Investigating Serotonin Signalling in IBD Patients

Alterations in normal serotonin (5-hydroxytryptamine;5-HT) signaling have been reported in ulcerative colitis (UC) and Crohn's disease (CD). Studies report an increase in enterochromaffin (EC) cell, main source of 5-HT in the gut, numbers in CD and UC patients. Up-regulated expression of mucosal Tryptophan hydroxylase (TPH)-1, catalytic enzyme in 5-HT production, messenger RNA (mRNA) have been found in CD patients in remission who are suffering the irritable bowel syndrome (IBS)-like symptoms. Alterations in normal 5-HT signaling has also been reported in animal models of inflammatory bowel disease (IBD). Thus, the aim of the proposed research project will be to study the alterations in 5-HT signalling accompanying GI inflammatory conditions, such as IBD.

The gut produces approximately 95% of serotonin (5-hydroxytryptamine; 5-HT) found in the human body; where, it is a very important mucosal signaling molecule participating in gut motility, sensation, and secretion.The vast majority of the gut-derived 5-HT is produced by specialized epithelial cells of The GI tract, called enterochromaffin (EC) cells. EC cells produce 5-HT from dietary tryptophan, this process involves the rate limiting enzyme tryptophan hydroxylase (TPH) 1, once produced this 5-HT can be released into the gut lumen, surrounding tissue and can enter the blood circulation.5-HT mediates many gastrointestinal functions, including secretion and peristalsis, by acting on a diverse range of 5-HT receptors. Five of the seven known receptor families of 5-HT (5-HT1, 5-HT2, 5-HT3, 5-HT4 and 5-HT7) are expressed in the gut. 5-HT has been evaluated in IBD and in animal models of colitis. An increase in numbers of EC cells expressing 5-HT is observed in CD and UC patients and consumption of selective 5-HT reuptake inhibitors is associated with microscopic colitis. In the present study, we plan to investigate the key elements of mucosal 5-HT signaling in CD patients for a better understanding of the role of 5-HT in pathogenesis of IBD.