Fecal Calprotectin: Beyond a Biomarker of Intestinal Inflammation
From Diagnostic Tool to a Link Between Gut, Immunity, and Systemic Disease
DOI:
https://doi.org/10.12775/JEHS.2026.93.72558Keywords
fecal calprotectin, intestinal inflammation, inflammatory bowel disease, gut microbiota, intestinal permeability', biomarkersAbstract
Background.
Fecal calprotectin (FC), a neutrophil-derived S100A8/S100A9 heterodimer, is a widely used non-invasive biomarker of intestinal inflammation, particularly in inflammatory bowel diseases (IBD). Emerging evidence suggests its broader role in gut barrier dysfunction and systemic inflammation.
Aim.
To evaluate the clinical relevance of fecal calprotectin, focusing on its diagnostic performance, limitations, and emerging applications beyond IBD.
Material and methods.
A narrative review of PubMed-indexed literature was conducted, including original studies and reviews addressing the biological role of calprotectin, its diagnostic accuracy, and its association with intestinal permeability, microbiota, and metabolic inflammation.
Results.
Fecal calprotectin demonstrates high sensitivity for detecting intestinal inflammation and is useful in differentiating IBD from functional disorders such as irritable bowel syndrome. Its levels correlate with disease activity and are valuable in monitoring treatment response and predicting relapse. However, its specificity is limited, as elevated levels may occur in infections, malignancies, and drug-related mucosal injury. Recent studies suggest associations between FC, gut microbiota alterations, and low-grade systemic inflammation.
Conclusions.
Fecal calprotectin is a valuable tool in the diagnosis and management of intestinal inflammation. Its expanding role in systemic conditions highlights the need for further research to improve standardization and clarify its clinical applications
References
Ayling, R. M., & Kok, K. (2018). Fecal Calprotectin. Advances in clinical chemistry, 87, 161–190. https://doi.org/10.1016/bs.acc.2018.07.005
Cai, J., Sun, L., & Gonzalez, F. J. (2022). Gut microbiota-derived bile acids in intestinal immunity, inflammation, and tumorigenesis. Cell host & microbe, 30(3), 289–300. https://doi.org/10.1016/j.chom.2022.02.004
Carvente, C. T., Ferraz, M. L. C. G., & Toledo, C. F. (2024). EVALUATING LACTOFERRIN AND CALPROTECTIN AS MARKERS OF INTESTINAL INFLAMMATION INCHRONIC PANCREATITIS. Arquivos de gastroenterologia, 61, e24003. https://doi.org/10.1590/S0004-2803.246102024-03
Chicco, F., Magrì, S., Cingolani, A., Paduano, D., Pesenti, M., Zara, F., Tumbarello, F., Urru, E., Melis, A., Casula, L., Fantini, M. C., & Usai, P. (2021). Multidimensional Impact of Mediterranean Diet on IBD Patients. Inflammatory bowel diseases, 27(1), 1–9. https://doi.org/10.1093/ibd/izaa097
D'Amico, F., Rubin, D. T., Kotze, P. G., Magro, F., Siegmund, B., Kobayashi, T., Olivera, P. A., Bossuyt, P., Pouillon, L., Louis, E., Domènech, E., Ghosh, S., Danese, S., & Peyrin-Biroulet, L. (2021). International consensus on methodological issues in standardization of fecal calprotectin measurement in inflammatory bowel diseases. United European gastroenterology journal, 9(4), 451–460. https://doi.org/10.1002/ueg2.12069
Danne, C., Skerniskyte, J., Marteyn, B., & Sokol, H. (2024). Neutrophils: from IBD to the gut microbiota. Nature reviews. Gastroenterology & hepatology, 21(3), 184–197. https://doi.org/10.1038/s41575-023-00871-3
Diez-Martin, E., Hernandez-Suarez, L., Muñoz-Villafranca, C., Martin-Souto, L., Astigarraga, E., Ramirez-Garcia, A., & Barreda-Gómez, G. (2024). Inflammatory Bowel Disease: A Comprehensive Analysis of Molecular Bases, Predictive Biomarkers, Diagnostic Methods, and Therapeutic Options. International journal of molecular sciences, 25(13), 7062. https://doi.org/10.3390/ijms25137062
