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. 2024 Jan 1;153(1):e2023063050.
doi: 10.1542/peds.2023-063050.

Zonulin as a Biomarker for the Development of Celiac Disease

Tracey M DaFonte  1   2   3 , Francesco Valitutti  4 , Victoria Kenyon  2   3 , Joseph J Locascio  5   6 , Monica Montuori  7 , Ruggiero Francavilla  8 , Tiziana Passaro  9 , Marco Crocco  10 , Lorenzo Norsa  11 , Pasqua Piemontese  12 , Mariella Baldassarre  13 , Alessio Fasano  1   2   3   4 , Maureen M Leonard  1   2   3 ; CD-GEMM Study Group
Affiliations

Zonulin as a Biomarker for the Development of Celiac Disease

Tracey M DaFonte et al. Pediatrics. .

Abstract

Objectives: Increased intestinal permeability seems to be a key factor in the pathogenesis of autoimmune diseases, including celiac disease (CeD). However, it is unknown whether increased permeability precedes CeD onset. This study's objective was to determine whether intestinal permeability is altered before celiac disease autoimmunity (CDA) in at-risk children. We also examined whether environmental factors impacted zonulin, a widely used marker of gut permeability.

Methods: We evaluated 102 children in the CDGEMM study from 2014-2022. We included 51 CDA cases and matched controls, who were enrolled for 12 months or more and consumed gluten. We measured serum zonulin from age 12 months to time of CDA onset, and the corresponding time point in controls, and examined clinical factors of interest. We ran a mixed-effects longitudinal model with dependent variable zonulin.

Results: Children who developed CDA had a significant increase in zonulin in the 18.3 months (range 6-78) preceding CDA compared to those without CDA (slope differential = β = 0.1277, 95% CI: 0.001, 0.255). Among metadata considered, zonulin trajectory was only influenced by increasing number of antibiotic courses, which increased the slope of trajectory of zonulin over time in CDA subjects (P = .04).

Conclusions: Zonulin levels significantly rise in the months that precede CDA diagnosis. Exposure to a greater number of antibiotic courses was associated with an increase in zonulin levels in CDA subjects. This suggests zonulin may be used as a biomarker for preclinical CeD screening in at-risk children, and multiple antibiotic courses may increase their risk of CDA by increasing zonulin levels.

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Conflict of interest statement

CONFLICT OF INTEREST DISCLOSURES: Ms Kenyon serves as a consultant for Takeda Pharmaceuticals; Dr Leonard acted as a consultant for Anokion; Dr Fasano is a stockholder at Alba Therapeutics, is an advisory board member for Axial Biotherapeutics and Ubiome, and has a speaker agreement with Mead Johnson Nutrition; and the other authors have declared that no conflicts of interest exist. None of the financial disclosures above are related to this study.

Figures

FIGURE 1
FIGURE 1
Values predicted for serum zonulin across months previous to CDA or last assessment, by the model fixed effects. (Pooled across countries. Predicted values for months less than −30 not shown because they are based on too few observations in that region - approximately 17% of total).
FIGURE 2
FIGURE 2
Zonulin values predicted by model fixed effects, for (A) controls or (B) CDA subjects versus months previous to CDA or last assessment and number of antibiotic courses. (Illustrated for USA). (Predicted values for months less than −30 not shown because of too few observations - approximately 17% of total).
See this image and copyright information in PMC

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