Study On the Regulation of OVA-Induced Food Allergy Via the Gut Immune–Microbiota Axis by Milk-Derived Extracellular Vesicles

Food allergy (FA) is an increasing global public health concern lacking effective preventive strategies. This study systematically evaluated the immunomodulatory effects of cow’s milk-derived extracellular vesicles (C-EVs), buffalo milk-derived extracellular vesicles (B-EVs), and yak milk-derived extracellular vesicles (Y-EVs) in an Ovalbumin (OVA) -induced FA mouse model. All EVs treatments significantly alleviated allergic symptoms, reduced OVA-specific IgE/IgG1 and MCPT-1 levels, and improved intestinal barrier integrity. Among them, Y-EVs showed the strongest protective effects, markedly upregulating ZO-1, Occludin, and Claudin-1 expression and restoring Th1/Th2 immune balance by suppressing IL-4, IL-5, and IL-13 levels in spleen and mesenteric lymph nodes. In addition, Y-EVs partially restored gut microbial diversity and reversed OVA-induced alterations in beneficial bacteria, including Lactobacillus, Ligilactobacillus, and Akkermansia. These findings suggest that milk-EVs, particularly Y-EVs, possess source-dependent antiallergic potential for precision nutrition applications.