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Mucosal inflammation as a potential etiological factor in irritable bowel syndrome: a systematic review

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Abstract

Background

The causes of irritable bowel syndrome (IBS) remain obscure. Some investigators have proposed chronic low-grade mucosal inflammation as a potential etiological factor. We performed a systematic review to examine this issue in detail.

Methods

MEDLINE, EMBASE, and EMBASE classic were searched up to December 2010 to identify studies of case–control design applying tests for low-grade inflammation to either full-thickness intestinal or endoscopic mucosal biopsies from patients with IBS. Controls were required to be healthy individuals, or asymptomatic patients undergoing investigation for reasons other than the reporting of upper or lower gastrointestinal symptoms. Individual study results were summarized descriptively.

Results

The literature search identified 1388 citations, of which 16 studies were eligible for inclusion. Individual study results were diverse, partly as a consequence of the different surrogate markers for inflammatory mechanisms studied. Mast cells, T lymphocytes, B lymphocytes, and mucosal cytokine production all appeared altered among cases with IBS in individual studies, while no study demonstrated a significant difference in numbers of plasma cells, neutrophils, or eosinophils. Some studies suggested a relationship between mast cell abnormalities and symptom severity and frequency, as well as co-existent fatigue and depression. Studies were limited by the lack of comparability of controls, and the fact that most were conducted in highly selected groups of patients with IBS.

Conclusions

Low-grade mucosal inflammation, particularly mast cell activation, may be a contributory factor in the pathogenesis of IBS. Mast cell stabilizers warrant further assessment as a potential therapy in the condition.

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References

  1. Longstreth GF, Thompson WG, Chey WD, et al. Functional bowel disorders. Gastroenterology. 2006;130:1480–91.

    Article  PubMed  Google Scholar 

  2. Agreus L, Talley NJ, Svardsudd K, et al. Identifying dyspepsia and irritable bowel syndrome: the value of pain or discomfort, and bowel habit descriptors. Scand J Gastroenterol. 2000;35:142–51.

    Article  PubMed  CAS  Google Scholar 

  3. Hillila MT, Farkkila MA. Prevalence of irritable bowel syndrome according to different diagnostic criteria in a non-selected adult population. Aliment Pharmacol Ther. 2004;20:339–45.

    Article  PubMed  CAS  Google Scholar 

  4. Hungin APS, Whorwell PJ, Tack J, et al. The prevalence, patterns and impact of irritable bowel syndrome: an international survey of 40,000 subjects. Aliment Pharmacol Ther. 2003;17:643–50.

    Article  PubMed  CAS  Google Scholar 

  5. Mearin F, Badia X, Balboa A, et al. Irritable bowel syndrome prevalence varies enormously depending on the employed diagnostic criteria: comparison of Rome II versus previous criteria in a general population. Scand J Gastroenterol. 2001;36:1155–61.

    Article  PubMed  CAS  Google Scholar 

  6. Agreus L, Svardsudd K, Nyren O, et al. Irritable bowel syndrome and dyspepsia in the general population: overlap and lack of stability over time. Gastroenterology. 1995;109:671–80.

    Article  PubMed  CAS  Google Scholar 

  7. Ford AC, Forman D, Bailey AG, et al. Irritable bowel syndrome: a 10-year natural history of symptoms, and factors that influence consultation behavior. Am J Gastroenterol. 2008;103:1229–39.

    Article  PubMed  Google Scholar 

  8. Halder SLS, Locke GR III, Schleck CD, et al. Natural history of functional gastrointestinal disorders: a 12-year longitudinal population-based study. Gastroenterology. 2007;133:799–807.

    Article  PubMed  Google Scholar 

  9. Kalantar JS, Locke GR, Zinsmeister AR, et al. Familial aggregation of irritable bowel syndrome: a prospective study. Gut. 2003;52:1703–7.

    Article  PubMed  CAS  Google Scholar 

  10. Stanghellini V, Tosetti C, Barbara G, et al. Dyspeptic symptoms and gastric emptying in the irritable bowel syndrome. Am J Gastroenterol. 2002;97:2738–43.

    Article  PubMed  Google Scholar 

  11. Cann PA, Read NW, Brown C, et al. Irritable bowel syndrome: relationship of disorders in the transit of a single solid meal to symptom patterns. Gut. 1983;24:405–11.

