The Role of the Microbiome in the Development/Prevention of Food Allergies

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DESCRIPTION (provided by applicant): The prevalence of food allergies in Western cultures has steadily increased in the last several decades. While the cause of the increased incidence of allergies is likely to be multifactoral, a growing body of data supports the hypothesis that the composition of the gastrointestinal tract microbiota can be a contributing factor in the generation of allergic responses to otherwise innocuous food proteins. We have recently developed a mouse model of food allergy to chicken ovalbumin (OVA), which develops in response to microbiota perturbation. Ag-specific T cell responses will be tracked through the adoptive transfer of OVA-specific naive DO11.10 CD4 T-cells. Our hypothesis is that disturbances of the gastrointestinal microbiota, including the temporary or long-term outgrowth of yeast, promote the priming of a Th2 response to high dose food allergen exposure by disrupting regulatory networks and/or augmenting priming of mucosal Th2 responses. Therefore, strategies aimed at the microbiota (probiotics & prebiotcs) have the potential to restore defective regulatory responses and/or prevent allergen priming. Our aims are 1) to determine the cellular, humoral and cytokine responses in the mesenteric lymph nodes and lamina propria of microbiota-disrupted mice following oral delivery of OVA; 2) to determine the effect of a Lactobacillus probiotic, a prebiotic (scFOS) or the combination of the two on the cellular, humoral and cytokine responses in the mesenteric lymph nodes and lamina propria of microbiota-disrupted mice following oral delivery of OVA; 3) to determine the relationship between butyrate and all-trans retinoic acid on regulating the activity of CD103- and CD103+ dendritic cells isolated from the MLN and LP of untreated and microbiota-disrupted mice. Public Health Relevance Numerous epidemiologic studies have implicated disruptions of the indigenous microbiota (by antibiotics, diet, disease, or other environmental factors) as a causative factor in the development of mucosal inflammatory disorders, including food allergies. The data from this proposal will increase our understanding of the mechanisms connecting the indigenous microbiota and food allergies, including the mechanisms of probiosis to treat food allergies.