7. Project Summary/AbstractThe prevalence of food allergies has increased dramatically in the United States and around the world. Giventhe rate at which allergic disease has increased, multiple environmental factors, including changes to our diet,are likely culprits. For example, increased consumption of fruits and vegetables and adherence to aMediterranean diet decreases the risk of allergic disease while diets high in fat and fast foods increase thisrisk. However, the role of non-nutritive components, such as bitter tasting phytochemicals, in the developmentor prevention of food allergies is not known. Bitter tasting phytochemicals were once ubiquitous in our diets butmodern agriculture and food science techniques have all but eliminated them from most of our food supply.Therefore, it is paramount that we understand how their absence in our modern diet shapes the intestinalimmune system and affects the development of food allergies.This project will investigate how sensory epithelial cells in the gastrointestinal tract sense bitter tastants andhow they integrate this information with other sensory modalities to evaluate the overall quality of the ingestedfood. Specifically, we will use an in vitro model system to study enteroendocrine cell responses to varyingratios of bitter tastants to macronutrients. Complementary to these studies, we propose to use single cell RNAsequencing to measure rare epithelial cell types? responses to bitter tastants in vivo. We will also study howbitter tastant sensing in the gut shapes the composition of the immune system and how this affects thedevelopment of allergic disease. Specifically, we will use a combination of flow cytometry, qPCR, and in vitromodels to investigate dendritic cells, T cells, and B cells in the small intestine and their activation, migration,and effector functions in response to bitter tastant sensing at steady state and in the context of allergicinflammation. The potential impact of this research will be the development of dietary guidelines and medicalinterventions that take into account the non-nutritive components of our food such as phytochemicals and bittertastants.