Skip to main content
SpringerLink
Log in

Review of Fecal Biomarkers in Inflammatory Bowel Disease

  • Current Status
  • Published:
Diseases of the Colon & Rectum

Abstract

Purpose

We reviewed potential fecal biomarkers of inflammatory bowel disease and assessed their utility in a range of clinical applications.

Methods

A literature search using PubMed, MEDLINE, and Embase database was performed, locating all language articles on fecal biomarkers, including calprotectin and lactoferrin. The references of these papers were searched manually for further references.

Results

A wide range of fecal biomarkers have been evaluated in the research setting. Only fecal calprotectin and lactoferrin have translated into useful clinical tools. These biomarkers have demonstrated high sensitivity for organic intestinal disease and good correlation with other measures of disease activity in inflammatory bowel disease.

Conclusions

Fecal calprotectin and lactoferrin are useful triage tools to differentiate organic intestinal disorders from functional disorders. They also have a role in monitoring inflammatory bowel disease activity and predicting relapse.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Desai D, Faubion WA, Sandborn WJ. Review article: biological markers in inflammatory bowel disease. Aliment Pharmacol Ther 2007;25:247–55.

    PubMed  CAS  Google Scholar 

  2. Angriman I, Scarpa M, D’Incà R, et al. Enzymes in feces: useful markers of chronic inflammatory bowel disease. Clin Chim Acta 2007;381:63–8.

    Article  PubMed  CAS  Google Scholar 

  3. Klass HJ, Neale G. Serum and fecal lysozyme in inflammatory bowel disease. Gut 1978;19:233–9.

    Article  PubMed  CAS  Google Scholar 

  4. Langhorst J, Elsenbruch S, Mueller T, et al. Comparison of 4 neutrophil-derived proteins in feces as indicators of disease activity in ulcerative colitis. Inflamm Bowel Dis 2005;11:1085–91.

    Article  PubMed  Google Scholar 

  5. Saiki T. Myeloperoxidase concentrations in the stool as a new parameter of inflammatory bowel disease. Kurume Med J 1998;45:69–73.

    PubMed  CAS  Google Scholar 

  6. Adeyemi EO, Hodgson HJ. Fecal elastase reflects disease activity in active ulcerative colitis. Scand J Gastroenterol 1992;27:139–42.

    Article  PubMed  CAS  Google Scholar 

  7. van der Sluys Veer A, Brouwer J, Biemond I, et al. Fecal lysozyme in assessment of disease activity in inflammatory bowel disease. Dig Dis Sci 1998;43:590–5.

    Article  PubMed  Google Scholar 

  8. Silberer H, Kuppers B, Mickisch O, et al. Fecal leukocyte proteins in inflammatory bowel disease and irritable bowel syndrome. Clin Lab 2005;51:117–26.

    PubMed  CAS  Google Scholar 

  9. Peterson CG, Eklund E, Taha Y, Raab Y, Carlson M. A new method for the quantification of neutrophil and eosinophil cationic proteins in feces: establishment of normal levels and clinical application in patients with inflammatory bowel disease. Am J Gastroenterol 2002;97:1755–62.

    Article  PubMed  CAS  Google Scholar 

  10. Biancone L, Fantini M, Tosti C, et al. Fecal alpha-1-antitrypsin clearance as a marker of clinical relapse in patients with Crohn’s disease of the distal ileum. European J Gastroenterol Hepatol 2003;15:261–6.

    Article  CAS  Google Scholar 

  11. Choudari CP, O’Mahony S, Brydon G, Mwantembe O, Ferguson A. Gut lavage fluid protein concentrations: objective measures of disease activity in inflammatory bowel disease. Gastroenterology 1993;104:1064–71.

    PubMed  CAS  Google Scholar 

  12. Saverymuttu SH, Camilleri M, Rees H, et al. Indium-111-granulocyte scanning in the assessment of disease extent and disease activity in inflammatory bowel disease: a comparison with colonoscopy, histology, and fecal indium 111-granulocyte excretion. Gastroenterology 1986;90:1121–8.

    PubMed  CAS  Google Scholar 

  13. Røseth AG, Schmidt PN, Fagerhol MK. Correlation between fecal excretion of indium-111-labelled granulocytes and calprotectin, a granulocyte marker protein, in patients with inflammatory bowel disease. Scand J Gastroenterol 1999;34:50–4.

