Abstract
Irritable bowel syndrome (IBS) is a disease without a clear cause which is associated with abdominal pain and altered bowel habits. A disturbed intestinal permeability and an increased sensitivity of internal organs are causal factors of disease. An important pathological role lies in the 'gut-brain interaction' in which signals from the intestine are conveyed to the brain and vice versa. This interaction is essential for a healthy bowel function and involves signaling molecules such as histamine, proteases, bile and fatty acids. Also the microbial content (the 'microbiome') of the intestine plays an important role in the gut-brain interaction. In this respect, we are particularly interested in the intestinal barrier function. The mucous membranes in the intestine provide an active barrier that allows passage of nutrients but impedes non-nutrients and toxins. It is well known that certain chronic diseases are associated with a disturbed intestinal barrier, also called 'leaky gut'. Possibly, a 'leaky gut' is also involved in IBS and that is what we will investigate in this project. We will study the role of different mediators such as vasoactive intestinal polypeptide, intestinal alkaline posphatase, serine protease inhibitors and mucoprotectants in a preclinical rat model and directly translate the importance of these mediators to the human situation validating their occurence and activity in human colonic samples. -
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