Gut fungi in irritable bowel syndrome : A painful recognition

Le résumé fourni par la source

This thesis focused on the role of fungi in the irritable bowel syndrome (IBS). IBS is a common, stress related, functional gastrointestinal disorder, characterized by chronic abdominal pain. A part of IBS patients show increased perception of pain to a rectal stimulus compared to healthy subjects. This so called hypersensitivity of the viscera is thought to represent a pathological mechanism behind the abdominal pain characteristic for IBS. The relevance of fungi was studied in the pre-clinical rat maternal separation model. In this model, rat pups are predisposed by maternal separation, and subjection to acute stress at adult age triggers, similar to IBS patients, hypersensitivity of the viscera. We observed that treatment with antifungals prevented the development of post stress visceral hypersensitivity. Remarkably, this hypersensitive phenotype in IBS model rats was accompanied by a specific fungal signature. Probably the development visceral hypersensitivity involves the recognition of fungal cell wall β-glucans by Dectine-1, a pathogen recognition receptor expressed on mast cells. After Dectine-1 activation, mast cells respond by the release of histamine which ultimately results in sensitization of afferent neurons. There is no current treatment for abdominal pain in IBS. Our research has identified a completely novel mechanism by which IBS develops and might thus lead to novel therapies. Less

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