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Göksel Bengi İlkay Şimşek


Abstract: Irritable Bowel Syndrome is one of the most frequently seen functional bowel diseases. Despite its high prevalence, the etiology and pathogenesis of IBS could not still be explained completely and diagnosing is quite difficult in some cases. IBS, being a multisymptomatic functional gastrointestinal system disease, has a broad clinical spectrum and in general, the symptoms are associated with gastrointestinal dysmotility and visceral hypersensitivity. The true diagnosis is based on four key factors: medical history, physical examination, minimal laboratory tests and colonoscopy or other appropriate tests in some cases. However, a homogeneous pathophysiological pattern has not been defined for IBS and this situation, with a high degree of probability, reflects that IBS is a multifactorial disorder that involves abnormalities in brain-gut interactions, visceral hypersensitivity, intestinal motility and secretion, psychosocial factors, composition of the gut microbiota, disturbed intestinal permeability and low grade immune activity.


Keywords: Irritable, bowel, gastrointestinal, IBS

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How to Cite
BENGI, Göksel; ŞIMŞEK, İlkay. NEW INSIGHTS INTO THE PATHOGENESIS OF IRRITABLE BOWEL SYNDROME. Medical Research Archives, [S.l.], v. 5, n. 10, oct. 2017. ISSN 2375-1924. Available at: <>. Date accessed: 29 mar. 2023.
İrritable, bowel, gastrointestinal, IBS
Review Articles