    Article  PubMed  CAS  Google Scholar 

  12. Moriarty KJ, Dawson AM. Functional abdominal pain: further evidence that whole gut is affected. Br Med J. 1982;284:1670–2.

    Article  CAS  Google Scholar 

  13. Trimble KC, Farouk R, Pryde A, et al. Heightened visceral sensation in functional gastrointestinal disease is not site-specific. Evidence for a generalized disorder of gut sensitivity. Dig Dis Sci. 1995;40:1607–13.

    Article  PubMed  CAS  Google Scholar 

  14. Tillisch K, Mayer EA, Labus JS. Quantitative meta-analysis identifies brain regions activated during rectal distension in irritable bowel syndrome. Gastroenterology. 2011;140:91–100. doi:10.1053/j.gastro.2010.07.053.

    Article  PubMed  Google Scholar 

  15. Collins SM. Is the irritable gut an inflamed gut? Scand J Gastroenterol. 1992;192(suppl):102–5.

    Article  CAS  Google Scholar 

  16. Marshall JK, Thabane M, Borgaonkar MR, et al. Postinfectious irritable bowel syndrome after a food-borne outbreak of gastroenteritis attributed to a viral pathogen. Clin Gastroenterol Hepatol. 2007;5:457–60.

    Article  PubMed  Google Scholar 

  17. Marshall JK, Thabane M, Garg AX, et al. Eight year prognosis of postinfectious irritable bowel syndrome following waterborne bacterial dysentery. Gut. 2010;59:605–11.

    Article  PubMed  Google Scholar 

  18. Mearin F, Perez-Oliveras M, Perello A, et al. Dyspepsia and irritable bowel syndrome after a Salmonella gastroenteritis outbreak: one year follow-up cohort study. Gastroenterology. 2005;(129):98–104.

    Article  Google Scholar 

  19. Tornblom H, Holmvall P, Svenungsson B, et al. Gastrointestinal symptoms after infectious diarrhea: a five-year follow-up in a Swedish cohort of adults. Clin Gastroenterol Hepatol. 2007;5:461–4.

    Article  PubMed  Google Scholar 

  20. Wang LH, Fang XC, Pan GZ. Bacillary dysentery as a causative factor of irritable bowel syndrome and its pathogenesis. Gut. 2004;53:1096–101.

    Article  PubMed  CAS  Google Scholar 

  21. Mearin F, Perello A, Balboa A, et al. Pathogenic mechanisms of postinfectious functional gastrointestinal disorders: results 3 years after gastroenteritis. Scand J Gastroenterol. 2009;44:1173–85.

    Article  PubMed  CAS  Google Scholar 

  22. Weston AP, Biddle WL, Bhatia PS, et al. Terminal ileal mucosal mast cells in irritable bowel syndrome. Dig Dis Sci. 1993;38:1590–5.

    Article  PubMed  CAS  Google Scholar 

  23. 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 

  24. 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 

  25. Bian ZX, Li Z, Huang ZX, et al. Unbalanced expression of protease-activated receptors-1 and -2 in the colon of diarrhea-predominant irritable bowel syndrome patients. J Gastroenterol. 2009;44:666–74.

    Article  PubMed  CAS  Google Scholar 

  26. Cenac N, Andrews CN, Holzhausen M, et al. Role for protease activity in visceral pain in irritable bowel syndrome. J Clin Invest. 2007;117:636–47.

    Article  PubMed  CAS  Google Scholar 

  27. Chadwick V, Chen W, Shu D, et al. Activation of the mucosal immune system in irritable bowel syndrome. Gastroenterology. 2002;122:1778–83.

    Article  PubMed  Google Scholar 

  28. Choung RS, Faubion WA, Saito YA et al. Cytokine expression in colonic mucosa and plasma in patients with irritable bowel syndrome. Neurogastroenterol Motil. 2010;22 (Suppl S1):57.

    Google Scholar 

  29. Coeffier M, Gloro R, Boukhettala N, et al. Increased proteasome-mediated degradation of occludin in irritable bowel syndrome. Am J Gastroenterol. 2010;105:1181–8.

