What biomarkers are used for the diagnosis of Irritable Bowel Syndrome (IBS)?

Biomarkers for Irritable Bowel Syndrome (IBS)

Currently, there are no specific biomarkers that can definitively diagnose IBS, and diagnosis remains primarily based on symptom criteria with biomarkers mainly used to rule out other conditions rather than to confirm IBS. 1

Current Diagnostic Approach for IBS

IBS diagnosis is based on:

1. Symptom-based criteria (Rome criteria): The primary diagnostic tool
2. Exclusion of alarm features
3. Selected biomarkers to rule out organic diseases

Biomarkers Used to Rule Out Other Conditions

These tests help differentiate IBS from other conditions with similar symptoms:

Inflammatory Markers

• Fecal Calprotectin (FC):

  • Most extensively studied biomarker in distinguishing IBS from IBD
  • A cutoff of 30 μg/g showed 100% sensitivity in discriminating active Crohn's disease from IBS 1
  • High specificity for detecting intestinal inflammation
  • Less reliable for disease localized to terminal ileum 1

• C-reactive Protein (CRP) and Erythrocyte Sedimentation Rate (ESR):

  • Used to screen for inflammatory conditions
  • Normal values help support IBS diagnosis by excluding IBD

Tests for Celiac Disease

• IgA-tTG (tissue transglutaminase) and IgA-EMA (endomysial antibodies):
  • Used to screen for celiac disease, which can present with IBS-like symptoms
  • Meta-analysis found 2.1% of individuals with IBS symptoms had positive serology for celiac disease 1

Stool Tests

• Stool cultures and ova/parasite examination:
  • To exclude infectious causes of diarrhea
  • Particularly important with history of travel to endemic areas
  • Giardia is the most commonly identified pathogen in chronic diarrhea evaluation 1

Emerging Biomarkers for "Ruling In" IBS

Anti-CdtB and Anti-vinculin Antibodies

• Mechanism: Antibodies to cytolethal distending toxin B (CdtB) produced by bacteria causing gastroenteritis cross-react with vinculin in gut mucosa 1
• Diagnostic value:
  • Higher levels in IBS-D patients compared to IBD, celiac disease, and healthy controls
  • Specificity is reasonably good with high positive predictive value
  • However, sensitivity is <50% 1
  • When positive, these tests increase confidence in IBS diagnosis
  • Negative results do not help rule out IBS 1

Combinations of Biomarkers

• Research suggests combinations of biomarkers may be more effective than single markers 2, 3
• One study found that combining fecal calprotectin, intestinal permeability, and Rome I criteria yielded a positive likelihood ratio of 26.4 3
• Another approach combining serum-based biomarkers with psychological markers showed a negative likelihood ratio of 0.18 3

Limitations of Current Biomarkers

• Most studies use case-control designs rather than prospective testing of consecutive patients
• This design can inflate sensitivity and specificity estimates 1
• Many studies were performed in secondary or tertiary care settings, introducing referral bias 1
• No single biomarker currently achieves both high sensitivity and specificity for IBS diagnosis 2

Clinical Implications

1. IBS remains a clinical diagnosis based primarily on symptom criteria
2. Biomarkers are currently more useful for excluding other conditions than for confirming IBS
3. Anti-CdtB and anti-vinculin antibodies show promise but have limited sensitivity
4. Combination approaches may offer better diagnostic accuracy in the future

Diagnostic Algorithm

1. Apply Rome criteria for symptom-based diagnosis
2. Screen for alarm features (weight loss, nocturnal symptoms, family history of colorectal cancer, etc.)
3. Use biomarkers to exclude organic disease:
   • Fecal calprotectin to rule out IBD
   • Celiac serology (IgA-tTG) to rule out celiac disease
   • Stool studies if infectious etiology suspected
4. Consider anti-CdtB and anti-vinculin antibodies if available (positive result increases confidence in IBS diagnosis)
5. If all tests are negative and symptoms meet Rome criteria, diagnose as IBS