Calprotectin

What calprotectin is

Calprotectin is a human immune protein complex formed by two calcium-binding proteins, S100A8 and S100A9, that is released in large amounts from activated neutrophils during inflammation.^[1] In the gut, calprotectin enters the intestinal lumen when neutrophils migrate into the mucosa and across the epithelium, making fecal calprotectin a direct, noninvasive marker of neutrophil-driven intestinal inflammation.^[2] Because it is relatively stable in stool and reflects local inflammatory activity, fecal calprotectin is widely used in clinical gastroenterology and microbiome-focused care pathways.^[3]

Why calprotectin matters in intestinal inflammation

Calprotectin is not only a marker; it also plays a role in host defense. It limits microbial growth by tightly binding essential metals, especially zinc and manganese, thus reducing microbial access to nutrients necessary for replication.^[4] This “metal sequestration” mechanism is a well-characterized antimicrobial strategy of innate immunity, relevant to the microbiome because nutrient limitation can alter microbial community structure during inflammation.^[5] Calprotectin’s antimicrobial activity has been demonstrated in mechanistic and infection models, including fungal infection settings where loss of calprotectin reduces host control of growth.^[6]

Clinical use in microbiome medicine

Fecal calprotectin is clinically valuable to distinguish inflammatory bowel disease (IBD) from non-inflammatory functional disorders such as irritable bowel syndrome, helping clinicians decide when endoscopic evaluation is more likely to be necessary.^[7] A recent systematic review and meta-analysis confirms that fecal calprotectin performs well for separating IBD from IBS-type presentations in adults, supporting its role as a front-line triage test in symptomatic patients.^[8] In IBD care, fecal calprotectin also supports monitoring, because it correlates with inflammatory activity and can contribute to relapse risk assessment in appropriate clinical contexts.^[9]

Microbiome signatures and interpretation

Elevated fecal calprotectin is increasingly linked to measurable microbiome differences. In a large cohort study, higher fecal calprotectin levels were associated with gut microbial dysbiosis and shifts in microbial abundance and diversity, reinforcing that calprotectin can act as a clinically interpretable bridge between inflammation biology and microbiome profiling.^[10] In microbiome medicine, calprotectin is best interpreted as a host-response signal: it indicates mucosal immune activation that can shape microbial ecology, rather than identifying a single causative organism.^[11][12] Clinically, results should be interpreted with symptoms, medications, and risk factors, because calprotectin increases in multiple inflammatory conditions, not only IBD.^[13]

Research Feed

Update History

References

1. Role of fecal calprotectin as a biomarker of intestinal inflammation in inflammatory bowel disease.. Konikoff MR, Denson LA.. (Inflamm Bowel Dis. 2006)
2. Role of fecal calprotectin as a biomarker of intestinal inflammation in inflammatory bowel disease.. Konikoff MR, Denson LA.. (Inflamm Bowel Dis. 2006)
3. Role of fecal calprotectin as a biomarker of intestinal inflammation in inflammatory bowel disease.. Konikoff MR, Denson LA.. (Inflamm Bowel Dis. 2006)
4. Molecular basis for manganese sequestration by calprotectin and roles in the innate immune response to invading bacterial pathogens.. Damo SM, Kehl-Fie TE, Sugitan N, et al.. (Proc Natl Acad Sci U S A. 2013)
5. Molecular basis for manganese sequestration by calprotectin and roles in the innate immune response to invading bacterial pathogens.. Damo SM, Kehl-Fie TE, Sugitan N, et al.. (Proc Natl Acad Sci U S A. 2013)
6. Zinc and manganese chelation by neutrophil S100A8/A9 (calprotectin) limits extracellular Aspergillus fumigatus hyphal growth and corneal infection.. Clark HL, Jhingran A, Sun Y, et al.. (J Immunol. 2016;196:000-000. Published online November 18, 2015)
7. Role of fecal calprotectin as a biomarker of intestinal inflammation in inflammatory bowel disease.. Konikoff MR, Denson LA.. (Inflamm Bowel Dis. 2006)
8. Systematic review with meta-analysis: Diagnostic performance of faecal calprotectin in distinguishing inflammatory bowel disease from irritable bowel syndrome in adults.. Dajti E, Frazzoni L, Iascone V, Secco M, Vestito A, Fuccio L, et al.. (Aliment Pharmacol Ther. 2023)
9. Diagnostic Accuracy of Fecal Calprotectin for Predicting Relapse in Inflammatory Bowel Disease: A Meta-Analysis.. Shi J-T, Chen N, Xu J, Goyal H, Wu Z-Q, Zhang J-X, Xu H-G.. (Journal of Clinical Medicine. 2023)
10. Elevated fecal calprotectin is associated with gut microbial dysbiosis, altered serum markers and clinical outcomes in older individuals.. Heinzel S, Jureczek J, Kainulainen V, et al.. (Sci Rep. 2024)
11. Molecular basis for manganese sequestration by calprotectin and roles in the innate immune response to invading bacterial pathogens.. Damo SM, Kehl-Fie TE, Sugitan N, et al.. (Proc Natl Acad Sci U S A. 2013)
12. Elevated fecal calprotectin is associated with gut microbial dysbiosis, altered serum markers and clinical outcomes in older individuals.. Heinzel S, Jureczek J, Kainulainen V, et al.. (Sci Rep. 2024)
13. Role of fecal calprotectin as a biomarker of intestinal inflammation in inflammatory bowel disease.. Konikoff MR, Denson LA.. (Inflamm Bowel Dis. 2006)