What is fecal lactoferrin?

Fecal Lactoferrin: A Diagnostic Biomarker for Intestinal Inflammation

Fecal lactoferrin is a glycoprotein expressed by activated neutrophils that serves as a sensitive and specific biomarker for detecting intestinal inflammation, particularly in inflammatory bowel disease (IBD), with a clinical threshold of 7.25 μg/g used to differentiate inflammatory from non-inflammatory causes of diarrhea. 1, 2

What is Fecal Lactoferrin?

• Biochemical nature: Lactoferrin is a glycoprotein released by activated neutrophils during intestinal inflammation
• Source: Primarily derived from neutrophil degranulation in the intestinal mucosa during inflammatory processes
• Normal values:
  • Healthy individuals: 1.45-3.15 μg/g fecal weight
  • Clinical threshold for inflammation: >7.25 μg/g 2, 3

Diagnostic Performance

• Sensitivity and specificity:

  • Sensitivity: 83% for detecting intestinal inflammation
  • Specificity: 75% for detecting intestinal inflammation 2
  • 90% specific for identifying inflammation in active IBD
  • 100% specific in ruling out irritable bowel syndrome (IBS) 4

• Comparison with other biomarkers:

  • Similar performance to fecal calprotectin
  • Superior to serum inflammatory markers (ESR, CRP) 2

Clinical Applications

IBD Diagnosis and Monitoring

• Diagnostic utility:

  • Helps differentiate IBD from functional disorders like IBS
  • Significantly elevated in active IBD:
    • Active ulcerative colitis: 1126.29 ± 431.21 μg/g
    • Active Crohn's disease: 1035.25 ± 456.59 μg/g 3
  • Minimal elevation in inactive IBD:
    • Inactive ulcerative colitis: 96.58 ± 82.46 μg/g
    • Inactive Crohn's disease: 133.52 ± 88.89 μg/g 3

• Disease activity assessment:

  • Correlates well with clinical disease activity indices
  • Correlates with endoscopic findings and histological inflammation
  • Higher levels indicate more severe disease activity 5, 6

• Treatment monitoring:

  • Useful for monitoring response to therapy
  • Declining levels suggest improving inflammation
  • Persistently elevated levels may indicate treatment failure 5

• Predicting disease flares:

  • Rising levels may predict clinical flares
  • Patients who experienced clinical flares within 2 months showed higher lactoferrin levels (845 ± 452 μg/g) than those who remained in remission (190 ± 90 μg/g) 5

Differential Diagnosis

• Distinguishing inflammatory from non-inflammatory conditions:
  • IBD: Significantly elevated (>1000 μg/g in active disease)
  • Infectious bowel disease: Moderately elevated (83.3 ± 29.9 μg/g)
  • IBS: Normal levels (2.54 ± 1.49 μg/g)
  • Healthy controls: Normal levels (3.15 ± 1.60 μg/g) 3

Clinical Interpretation

• Normal level (<7.25 μg/g):

  • Suggests non-inflammatory causes like IBS or functional diarrhea
  • In known IBD patients, suggests remission or minimal inflammation 2

• Elevated level (>7.25 μg/g):

  • Strongly suggestive of inflammatory etiology, particularly IBD
  • Warrants further investigation with endoscopy if diagnosis is uncertain 1, 2

Limitations and Considerations

• Potential false positives:

  • NSAID use
  • Colorectal cancer
  • Infectious gastroenteritis
  • Recent colonoscopy or bowel preparation 2

• Technical considerations:

  • Different commercial assays may have varying thresholds
  • Age-related variations (higher in infants, especially breastfed) 2

Clinical Algorithm for Use

1. Initial evaluation of patients with suspected inflammatory diarrhea
2. Interpretation:
   • If elevated (>7.25 μg/g): Consider IBD or other inflammatory conditions
   • If normal (<7.25 μg/g): Consider functional disorders like IBS
3. Next steps:
   • If IBD is suspected: Refer for colonoscopy with biopsies
   • For established IBD: Use for monitoring disease activity and treatment response

Fecal lactoferrin provides a non-invasive, sensitive, and specific method for detecting intestinal inflammation, helping clinicians distinguish between inflammatory and non-inflammatory causes of gastrointestinal symptoms 7.