METABOLOMIC PATHWAYS IN FOOD ALLERGY

Food allergy (FA) has become a public health concern, affecting a sizeable segment of the population. Despitethe alarming increase in its prevalence, efforts to contain the food allergy epidemic have been stymied by thelimited understanding of disease pathogenesis and the dearth of biomarkers predictive of disease onset, itscourse and outcome. To that end, our preliminary studies in a mouse model of FA using untargetedmetabolomic profiling revealed a dysregulation in carbohydrate metabolism, which led us to hypothesize a rolefor the adipokine resistin like molecule beta (RELM?) in the pathogenesis of FA. RELM? transcripts wereincreased in the gut of FA-prone Il4raF709 mice, together with increased serum levels of RELM? but not therelated adopkine RELM?. Deletion in these mice of the RELM?-encoding gene, Retnlb, protected them fromFA. Importantly, RELM? levels were strongly elevated in sera of children with FA as compared to asthmaticsand to healthy controls. According, we hypothesize that subjects with FA will manifest a metabolomic signaturein their serum reflective of disease activity which, together with serum RELM?, will be predictive of diseaseattributes such as severity and outcome. In Aim 1, we will identify the mechanisms by which RELM? promotesFA in Il4raF709 mice and its contribution to the metabolomic signature in these mice. In Aim 2, we will validatethe role of RELM? as a biomarker for human FA by extending serum RELM? analysis to other comparisongroups ? including atopic dermatitis and eosinophilic esophagitis, and to identify disease attributes of FA thatcorrelate with RELM? elevation. In Aim 3, we will establish the metabolomic profiles associated with FA inchildren using untargeted metabolomics and relate to measures of disease outcome. Our proposed studies willvalidate novel biomarkers of food allergy, including metabolomics markers and RELM?, and elucidate the roleof RELM? and metabolomic abnormalities in disease pathogenesis.