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The Nagler Lab studies the mechanisms governing tolerance to dietary antigens. They were one of the first to identify a link between resident intestinal bacteria and the regulation of mucosal immunity. During the last fifteen years, their work has focused on examining how commensal bacteria regulate susceptibility to allergic responses to food. They have proposed that the striking generational increase in food allergies can be explained, in part, by alterations in the composition and function of the commensal microbiome.
In support of this hypothesis, Nagler Lab described a role for a particular population of mucosa-associated commensal bacteria in protection from allergic sensitization in mice. Initial translational studies showed that the composition of the fecal microbiota is altered in infants with cow’s milk allergy. To understand how the microbiota regulates allergic disease in humans they have colonized germ free mice with human bacteria from the feces of healthy or cow’s milk allergic (CMA) infants.
The group discovered that mice colonized with CMA infants’ microbiota exhibited an anaphylactic response to the cow’s milk allergen b-lactoglobulin, while mice colonized with healthy infants’ microbiota were protected against an allergic response. They defined a microbiota signature that distinguishes the CMA and healthy populations in both the human donors and the colonized mice. Analysis of gene expression in ileal intestinal epithelial cells of colonized mice identified a significant correlation between the genes associated with allergy protection and taxa from the Lachnospiraceae family, supporting a causal role for specific bacterial species in protection against food allergy.
These robust, pre-clinical, gnotobiotic models are an ideal system to identify key host-microbial interactions that contribute to allergic sensitization to food. With support from the Polsky Center for Entrepreneurship and Innovation, Nagler Lab has created a start-up company, ClostraBio, to develop novel microbiome-modulating therapeutics to prevent or treat food allergy.
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