Funded by the Food Allergy Fund

Cathryn R. Nagler , Ph.D., Pritzker School of Molecular Engineering and Departments of Pathology, Pediatrics and Medicine Biological Sciences Division, University of Chicago as Principal Investigator

The recent dramatic rise in the incidence of food allergy has paralleled various 21st century lifestyle factors which have reduced gut microbial diversity and depleted key protective bacteria. We, and others, have shown that individuals with food allergy lack many bacteria in the Clostridia class, both in infant cohorts and adults. Clostridia and their metabolic products, particularly butyrate, regulate intestinal barrier function, induce regulatory T cells, and protect against allergy. Depletion of butyrate-producing bacteria in early life is associated with the development of atopic diseases in childhood. We have proven that colonization with a single bacterial species, A. caccae, mimicks the effects of the healthy microbiota, supporting a causal role for specific bacterial taxa in protection against food allergy. We hypothesize that re-introduction of butyrate-producing Clostridia to dysbiotic, allergy-prone hosts is a promising method for prevention of food allergy.

There is significant clinical interest in developing live biotherapeutic products (LBPs), from specific commensal species to prevent or treat various disease indications. LBPs are becoming increasingly common; however, they often exhibit limited engraftment. To overcome this limitation, many clinical (and pre-clinical) studies require a pre-treatment course of antibiotics, further depleting the resident microbiota in potentially adverse ways. We propose an alternative strategy: co-delivery of the LBP with prebiotics, i.e., as a synbiotic, to create an ecological niche in the gut to maximize engraftment and butyrate production. We have isolated a novel strain of A. caccae, A. caccae_lahuc, from the feces of a healthy infant and demonstrated that co-delivery of this isolate with a prebiotic (i.e., as a synbiotic) prevents food allergy in mice with a dysbiotic human microbiota. In this proposal we will screen a variety of clinically relevant prebiotics in vitro and in vivo to optimize our synbiotic formulation for maximal efficacy and translatability. We will also examine the mechanisms by which our synbiotic(s) prevent or treat food allergy.

Synbiotic Therapy modifies the fecal microbiome and regulates host immunity to prevent and treat food allergy