A shift in gut microbial community alters antigen-specific regulatory T cells and disease phenotype in a model of food allergy 3125

Abstract Description The intestinal immune system must handle the conundrum of maintaining barrier function in the face of a dense and complex microbial community, while allowing uptake of and tolerance to food. However, little is known about the influence of gut microbes on immune responses to food antigens. We identified substantial differences in a food allergy model in mice with distinct fecal microbial communities. Mice from either Jackson (Jax) or Taconic (Tac) vendors were sensitized via injection of ovalbumin (OVA) plus alum. Two weeks after sensitization, mice underwent oral gavage every 2-3 days with OVA. Allergic response was marked by production of profuse watery stool within 60 minutes following gavage. After 3 gavages, 74% of Tac mice developed diarrhea compared to 23% of Jax mice. In the small intestine, Tac mice had significantly fewer OVA-specific regulatory T cells and significantly more mucosal mast cells. Tac and Jax mice had substantially different stool bacterial communities as determined by shotgun metagenomic sequencing. However when mice were cohoused prior to OVA sensitization, Jax mice had stool communities resembling those from Tac and developed diarrhea at the same rate as Tac animals. We found that shifts in bacterial communities led to changes in allergen-specific CD4+ T cells, mucosal mast cells, and severity of food allergy. Ultimately, these findings can help us understand why certain individuals develop food allergy and might lead to new therapies. Funding Sources ARW is supported by the Life Science Research Foundation and Open Philanthropy. Topic Categories Mucosal and Regional Immunology (MUC)