Engineering Allergenicity: A Review of Non-Thermal Processing Approaches to Reduce Immune Reactivity in Foods

Food allergy rates are escalating globally, driven by the interplay of inherited traits, environmental triggers, diet, and gut microbiome composition. Sensitization typically occurs through dermal, respiratory, or gastrointestinal routes, with epithelial barrier dysfunction and Th2-skewed immune responses playing key roles. Understanding the mechanisms and pathways of sensitization is critical to developing effective mitigation strategies. Efforts are underway to evaluate how both traditional heating and innovative non-thermal techniques can modify allergenic proteins in commonly allergenic foods. Thermal methods can denature allergenic proteins but may also compromise nutritional and sensory quality. Unlike heat-based processes, innovative non-thermal methods—including pressure-based, light-based, plasma, and sound technologies—can restructure proteins and diminish IgE reactivity without compromising food integrity. However, outcomes are highly context-dependent, influenced by food matrix, processing parameters, and assessment methods. Limitations in current in vitro and in vivo models, lack of standardized allergenicity testing protocols, and insufficient clinical validation remain key barriers. This review synthesizes current knowledge of allergy mechanisms with technological approaches for allergen reduction, highlighting promising interventions, existing constraints, and the need for integrated research to develop safe, hypoallergenic foods.