Gut microbial composition modulates endogenous food-specific CD4+ T cells in food allergy

Abstract

Abstract The growing food allergy epidemic is thought to be related to changing environmental factors, particularly changes in the gut microbiome. While prior work has demonstrated that food allergy can be modulated by gut microbes, little is known about how food allergen-specific CD4+ T cells are affected by gut microbial composition. Here, we report that food allergy severity differs between mice obtained from 2 different specific pathogen-free mouse vendors (Jackson Labs [Jax] and Taconic Biosciences [Tac]). Mice from Tac develop diarrhea and anaphylaxis after fewer allergen exposures than mice from Jax. Using food allergen peptide: MHCII tetramers, we also find that Tac mice have fewer allergen-specific regulatory T cells in the small intestine compared to mice from Jax with concomitant increase in allergen-specific Th2 cells. In addition, Tac mice have increased intestinal permeability. Increased food allergy severity, phenotype of allergen-specific T cells, and increased gut permeability were transferable to Jax animals via co-housing, which corresponded to a shift in Jax microbial communities towards those found in Tac mice. Our findings demonstrate that food allergen-specific Treg cells can be modulated by gut microbial community composition, which in turn is correlated to food allergy severity.