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.

Inclusion Criteria:

• Patient groups: Disease diagnosis (CD or UC),duration of disease, previous/type of treatments, duration of treatment and disease prognosis.
• Healthy controls: No diagnosis of CD or UC and no diagnosis of IBS.

Exclusion Criteria:

• Patient groups: Drugs that directly affect components of 5-HT signaling, any other disease or condition that may interfere with study assessments as judged by the investigator.
• Healthy controls:Chronic use of any anti-inflammatory drugs, drugs that directly affect components of 5-HT signalling and any other disease or condition that may interfere with study assessments as judged by the investigator.

All potential participants will be included only if they meet the stringent inclusion criteria in place. Only when their eligibility is confirmed the potential participants will be approached for consent prior to endoscopy. For healthy subjects, they will be screened and consented from the colorectal screening list, also prior to endoscopy.