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Project

Transcriptional and Functional Characterization of Enterochromaffin cells in Irritable Bowel Syndrome

Irritable bowel syndrome (IBS) is a gastrointestinal disorder characterized by altered bowel habits and severe abdominal pain, which is caused by sensory nerve fibre sensitization via soluble mediators released from neighbouring cells. Intriguingly, IBS patients develop symptoms upon food ingestion, even though sensory nerve endings do not reach the intestinal lumen. Therefore, the colorectal mucosa must host cells able to transduce chemical signals from the lumen. Enterochromaffin (EC) cells are prime candidates to play this role, since they reside in the mucosal surface and establish synapses with nerve terminals. Indeed, recent studies indicated that EC cells have receptors to bacterial metabolites and dietary irritants that promote release of 5-hydroxytryptamine (5-HT) upon activation. The release of 5-HT is increased in the colorectal mucosa of IBS patients and antagonists to 5-HT receptors 3 (5-HT3) significantly improve pain in 50% of IBS patients. Unfortunately, these antagonists were withdrawn from most markets due to rare, yet serious side effects, suggesting that blocking pathways promoting aberrant 5-HT release aiming at its normalization rather than fully blocking its action might be a safer therapeutic strategy. Nevertheless, the mechanisms underlying aberrant 5-HT release in IBS remain unknown. Therefore, we designed a comprehensive study aiming to identify transcriptional and functional alterations to EC cells in IBS.

Date:1 Jan 2020 →  31 Dec 2023
Keywords:Irritable bowel syndrome (IBS), Enterochromaffin (EC) cells, 5-hydroxytryptamine (5-HT)
Disciplines:Gastro-enterology, Endocrinology, Medical transcriptomics, Cell signalling, Pathophysiology