< Back to previous page

Project

Mechanisms of afferent nerve sensitization underlying visceral hypersensitivity

About 10- 20 % of individuals worldwide suffer from Irritable Bowel Syndrome (IBS), which is one of the most common gastrointestinal diseases in the western world. Characteristic symptoms vary from patient to patient but include chronic discomfort and abdominal pain associated with altered bowel habits in the absence of an organic cause. About 60% of IBS patients suffer from increased abdominal pain perception or visceral hypersensitivity (VHS). The two best characterized triggers for the development of IBS are psychological stress on the one hand, and an episode of bacterial gastroenteritis on the other hand. We hypothesized that an infection would not only trigger an immune response to the infectious agent, but also to innocent bystander antigens with production of antibodies and subsequent mast cell activation. To proof this hypothesis, we selected ovalbumin (OVA) as “innocent bystander antigen” and exposed mice to OVA during infection. Of great interest, we showed that re-exposure to OVA (oral gavage) indeed resulted in VHS and increased permeability, but only in mice that received OVA during infection. Of note, this phenomenon was only observed in mice with a predominant Th2 immunogenetic background (Balb/c). Our findings are in line with a recent study in IBS patients showing food-induced changes in epithelial morphology and secretion. In my PhD, I will further explore the hypothesis that visceral hypersensitivity, triggered by an infectious episode, results from a bystander Th2-response to innocent antigens. Re-exposure to these innocent antigens after clearance of the infection will re-active the Th2 response with activation of mast cells and subsequent activation / sensitization of afferent nerve fibers. My PhD thesis aims to further validate this model and explore the mechanisms, mediators and nociceptors involved in the post-infectious visceral hypersensitivity

Date:1 Sep 2014 →  19 Sep 2023
Keywords:IBS, Visceral Hypersensitivity, Irritable Bowel Syndrome
Disciplines:Biomarker discovery and evaluation, Drug discovery and development, Medicinal products, Pharmaceutics, Pharmacognosy and phytochemistry, Pharmacology, Pharmacotherapy, Toxicology and toxinology, Other pharmaceutical sciences, Gastro-enterology and hepatology, Endocrinology and metabolic diseases
Project type:PhD project