What other hormones, besides serotonin, are involved in managing Irritable Bowel Syndrome (IBS)?

Hormones Involved in Irritable Bowel Syndrome (IBS) Beyond Serotonin

Beyond serotonin, multiple hormones including peptide YY (PYY), cholecystokinin (CCK), and various cytokines play crucial roles in IBS pathophysiology, with their imbalances contributing to different IBS subtypes and symptom patterns.

Key Enteroendocrine Hormones in IBS

• Serotonin (5-HT) remains the primary neurotransmitter involved in IBS pathophysiology, affecting gut motility, secretion, and visceral sensitivity 1
• Peptide YY (PYY) levels are increased in Shigella-associated post-infection IBS, contributing to altered gut motility and sensation 2
• Cholecystokinin (CCK) positive cells are increased in duodenal tissue of Giardia-associated IBS patients, potentially affecting gut motility and pain signaling 2
• Inflammatory cytokines including IL-1β, IFN-γ, IL-10, and IL-13 show altered expression in IBS, mediating low-grade inflammation 2

Pathophysiological Mechanisms of Hormonal Involvement

Enteroendocrine Cell Alterations

• Enterochromaffin (EC) cell counts are higher in Campylobacter-associated IBS and correlate with CD3 T cell counts, linking immune activation with hormonal dysregulation 2
• Different pathogens affect enteroendocrine cells differently - Shigella increases 5-HT and PYY-containing cells, while Giardia decreases duodenal EC cells but increases CCK-positive cells 2

Cytokine Imbalance

• Mucosal IL-1β mRNA expression is elevated in IBS patients compared to healthy subjects 2
• Increased IFN-γ and decreased IL-10 levels suggest involvement of Th1 and Th2 cells in IBS pathophysiology 2
• Lower IL-13 release from mucosal biopsies of IBS patients indicates altered Th2-mediated immune response 2

Neurotransmitter Dysregulation

• Altered serotonin metabolism is evident in IBS subtypes - increased levels in IBS-D and decreased levels in IBS-C 3
• Serotonin reuptake transporter (SERT) expression changes affect 5-HT levels, with decreased SERT leading to increased serotonin (IBS-D) and increased SERT causing decreased serotonin (IBS-C) 3, 4
• Tryptophan metabolism shows pathway differences between IBS subtypes - increased serotonin pathway activity in IBS-D and higher kynurenine pathway activity in IBS-C 5

Autonomic Nervous System and Stress Hormones

• Reduced parasympathetic activity and increased sympathetic nervous system activity are frequently observed in IBS 2
• Reduced vagal tone affects gut motility, sensitivity, peripheral inflammation, and gut permeability 2
• Stress hormones influence gut-brain axis communication, affecting symptom severity and frequency 2

Therapeutic Implications

• Tricyclic antidepressants (TCAs) are recommended for IBS due to their effects on multiple neurotransmitter systems including serotonin, providing relief of global symptoms and abdominal pain 2, 1
• 5-HT3 receptor antagonists are beneficial for IBS-D by blocking excessive serotonin activity, while 5-HT4 receptor agonists help IBS-C by promoting gut motility 3, 6
• SSRIs have shown limited efficacy in IBS despite their serotonergic effects, suggesting other neurotransmitter systems are important 2
• Antispasmodics may work by affecting smooth muscle contraction and possibly visceral hypersensitivity through various neurotransmitter pathways 2

Clinical Considerations and Pitfalls

• The hormonal profile varies significantly between IBS subtypes, explaining why treatments effective for one subtype may worsen symptoms in another 2, 3
• Pathogen-specific responses lead to different hormonal alterations, suggesting personalized approaches based on IBS etiology may be beneficial 2
• Comorbid psychological conditions may both influence and be influenced by hormonal dysregulation in IBS, creating a bidirectional relationship 2, 5
• Measuring hormonal levels clinically remains challenging, limiting the practical application of hormonal profiling in routine IBS management 2, 4