Dietary fiber-based oral nanovaccine promotes gut-to-nose trafficking of regulatory cells and drives antigen-specific tolerance to relieve airway allergy.

Current therapies for allergic rhinitis primarily provide symptomatic relief but fail to establish durable antigen-specific immune tolerance. Here, we developed an oral nano-dietary fiber (NDF) platform that integrates allergen delivery with microbiota-driven immunomodulation, using dextran as both an antigen carrier and a fermentable substrate for intestinal bacteria. NDF enabled coordinated allergen release and sustained short-chain fatty acid (SCFA) production in the gut, promoting SCFA-FFAR2-dependent expansion of regulatory B and T cells and their trafficking to the nasal mucosa. In murine models, NDF slowed disease progression, improved airway function, and reduced allergen-specific IgE levels. Together, these findings establish NDF as an oral tolerogenic vaccine that provides durable protection against allergic airway disease through the gut-nasal axis.