The prevalence of food allergy has experienced an unprecedented increase in Western societies, rising by as much as 20% in a recent ten-year period. We have previously described a role for mucosa- associated commensal bacteria in protection from allergic sensitization in mice. To understand how the microbiota regulates allergic disease in humans, we colonized germ free mice with human bacteria from the feces of healthy or cow?s milk allergic (CMA) infants. Our data shows that colonization with bacteria derived from healthy human infant feces is sufficient to protect mice against sensitization to the cow?s milk allergen b-lactoglobulin (BLG), whereas colonization with feces from human CMA infants fails to protect. By analyzing operational taxonomic units (OTUs) differentially abundant between our human fecal donors (4 healthy, 4 CMA) we have defined a microbial signature that distinguishes the CMA and heathy populations in both the human donors and the colonized mice, emphasizing the clinical relevance of our gnotobiotic model. RNASeq analysis of ileal intestinal epithelial cells revealed differentially expressed genes (DEGs) that distinguished healthy- and CMA-colonized mice across all donors. Correlation of ileal OTUs with DEGs in the ileum of healthy-colonized mice identified a Clostridial species, Anaerostipes caccae, that protected against an allergic response to food. Our findings demonstrate a causal role for the healthy infant microbiota in protection against food allergy and suggest that interventions that modulate bacterial communities may inform the development of novel therapeutic strategies for this disease. In this proposal we will further refine our OTU signature and examine whether the CMA infant microbiome is an atopic microbiome in Aim 1.
Aim 2 will explore how healthy intestinal bacteria influence the response to food allergens by examining their impact on innate lymphoid cell function, early T/B priming and effector T cell differentiation and migration. The robust, pre-clinical gnotobiotic models we describe will provide an ideal system in which to identify key host-microbial interactions that contribute to the maintenance of tolerance to dietary antigen in food allergy.

Public Health Relevance

Food allergies have become a major public health concern and represent an unmet clinical need. The scientific premise of our proposal is that the increasing prevalence of food allergies can be explained, in part, by alterations in the composition and function of the commensal microbiome. We have created robust, pre-clinical gnotobiotic models to identify key host-microbial interactions that contribute to the maintenance of tolerance in food allergy and will inform the development of novel microbiome modulating therapeutics to prevent or treat this disease.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
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Gastrointestinal Mucosal Pathobiology Study Section (GMPB)
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Dong, Gang
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University of Chicago
Schools of Arts and Sciences
United States
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