Microbial Therapeutics for the Prevention and Treatment of Food Allergy

Food allergy affects approximately 8% of children and 11% of adults in the United States. Available treatments, including oral immunotherapy and anti-IgE, are not known to lead to remission. There is now increasing evidence implicating the gut microbiome as a key regulator of allergic inflammation. Distinct microbial and metabolomic alterations characterize food-allergic individuals, and gnotobiotic mouse models show that fecal microbiota from food-allergic donors transfer allergic sensitization, whereas microbiota from healthy donors protect from anaphylaxis through induction of tolerogenic Foxp3⁺RORγt⁺ regulatory T cells (Tregs). Goblet cell-derived resistin-like molecule beta induces food allergy through modulation of the gut microbiome and depletion of indole-producing species. These findings have inspired the development of 5 microbial therapeutic approaches: probiotics, rationally defined bacterial consortia, fecal microbiota transplantation, metabolite-based approaches, and biologics targeting dysbiosis-associated pathways. Early-phase clinical studies support feasibility, yet long-term safety, durability, and reproducibility remain uncertain. Major challenges include interindividual variability, ecological complexity, and regulatory standardization. Microbiome-directed therapeutics hold promise to transform food allergy management from temporary desensitization toward remission and durable immune tolerance. The application of systems biology approaches integrating metabolomics, transcriptomics, and immune phenotyping will be essential to unravel the complex host-microbial interactions that underlie the efficacy of these approaches.