Food allergy is associated with altered epithelial gene expression driven by early life dysbiosis

Abstract

Abstract A marked increase in disease prevalence has made food allergies a major public health concern. One hypothesis for this rise is that recent lifestyle factors have altered the composition of the intestinal microbiota, increasing susceptibility to allergic disease. Host-microbiota interactions are essential for immune homeostasis, and perturbations of naturally-selected bacterial populations, a condition called dysbiosis, are linked to many different pathologies. To investigate the role of the microbiota in regulating food allergies, we colonized germ free mice with bacteria from healthy or cow’s milk allergic (CMA) infants. We found that colonization with bacteria from healthy infants is sufficient to protect against sensitization to the milk allergen β-lactoglobulin (BLG). In contrast, colonization with bacteria from CMA infants fails to protect, resulting in high concentrations of BLG-specific IgE and anaphylactic responses following BLG challenge. Analysis of bacterial taxa in feces from multiple healthy and CMA infants identified significant differences in bacterial composition that distinguished health status in both the human donors and the colonized mice, emphasizing the clinical relevance of our gnotobiotic model. RNAseq of ileal epithelial cells revealed differentially expressed genes (DEGs) that separate healthy- and CMA-colonized mice. Integration of ileal bacteria and ileal DEGs identified taxa that were significantly correlated with gene expression changes. Together, these results demonstrate that the composition of the intestinal microbiota regulates systemic responses to dietary antigen and suggest that modulation of these communities may be useful in treatment or prevention of food allergy.