Allergic rhinitis (AR) affects over 400 million people worldwide, and its prevalence keeps rising with urbanization and dietary change. The disease stems from a breakdown of mucosal tolerance and allergen-specific type 2 inflammation. Antihistamines and intranasal corticosteroids ease symptoms, and sublingual immunotherapy remains the only approved allergen-specific option, but none reliably restores durable tolerance, while long treatment courses and local adverse reactions erode patient compliance.
In a study published in iMeta, a team led by Prof. ZHAO Ruifang and Prof. NIE Guangjun from the National Center for Nanoscience and Technology (NCNST) of the Chinese Academy of Sciences, together with collaborators from Peking University First Hospital and Capital Medical University, developed an oral nano-dietary fiber (NDF) platform that works as a tolerance-inducing nanovaccine, and uncovered a surprising cellular route through which it protects the airway.
The project began with a population clue. Analyzing data from 8,092 adults in the NHANES cohort, the researchers found that AR prevalence fell progressively as dietary fiber intake rose. Compared with people eating more than 25 g of fiber per day, those eating less than 15 g faced significantly higher odds of AR (odds ratio 1.39), and every additional 10 g per day was associated with a 13.4% reduction in prevalence. Gut microbes ferment fiber into short-chain fatty acids (SCFAs), metabolites known to expand regulatory immune cells, so the team set out to turn this protective association into a medicine.
Their design combines allergen delivery with in situ metabolite production. The model allergen ovalbumin (OVA) was encapsulated inside β-dextran nanoparticles through a freezing-induced aqueous phase separation method, yielding uniform spheres of about 89 nm with an encapsulation efficiency exceeding 96%. After oral dosing, the particles lingered in the intestine for more than 16 hours, far longer than free allergen, while microbial fermentation raised fecal levels of acetate, propionate, butyrate and isobutyrate. In cell experiments, butyrate steered dendritic cells toward a tolerogenic state, restoring IL-10 production and dampening activation markers, creating a regulatory microenvironment in which the released allergen is presented to the immune system.
In an OVA-induced AR mouse model, an eight-day oral course of NDF markedly reduced sneezing, nasal allergen-specific IgE and nasal surface temperature after challenge. The treatment boosted IL-10 while suppressing the Th2 cytokines IL-4, IL-5 and IL-13, and eased eosinophil infiltration and tissue swelling in the nasal mucosa. Mechanistic studies showed that the effect runs through SCFA signaling: in mice lacking the metabolite receptor FFAR2, NDF lost its ability to suppress Th2 cytokines, raise IL-10, or expand regulatory T and B cells.
The most striking finding concerns where tolerance is enforced. Using photoconvertible KikGR mice, the team irreversibly labeled gut cells with a fluorescent tag and watched them travel. After NDF treatment, gut-derived cells accumulated in the nasal mucosa, where they displayed a regulatory gene program and produced abundant IL-10 upon allergen re-encounter. Among these IL-10 producers, 73.4% were B cells and 25.6% were T cells, identifying IL-10-producing regulatory B cells as the primary gut-trained peacekeepers that migrate to the nose, a result that challenges the conventional T-cell-centric view of oral tolerance.
Protection proved both durable and broad. Rechallenged four months after the eight-day course ended, NDF-treated mice kept nasal histamine, IL-4 and allergen-specific IgE at levels comparable to healthy animals, while the clinical antihistamine desloratadine offered only partial protection. The platform also generalized: loaded with mugwort pollen extract, it relieved pollen-induced AR, and in an asthma model it improved pulmonary function and lowered serum IgE. Because the design is modular, the authors note, it could in principle be adapted to different allergens and developed toward personalized therapy for polysensitized patients, though dosing, long-term safety and the microbial taxa responsible for fermentation still need further study.
