Food Allergen Dose Differentially Controls the Intensity of the Developing Food Allergy Response in an Oral Sensitization-Based Murine Model.

Abstract

Although mouse models are invaluable tools for allergenicity assessment, the relationship between allergen dose and the intensity of induced food allergy (FA) response remains poorly understood in oral sensitization-based murine models. This study aimed to develop an oral sensitization BALB/c mouse model and identify the optimal antigen dose required to elicit a maximal response, thereby establishing a robust framework for assessing the allergenicity of food proteins. BALB/c mice were orally administered varying doses of ovalbumin with cholera toxin as an adjuvant. The optimal sensitization dose was determined by assessing allergic symptoms (hypothermia, diarrhea) and immunological parameters (IgE, mouse mast cell protease-1 [mMCPT-1], Th2 responses). Furthermore, mass spectrometry-based untargeted metabolome profiling was employed to characterize jejunal metabolomic alterations. Our results demonstrated that mice receiving a medium dose of ovalbumin per immunization developed the most severe anaphylactic reactions upon challenge. This was accompanied by significantly elevated levels of mMCPT-1 and ovalbumin-specific IgE/IgG1, enhanced Th2 responses, and an increase in germinal center B cells and cDC2 cells. Notably, post-challenge serum IgE levels strongly correlated with the severity of anaphylactic reactions. Moreover, metabolomic profiling revealed a coordinated dysregulation of purine metabolism in the small intestine of allergic mice. In conclusion, this study established an optimized, medium-dose FA murine model and suggested potential intestine-related metabolic changes in FA responses. This dual immunological and metabolic framework provides new insights into FA pathogenesis and offers valuable guidance for evaluating the allergenicity of novel proteins.