Luminal Clinical

Abstract

Background: Dysregulation of the zonulin pathway has been linked to a "leaky gut" due to zonulin's putative role as a modulator of intestinal epithelial tight junctions. Zonulin is a proposed contributor to the pathogenesis of non-celiac gluten sensitivity/irritable bowel syndrome (NCGS), celiac disease (CD), and inflammatory bowel disease (IBD). However, controversy lies in zonulin's utility as a serum biomarker of disease and in the assays used for its assessment. Aims: To characterize serum zonulin levels among individuals with gastrointestinal conditions (NCGS, CD, and IBD) and healthy individuals and to verify existing commercially available assays for zonulin quantification. Methods: Serum zonulin was measured in patients with self-reported NCGS (n = 36), CD (n = 37), and IBD (n = 20), as well as healthy participants (n = 49) by ELISA (CUSABIO). Zonulin non-producers were determined by western blot-based haptoglobin phenotyping. The commercial assay was spiked with recombinant zonulin for verification. Zonulin levels in selected sera were compared with those determined by another commercially available assay (Immundiagnostik). Results: Overall, 33 of 36 patients with NCGS, 34 of 37 with untreated CD, 19 of 20 with IBD, and 46 of 49 healthy participants were zonulin producers. Compared with healthy individuals (median, 0.00 ng/mL; interquartile range [IQR], 0.00 ng/mL), patients with NCGS (median, 0.25 ng/mL; IQR, 0.88 ng/mL), CD (median, 0.07 ng/mL; IQR, 1.27 ng/mL), and IBD (median, 1.73 ng/mL; IQR, 2.02 ng/mL; all P < 0.0001) had elevated serum zonulin levels ( Figure 1). Levels in IBD were higher than those in NCGS (P = 0.001) and CD (P = 0.002), with no differences between NCGS and CD.However, recombinant zonulin protein was not detected by the assay. In addition, two of 19 participants who were zonulin non-producers had levels of the protein detected by the assay. There was poor correlation between the results of the two commercially available assays (for levels expressed in ng/mL, n = 29; r = 0.24; P = 0.22). Conclusion: Serum zonulin levels are elevated in patients with NCGS, CD, and IBD, with the highest levels in IBD when tested using a previously applied commercial ELISA. However, recombinant zonulin protein was not detected by this assay, zonulin non-producers had zonulin detected, and there was no concordance with the results from an alternative assay. Rather than support a role for zonulin in intestinal disease pathogenesis, these results cast doubt on the validity of commercially available zonulin assays.Unexpectedly high rates of significant findings at capsule endoscopy in young women with suspected small intestinal bleeding: Don't be ageist S ALUKAIDEY,* R KNIGHT, † L BESWICK,* , † C HAIR* , † *University Hospital Geelong, Geelong, † Deakin University, School of Medicine, Melbourne, Victoria, AustraliaBackground: Capsule endoscopy (CE) is widely used in female patients who present with suspected recurrent small intestine bleeding. However, the yield from CE in young women (aged < 50 years)...