Skip to main content

Advertisement

Log in

Colonic Mucosal Immune Activity in Irritable Bowel Syndrome: Comparison with Healthy Controls and Patients with Ulcerative Colitis

  • Original Article
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Background and Aim

Mucosal immune activity may participate in irritable bowel syndrome (IBS) pathogenesis. Mast- and T cell numbers from patients with IBS or ulcerative colitis (UC) and healthy controls were determined.

Methods

Between November 2007 and May 2012, patients with diarrhea-predominant IBS (D-IBS, n = 83), 49 patients with UC, and 25 healthy controls were recruited. Of the UC group, 28 were in remission and 21 had mildly active UC. Biopsies from each colon segment were subjected to immunohistochemical analysis. The mast cells, intraepithelial lymphocytes (IELs), and lamina proprial lymphocytes (LPLs) were counted.

Results

Compared to the healthy controls, the patients with D-IBS, UC in remission, and mildly active UC had significantly higher mean colorectal mucosal mast-cell, IEL, and LPL counts. Comparison with the colon segments (ascending, transverse, descending, and sigmoid segments) that had once been involved in UC (in the patients with remission) revealed that the D-IBS colons had similar immune-cell counts. However, they had significantly fewer immune cells than the colon segments that presently showed involvement in the patients with mildly-activated UC. The mast-cell and IEL counts were similar in the D-IBS rectums and once-involved UC rectums but significantly higher in the presently-involved UC rectums. However, both the once-involved and presently-involved UC rectums had significantly higher LPL counts than the D-IBS rectums.

Conclusions

Patients with D-IBS had significantly higher colonic mucosal immune-cell counts than healthy controls but had similar counts to patients with UC in remission. The symptoms in both conditions may originate from low-grade inflammation in the colonic mucosa.

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

Access this article

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Longstreth GF, Thompson WG, Chey WD, Houghton LA, Mearin F, Spiller RC. Functional bowel disorders. Gastroenterology. 2006;130:1480–1491.

    Article  PubMed  Google Scholar 

  2. Cremon C, Gargano L, Morselli-Labate AM, et al. Mucosal immune activation in irritable bowel syndrome: gender-dependence and association with digestive symptoms. Am J Gastroenterol. 2009;104:392–400.

    Article  PubMed  CAS  Google Scholar 

  3. Barbara G, Stanghellini V, De Giorgio R, et al. Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome. Gastroenterology. 2004;126:693–702.

    Article  PubMed  Google Scholar 

  4. Wang LH, Fang XC, Pan GZ. Bacillary dysentery as a causative factor of irritable bowel syndrome and its pathogenesis. Gut. 2004;53:1096–1101.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  5. Dunlop SP, Jenkins D, Spiller RC. Distinctive clinical, psychological, and histological features of postinfective irritable bowel syndrome. Am J Gastroenterol. 2003;98:1578–1583.

    Article  PubMed  Google Scholar 

  6. Spiller RC, Jenkins D, Thornley JP, et al. Increased rectal mucosal enteroendocrine cells, T lymphocytes, and increased gut permeability following acute Campylobacter enteritis and in post-dysenteric irritable bowel syndrome. Gut. 2000;47:804–811.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  7. Lee KJ, Kim YB, Kim JH, Kwon HC, Kim DK, Cho SW. The alteration of enterochromaffin cell, mast cell, and lamina propria T lymphocyte numbers in irritable bowel syndrome and its relationship with psychological factors. J Gastroenterol Hepatol. 2008;23:1689–1694.

    Article  PubMed  Google Scholar 

  8. Wheatcroft J, Wakelin D, Smith A, Mahoney CR, Mawe G, Spiller R. Enterochromaffin cell hyperplasia and decreased serotonin transporter in a mouse model of postinfectious bowel dysfunction. Neurogastroenterol Motil. 2005;17:863–870.

    Article  PubMed  CAS  Google Scholar 

  9. Park JH, Rhee PL, Kim HS, et al. Mucosal mast cell counts correlate with visceral hypersensitivity in patients with diarrhea predominant irritable bowel syndrome. J Gastroenterol Hepatol. 2006;21:71–78.

    Article  PubMed  Google Scholar 

  10. Barbara G, Wang B, Stanghellini V, et al. Mast cell-dependent excitation of visceral-nociceptive sensory neurons in irritable bowel syndrome. Gastroenterology. 2007;132:26–37.

    Article  PubMed  CAS  Google Scholar 

  11. Cenac N, Andrews CN, Holzhausen M, et al. Role for protease activity in visceral pain in irritable bowel syndrome. J Clin Invest. 2007;117:636–647.

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  12. Barbara G, De Giorgio R, Stanghellini V, Cremon C, Corinaldesi R. A role for inflammation in irritable bowel syndrome? Gut. 2002;51:i41–i44.