    Article  PubMed  Google Scholar 

  14. Tibble J, Teahon K, Thjodleifsson B, et al. A simple method for assessing intestinal inflammation in Crohn’s disease. Gut 2000;47:506–13.

    Article  PubMed  CAS  Google Scholar 

  15. D’Incà R, Dal Pont E, Di Leo V, et al. Calprotectin and lactoferrin in the assessment of intestinal inflammation and organic disease. Int J Colorectal Dis 2007;22:429–37.

    Article  PubMed  Google Scholar 

  16. Bremner A, Roked S, Robinson R, Phillips I, Beattie M. Fecal calprotectin in children with chronic gastrointestinal symptoms. Acta Paediatr 2005;94:1855–8.

    Article  PubMed  Google Scholar 

  17. Røseth AG, Aadland E, Jahnsen J, Raknerud N. Assessment of disease activity in ulcerative colitis by fecal calprotectin, a novel granulocyte marker protein. Digestion 1997;58:176–80.

    Article  PubMed  Google Scholar 

  18. Røseth AG, Fagerhol MK, Aadland E, Schjønsby H. Assessment of the neutrophil dominating protein calprotectin in feces. A methodologic study. Scand J Gastroenterol 1992;27:793–8.

    Article  PubMed  Google Scholar 

  19. Kane SV, Sandborn WJ, Rufo PA, et al. Fecal Lactoferrin is a sensitive and specific marker in identifying intestinal inflammation. Am J Gastroenterol 2003;98:1309–14.

    Article  PubMed  CAS  Google Scholar 

  20. Sugi K, Saitoh O, Hirata I, Katsu K. Fecal lactoferrin as a marker for disease activity in inflammatory bowel disease: comparison with other neutrophil-derived proteins. Am J Gastroenterol 1996;91:927–34.

    PubMed  CAS  Google Scholar 

  21. Uchida K, Matsuse R, Tomita S, Sugi O, et al. Immunochemical detection of human lactoferrin in feces as a new marker of inflammatory gastrointestinal disorders and colon cancer. Clin Biochem 1994;27:259–64.

    Article  PubMed  CAS  Google Scholar 

  22. Grill BB, Hillemeier AC, Gryboski JD. Fecal alpha-1-antitrypsin clearance in patients with inflammatory bowel disease. J Pediatr Gastroenterol Nutr 1984;3:56–61.

    PubMed  CAS  Google Scholar 

  23. van der Sluys Veer A, Biemond I, Verspaget HW, Lamers CB. Fecal parameters in the assessment of activity of inflammatory bowel disease. Scand J Gastroenterol 1999;34(Suppl 230):106–10.

    Article  Google Scholar 

  24. Meyers S, Wolke A, Field SP, et al. Fecal alpha-1-antitrypsin measurement: An indicator of Crohn’s disease activity. Gastroenterology 1985;89:13–8.

    PubMed  CAS  Google Scholar 

  25. Segal AW, Ensell J, Munro JA, Sarner M. Indium-111-tagged leukocytes in the diagnosis of inflammatory bowel disease. Lancet 1981;ii:230–2.

    Article  Google Scholar 

  26. Saverymuttu SH, Peters AM, Crofton ME, et al. 111 Indium labelled autologous granulocytes in the detection of inflammatory bowel disease. Gut 1985;26:955–60.

    Article  PubMed  CAS  Google Scholar 

  27. Saverymuttu SH, Hodgson HJ, Chadwick VS. Comparison of fecal granulocyte excretion in ulcerative colitis and Crohn’s colitis. Dig Dis Sci 1984;29:1000–4.

    Google Scholar 

  28. Steinbakk M, Naess-Andresen C-F, Lingaas E, et al. Antimicrobial actions of calcium binding leucocyte L1 protein, calprotectin. Lancet 1990;336:763–5.

    Article  PubMed  CAS  Google Scholar 

  29. Fagerhol MK, Dale I, Anderson I. Release and quantification of leukocyte derived protein (L1). Scand J Haematol 1980;24:393–8.