Effenberger, M., Grabherr, F., Mayr, L., Schwaerzler, J., Nairz, M., Seifert, M., Hilbe, R., Seiwald, S., Scholl-Buergi, S., Fritsche, G., Bellmann-Weiler, R., Weiss, G., Müller, T., Adolph, T. E., & Tilg, H. (2020). Faecal calprotectin indicates intestinal inflammation in COVID-19. Gut, 69(8), 1543–1544. https://doi.org/10.1136/gutjnl-2020-321388
Gallo, A., Covino, M., Baroni, S., Camilli, S., Ibba, F., Andaloro, S., Agnitelli, M. C., Rognoni, F. M., Landi, F., & Montalto, M. (2024). Diagnostic Accuracy of Fecal Calprotectin in Discriminating Organic-Inflammatory Gastrointestinal Diseases and Functional Gastrointestinal Disorders in Older Patients. Journal of personalized medicine, 14(3), 227. https://doi.org/10.3390/jpm14030227
González, R., Ceacero-Heras, D., Tena-Garitaonaindia, M., Álvarez-Mercado, A., Gámez-Belmonte, R., Chazin, W. J., Sánchez de Medina, F., & Martínez-Augustin, O. (2024). Intestinal inflammation marker calprotectin regulates epithelial intestinal zinc metabolism and proliferation in mouse jejunal organoids. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 174, 116555. https://doi.org/10.1016/j.biopha.2024.116555
Hardis, K., Johansen, S. B., Eriksen, J., Damgaard, K., Leutscher, P. D. C., & Jepsen, S. (2022). Fecal calprotectin as a biomarker of intestinal inflammation in ICU patients with diarrhea - testing the pipette method against the collection pin and weighing methods. Scandinavian journal of clinical and laboratory investigation, 82(6), 504–507. https://doi.org/10.1080/00365513.2022.2107567
Henderson, P., Anderson, N. H., & Wilson, D. C. (2014). The diagnostic accuracy of fecal calprotectin during the investigation of suspected pediatric inflammatory bowel disease: a systematic review and meta-analysis. The American journal of gastroenterology, 109(5), 637–645. https://doi.org/10.1038/ajg.2013.131
Ivković, L., Hojsak, I., Trivić, I., Sila, S., Hrabač, P., Konjik, V., Senečić-Čala, I., Palčevski, G., Despot, R., Žaja, O., & Kolaček, S. (2020). IBD phenotype at diagnosis, and early disease-course in pediatric patients in Croatia: data from the Croatian national registry. Pediatric research, 88(6), 950–956. https://doi.org/10.1038/s41390-020-0853-2
Jukic, A., Bakiri, L., Wagner, E. F., Tilg, H., & Adolph, T. E. (2021). Calprotectin: from biomarker to biological function. Gut, 70(10), 1978–1988. https://doi.org/10.1136/gutjnl-2021-324855
Jung, E. S., Lee, S. P., Kae, S. H., Kim, J. H., Kim, H. S., & Jang, H. J. (2021). Diagnostic Accuracy of Fecal Calprotectin for the Detection of Small Bowel Crohn's Disease through Capsule Endoscopy: An Updated Meta-Analysis and Systematic Review. Gut and liver, 15(5), 732–741. https://doi.org/10.5009/gnl20249
Khaki-Khatibi, F., Qujeq, D., Kashifard, M., Moein, S., Maniati, M., & Vaghari-Tabari, M. (2020). Calprotectin in inflammatory bowel disease. Clinica chimica acta; international journal of clinical chemistry, 510, 556–565. https://doi.org/10.1016/j.cca.2020.08.025
Kostrzewska, P., Całkosiński, A., Majewski, M., & Malinowski, K. (2022). Kalprotektyna w kale jako marker diagnostyczny w nieswoistych zapaleniach jelit [Fecal calprotectin as a diagnostic marker of inflammatory bowel disease]. Polski merkuriusz lekarski : organ Polskiego Towarzystwa Lekarskiego, 50(295), 58–61.
Li, L., Cheng, R., Wu, Y., Lin, H., Gan, H., & Zhang, H. (2024). Diagnosis and management of inflammatory bowel disease. Journal of evidence-based medicine, 17(2), 409–433. https://doi.org/10.1111/jebm.12626
Ni, J., Wu, G. D., Albenberg, L., & Tomov, V. T. (2017). Gut microbiota and IBD: causation or correlation?. Nature reviews. Gastroenterology & hepatology, 14(10), 573–584. https://doi.org/10.1038/nrgastro.2017.88
Pan, Y., Zhang, H., Li, M., He, T., Guo, S., Zhu, L., Tan, J., & Wang, B. (2024). Novel approaches in IBD therapy: targeting the gut microbiota-bile acid axis. Gut microbes, 16(1), 2356284. https://doi.org/10.1080/19490976.2024.2356284
Pathirana, W. G. W., Chubb, S. P., Gillett, M. J., & Vasikaran, S. D. (2018). Faecal Calprotectin. The Clinical biochemist. Reviews, 39(3), 77–90.
