Journal List > Korean J Gastroenterol > v.68(3) > 1007551

Kwon and Kim: Current Status of Translational Research on Irritable Bowel Syndrome

Abstract

Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder. The pathophysiology of IBS is not completely understood. Genetic, immune, environmental, inflammatory, neurological and psychological factors contribute to the risk of this condition. Traditional research explored gastrointestinal motor abnormalities, central neural dysregulation, abnormal psychological features, and visceral hypersensitivity. More recent investigations consider bacterial overgrowth, abnormal serotonin pathways, altered gut flora, immune activation and mucosal inflammation. The purpose of this article is to review recent translational research concerning the pathophysiology, biomarker and genetic factors of IBS and to encourage IBS research in Korea.

References

1. Drossman DA, Li Z, Andruzzi E, et al. U.S. householder survey of functional gastrointestinal disorders. Prevalence, sociodemo-graphy, and health impact. Dig Dis Sci. 1993; 38:1569–1580.
2. Lee SY, Lee KJ, Kim SJ, Cho SW. Prevalence and risk factors for overlaps between gastroesophageal reflux disease, dyspepsia, and irritable bowel syndrome: a population-based study. Digestion. 2009; 79:196–201.
crossref
3. Park DW, Lee OY, Shim SG, et al. The differences in prevalence and sociodemographic characteristics of irritable bowel syndrome according to Rome II and Rome III. J Neurogastroenterol Motil. 2010; 16:186–193.
crossref
4. El-Serag HB, Olden K, Bjorkman D. Health-related quality of life among persons with irritable bowel syndrome: a systematic review. Aliment Pharmacol Ther. 2002; 16:1171–1185.
crossref
5. Lu CL, Chang FY, Lang HC, Chen CY, Luo JC, Lee SD. Gender difference on the symptoms, health-seeking behaviour, social impact and sleep quality in irritable bowel syndrome: a Rome II-based survey in an apparent healthy adult Chinese population in Taiwan. Aliment Pharmacol Ther. 2005; 21:1497–1505.
crossref
6. Rey E, García-Alonso MO, Moreno-Ortega M, Alvarez-Sanchez A, Diaz-Rubio M. Determinants of quality of life in irritable bowel syndrome. J Clin Gastroenterol. 2008; 42:1003–1009.
crossref
7. Drossman DA. Functional gastrointestinal disorders: history, pathophysiology, clinical features and Rome IV. Gastroenterology. 2016. DOI: doi:10.1053/j.gastro.2016.02.032. [Epub ahead of print].
crossref
8. Enck P, Aziz Q, Barbara G, et al. Irritable bowel syndrome. Nat Rev Dis Primers. 2016; 2:16014.
crossref
9. Bischoff SC, Barbara G, Buurman W, et al. Intestinal permeability–a new target for disease prevention and therapy. BMC Gastroenterol. 2014; 14:189.
crossref
10. Martínez C, Lobo B, Pigrau M, et al. Diarrhoea-predominant irritable bowel syndrome: an organic disorder with structural abnormalities in the jejunal epithelial barrier. Gut. 2013; 62:1160–1168.
crossref
11. Fritscher-Ravens A, Schuppan D, Ellrichmann M, et al. Confocal endomicroscopy shows food-associated changes in the intestinal mucosa of patients with irritable bowel syndrome. Gastroenterology. 2014; 147:1012–1020.e4.
crossref
12. Barbara G, Cremon C, Carini G, et al. The immune system in irritable bowel syndrome. J Neurogastroenterol Motil. 2011; 17:349–359.
crossref
13. 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.
crossref
14. Nasser Y, Boeckxstaens GE, Wouters MM, Schemann M, Vanner S. Using human intestinal biopsies to study the pathogenesis of irritable bowel syndrome. Neurogastroenterol Motil. 2014; 26:455–469.
crossref
15. Barbara G, Wang B, Stanghellini V, et al. Mast cell-dependent ex-citation of visceral-nociceptive sensory neurons in irritable bowel syndrome. Gastroenterology. 2007; 132:26–37.
crossref
16. 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.
crossref