    CAS  Google Scholar 

  30. Ton H, Brandnes O, Dale S, et al. Improved assay for fecal calprotectin. Clin Chim Acta 2000;292:41–54.

    Article  PubMed  CAS  Google Scholar 

  31. Buderus S, Boone J, Lyerly D, Lentze MJ. Fecal lactoferrin: a new parameter to monitor infliximab therapy. Digestive Dis Sci 2004;49:1036–9.

    Article  CAS  Google Scholar 

  32. Parsi MA, Shen B, Achkar JP, et al. Fecal lactoferrin for diagnosis of symptomatic patients with ileal pouch-anal anastomosis. Gastroenterology 2004;126:1280–6.

    Article  PubMed  Google Scholar 

  33. Bernier JJ, Florent C, Desmazures C, Aymes C, L’Hirondel C. Diagnosis of protein losing enteropathy by gastrointestinal clearance of alpha-1-antitrypsin. Lancet 1978;2:763–4.

    Article  PubMed  CAS  Google Scholar 

  34. Florent C, L’Hirondel C, Desmazures C, Giraudeaux V, Bernier JJ. Evaluation of ulcerative colitis and Crohn’s disease activity by measurement of alpha-1-antitrypsin intestinal clearance. Gastroenterol Clin Biol 1981;5:193–7.

    PubMed  CAS  Google Scholar 

  35. Lundberg JO, Hellström PM, Fagerhol MK, Weitzberg E, Røseth AG. Technology insight: calprotectin, lactoferrin and nitric oxide as novel markers of inflammatory bowel disease. Gastroenterol Hepatol 2005;2:96–102.

    CAS  Google Scholar 

  36. Lundberg JO, Hellström PM, Lundberg JM, Alving K. Greatly increased luminal nitric oxide in ulcerative colitis. Lancet 1994;344:1673–4.

    Article  PubMed  CAS  Google Scholar 

  37. Perner A, Nordgaard I, Matzen P, Rask-Madsen J. Colonic production of nitric oxide gas in ulcerative colitis, collagenous colitis and uninflamed bowel. Scand J Gastroenterol 2002;37:183–8.

    Article  PubMed  CAS  Google Scholar 

  38. Thompson WG, Longstreth GF, Drossman DA, et al. Functional bowel disorders and functional abdominal pain. Gut 1999;45(Suppl 2):II43–7.

    Article  PubMed  Google Scholar 

  39. Tibble JA, Sigthorsson G, Foster R, et al. Use of surrogate markers of inflammation and Rome criteria to distinguish organic from nonorganic intestinal disease. Gastroenterology 2002;123:450–60.

    Article  PubMed  Google Scholar 

  40. Canani RB, de Horatio LT, Terrin G, et al. Combined use of non-invasive tests is useful in the initial diagnostic approach to a child with suspected inflammatory bowel disease. J Pediatr Gastroenterol Nutr 2006;42:9–15.

    Article  PubMed  Google Scholar 

  41. Carroccio A, Iacono G, Cottone M, et al. Diagnostic accuracy of fecal calprotectin assay in distinguishing organic causes of chronic diarrhea from irritable bowel syndrome: a prospective study in adults and children. Clin Chem 2003;49:861–7.

    Article  PubMed  CAS  Google Scholar 

  42. von Roon AC, Karamountzos L, Purkayastha S, et al. Diagnostic precision of fecal calprotectin for inflammatory bowel disease and colorectal malignancy. Am J Gastroenterol 2007;102:803–13.

    Article  CAS  Google Scholar 

  43. Dolwani S, Metzner M, Wassell JJ, Yong A, Hawthorne AB. Diagnostic accuracy of fecal calprotectin estimation in prediction of abnormal small bowel radiology. Aliment Pharmacol Ther 2004;20:615–21.

    Article  PubMed  CAS  Google Scholar 

  44. Tibble J, Sigthorsson G, Foster R, et al. Fecal calprotectin and fecal occult blood tests in the diagnosis of colorectal carcinoma and adenoma. Gut 2001;49:402–8.

    Article  PubMed  CAS  Google Scholar 

  45. Hoff G, Grotmol T, Thiis-Evensen E, et al. Testing for fecal calprotectin (PhiCal) in the Norwegian Colorectal Cancer Prevention trial on flexible sigmoidoscopy screening: comparison with an immunochemical test for occult blood (FlexSure OBT). Gut 2004;53:1329–33.

