Internship Report

Abstract

Background Eosinophilic Esophagitis (EoE) is a rapidly emerging disorder with a current estimated prevalence of 1:1000 persons. It is an allergic disease of the esophagus, characterized by an infiltration of eosinophils and mastocytosis. EoE patients display by a variety of symptoms, including feeding difficulties, dysphagia, abdominal and chest pain, failure to thrive and food impaction. An important feature of the disease is dysmotility of the esophagus. Since pre-, pro and synbiotic diets have proven their worth in other allergies, it is hypothesized that they will also be effective in EoE patients. In order to provide a tool for future research on the effect of pre-, pro and synbiotic diets, two animal models have been developed. Furthermore, this report addresses in vitro data on migration of mast cells, an essential feature in the pathogenesis of EoE.

Chapter 2 In chapter 2, we report the functional impairment and allergen-specific contraction of the esophagus in a guinea pig model for EoE. It was shown that the allergen OVA induces a large contraction of the esophagus in EoE animals. Moreover, the EC50 values of the EoE animals for bethanechol and histamine were significantly shifted to the right, indicating functional impairments of the smooth muscle layer.

Chapter 3 Here, we established a murine model for EoE. We demonstrated a significant eosinophilic infiltration in the esophagus of the animals. Moreover, different biomarkers are shown of to be significantly different in EoE animals, including eotaxin-1 MRNA overexpression, epithelial thickness increase and luminal area decrease.

Chapter 4 In this chapter, we showed the pharmacological properties of histamine and the histamine H4 receptor (H4R) agonist VUF8430 on mast cell chemotaxis. Histamine-induced mast cell chemotaxis is regulated on a H4R dependent manner.

Conclusion In conclusion, this report described the development of two animal models of EoE. Moreover, several biomarkers are identified. Lastly, the role of histamine on the chemotaxis of mast cells is described. This research could be used to study new dietary interventions in EoE.