Food allergy is an increasing health problem with impacts on both children and adults. Despite the increasing impact of food allergy on human health and the US economy ($25B in children alone) and extensive research efforts, there is still no cure for food allergies. One of the devastating symptoms of food allergies is a disorder known as eosinophilic esophagitis (EoE) where the reaction to foods causes severe inflammation in the esophagus (throat). The swelling is painful and prevents the ingestion of solid foods. Children and adults of any age can develop EoE; children can fail to thrive, and EoE can progress in adolescents and adults to esophageal strictures which cause dysphagia and food impaction. In this proposal funds are requested to develop a new, translational, large animal model for EoE. We propose using young, food allergic pigs, as a model for human EoE. The pig combines high biological relevance based on their similarities to humans with a well-equipped immunological toolbox to study relevant disease-related immune responses. We believe that this large animal model will strongly impact research into EoE, and food allergy in general, and hasten development of new treatments and diagnostic procedures. Drawing on the NC State University College of Veterinary Medicine, the College of Sciences, and the School of Medicine at UNC we have assembled an interdisciplinary team with expertise in porcine immunology, the porcine gastrointestinal tract, and the clinical diagnosis and treatment of food allergy and EoE. Our preliminary, short term experiments show that we can indeed produce food allergic pigs (egg allergic) and we have observed the onset of inflammation in the esophagus. We are requesting funds to create a long-term state of chronic egg allergy to induce EoE in pigs, as it appears in humans. In addition, funding will be used to fully characterize the clinical and immunological features of disease. Once complete our model will be ready for scientists to test new treatments to slow or reverse disease or develop new diagnostic tests for early detection of EoE and food allergy.
The proposed research is relevant to public health because it develops the pig as a biologically relevant animal model to study the underlying immune mechanisms of eosinophilic esophagitis (EoE) and to develop a desperately needed cure for food allergy and EoE. Thus, the proposed research aligns well with both parts of the NIH's mission, the side that seeks fundamental knowledge as well as the side that promotes the application of that knowledge to enhance health, and reduce illness and disability. The research is also pertinent to the part of the NIAID's mission that supports research on basic and applied research to better understand, treat and ultimately prevent allergic diseases.