What does stool lactoferrin indicate?

Stool Lactoferrin as a Biomarker for Intestinal Inflammation

Stool lactoferrin is a sensitive and specific biomarker that detects intestinal inflammation, particularly in inflammatory bowel disease (IBD), and helps differentiate inflammatory from non-inflammatory conditions such as irritable bowel syndrome (IBS). 1

Mechanism and Significance

Lactoferrin is a glycoprotein expressed by activated neutrophils during inflammatory processes in the intestine. It serves as a surrogate marker for neutrophil infiltration in the intestinal mucosa, which occurs during active inflammation. Key characteristics include:

• Sensitivity of 83% and specificity of 75% at the standard threshold (7.25 μg/g) for detecting intestinal inflammation 2, 1
• Remains stable during stool transport and processing, unlike fecal leukocytes which degrade rapidly 2
• Commercial assays typically report results as positive/negative at the 7.25 μg/g cutoff 1

Clinical Applications

Differentiating IBD from IBS

• Elevated in patients with inflammatory bowel disease (both Crohn's disease and ulcerative colitis)
• Normal levels in patients with IBS and healthy controls 3, 4
• 100% specific for ruling out IBS when elevated 3
• Helps avoid unnecessary invasive procedures in patients with functional disorders

Monitoring Disease Activity in IBD

• Correlates well with clinical and endoscopic disease activity in IBD patients 5, 6
• Significantly higher in active IBD compared to inactive disease 4, 6
• Can predict clinical flares when elevated in otherwise asymptomatic patients 5
• Useful for monitoring response to treatment

Interpretation Guidelines

1. Normal lactoferrin (<7.25 μg/g):

   • In patients with IBD-like symptoms: Suggests functional disorder rather than active inflammation
   • In established IBD patients: Indicates likely remission or minimal inflammation

2. Elevated lactoferrin (>7.25 μg/g):

   • In patients with IBD-like symptoms: Suggests active inflammation, warrants endoscopic evaluation
   • In established IBD patients: Indicates active disease, may require treatment adjustment

Limitations and Caveats

• False positives can occur with:

  • Gastrointestinal infections
  • NSAID-induced enteropathy
  • Colorectal cancer
  • Liver cirrhosis
  • Other inflammatory conditions of the gut 1

• False negatives can occur in:

  • Approximately 17% of patients with active IBD 2, 1
  • Isolated small bowel Crohn's disease
  • Mild inflammation

• Not recommended for establishing the cause of acute infectious diarrhea (strong recommendation, moderate evidence) 2

• Normal in infants consuming human milk (lactoferrin is a normal component of breast milk) 2

Comparison with Other Biomarkers

• Fecal calprotectin has a more extensive evidence base and multiple validated cutoff values 1
• Lactoferrin has slightly higher sensitivity but lower specificity than calprotectin at standard thresholds 1
• Either biomarker is appropriate for initial screening, with calprotectin more commonly used in current practice 1

Clinical Decision Algorithm

1. Initial evaluation of chronic diarrhea/abdominal pain:

   • Normal lactoferrin + IBS-like symptoms → Consider functional disorder
   • Elevated lactoferrin → Proceed to endoscopic evaluation to confirm IBD

2. Established IBD monitoring:

   • Normal lactoferrin + asymptomatic → Continue current management
   • Normal lactoferrin + symptomatic → Consider non-inflammatory causes
   • Elevated lactoferrin + asymptomatic → Consider endoscopic assessment
   • Elevated lactoferrin + symptomatic → Consider treatment adjustment

By incorporating stool lactoferrin testing into clinical practice, physicians can more effectively distinguish inflammatory from non-inflammatory intestinal conditions and monitor disease activity in IBD patients, ultimately improving patient outcomes by enabling appropriate treatment decisions.