AbstractsBiology & Animal Science

Visceral hypersensitivity in Irritable Bowel Syndrome:pathophysiological mechanisms

by A.P.M. Kerckhoffs

Institution: Universiteit Utrecht
Year: 2009
Keywords: Geneeskunde; Irritable Bowel Syndrome; visceral hypersensitivity; microbiota; intestinal permeability; serine protease and serotonergic signaling
Record ID: 1250376
Full text PDF: http://dspace.library.uu.nl:8080/handle/1874/31897


Irritable Bowel Syndrome (IBS) is a functional bowel disease characterized by abdominal pain or discomfort associated with a disordered defecation. No unique pathophysiological mechanism has been identified. It is most likely a multifactorial disease involving alterations in intestinal microbiota composition, intestinal mucosal barrier, serine protease and serotonergic signalling components which may play a role in the visceral hypersensitivity. We showed alterations in microbiota composition including that bifidobacteria and especially Bifidobacterium catenulatum were significantly decreased and Pseudomonas aeruginosa was significantly increased in both small intestinal mucosa-associated samples as in faecal samples of IBS patients compared to healthy controls. If this change in the microbial composition is causal, consequential or merely the result of the IBS symptoms remains unclear. Furthermore we showed that IBS patients have an altered response of the intestinal barrier to NSAIDs. This might expose the mucosa to an abnormal challenge of luminal antigens of dietary and bacterial origin. Protease activated receptor(PAR)-2 activation leads to increased intestinal permeability which promotes hyperalgesia to mechanical distension. We showed in the small intestine increased expression of the PAR-2 agonist, trypsinogen IV expression. Furthermore in the small intestine increased SERT expression and 5-HT content has been shown suggesting higher 5-HT availability which may also contribute to small intestinal visceral hypersensitivity. In the colorectal region, however, abnormalities in serine protease and serotonergic signalling components showed no differences between rectal hypersensitive and normosensitive IBS patients. Irrespective of visceral hypersensitivity state, the serotonergic signalling components are altered in IBS. Low grade inflammation might also play a role in the visceral hypersensitivity of IBS patients due to sensitization of sensory neural endings in the intestine. We have shown that mast cells are significantly more observed in the vicinity of PAR-2 positive neurons than PAR-2 negative neurons in both IBS patients and controls. In conclusion the pathophysiology of visceral hypersensitivity in IBS is multi-factorial including microbiota, intestinal permeability and serotonin and serine protease signalling components however more work has to be done to yield pathogenetic, diagnostic and therapeutic value for IBS patients.