Emerging Biomarkers in Pediatric Food Allergy: From Mechanistic Endotyping to Precision Diagnosis and Therapeutic...

Background: Food allergy is a heterogeneous pediatric disease involving IgE-mediated, non-IgE-mediated, and mixed immune mechanisms, with manifestations ranging from mild symptoms to life-threatening anaphylaxis. Current diagnostic tools, including clinical history, skin prick testing, serum-specific IgE measurement, and oral food challenge, have limitations in specificity, invasiveness, prognostic value, and ability to guide personalized management. Methods: This narrative review summarizes emerging biomarkers in pediatric food allergy and evaluates their diagnostic, prognostic, predictive, and therapeutic potential. A literature search was conducted in PubMed/MEDLINE and Cochrane Central for English-language studies published between December 2015 and March 2026. Eligible studies included original clinical or translational research involving children aged 0-18 years and assessing functional cellular assays, epithelial barrier markers, intestinal permeability, gut microbiota, metabolomics, transcriptomics, proteomics, epigenetics, and immune biomarkers. Findings were synthesized qualitatively according to biomarker category and biological function. Results: Functional cellular biomarkers, particularly the basophil activation test, show the greatest translational readiness, with high diagnostic specificity, utility in reaction threshold and severity assessment, and potential value for monitoring oral immunotherapy. Biomarkers of epithelial barrier dysfunction, including zonulin, tight junction proteins, epithelial injury markers, filaggrin variants, and epithelial-derived cytokines, provide mechanistic insight into allergic sensitization and gastrointestinal phenotypes but remain insufficiently validated. Microbiota-derived, metabolomic, transcriptomic, proteomic, epigenetic, and integrated multi-omics approaches offer promising tools for risk prediction, tolerance monitoring, endotype identification, and precision medicine. Conclusions: Emerging biomarkers may improve diagnosis, risk stratification, therapeutic monitoring, and personalized care in pediatric food allergy. However, standardized assays, large longitudinal pediatric studies, and external validation are required before routine clinical implementation.