    Article  PubMed Central  PubMed  Google Scholar 

  13. Burgmann T, Clara I, Graff L, et al. The Manitoba Inflammatory Bowel Disease Cohort Study: prolonged symptoms before diagnosis—how much is irritable bowel syndrome? Clin Gastroenterol Hepatol. 2006;4:614–620.

    Article  PubMed  Google Scholar 

  14. Limsui D, Pardi DS, Camilleri M, et al. Symptomatic overlap between irritable bowel syndrome and microscopic colitis. Inflamm Bowel Dis. 2007;13:175–181.

    Article  PubMed  Google Scholar 

  15. Simren M, Axelsson J, Gillberg R, Abrahamsson H, Svedlund J, Bjornsson ES. Quality of life in inflammatory bowel disease in remission: the impact of IBS-like symptoms and associated psychological factors. Am J Gastroenterol. 2002;97:389–396.

    Article  PubMed  Google Scholar 

  16. Choi CH, Jung SA, Lee BI, Lee KM, Kim JS, Han DS. Diagnostic guideline of ulcerative colitis. Korean J Gastroenterol. 2009;53:145–160.

    PubMed  Google Scholar 

  17. Kornbluth A, Sachar DB. Ulcerative colitis practice guidelines in adults (update): American College of Gastroenterology. Practice Parameters Committee. Am J Gastroenterol. 2004;99:1371–1385.

    Google Scholar 

  18. Kornbluth A, Sachar DB. Ulcerative colitis practice guidelines in adults: American College Of Gastroenterology, Practice Parameters Committee. Am J Gastroenterol. 2010;105:501-523; quiz 524.

    Google Scholar 

  19. Schroeder KW, Tremaine WJ, Ilstrup DM. Coated oral 5-aminosalicylic acid therapy for mildly to moderately active ulcerative colitis. A randomized study. N Engl J Med. 1987;317:1625–1629.

    Article  PubMed  CAS  Google Scholar 

  20. O’Mahony L, McCarthy J, Kelly P, et al. Lactobacillus and bifidobacterium in irritable bowel syndrome: symptom responses and relationship to cytokine profiles. Gastroenterology. 2005;128:541–551.

    Article  PubMed  Google Scholar 

  21. Veldhuyzen van Zanten SJ, Talley NJ, Bytzer P, Klein KB, Whorwell PJ, Zinsmeister AR. Design of treatment trials for functional gastrointestinal disorders. Gut. 1999;45:II69-77.

  22. Ware JE Jr. Sherbourne CD. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Med Care. 1992;30:473–483.

    Article  PubMed  Google Scholar 

  23. Patrick DL, Drossman DA, Frederick IO, DiCesare J, Puder KL. Quality of life in persons with irritable bowel syndrome: development and validation of a new measure. Dig Dis Sci. 1998;43:400–411.

    Article  PubMed  CAS  Google Scholar 

  24. Park JM, Choi MG, Oh JH, et al. Cross-cultural validation of Irritable Bowel Syndrome Quality of Life in Korea. Dig Dis Sci. 2006;51:1478–1484.

    Article  PubMed  Google Scholar 

  25. Ohman L, Isaksson S, Lindmark AC, et al. T-cell activation in patients with irritable bowel syndrome. Am J Gastroenterol. 2009;104:1205–1212.

    Article  PubMed  CAS  Google Scholar 

  26. Vivinus-Nebot M, Dainese R, Anty R, et al. Combination of allergic factors can worsen diarrheic irritable bowel syndrome: role of barrier defects and mast cells. Am J Gastroenterol. 2012;107:75–81.

    Article  PubMed  CAS  Google Scholar 

  27. De Silva AP, Nandasiri SD, Hewavisenthi J, et al. Subclinical mucosal inflammation in diarrhea-predominant irritable bowel syndrome (IBS) in a tropical setting. Scand J Gastroenterol. 2012;47:619–624.

    Article  PubMed  CAS  Google Scholar 

  28. Bashashati M, Rezaei N, Bashashati H, et al. Cytokine gene polymorphisms are associated with irritable bowel syndrome: a systematic review and meta-analysis. Neurogastroenterol Motil. 2012;24:1102-e1566.

    Article  CAS  Google Scholar 

  29. Yamagata K, Tanaka M, Kudo H. A quantitative immunohistochemical evaluation of inflammatory cells at the affected and unaffected sites of inflammatory bowel disease. J Gastroenterol Hepatol. 1998;13:801–808.

    Article  PubMed  CAS  Google Scholar 

  30. Quist RG, Ton-Nu HT, Lillienau J, Hofmann AF, Barrett KE. Activation of mast cells by bile acids. Gastroenterology. 1991;101:446–456.

    PubMed  CAS  Google Scholar 

  31. Gui XY. Mast cells: a possible link between psychological stress, enteric infection, food allergy and gut hypersensitivity in the irritable bowel syndrome. J Gastroenterol Hepatol. 1998;13:980–989.

