What is the primary neurotransmitter involved in Irritable Bowel Syndrome (IBS)?

Primary Neurotransmitter Involved in Irritable Bowel Syndrome (IBS)

Serotonin (5-hydroxytryptamine or 5-HT) is the primary neurotransmitter involved in the pathophysiology of Irritable Bowel Syndrome (IBS), playing a critical role in gut motility, secretion, and visceral hypersensitivity.

Role of Serotonin in IBS Pathophysiology

• Serotonin is predominantly found in the gut and serves as a vital link in IBS pathophysiological processes, including altered gut motility, abnormal intestinal secretion, and visceral hypersensitivity 1, 2
• Approximately 95% of the body's serotonin is located in the gastrointestinal tract, primarily in enterochromaffin cells, making it a key mediator of gut function 2
• Serotonin acts as a critical mediator in the brain-gut axis, which is fundamental to the pathophysiology of IBS 3

Serotonin Regulation and IBS Subtypes

• The serotonin reuptake transporter (SERT) maintains serotonin levels by regulating its reuptake in the gut 2
• Alterations in SERT expression correlate with IBS subtypes:
  • Increased SERT expression leads to decreased serotonin levels, associated with constipation-predominant IBS (IBS-C) 2
  • Decreased SERT expression causes increased serotonin levels, associated with diarrhea-predominant IBS (IBS-D) 2

Evidence from Pharmacological Treatments

• The efficacy of serotonergic agents in IBS treatment provides strong evidence for serotonin's central role:
  • 5-HT3 receptor antagonists (such as alosetron) are effective for IBS-D, confirming serotonin's involvement 4, 5
  • 5-HT4 receptor agonists are beneficial for IBS-C, further supporting serotonin's role in gut motility 5, 6
  • Tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) are effective second-line treatments for IBS, working by modulating serotonin levels 1

Mechanisms of Serotonin Action in IBS

• Serotonin is involved in three major actions in the gut that are directly relevant to IBS symptoms:
  • Mediating intestinal motility - affecting bowel movement patterns 3
  • Regulating intestinal secretion - influencing stool consistency 3
  • Modulating visceral perception - affecting pain sensation in the bowels 3

Clinical Implications of Targeting Serotonin

• British Society of Gastroenterology guidelines recommend tricyclic antidepressants as effective second-line drugs for global symptoms and abdominal pain in IBS, working primarily through serotonergic mechanisms 1
• 5-HT3 receptor antagonists are recognized as among the most efficacious treatments for IBS-D, directly targeting serotonin's effects 1
• The American Gastroenterological Association suggests using TCAs in patients with IBS due to their effects on serotonin signaling 1

Other Neurotransmitters in IBS

• While serotonin is primary, other neurotransmitters also play roles in IBS:
  • Norepinephrine - IBS patients with altered colorectal motility show augmented norepinephrine levels 6
  • Acetylcholine - Increased levels correlate with motility disorders in IBS 6
  • GABA - Lower levels are associated with visceral hypersensitivity in IBS 6

Therapeutic Targeting of Serotonin

• Pharmacological approaches targeting serotonin receptors represent an important advancement in IBS management 3
• For IBS-D: 5-HT3 receptor antagonists block excessive serotonin activity to reduce gut motility 2
• For IBS-C: 5-HT4 receptor agonists promote gut motility by enhancing serotonin's effects 2
• TCAs and SSRIs modulate serotonin levels in the gut, providing relief of global IBS symptoms 1

Understanding serotonin's central role in IBS pathophysiology has led to targeted therapeutic approaches that address the underlying mechanisms rather than just symptom management, resulting in improved outcomes for patients with this challenging disorder.