declared