The Pathophysiology of Visceral Hypersensitivity and Food-Induced Abdominal Pain Revised: Novel Opportunities for Treatment

Irritable bowel syndrome (IBS) is a prevalent gastrointestinal disorder characterized by chronic discomfort and abdominal pain associated with altered defecation in the absence of an organic cause. It is becoming increasingly clear that mast cell activation, leading to activation and sensitization of afferent nerves, plays a crucial role in abnormal visceral pain sensation (visceral hypersensitivity), one of the hallmarks of IBS. However, the underlying mechanisms remain unclear. During PhD, I will investigate the hypothesis that mast cell activation results from an aberrant immune response to intraluminal innocent antigens (food, commensals). The latter is triggered by a danger signal, such as an invading organism or the presence of bacterial superantigens. In my laboratory, we developed a mouse model where a bacterial infection indeed resulted in the development of an immune response against a harmless bystander antigen, leading to characteristic IBS features such as increased visceral pain perception and mucosal permeability. Similarly, in another murine model, we have observed that the superantigen enterotoxin B from Staphylococcus aureus induces an aberrant immune response to innocent bystander antigens, also leading to visceral hypersensitivity and increased mucosal permeability. Hence, I will assess the aberrant immune response in our murine models and in a subpopulation of IBS patients. In addition, I will evaluate if bacterial toxins, such as superantigens, are able to induce a similar aberrant immune response. The results of this project will be of crucial importance to improve our insight in the pathogenesis of IBS and will ultimately lead to more efficient treatment strategies for IBS.

Publication year:2019

Accessibility:Closed