    Article  PubMed  CAS  Google Scholar 

  32. El-Salhy M, Gundersen D, Hatlebakk JG, Hausken T. Low-grade inflammation in the rectum of patients with sporadic irritable bowel syndrome. Mol Med Rep. 2013;7:1081–1085.

    PubMed  CAS  Google Scholar 

  33. Weston AP, Biddle WL, Bhatia PS, Miner PB Jr. Terminal ileal mucosal mast cells in irritable bowel syndrome. Dig Dis Sci. 1993;38:1590–1595.

    Article  PubMed  CAS  Google Scholar 

  34. O’Sullivan M, Clayton N, Breslin NP, et al. Increased mast cells in the irritable bowel syndrome. Neurogastroenterol Motil. 2000;12:449–457.

    Article  PubMed  Google Scholar 

  35. Nishida Y, Murase K, Isomoto H, et al. Different distribution of mast cells and macrophages in colonic mucosa of patients with collagenous colitis and inflammatory bowel disease. Hepatogastroenterology. 2002;49:678–682.

    PubMed  Google Scholar 

  36. van Hoboken EA, Thijssen AY, Verhaaren R, et al. Symptoms in patients with ulcerative colitis in remission are associated with visceral hypersensitivity and mast cell activity. Scand J Gastroenterol. 2011;46:981–987.

    Article  PubMed  Google Scholar 

  37. Liebregts T, Adam B, Bredack C, et al. Immune activation in patients with irritable bowel syndrome. Gastroenterology. 2007;132:913–920.

    Article  PubMed  CAS  Google Scholar 

  38. Dinan TG, Quigley EM, Ahmed SM, et al. Hypothalamic-pituitary-gut axis dysregulation in irritable bowel syndrome: plasma cytokines as a potential biomarker? Gastroenterology. 2006;130:304–311.

    Article  PubMed  CAS  Google Scholar 

  39. Chadwick VS, Chen W, Shu D, et al. Activation of the mucosal immune system in irritable bowel syndrome. Gastroenterology. 2002;122:1778–1783.

    Article  PubMed  Google Scholar 

  40. Dunlop SP, Jenkins D, Neal KR, Spiller RC. Relative importance of enterochromaffin cell hyperplasia, anxiety, and depression in postinfectious IBS. Gastroenterology. 2003;125:1651–1659.

    Article  PubMed  Google Scholar 

  41. Arevalo F, Aragon V, Montes P, Guzman E, Monge E. Increase of intraepithelial lymphocytes in patients with irritable bowel syndrome. Rev Gastroenterol Peru. 2011;31:315–318.

    PubMed  CAS  Google Scholar 

  42. Reichman-Warmusz E, Kurek J, Gabriel A, et al. Tissue hemostasis and chronic inflammation in colon biopsies of patients with inflammatory bowel disease. Pathol Res Pract. 2012;208:553–556.

    Article  PubMed  CAS  Google Scholar 

  43. Dai SX, Wu G, Zou Y, et al. Balance of CD8(+)CD28 (+)/CD8 (+)CD28 (−) T lymphocytes is vital for patients with ulcerative colitis. Dig Dis Sci. 2013;58:88–96.

    Google Scholar 

  44. Cho HS, Park JM, Lim CH, et al. Anxiety, depression and quality of life in patients with irritable bowel syndrome. Gut Liver. 2011;5:29–36.

    Article  PubMed Central  PubMed  Google Scholar 

  45. Gralnek IM, Hays RD, Kilbourne A, Naliboff B, Mayer EA. The impact of irritable bowel syndrome on health-related quality of life. Gastroenterology. 2000;119:654–660.

    Article  PubMed  CAS  Google Scholar 

  46. Whitehead WE, Burnett CK, Cook EW III, Taub E. Impact of irritable bowel syndrome on quality of life. Dig Dis Sci. 1996;41:2248–2253.

    Article  PubMed  CAS  Google Scholar 

  47. Drossman DA, Patrick DL, Mitchell CM, Zagami EA, Appelbaum MI. Health-related quality of life in inflammatory bowel disease. Functional status and patient worries and concerns. Dig Dis Sci. 1989;34:1379–1386.

    Article  PubMed  CAS  Google Scholar 

  48. Bercik P, Verdu EF, Collins SM. Is irritable bowel syndrome a low-grade inflammatory bowel disease? Gastroenterol Clin N Am. 2005;34:235–245, vi–vii.

    Google Scholar 

Download references

Acknowledgments

The authors confirm that they have no financial arrangements with anyone in relation to this work.

Conflict of interest

None.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Chang Hwan Choi.

Additional information

Ji Yong Ahn and Kyung Hun Lee contributed equally to this article.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ahn, J.Y., Lee, K.H., Choi, C.H. et al. Colonic Mucosal Immune Activity in Irritable Bowel Syndrome: Comparison with Healthy Controls and Patients with Ulcerative Colitis. Dig Dis Sci 59, 1001–1011 (2014). https://doi.org/10.1007/s10620-013-2930-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-013-2930-4

Keywords

Navigation