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.