    Article  PubMed  CAS  Google Scholar 

  30. 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 

  31. Forshammar J, Isaksson S, Strid H, et al. A pilot study of colonic B cell pattern in irritable bowel syndrome. Scand J Gastroenterol. 2008;43:1461–6.

    Article  PubMed  CAS  Google Scholar 

  32. Guilarte M, Santos J, de Torres I, et al. Diarrhoea-predominant IBS patients show mast cell activation and hyperplasia in the jejunum. Gut. 2007;56:203–9.

    Article  PubMed  Google Scholar 

  33. Lee KJ, Kim YB, Kim JH, et al. 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;23:1689–94.

    Article  PubMed  Google Scholar 

  34. MacSharry J, O’Mahony L, Fanning A, et al. Mucosal cytokine imbalance in irritable bowel syndrome. Scand J Gastroenterol. 2008;43:1467–76.

    Article  PubMed  CAS  Google Scholar 

  35. O’Sullivan M, Clayton N, Breslin NP, et al. Increased mast cells in the irritable bowel syndrome. Neurogastroenterol Motil. 2000;12:449–57.

    Article  PubMed  Google Scholar 

  36. Piche T, Saint-Paul MC, Dainese R, et al. Mast cells and cellularity of the colonic mucosa correlated with fatigue and depression in irritable bowel syndrome. Gut. 2008;57:468–73.

    Article  PubMed  CAS  Google Scholar 

  37. Tornblom H, Lindberg G, Nyberg B, et al. Full-thickness biopsy of the jejunum reveals inflammation and enteric neuropathy in irritable bowel syndrome. Gastroenterology. 2002;123:1972–9.

    Article  PubMed  Google Scholar 

  38. Walker MM, Talley NJ, Prabhakar M, et al. Duodenal mastocytosis, eosinophilia, and intraepithelial lymphocytosis as possible disease markers in the irritable bowel syndrome and functional dyspepsia. Aliment Pharmacol Ther. 2009;29:765–73.

    Article  PubMed  CAS  Google Scholar 

  39. Lijmer JG, Mol BW, Heisterkamp S. Empirical evidence of design-related bias in studies of diagnostic tests. JAMA. 1999;282:1061–6.

    Article  PubMed  CAS  Google Scholar 

  40. Marshall JK, Thabane M, Garg AX, et al. Intestinal permeability in patients with irritable bowel syndrome after a waterborne outbreak of acute gastroenteritis in Walkerton, Ontario. Aliment Pharmacol Ther. 2004;20:1317–22.

    Article  PubMed  CAS  Google Scholar 

  41. Pimentel M, Lembo A, Chey WD, et al. Rifaximin therapy for patients with irritable bowel syndrome without constipation. N Engl J Med. 2011;364:22–32.

    Article  PubMed  CAS  Google Scholar 

  42. Ford AC, Marwaha A, Lim A, et al. Systematic review and meta-analysis of the prevalence of irritable bowel syndrome in individuals with dyspepsia. Clin Gastroenterol Hepatol. 2010;8:401–9.

    Article  PubMed  Google Scholar 

  43. Lembo AJ, Neri B, Tolley J, et al. Use of serum biomarkers in a diagnostic test for irritable bowel syndrome. Aliment Pharmacol Ther. 2009;29:834–42.

    Article  PubMed  CAS  Google Scholar 

  44. Klooker TK, Braak B, Koopman KE, et al. The mast cell stabiliser ketotifen decreases visceral hypersensitivity and improves intestinal symptoms in patients with irritable bowel syndrome. Gut. 2010;59:1213–21

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Leeds Gastroenterology Institute, D Floor, Clarendon Wing, Leeds General Infirmary, Great George Street, Leeds, LS1 3EX, UK

    Alexander C. Ford

  2. Leeds Institute of Molecular Medicine, Leeds University, Leeds, UK

    Alexander C. Ford

  3. Faculty of Health, University of Newcastle, New South Wales, Australia

    Nicholas J. Talley

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  1. Alexander C. Ford
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Correspondence to Alexander C. Ford.

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Ford, A.C., Talley, N.J. Mucosal inflammation as a potential etiological factor in irritable bowel syndrome: a systematic review. J Gastroenterol 46, 421–431 (2011). https://doi.org/10.1007/s00535-011-0379-9

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  • DOI: https://doi.org/10.1007/s00535-011-0379-9

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