Fecal calprotectin biomarker in IBD: Clinical Use Original paper

What was reviewed?

This systematic review evaluated fecal calprotectin biomarker in IBD as a noninvasive stool test that reflects neutrophil-driven intestinal inflammation and can support diagnosis and monitoring of inflammatory bowel disease (IBD). The authors summarized assay performance characteristics, reference ranges, and clinical applications across published studies indexed through January 2006, focusing on how fecal calprotectin correlates with endoscopic and histologic inflammation, distinguishes IBD from irritable bowel syndrome (IBS), predicts relapse, and helps detect pouchitis after ileal pouch–anal anastomosis.

Who was reviewed?

The review synthesized evidence from multiple cohorts, including healthy adults and children (to establish normal ranges), infants (noted to have substantially higher baseline fecal calprotectin), and patients with Crohn disease (CD) and ulcerative colitis (UC) across adult and pediatric settings. It also included symptomatic, undiagnosed patients referred for evaluation of possible organic bowel disease versus functional disorders (e.g., IBS), plus post-surgical patients with ileoanal pouches to evaluate pouchitis. Smaller datasets in other inflammatory intestinal conditions (e.g., infectious gastroenteritis, NSAID enteropathy, microscopic colitis, celiac disease, allergic colitis, diverticular disease) were discussed primarily to clarify where calprotectin does—and does not—track neutrophilic inflammation.

Most important findings

Across studies, fecal calprotectin is consistently elevated in active IBD and correlates well with tissue-level inflammation on colonoscopy with biopsies, supporting its role as a surrogate for neutrophil migration into the gut lumen. It performs especially well as a “rule-out” test: a low value has strong negative predictive value for excluding IBD in symptomatic patients and for separating IBD from IBS, where calprotectin is typically similar to healthy controls. The review highlights clinically important thresholds (upper limit of normal ~50 mg/g with newer assays; higher cutoffs such as 150 mg/g improving discrimination in some comparisons) and notes the protein’s stability in stool, enabling practical sample handling. Although the paper is not a microbiome sequencing study, its relevance to microbiome-signature work is that calprotectin provides a standardized inflammation phenotype that can contextualize dysbiosis signals—helping differentiate microbial patterns associated with neutrophilic mucosal inflammation (active IBD) from patterns seen in noninflammatory symptom states (IBS-like presentations). The review also summarizes evidence that elevated calprotectin can predict relapse during clinical remission (with high sensitivity and moderate-to-high specificity depending on assay/cutoff) and can detect pouchitis with excellent sensitivity, making it useful for triaging who needs endoscopy.

Key implications

Fecal calprotectin offers clinicians an actionable, noninvasive measure of neutrophilic intestinal inflammation that complements (but does not replace) endoscopy. Its greatest clinical leverage is in reducing unnecessary invasive testing by ruling out active inflammatory disease in undiagnosed symptomatic patients, distinguishing inflammatory flares from IBS-like symptoms in known IBD, monitoring objective response to therapy, and screening for pouchitis. For microbiome-informed care and microbiome signature databases, calprotectin functions as a robust host-response anchor—enabling microbial associations to be stratified by inflammatory activity rather than symptoms alone, improving interpretability and translational relevance.

Citation

Konikoff MR, Denson LA. Role of fecal calprotectin as a biomarker of intestinal inflammation in inflammatory bowel disease. Inflamm Bowel Dis. 2006;12(6):524-534