Qiu, P., Ishimoto, T., Fu, L., Zhang, J., Zhang, Z., & Liu, Y. (2022). The Gut Microbiota in Inflammatory Bowel Disease. Frontiers in cellular and infection microbiology, 12, 733992. https://doi.org/10.3389/fcimb.2022.733992
Qu, Y., Xu, W., Han, J., Zhou, W., & Wu, H. (2020). Diagnostic value of fecal calprotectin in necrotizing enterocolitis: A meta-analysis. Early human development, 151, 105170. https://doi.org/10.1016/j.earlhumdev.2020.105170
Radillo, O., Pascolo, L., Martelossi, S., Dal Bo, S., & Ventura, A. (2016). Fecal Calprotectin: Diagnostic Accuracy of the Immunochromatographic CalFast Assay in a Pediatric Population. Journal of clinical laboratory analysis, 30(5), 500–505. https://doi.org/10.1002/jcla.21886
Ricciuto, A., & Griffiths, A. M. (2019). Clinical value of fecal calprotectin. Critical reviews in clinical laboratory sciences, 56(5), 307–320. https://doi.org/10.1080/10408363.2019.1619159
Roda, G., Chien Ng, S., Kotze, P. G., Argollo, M., Panaccione, R., Spinelli, A., Kaser, A., Peyrin-Biroulet, L., & Danese, S. (2020). Crohn's disease. Nature reviews. Disease primers, 6(1), 22. https://doi.org/10.1038/s41572-020-0156-2
Rokkas, T., Portincasa, P., & Koutroubakis, I. E. (2018). Fecal calprotectin in assessing inflammatory bowel disease endoscopic activity: a diagnostic accuracy meta-analysis. Journal of gastrointestinal and liver diseases : JGLD, 27(3), 299–306. https://doi.org/10.15403/jgld.2014.1121.273.pti
Sakurai, T., & Saruta, M. (2023). Positioning and Usefulness of Biomarkers in Inflammatory Bowel Disease. Digestion, 104(1), 30–41. https://doi.org/10.1159/000527846
Shi, J. T., Chen, N., Xu, J., Goyal, H., Wu, Z. Q., Zhang, J. X., & Xu, H. G. (2023). Diagnostic Accuracy of Fecal Calprotectin for Predicting Relapse in Inflammatory Bowel Disease: A Meta-Analysis. Journal of clinical medicine, 12(3), 1206. https://doi.org/10.3390/jcm12031206
Stevens, T. W., D'Haens, G. R., Duijvestein, M., Bemelman, W. A., Buskens, C. J., & Gecse, K. B. (2019). Diagnostic accuracy of faecal calprotectin in patients with active perianal fistulas. United European gastroenterology journal, 7(4), 496–506. https://doi.org/10.1177/2050640619834464
Stevens, T. W., Gecse, K., Turner, J. R., de Hertogh, G., Rubin, D. T., & D'Haens, G. R. (2021). Diagnostic Accuracy of Fecal Calprotectin Concentration in Evaluating Therapeutic Outcomes of Patients With Ulcerative Colitis. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association, 19(11), 2333–2342. https://doi.org/10.1016/j.cgh.2020.08.019
Szczubełek, M., Pomorska, K., Korólczyk-Kowalczyk, M., Lewandowski, K., Kaniewska, M., & Rydzewska, G. (2021). Effectiveness of Crohn's Disease Exclusion Diet for Induction of Remission in Crohn's Disease Adult Patients. Nutrients, 13(11), 4112. https://doi.org/10.3390/nu13114112
Walker, G. J., Lin, S., Chanchlani, N., Thomas, A., Hendy, P., Heerasing, N., Moore, L., Green, H. D., Chee, D., Bewshea, C., Mays, J., Kennedy, N. A., Ahmad, T., & Goodhand, J. R. (2020). Quality improvement project identifies factors associated with delay in IBD diagnosis. Alimentary pharmacology & therapeutics, 52(3), 471–480. https://doi.org/10.1111/apt.15885
Wang, Z., Yuan, H., Zhu, X., Wang, J., Xiu, W., Chen, Y., Zhang, G., Fu, J., Peng, K., Li, A., Liu, D., Huang, X., He, C., & Lu, F. (2023). Fecal calprotectin as an intestinal inflammation marker is elevated in glaucoma. Biomarkers in medicine, 17(9), 465–473. https://doi.org/10.2217/bmm-2023-0352
Ye, X., Huai, J., & Ding, J. (2018). Diagnostic accuracy of fecal calprotectin for screening patients with colorectal cancer: A meta-analysis. The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology, 29(4), 397–405. https://doi.org/10.5152/tjg.2018.17606
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2026 Kamil Bronikowski, Maksymilian Ryszkowski, Krystian Fornal, Natalia Będkowska-Kuśmierek, Sabina Zaborowska, Paulina Pawlak, Olaf Wojcieszuk, Łukasz Starczewski, Adrianna Babik, Kamila Kamińska
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
The periodical offers access to content in the Open Access system under the Creative Commons Attribution-NonCommercial-ShareAlike 4.0
Stats
Number of views and downloads: 146
Number of citations: 0
