Dietary Interventions to Mitigate Microbiome-mediated Food Allergic Responses

Funded by Food Allergy Fund

Susan Lynch, PhD as Principal Investigator

Thirty-three million Americans, or one-in-ten adults and one-in-thirteen children, have IgE-mediated food allergies. Studies from our group and others have linked gut microbiome composition and, more specifically, microbial metabolic dysfunction with food allergy. Evidence that the fecal microbiome promotes food allergy and represents a target for intervention, comes from studies of germ-free mice, in which transfer of the fecal microbiome from a milk-allergic patient was sufficient to induce cow’s milk allergy and anaphylaxis in recipient animals. More recently, in peanut allergic children, we identified microbial metabolic features associated with resolution of peanut allergy. These include immunomodulatory metabolites that control regulatory T cell populations that are critical to down-regulating allergic responses. These data indicate that manipulation of the gut microbiome to promote production of metabolites that resolve food allergy represents a novel and accessible therapeutic strategy for food allergic patients.

Diet profoundly impacts gut microbiomes and their metabolic productivity. However, consumption of identical meals or even specific dietary substrates leads to distinct metabolic products, the variance of which relates to fecal microbiome function. Our previous studies demonstrated that specific microbial-derived metabolites influence allergic inflammation. Yet, how food allergic gut microbiomes process dietary substrates to produce metabolites that shape immune function and hyper-responsiveness to food allergens is unknown, and whether dietary substrates can be used to mitigate food allergic immune responses remains entirely unexplored. We hypothesize that microbial metabolism of specific dietary substrates promotes hyper-responsive immunity to food allergens, while others mitigate allergic response and aim to identify those that reproducibly suppress allergic response. Thus, we propose to leverage a large (n=127) collection of banked fecal samples from peanut allergic patients to model diet by gut microbiome interactions in vitro to identify dietary substrates that reduce immune responsiveness to peanut allergen. If successful, this approach will be expanded to include patients of varying ages with additional food allergies e.g. milk, egg or tree nut, data that will be fed into our model. Addition of such data would improve prediction accuracy and facilitate our ultimate aim of precision nutritional interventions to manipulate the gut microbiome and mitigate food allergic responses, particularly in those with severe disease.