Fecal Zonulin as a Noninvasive Biomarker of Intestinal Permeability in Pediatric Patients with Inflammatory Bowel Diseases-Correlation with Disease Activity and Fecal Calprotectin.

Edyta Szymanska,Jaroslaw Kierkus,Aldona Wierzbicka,Maciej Dadalski

doi:10.3390/jcm10173905

Edyta Szymanska, Jaroslaw Kierkus + Show 2 more

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https://doi.org/10.3390/jcm10173905

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Abstract

Background: Recent data indicate that increased intestinal permeability plays a key role in the pathogenesis of inflammatory bowel diseases (IBD) and correlates with disease flare. Since zonulin related proteins (ZRP) are the proteins that increase permeability in the epithelial layer of the small intestine by reversibly modulating the intercellular tight junctions, they may serve as a new, noninvasive biomarker of disease activity. The aim of this study was to investigate fecal ZRP in pediatric IBD patients as well as its correlation with disease activity and fecal calprotectin (FCP). Methods: Ninety-four individuals: 47 Crohn’s disease (CD) patients, 41 ulcerative colitis (UC) patients, and 6 healthy controls were examined for fecal ZRP. Values were correlated to IBD type, disease activity for IBD patients, and FCP for all children included in the study. A stool specimen was collected the day before the visit to the hospital, then fecal ZRP and FCP were tested using the ELISA test. Non-parametric statistical tests were used for data analysis. Results: The level of fecal ZRP was higher among IBD patients compared to the control group (CG): medians for CD—113.3 (53.6–593.6) ng/mL; UC—103.6 (50.7–418.3) ng/mL; and CG—46.9 (31.8–123.0) ng/mL (p < 0.05). No difference in fecal ZRP concentration was observed between children with CD and those with UC (p = 0.55). A slight correlation between disease activity (PCDAI for CD and PUCAI for UC) and the fecal ZRP level was found for CD (p = 0.03/R = 0.33), but not UC (p = 0.62/R = 0.08), patients. A correlation between fecal ZRP and FCP was observed (R = 0.73, p = 0.00). Conclusions: Fecal ZRP levels are increased among those with IBD, are associated with CD activity, and strongly correlate with FCP. Further research into the role of intestinal permeability in IBD and the clinical usefulness of ZRP in IBD is warranted.

Highlights

Recent studies on the pathogenesis of inflammatory bowel disease (IBD)—Crohn’s disease (CD) and ulcerative colitis (UC)—indicate a significant role of increased intestinal epithelial permeability in disease development [1].Zonulin is a 47-kDa human protein that increases permeability in the epithelial layer of the small intestine through reversibly modulating the intercellular tight junctions, whose proper functioning is crucial for maintaining physiologic processes in the intestine [2]
Values were correlated to inflammatory bowel diseases (IBD) type, disease activity for IBD patients (PCDAI, PUCAI), and fecal calprotectin (FCP) for all children included in the study
PCDAI was 2.5 (0.0–52.5), and the median PUCAI for children with UC was 5.0 (0.0–40.0), which means that the majority of patients included in the study had mildly active disease at this time. (Table 1)

Summary

Introduction

Zonulin is a 47-kDa human protein that increases permeability in the epithelial layer of the small intestine through reversibly modulating the intercellular tight junctions, whose proper functioning is crucial for maintaining physiologic processes in the intestine [2]. It is not exclusively the pre-haptoglobin 2 protein that is required, but a family of structurally and functionally related proteins called zonulin related proteins (ZRP); it is recommended to indicate ZRP rather zonulin [3].

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