Korean red ginseng extract suppresses food allergy by remodeling the gut microbiota and restoring immune homeostasis in IL4raF709 mice

Food allergy (FA) is a growing health concern with limited therapeutic options. While Korean Red Ginseng Extract (KRGE) exhibits immunomodulatory and microbiota-modulating properties, its specific effects and mechanisms in FA are not fully understood. We evaluated the anti-allergic efficacy of KRGE in IL4ra F709 mice, a model genetically predisposed to IgE-mediated anaphylaxis. Mice were sensitized with ovalbumin (OVA) and staphylococcal enterotoxin B (SEB) and challenged with OVA. KRGE was administered orally prior to and during sensitization. Clinical symptoms, serum IgE levels, IL-33 levels, and intestinal histology were assessed. Mesenteric lymph nodes and Peyer’s patches immune cell populations were analyzed by flow cytometry. Fecal microbiota composition was profiled using 16S rRNA sequencing and quantitative PCR; correlations between phenotype and microbiota were investigated. Results showed KRGE significantly suppressed anaphylactic symptoms, including hypothermia and mortality, and reduced OVA-specific IgE and IL-33 levels. KRGE restored intestinal epithelial integrity and normalized Peyer's patch hypertrophy. Immunologically, it decreased IL-13-producing T follicular helper cells and rebalanced dendritic cell subsets, increasing tolerogenic CD103 + cDC1 and reducing pro-allergic CD11b + cDC2. Microbiome analysis revealed that OVA/SEB increased pro-inflammatory Lachnospiraceae and Ruminococcaceae while depleting beneficial Lactobacillaceae and Bifidobacteriaceae. KRGE reversed these changes, notably enriching Akkermansia muciniphila and Lactobacillus gasseri. Correlation analysis revealed that Akkermansia, Lactobacillus, and Christensenellaceae were negatively correlated with allergic markers and positively correlated with epithelial integrity. In contrast, Oscillospiraceae (Eubacteriumg8, Acetobacter, and Pseudoflavonifractor) was associated with allergy exacerbation. KRGE mitigates FA in IL4ra F709 mice by restoring gut microbiota balance and immune homeostasis, suggesting its potential as a microbiota-targeted intervention for FA.