What is the pathophysiology and management of Irritable Bowel Syndrome (IBS)?

Pathophysiology and Management of Irritable Bowel Syndrome (IBS)

Pathophysiology

IBS is a complex disorder characterized by dysregulation of the gut-brain axis with multiple physiological determinants contributing to symptoms rather than a single disease entity. 1

The key pathophysiological mechanisms include:

• Visceral Hypersensitivity: Enhanced perception of pain and discomfort from normal gut stimuli, considered one of the most important pathophysiological factors in IBS 1
• Gut-Brain Axis Dysregulation: Altered bidirectional communication between the central nervous system and enteric nervous system, affecting stress reactivity and abnormal perception/modulation of visceral afferent signals 1, 2
• Transit and Motility Abnormalities:
  • IBS-C: Reduced motility, fewer high-amplitude propagating contractions, delayed transit 1
  • IBS-D: Increased motility, more high-amplitude propagating contractions, accelerated transit 1
• Immune Regulation and Low-Grade Inflammation: Compromised epithelial barrier function leading to mucosal inflammation 1, 3
• Microbiome Alterations: Reduced bacterial diversity, temporal instability of microbiota, and different compositions between IBS patients with and without psychological comorbidity 1, 4, 5
• Post-Infectious IBS: Develops in approximately 10% of patients following infectious enteritis, with persistent low-grade inflammation 1, 3
• Genetic and Epigenetic Factors: Shared genetic risk factors between IBS and mood/anxiety disorders, with emerging evidence of epigenetic mechanisms including altered gene methylation and microRNA profiles 1, 6
• HPA Axis Dysregulation: Impaired stress response system affecting gut function and reduced psychological and physiological resilience to stress 1

Diagnosis and Assessment

• Diagnosis based on Rome criteria with cardinal symptoms of abdominal pain/discomfort associated with altered bowel habits 1
• Limited testing to exclude organic disorders that mimic IBS rather than exhaustive investigation 1
• Consider colonoscopy only in patients with alarm symptoms or those with IBS-D who have risk factors for microscopic colitis 1

Management Approach

Medical Treatment

For IBS-D:

• First-line treatment: Loperamide for loose stools 1
• Second-line treatments:
  • Rifaximin 550 mg three times daily for 14 days - shown to provide adequate relief of IBS symptoms in 41% of patients compared to 31-32% with placebo 1, 7
  • Alosetron, ramosetron, or eluxadoline where available 1

For IBS-C:

• First-line treatment: Osmotic laxatives and stimulant laxatives 1
• Second-line treatments: Secretagogues like linaclotide or plecanatide 1

For Abdominal Pain:

• First-line treatment: Antispasmodics or peppermint oil 1
• Second-line treatment: Tricyclic antidepressants or SSRIs for refractory pain 1

Dietary Management

• Consider dietary modifications as part of a personalized treatment plan 1
• Low FODMAP diet may help reduce symptoms in some patients 1
• Probiotic supplementation has shown beneficial effects on both gastrointestinal symptoms and mood 1

Psychological and Behavioral Approaches

• Psychological therapies should be considered early in the treatment journey 1
• Effective options include:
  • Cognitive behavioral therapy 1
  • Gut-directed hypnotherapy 1
  • Brain-gut behavior therapy (BGBT) targeting resilience 1
• Address psychological comorbidities like anxiety (39% of IBS patients) and depression (29% of IBS patients) 1

Common Pitfalls and Caveats

• Avoid excessive diagnostic testing - the yield of colonoscopy in typical IBS without alarm features is extremely low 1
• Recognize that psychological factors are not characteristic of IBS but can contribute to symptom severity and should be addressed in treatment 1
• Understand that the relative contribution of gut and brain factors is unique to each patient, requiring individualized treatment approaches 1
• Be aware that up to 80% of IBS patients will report at least one alarm symptom, but the diagnostic performance of these symptoms is modest 1
• Explain to patients that cure is unlikely, but substantial improvement in symptoms, functioning, and quality of life is achievable 1
• Clearly communicate that IBS is not associated with increased cancer risk or mortality but affects quality of life significantly 1