Review article: intestinal serotonin signalling in irritable bowel syndrome

Abstract

SUMMARYAlterations in motility, secretion and visceral sensation are hallmarks of irritable bowel syndrome. As all of these aspects of gastrointestinal function involve serotonin signalling between enterochromaffin cells and sensory nerve fibres in the mucosal layer of the gut, potential alterations in mucosal serotonin signalling have been explored as a possible mechanism of altered function and sensation in irritable bowel syndrome. Literature related to intestinal serotonin signalling in normal and pathophysiological conditions has been searched and summarized.Elements of serotonin signalling that are altered in irritable bowel syndrome include: enterochromaffin cell numbers, serotonin content, tryptophan hydroxylase message levels, 5-hydroxyindoleacedic acid levels, serum serotonin levels and expression of the serotonin-selective reuptake transporter. Both genetic and epigenetic factors could contribute to decreased serotonin-selective reuptake transporter in irritable bowel syndrome. A serotonin-selective reuptake transporter gene promoter polymorphism may cause a genetic predisposition, and inflammatory mediators can induce serotonin-selective reuptake transporter downregulation.While a psychiatric co-morbidity exists with IBS, changes in mucosal serotonin handling support the concept that there is a gastrointestinal component to the aetiology of irritable bowel syndrome. Additional studies will be required to gain a more complete understanding of changes in serotonin signalling that are occurring, their cause and effect relationship, and which of these changes have pathophysiological consequences.

Decreased expression of serotonin in the jejunum and increased numbers of mast cells in the terminal ileum in patients with irritable bowel syndrome

“…Studies have found that alterations of many elements in the gastrointestinal mucosa serotonin (5-HT) signaling pathway occurs in IBS patients [6] , and this was one of the mechanisms for the disrupted visceral sensation and gastrointestinal motility in IBS patients. It has been shown that mast cells also play a role in the visceral hypersensitivity of IBS patients.…”

Efficacy and Safety of 5-Hydroxytryptamine 3 Receptor Antagonists in Irritable Bowel Syndrome: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

“…5-HT acts on the 5-HT 3 receptors on the parasympathetic ganglia to cause smooth muscle contraction and increased intestinal secretion by stimulating nerve terminal acetylcholine release [5]. 5-HT 3 receptor antagonists inhibit the activation of 5-HT 3 receptors on the mucosal processes of the intrinsic and extrinsic primary afferent neurons and attenuate motor and secretory reflex activity while decreasing the depolarization of extrinsic sensory neurons that transmit signals to the brain, thereby inhibiting the sensory signals leading to abdominal pain and discomfort and are likely directly or indirectly related to the pathophysiology of IBS [6]. This has been exploited therapeutically in patients with IBS-D in whom 5-HT 3 receptor antagonists improve gastrointestinal (GI) symptoms, reducing stool frequency, urgency, and abdominal discomfort while increasing stool consistency [7].…”

A biomarker panel and psychological morbidity differentiates the irritable bowel syndrome from health and provides novel pathophysiological leads

“…As a result, patients with IBS visit physicians more often, consume more medications and undergo more diagnostic tests than non-IBS patients. 8,9 While the aetiology of this disorder remains obscure, there is a body of evidence suggesting dysregulation of several pathophysiological pathways including serotonin biosynthesis and metabolism, [10][11][12] mast cell infiltration and degranulation, [13][14][15][16][17] visceral hypersensitivity, an exaggerated stress response, immune activation and bacterial infection (post-infectious IBS) or microbiota alterations. [18][19][20][21][22] Gene expression profiling in tissue samples taken from patients with IBS has been reported using sigmoid colonic mucosal tissue.…”