Zonulin serum levels increase in nonceliac gluten sensitivity, IBS

Zonulin serum levels were found to be increased in patients with nonceliac gluten sensitivity and irritable bowel syndrome comparable to those with celiac disease, according to data presented at UEG Week 2015.

“Increased intestinal permeability has been implicated in a range of autoimmune conditions including celiac disease, type 1 diabetes, rheumatoid arthritis and multiple sclerosis,” Giovanni Barbara, MD, PhD, a professor from the departments of digestive diseases and internal medicine at University of Bologna, Italy, said in a press release. “Since zonulin is a key regulator of intestinal permeability, it is possible that this protein provides a common link between all these conditions.”

Giovanni and colleagues used an ELISA assay to measure serum zonulin levels and qPCR to evaluate zonulin gene expression in the colonic mucosa of 27 patients with nonceliac gluten sensitivity (NCGS), 15 patients with diarrhea-predominant IBS (IBS-D), 15 positive controls with celiac disease and 15 healthy negative controls. The researchers also evaluated clinical data, abdominal symptoms, bowel habits and HLA alleles, and serum zonulin levels in subgroups of NCGS patients on and off gluten-free diet.

They found higher serum zonulin levels among patients with celiac disease compared with healthy controls (0.033 ± 0.004 ng/mg total proteins vs. 0.007 ± 0.001 ng/mg total proteins; P < .0001) and compared with IBS-D patients (0.012 ± 0.002 ng/mg total proteins; P < .001). They also found higher serum zonulin levels among patients with NCGS (0.03 ± 0.006 ng/mg total proteins) compared with healthy controls and IBS-D patients (both P < .05). Furthermore, they found IBS-D patients had higher serum zonulin levels and colonic mRNA expression compared with healthy controls.

Positive correlations were observed between zonulin levels and anti-TTG and anti-DGP antibody titers (both r = .06; P < .05). Serum zonulin levels and AGA IgG levels decreased during gluten-free diet compared with gluten-containing diet (both P = .06), but only HLA-DQ2-positive patients had a significant decrease in zonulin levels during gluten-free vs. gluten-containing diet (P < .05). Serum zonulin levels were also significantly different between HLA-DQ2-positive and HLA-DQ2/DQ8-negative patients on a gluten-free diet (P < .05).

“This study has increased our understanding of zonulin and how it might contribute to the development of these common and disabling bowel conditions,” Barbara said in the press release. “Hopefully, our work will lead to new diagnostic and therapeutic strategies for patients with these and possibly other autoimmune conditions.” – by Adam Leitenberger

Reference:

Barbara G, et al. Abstract OP269. Presented at: UEG Week; Oct. 24-27, 2015; Barcelona, Spain.

Disclosures: Healio Gastroenterology was unable to confirm relevant financial disclosures at the time of publication.