It has been proposed that zonulin, a tight junction protein regulator, is involved in the pathogenesis of celiac disease (CD). In this regard, various studies compared the mean serum zonulin in patients with CD and healthy controls. However, this remains a subject of controversy due to contradictory results. Therefore, the goal of the present study was to summarize the findings of studies comparing CD patients’ serum zonulin levels to healthy controls.

We searched PubMed, Scopus, and ISI Web of Science databases up to May 2022. All observational studies measured serum zonulin in adult patients with CD and healthy controls were included without language or date restrictions. The standardized mean differences (SMDs) and standard deviations were pooled using a random-effects model.

Of 708 studies, six studies with 184 CD and 206 control participants were included in the systematic review and meta-analysis. According to a pooled analysis, CD patients had significantly higher zonulin levels than healthy controls (SMD=1.08ng/mL; 95% CI=0.64, 1.52; P<0.001). Subgroup analyses were performed according to adherence to a gluten-free diet (GFD), zonulin assessment method, and CD diagnosis. The significant effect was maintained in all subgroups.

CD is significantly correlated with a higher level of serum zonulin. Thus, zonulin could be a potential biomarker for the diagnosis of CD, which deserves further investigation.