17. Annaházi A, Gecse K, Dabek M, et al. Fecal proteases from diar-rheic-IBS and ulcerative colitis patients exert opposite effect on visceral sensitivity in mice. Pain. 2009; 144:209–217.
crossref
18. Annaházi A, Ferrier L, Bézirard V, et al. Luminal cys-teine-proteases degrade colonic tight junction structure and are responsible for abdominal pain in constipation-predominant IBS. Am J Gastroenterol. 2013; 108:1322–1331.
crossref
19. Buhner S, Braak B, Li Q, et al. Neuronal activation by mucosal biopsy supernatants from irritable bowel syndrome patients is linked to visceral sensitivity. Exp Physiol. 2014; 99:1299–1311.
crossref
20. Valdez-Morales EE, Overington J, Guerrero-Alba R, et al. Sensitization of peripheral sensory nerves by mediators from colonic biopsies of diarrhea-predominant irritable bowel syndrome patients: a role for PAR2. Am J Gastroenterol. 2013; 108:1634–1643.
crossref
21. Cenac N, Bautzova T, Le Faouder P, et al. Quantification and potential functions of endogenous agonists of transient receptor potential channels in patients with irritable bowel syndrome. Gastroenterology. 2015; 149:433–444.e7.
crossref
22. Dothel G, Barbaro MR, Boudin H, et al. Nerve fiber outgrowth is increased in the intestinal mucosa of patients with irritable bowel syndrome. Gastroenterology. 2015; 148:1002–1011.e4.
crossref
23. Ford AC, Bercik P, Morgan DG, Bolino C, Pintos-Sanchez MI, Moayyedi P. Validation of the Rome III criteria for the diagnosis of irritable bowel syndrome in secondary care. Gastroenterology. 2013; 145:1262–1270.e1.
crossref
24. Sood R, Law GR, Ford AC. Diagnosis of IBS: symptoms, symp-tom-based criteria, biomarkers or ‘psychomarkers’? Nat Rev Gastroenterol Hepatol. 2014; 11:683–691.
crossref
25. Camilleri M. Peripheral mechanisms in irritable bowel syndrome. N Engl J Med. 2012; 367:1626–1635.
crossref
26. Mujagic Z, Ludidi S, Keszthelyi D, et al. Small intestinal permeability is increased in diarrhoea predominant IBS, while alterations in gastroduodenal permeability in all IBS subtypes are largely attributable to confounders. Aliment Pharmacol Ther. 2014; 40:288–297.
crossref
27. Sood R, Gracie DJ, Law GR, Ford AC. Systematic review with metaanalysis: the accuracy of diagnosing irritable bowel syndrome with symptoms, biomarkers and/or psychological markers. Aliment Pharmacol Ther. 2015; 42:491–503.
crossref
28. Sood R, Ford AC. Combining biomarkers in irritable bowel syndrome: a forward step toward making a positive diagnosis and directing therapy? Gastroenterology. 2015; 148:1471–1473.
crossref
29. Crenn P, Messing B, Cynober L. Citrulline as a biomarker of intestinal failure due to enterocyte mass reduction. Clin Nutr. 2008; 27:328–339.
crossref
30. Windmueller HG, Spaeth AE. Source and fate of circulating citrulline. Am J Physiol. 1981; 241:E473–E480.
crossref
31. Lutgens LC, Blijlevens NM, Deutz NE, Donnelly JP, Lambin P, de Pauw BE. Monitoring myeloablative therapy-induced small bowel toxicity by serum citrulline concentration: a comparison with sugar permeability tests. Cancer. 2005; 103:191–199.
32. Bashashati M, Rezaei N, Shafieyoun A, et al. Cytokine imbalance in irritable bowel syndrome: a systematic review and metaanalysis. Neurogastroenterol Motil. 2014; 26:1036–1048.
crossref
33. Lembo AJ, Neri B, Tolley J, Barken D, Carroll S, Pan H. Use of serum biomarkers in a diagnostic test for irritable bowel syndrome. Aliment Pharmacol Ther. 2009; 29:834–842.
crossref
34. Jones MP, Chey WD, Singh S, et al. A biomarker panel and psychological morbidity differentiates the irritable bowel syndrome from health and provides novel pathophysiological leads. Aliment Pharmacol Ther. 2014; 39:426–437.
crossref
35. van Vliet MJ, Tissing WJ, Rings EH, et al. Citrulline as a marker for chemotherapy induced mucosal barrier injury in pediatric patients. Pediatr Blood Cancer. 2009; 53:1188–1194.
crossref
36. 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.