    Article  PubMed  CAS  Google Scholar 

  46. Poullis A, Foster R, Shetty A, Fagerhol MK, Mendall MA. Bowel inflammation as measured by fecal calprotectin: a link between lifestyle factors and colorectal cancer risk. Cancer Epidemiol Biomarkers Prev 2004;13:279–84.

    Article  PubMed  CAS  Google Scholar 

  47. Fagerberg UL, Lööf L, Myrdal U, Hansson L-O, Finkel Y. Colorectal inflammation is well predicted by fecal calprotectin in children with gastrointestinal symptoms. J Pediatr Gastroenterol Nutr 2005;40:450–5.

    Article  PubMed  Google Scholar 

  48. Fagerberg UL, Lööf L, Merzoug RD, Hansson L-O, Finkel Y. Fecal calprotectin levels in healthy children studied with an improved assay. J Pediatr Gastroenterol Nutr 2003;37:468–72.

    Article  PubMed  CAS  Google Scholar 

  49. Tibble JA, Bjarnason I. Non-invasive investigation of inflammatory bowel disease. World J Gastroenterol 2001;7:460–5.

    PubMed  CAS  Google Scholar 

  50. Røseth AG, Aadland E, Grzyb K. Normalization of fecal calprotectin: a predictor of mucosal healing in patients with inflammatory bowel disease. Scand J Gastroenterol 2004;39:1017–20.

    Article  PubMed  CAS  Google Scholar 

  51. Gomes P, Du Bolay C, Smith CL, Holdstock G. Relationship between disease activity indices and colonoscopic findings in patients with colonic inflammatory bowel disease. Gut 1986;27:92–5.

    Article  PubMed  CAS  Google Scholar 

  52. Tibble JA, Sigthorsson G, Bridger S, Fagerhol MK, Bjarnason I. Surrogate markers of intestinal inflammation are predictive of relapse in patients with inflammatory bowel disease. Gastroenterology 2000;119:15–22.

    Article  PubMed  CAS  Google Scholar 

  53. Costa F, Mumolo MG, Ceccarelli L, et al. Calprotectin is a stronger predictive marker of relapse in ulcerative colitis than in Crohn’s disease. Gut 2005;54:364–8.

    Article  PubMed  CAS  Google Scholar 

  54. Scarpa M, D’Inca R, Basso D, et al. Fecal lactoferrin and calprotectin after ileocolonic resection for Crohn’s disease. Dis Colon Rectum 2007;50:861–9.

    Article  PubMed  Google Scholar 

  55. Parsi MA, Ellis JJ, Lashner BA. Cost-effectiveness analysis of fecal lactoferrin assay as the initial diagnostic approach to symptomatic patients with ileal pouch-anal anastomosis. Gastroenterology 2004;128(Suppl 2):A208.

    Google Scholar 

  56. Thomas P, Rihani H, Røseth A, et al. Assessment of ileal pouch inflammation by single stool calprotectin assay. Dis Colon Rectum 2000;43:214–20.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Surgery, Christchurch Hospital, Christchurch, New Zealand

    Andrew D. Sutherland M.B.B.S., F.R.A.C.S. & Frank A. Frizelle M.B.Ch.B., M.Med.Sc., F.R.A.C.S

  2. Department of Gastroenterology, Christchurch Hospital, Christchurch, New Zealand

    Richard B. Gearry M.B.Ch.B., Ph.D., F.R.A.C.P.

Authors
  1. Andrew D. Sutherland M.B.B.S., F.R.A.C.S.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Richard B. Gearry M.B.Ch.B., Ph.D., F.R.A.C.P.
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Frank A. Frizelle M.B.Ch.B., M.Med.Sc., F.R.A.C.S
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Frank A. Frizelle M.B.Ch.B., M.Med.Sc., F.R.A.C.S.

Additional information

Reprints are not available.

About this article

Cite this article

Sutherland, A.D., Gearry, R.B. & Frizelle, F.A. Review of Fecal Biomarkers in Inflammatory Bowel Disease. Dis Colon Rectum 51, 1283–1291 (2008). https://doi.org/10.1007/s10350-008-9310-8

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10350-008-9310-8

Key words

Search

Navigation