The role of serotonin and its pathways in gastrointestinal disorders

Serotonin (5-hydroxytryptamine or 5-HT) is a mediator with primary functions, both in the central nervous system and digestive system. At the digestive level, about 90% of 5-HT is localized in enterochromaffin cells, and about 10% in enteric neurons. In the gastrointestinal tract, 5-HT affects motor, secretory, and sensory functions via activation of seven subclasses of receptors, which differ on the basis of structure, function, and signaling mechanisms. The 5-HT transporter, deputed specifically to 5-HT reuptake, plays also an important role in the modulation of serotonergic pathways. There is increasing evidence that the serotonergic system is involved in the pathogenic mechanisms of gastrointestinal diseases, with particular regard for functional gastrointestinal disorders, and the pathophysiology of some frequently associated psychiatric and psychological comorbidities. The constant bidirectional interplay between brain and gut (brain-gut axis), in which 5-HT is deeply involved, can account for the multifaceted central and peripheral actions of this mediator. In this context, the role of the intestinal microbiota, with its ability of both producing 5-HT and being modulated by 5-HT, represents a field of high interest deserving preclinical and clinical investigations. © 2021 Copyright © 2021 Elsevier Inc. All rights reserved.