What Is Calprotectin?

Calprotectin is a protein found primarily in neutrophils (the most abundant white blood cells involved in acute inflammation). When neutrophils migrate into the gut wall in response to inflammation, they release calprotectin into the intestinal lumen, where it can be measured in a stool sample. The level of faecal calprotectin directly reflects the degree of neutrophilic infiltration in the gut wall, making it a reliable, quantitative surrogate marker for intestinal inflammation.

Calprotectin is remarkably stable in stool, remaining measurable for up to 7 days at room temperature. This stability makes it an ideal biomarker for clinical use because samples do not require special handling or immediate processing.

The Clinical Question It Answers

The primary clinical value of faecal calprotectin is its ability to distinguish between inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS). This distinction is critically important because the symptoms can overlap significantly, but the diseases require entirely different management approaches.

  • In IBD (Crohn's disease and ulcerative colitis), calprotectin is typically elevated, often significantly
  • In IBS, calprotectin is typically normal (below 50 micrograms per gram of stool)

Multiple meta-analyses have shown that faecal calprotectin has a sensitivity of 93-100% and specificity of 80-96% for detecting IBD. This means a normal calprotectin result makes IBD extremely unlikely, potentially avoiding the need for invasive colonoscopy in many patients.

Interpreting Calprotectin Levels

Normal Range (Below 50 mcg/g)

A calprotectin level below 50 mcg/g strongly suggests the absence of significant intestinal inflammation. This result makes IBD very unlikely and supports a diagnosis of functional bowel disorder (IBS). However, it does not rule out microscopic colitis, celiac disease, or upper GI pathology, which do not always elevate faecal calprotectin.

Borderline Range (50-200 mcg/g)

Levels in this range are indeterminate. They may reflect mild intestinal inflammation from various causes including infections, NSAID use, mild diverticulitis, or early or quiescent IBD. Most guidelines recommend repeating the test after 4-6 weeks and considering further investigation if levels remain elevated or rise.

Elevated Range (Above 200 mcg/g)

Levels consistently above 200 mcg/g strongly suggest significant intestinal inflammation and warrant further investigation, typically with colonoscopy and biopsies. In known IBD patients, levels above 250 mcg/g correlate with endoscopically active disease.

Calprotectin levels correlate with the degree of mucosal healing in IBD. This makes serial calprotectin measurements valuable for monitoring treatment response without repeated colonoscopies. Many gastroenterologists now use calprotectin as a primary tool for IBD treatment monitoring.

When to Test Calprotectin

Faecal calprotectin testing is most valuable in these clinical scenarios:

  • Chronic diarrhoea of unclear cause — to distinguish IBD from IBS before committing to colonoscopy
  • Monitoring known IBD — to assess disease activity, mucosal healing, and treatment response without invasive procedures
  • Predicting IBD relapse — rising calprotectin levels often precede clinical flares by weeks, enabling pre-emptive treatment intensification
  • Post-surgical monitoring in Crohn's disease — early detection of endoscopic recurrence at the anastomosis

Limitations and Caveats

Calprotectin is a powerful but imperfect marker:

  • Not disease-specific — any cause of intestinal inflammation elevates calprotectin, including infections, NSAID use, colorectal cancer, and diverticulitis
  • Age-related variation — infants and young children have higher baseline calprotectin levels; adult reference ranges do not apply to paediatric populations
  • Upper GI disease — calprotectin is less sensitive for inflammation above the ligament of Treitz (oesophageal, gastric, duodenal pathology)
  • PPI use — proton pump inhibitors may mildly elevate calprotectin levels

Calprotectin in the Context of Comprehensive Gut Assessment

Faecal calprotectin is one piece of a larger diagnostic picture. For a complete understanding of gut health, it should be interpreted alongside symptom patterns, dietary history, stool consistency records, and potentially other markers like zonulin (for permeability) and stool microbial analysis (for dysbiosis). GutIQ helps you build this comprehensive picture by systematically evaluating the symptom patterns and lifestyle factors that inform when calprotectin testing and other investigations are clinically appropriate.