Disruption of mucosal immune homeostasis in food allergy: a convergence of genetic, barrier, microbiome, and environmental triggers

Food allergy is a pathological immune response to food antigens. Its global prevalence continues to rise, making it a significant public health and food safety concern. This review describes the pathogenesis of food allergy, proposing that its development results from the interplay of multiple factors, including genetic background, disruption of the intestinal barrier, breakdown of oral tolerance, gut microbiome dysbiosis, and early-life environmental exposures. Genetic background establishes a baseline risk for the disease. Compromised intestinal barrier integrity facilitates abnormal allergen translocation and alarmin release, thereby initiating a type 2 immune response. The collapse of oral tolerance is marked by impaired regulatory T cell function and a dominant Th2 response. Gut microbiome dysbiosis, by altering key metabolites such as short-chain fatty acids, further exacerbates immune dysregulation. Dietary and environmental factors program these processes during critical early-life windows. Together, these elements form a dynamic, interactive pathogenic network. Future research should integrate multi-omics and systems biology approaches to better elucidate the interaction mechanisms within this network, thereby advancing the development of precise preventive and therapeutic strategies for food allergy.