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

Pathophysiology and Management of Irritable Bowel Syndrome (IBS)

Pathophysiology of IBS

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

Key Pathophysiological Mechanisms

• Altered Gut Reactivity: Changes in motility and secretion in response to luminal or environmental stimuli, resulting in diarrhea and/or constipation 1

• Visceral Hypersensitivity: Enhanced perception of pain and discomfort from normal gut stimuli, considered one of the most important pathophysiological factors 1, 2

• Brain-Gut Axis Dysregulation: Altered stress reactivity and abnormal perception/modulation of visceral afferent signals 1

• 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
  • Serotonin (5-HT) metabolism alterations: high levels in IBS-D, low levels in IBS-C 1

• Immune Regulation and Inflammation:

  • Low-grade mucosal inflammation from compromised epithelial barrier, dysbiosis, or altered stress levels 1
  • Post-infectious IBS (PI-IBS) develops in approximately 10% of patients following infectious enteritis 1
  • Increased mast cells in the descending colon and rectosigmoid region 1

• Microbiome Alterations:

  • Reduced bacterial diversity and increased temporal instability 3
  • Different microbiome compositions between IBS patients with and without psychological comorbidity 1
  • Small intestinal bacterial overgrowth associated with IBS-D 4
  • Increased levels of methanogenic archaea associated with IBS-C 4

• HPA Axis Dysregulation:

  • Impaired stress response system affecting gut function 1
  • Reduced psychological and physiological resilience to stress 1
  • Shared pathophysiological mechanism with depression 1

• Genetic and Epigenetic Factors:

  • Shared genetic risk factors between IBS and mood/anxiety disorders 1
  • Altered profiles of methylated genes and micro-RNAs 5
  • Epigenetic changes affecting gut permeability and visceromotor function 5

Management of IBS

Assessment and Diagnosis

• 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 (e.g., celiac disease) 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 (female sex, age ≥50 years, autoimmune disease, severe watery diarrhea, weight loss, or use of NSAIDs/PPIs/SSRIs) 1

• Consider testing for bile acid diarrhea in IBS-D patients with atypical features like nocturnal diarrhea or prior cholecystectomy 1

Medical Treatment

• For IBS-D:

  • First-line: Loperamide for loose stools 1
  • Second-line: Alosetron, ramosetron, rifaximin, or eluxadoline where available 1
  • Rifaximin 550 mg three times daily for 14 days has shown efficacy in IBS-D, with 41% of patients experiencing adequate relief of symptoms versus 31-32% with placebo 6

• For IBS-C:

  • First-line: Osmotic laxatives (polyethylene glycol) and stimulant laxatives (senna) 1
  • Second-line: Secretagogues like linaclotide or plecanatide that activate ion channels on enterocytes 1

• For Abdominal Pain:

  • First-line: Antispasmodics (e.g., hyoscine) or peppermint oil 1
  • Consider 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 in IBS patients 1

Psychological and Behavioral Approaches

• Psychological therapies should be considered early in the treatment journey rather than after multiple failed drug treatments 1

• Effective options include:

  • Cognitive behavioral therapy
  • Gut-directed hypnotherapy
  • Brain-gut behavior therapy (BGBT) targeting resilience 1

• Addressing psychological comorbidities like anxiety and depression is crucial, as they affect approximately 39% and 29% of IBS patients, respectively 1

Patient Education and Communication

• Clearly communicate the diagnosis using simple explanations of gut-brain interactions 1
• Emphasize that IBS is not associated with increased cancer risk or mortality but affects quality of life significantly 1
• Explain that cure is unlikely, but substantial improvement in symptoms, functioning, and quality of life is achievable 1

Common Pitfalls and Caveats

• Avoid excessive diagnostic testing, as the yield of colonoscopy in typical IBS 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