Epicutaneous Exposure to Egg Ovalbumin Highlights a Potential Skin-Gut Immune-Microbiota Axis in Food Allergy Risk

Food allergy is an increasing concern in food safety and public health, yet risk assessment of food proteins remains largely limited to oral exposure. Here, ovalbumin (OVA) was used to establish a murine model of epicutaneous exposure under impaired skin barrier conditions. Epicutaneous OVA exposure induced pronounced Th2-skewed immunity, dendritic cell activation, and allergic phenotypes, with a hierarchical pattern involving initial activation in skin-draining lymph nodes, followed by amplified responses in mesenteric lymph nodes. This was accompanied by gut microbiota dysbiosis, including enrichment of Staphylococcaceae and depletion of beneficial bacteria, along with altered immunoregulatory metabolic pathways. The differential metabolites were significantly associated with Th2-related immune parameters. Collectively, these results suggest that epicutaneous exposure to food proteins may increase susceptibility to food allergy and is associated with coordinated immune and microbial alterations across the skin and gut. These findings support the consideration of multiple exposure routes in food protein risk assessment.