Daidzein Confers Prophylactic Protection against Food Allergy by Restoring Immune Regulation, Intestinal Barrier Integrity, and Microbiota-Metabolite Homeostasis

Food allergy (FA) is characterized by impaired immune tolerance, intestinal barrier disruption, and gut microbiota dysbiosis. However, whether dietary bioactive compounds such as daidzein can simultaneously modulate these interconnected immune-barrier-microbiota alterations in a preventive context remains poorly understood. The effects and mechanisms of daidzein were systematically investigated in an ovalbumin (OVA)-induced murine FA model through the integration of immunological, histological, and microbiota-metabolite analyses. Results demonstrated that daidzein pretreatment attenuated allergic manifestations and mast-cell activation while shifted toward a T-helper 1 (Th)-biased profile, effectively reducing Th2- and Th17-associated cytokines. Daidzein also strengthened intestinal barrier integrity by upregulating the expression of Claudin-1 and ZO-1. Furthermore, daidzein remodeled the gut microbial community by enriching butyrate-producing genera such as <i>Roseburia</i>, this enrichment was positively associated with elevated fecal butyrate levels. Collectively, these findings highlight the coordinated effects of daidzein on Th-cell-mediated immunity, epithelial barrier function, and microbiota-metabolite profiles, supporting its potential as a dietary candidate for the preventive management of FA in this murine model.