Early-Life Biomarkers in Food Allergy Development: A Systematic Review of Immunological and Intestinal Pathways

Background: The increasing incidence of pediatric food allergy (FA) drives an imperative for mechanistically driven risk stratification beyond descriptive diagnostics. The current systematic review aims to assess the predictive and diagnostic value of early-life non-invasive biomarkers: cord blood IgE (CS-IgE), fecal calprotectin (FC), fecal zonulin (FZ) and secretory IgA (SIgA). Methods: In accordance with the PRISMA guidelines, we performed a systematic literature search on PubMed/MEDLINE and Scopus for English observational studies published in 2009-2025. The titles and abstracts were screened by two independent reviewers and methodological quality was assessed using the Newcastle-Ottawa Scale (NOS). Results: A total of 17 studies met the inclusion criteria. This synthesis demonstrates that CS-IgE reflects a systemic atopic predisposition rather than serving as a highly sensitive predictor for isolated FA. Fecal calprotectin was the most consistent marker of inflammatory activity in non-IgE-mediated food allergies, with median values in food allergy ranging from approximately 200 to 410 µg/g and proven useful in dietary monitoring. Fecal zonulin reflects epithelial barrier dysfunction; however, its clinical utility is limited by suboptimal assay specificity. SIgA primarily reflects mucosal immune maturation and tolerance development rather than serving as a direct diagnostic marker. Conclusions: Although CS-IgE, FC, FZ and SIgA exhibit potential in the risk stratification of early FA, their clinical implementation is complicated by methodological heterogeneity and concerns regarding analytical specificity, especially with respect to zonulin assays. We propose an integrated multi-biomarker risk stratification model as a conceptual hypothesis requiring prospective validation in future large-scale studies.