37. Dolwani S, Metzner M, Wassell JJ, Yong A, Hawthorne AB. Diagnostic accuracy of faecal calprotectin estimation in prediction of abnormal small bowel radiology. Aliment Pharmacol Ther. 2004; 20:615–621.
crossref
38. Ohman L, Stridsberg M, Isaksson S, Jerlstad P, Simrén M. Altered levels of fecal chromogranins and secretogranins in IBS: relevance for pathophysiology and symptoms? Am J Gastroenterol. 2012; 107:440–447.
39. Vora P, Youdim A, Thomas LS, et al. Beta-defensin-2 expression is regulated by TLR signaling in intestinal epithelial cells. J Immunol. 2004; 173:5398–5405.
40. Langhorst J, Junge A, Rueffer A, et al. Elevated human beta-de-fensin-2 levels indicate an activation of the innate immune system in patients with irritable bowel syndrome. Am J Gastroenterol. 2009; 104:404–410.
41. Tana C, Umesaki Y, Imaoka A, Handa T, Kanazawa M, Fukudo S. Altered profiles of intestinal microbiota and organic acids may be the origin of symptoms in irritable bowel syndrome. Neurogastroenterol Motil. 2010; 22:512–519. e114-e115.
crossref
42. Facer P, Bishop AE, Lloyd RV, Wilson BS, Hennessy RJ, Polak JM. Chromogranin: a newly recognized marker for endocrine cells of the human gastrointestinal tract. Gastroenterology. 1985; 89:1366–1373.
crossref
43. Ford AC, Talley NJ. IBS in 2010: advances in pathophysiology, diagnosis and treatment. Nat Rev Gastroenterol Hepatol. 2011; 8:76–78.
44. Saito YA, Petersen GM, Larson JJ, et al. Familial aggregation of irritable bowel syndrome: a family casecontrol study. Am J Gastroenterol. 2010; 105:833–841.
crossref
45. Bengtson MB, Rønning T, Vatn MH, Harris JR. Irritable bowel syndrome in twins: genes and environment. Gut. 2006; 55:1754–1759.
crossref
46. van der Veek PP, van den Berg M, de Kroon YE, Verspaget HW, Masclee AA. Role of tumor necrosis factoralpha and inter-leukin-10 gene polymorphisms in irritable bowel syndrome. Am J Gastroenterol. 2005; 100:2510–2516.
crossref
47. Lesch KP, Bengel D, Heils A, et al. Association of anxiety-related traits with a polymorphism in the serotonin transporter gene regulatory region. Science. 1996; 274:1527–1531.
crossref
48. Pata C, Erdal ME, Derici E, Yazar A, Kanik A, Ulu O. Serotonin transporter gene polymorphism in irritable bowel syndrome. Am J Gastroenterol. 2002; 97:1780–1784.
crossref
49. Van Kerkhoven LA, Laheij RJ, Jansen JB. Meta-analysis: a functional polymorphism in the gene encoding for activity of the serotonin transporter protein is not associated with the irritable bowel syndrome. Aliment Pharmacol Ther. 2007; 26:979–986.
crossref
50. Kim HJ, Camilleri M, Carlson PJ, et al. Association of distinct alpha(2) adrenoceptor and serotonin transporter polymorphisms with constipation and somatic symptoms in functional gastrointestinal disorders. Gut. 2004; 53:829–837.
51. Andresen V, Camilleri M, Kim HJ, et al. Is there an association between GNbeta3-C825T genotype and lower functional gastrointestinal disorders? Gastroenterology. 2006; 130:1985–1994.
52. Saito YA, Locke GR 3rd, Zimmerman JM, et al. A genetic association study of 5-HTT LPR and GNbeta3 C825T polymorphisms with irritable bowel syndrome. Neurogastroenterol Motil. 2007; 19:465–470.
53. Gazouli M, Wouters MM, Kapur-Pojskić L, et al. Lessons learned–resolving the enigma of genetic factors in IBS. Nat Rev Gastroenterol Hepatol. 2016; 13:77–87.
54. Beyder A, Mazzone A, Strege PR, et al. Loss-of-function of the voltage-gated sodium channel NaV1.5 (channelopathies) in patients with irritable bowel syndrome. Gastroenterology. 2014; 146:1659–1668.
crossref
55. Camilleri M, Carlson P, Valentin N, et al. Pilot study of small bowel mucosal gene expression in patients with irritable bowel syndrome with diarrhea. Am J Physiol Gastrointest Liver Physiol. 2016. DOI: doi:10.1152/ajpgi.00037.2016. [Epub ahead of print].
crossref
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