1. Saha L. Irritable bowel syndrome: pathogenesis, diagnosis, treatment, and evidence-based medicine. World J Gastroenterol 2014;20(22):6759–73.
2. Canavan C, West J, Card T. The epidemiology of irritable bowel syndrome. Clin Epidemiol. 2014;4(6):71-80.
3. O’swiecimska J, Szymlak A, Roczniak W, Girczys-Polednik K, Kwiecien J. New insights into the pathogenesis and treatment of irritable bowel syndrome. Adv Med Sci. 2017 Mar;62(1):17-30.
4. Şimşek İ. Irritable Bowel Syndrome and other functional Gastrointestinal disorders. J Clin Gastroenterol 2011;45:86-88.
5. Lacy BE, Mearin F, Chang L, Chey WD, Lembo AJ, Simren M, Spiller R. Bowel Disorders. Gastroenterology. 2016; 150:1393–1407.
6. Longstreth GF, Thompson WG, Chey WD, Houghton LA, Mearin F, Spiller RC. Functional bowel disorders. Gastroenterology. 2006;130(5):1480-91.
7. Spiegel BM, Bolus R, Agarwal N, Sayuk G, Harris LA, Lucak S et al. Measuring symptoms in the irritable bowel syndrome: development of a framework for clinical trials. Aliment Pharmacol Ther. 2010;32(10):1275-91.
8. Palsson OS, Baggish J, Whitehead WE. Episodic nature of symptoms in irritable bowel syndrome. Am J Gastroenterol. 2014;109(9):1450-60.
9. Drossman DA. Functional gastrointestinal disorders: history, pathophysiolo- gy, clinical features and Rome IV. Gastroenterology 2016;150:1262–79.
10. Black TP, Manolakis CS, Di Palma JA. ‘‘Red flag’’ evaluation yield in irritable bowel syndrome. J Gastrointestin Liver Dis 2012;21(2):153–6.
11. Desipio, J.; Friedenberg, F.K.; Korimilli, A.; Richter, J.E.; Parkman, H.P.; Fisher, R.S. High-resolution solid-state manometry of the antropyloroduodenal region. Neurogastroenterol. Motil. 2007, 19, 188–195.
12. Malik, A.; Lukaszewski, K.; Caroline, D.; Parkman, H. A retrospective review of enteroclysis in patients with obscure gastrointestinal bleeding and chronic abdominal pain of undetermined etiology. Dig. Dis. Sci. 2005,50, 649–655.
13. Bellini M, Gambaccini D, Stasi C, Urbano MT, Marchi S, Usai-Satta P. Irritable bowel syndrome: a disease still searching for pathogenesis, diagnosis and therapy. World J Gastroenterol 2014;20(27):8807–20.
14. Hyams JS, Di Lorenzo C, Saps M, Shulman RJ, Staiano A, van Tilburg M. Functional disorders: children and adolescents. Gastroenterology 2016; 150:1456–68.
15. El-Salhy M, Gundersen D, Gilja OH, Hatlebakk JG, Hausken T. Is irritable bowel syndrome an organic disorder? World J Gastroenterol 2014;20(2): 384–400.
16. Pyleris E, Giamarellos-Bourboulis EJ, Tzivras D, Koussoulas V, Barbatzas C, Pimentel M. The prevalence of overgrowth by aerobic bacteria in the small intestine by small bowel culture: relationship with irritable bowel syndrome. Dig Dis Sci 2012;57(5):1321–9.
17. Sood R, Law GR, Ford AC. Diagnosis of IBS: symptoms, symptom-based criteria, biomarkers or ‘psychomarkers’? Nat Rev Gastroenterol Hepatol 2014;11(11):683–91.
18. Moloney RD, Johnson AC, O'Mahony SM, Dinan TG, Greenwood-Van Meerveld B, Cryan JF. Stress and the Microbiota-Gut-Brain Axis in Visceral Pain: Relevance to Irritable Bowel Syndrome. CNS Neurosci Ther. 2016;22(2):102-17.
19. Keszthelyi D, Troost FJ, Jonkers DM, van Eijk HM, Dekker J, Buurman WA, Masclee AA. Visceral hypersensitivity in irritable bowel syndrome: evidence for involvement of serotonin metabolism--a preliminary study. Neurogastroenterol Motil. 2015;27(8):1127-37.
20. Sikander A, Rana SV, Prasad KK. Role of serotonin in gastrointestinal motility and irritable bowel syndrome. Clin Chim Acta. 2009;403(1-2):47-55.
21. Van Oudenhove L, Tornblom H, Storsrud S, Tack J, Simren M. Depression and Somatization Are Associated With Increased Postprandial Symptoms in Patients With Irritable Bowel Syndrome. Gastroenterology. 2016;150(4):866-74.
22. Carroll IM, Ringel-Kulka T, Siddle JP, Ringel Y. Alterations in composition and diversity of the intestinal microbiota in patients with diarrhea-predominant irritable bowel syndrome. Neurogastroenterol Motil. 2012;24(6):521-30, e248.
23. Scheppach W, Sommer H, Kirchner T, Paganelli GM, Bartram P, Christl S, Richter F, Dusel G, Kasper H. Effect of butyrate enemas on the colonic mucosa in distal ulcerative colitis. Gastroenterology. 1992;103(1):51-6.
24. Spiller R, Lam C. An Update on Post-infectious Irritable Bowel Syndrome: Role of Genetics, Immune Activation, Serotonin and Altered Microbiome. J Neurogastroenterol Motil. 2012;18(3):258-68.
25. Moloney RD, Johnson AC, O’Mahony SM, Dinan TG, Greenwood-Van Meer- veld B, Cryan JF. Stress and the microbiota-gut-brain axis in visceral pain: relevance to irritable bowel syndrome. CNS Neurosci Ther 2016;22(2): 102–17.
26. Gaman A, Kuo B. Neuromodulatory processes of the brain-gut axis. Neuro- modulation 2008;11(4):249–59.
27. Vanner S, Greenwood-Van Meerveld B, Mawe G, Shea-Donohue T, Verdu EF, Wood J, et al. Fundamentals of neurogastroenterology: basic science. Gastro-enterology 2016;150:1280–91.
28. Barbara G, Feinle-Bisset C, Ghoshal UC, Quigley EM, Santos J, Vanner S, et al. The intestinal microenvironment and functional gastrointestinal disorders. Gastroenterology 2016;150:11305–18.
29. Mearin F, Lacy BE, Chang L, Chey WD, Lembo AJ, Simren M, et al. Bowel disorders. Gastroenterology 2016;150:1393–407.
30. El-Salhy M, Gilja OH, Gundersen D, Hatlebakk JG, Hausken T. Endocrine cells in the ileum of patients with irritable bowel syndrome. World J Gastroenterol 2014;20(9):2383–91.
31. Boeckxstaens G, Camilleri M, Sifrim D, Houghton LA, Elsenbruch S, Lindberg G, et al. Fundamentals of neurogastroenterology: physiology/motility – sensation. Gastroenterology 2016. 02.030
32. Matricon J, Meleine M, Gelot A, Piche T, Dapoigny M, Muller E, et al. Review article: Associations between immune activation, intestinal permeability and the irritable bowel syndrome. Aliment Pharmacol Ther 2012;36(11– 12):1009–31.
33. Nehring P, Mrozikiewicz-Rakowska B, Krasnode˛bski P, Karnafel W. Zespo´ ł jelita draz˙ liwego - nowe spojrzenie na etiopatogeneze˛. Prz Gastroenterol 2011;6(1):17–22.
34. Grundmann O, Yoon SL. Irritable bowel syndrome: epidemiology, diagnosis and treatment:an update for health-care practitioners. J Gastroenterol Hepatol 2010;25(4):691–9.
35. Van Oudenhove L, Crowell MD, Drossman DA, Halpert AD, Keefer L, Lackner JM, et al. Biopsychosocial aspects of functional gastrointestinal disorders. Gastroenterology 2016;150:1355–67.
36. El-Salhy M. Irritable bowel syndrome: diagnosis and pathogenesis. World J Gastroenterol 2012;18(37):5151–63.
37. Katiraei P, Bultron G. Need for a comprehensive medical approach to the neuro-immuno-gastroenterology of irritable bowel syndrome. World J Gas- troenterol 2011;17(23):2791–800.
38. Colucci R, Gambaccini D, Ghisu N, Rossi G, Costa F, Tuccori M, et al. Influence of the serotonin transporter 5HTTLPR polymorphism on symptom severity in irritable bowel syndrome. PLoS One 2013;8(2):e54831.
39. Weaver IC, Cervoni N, Champagne FA, D’Alessio AC, Sharma S, Seckl JR, et al. Epigenetic programming by maternal behavior. Nat Neurosci 2004;7(8): 847–54.
40. Marlicz W, Zawada I, Starzyn´ ska T. Zespo´ ł nadwraz˙ liwego jelita - nadwra- z˙ liwe jelito czy nadwraz˙ liwy umysł? Pol Merkur Lekarski 2012;32(187): 64–9.
41. Francis CY, Morris J, Whorwell PJ. The irritable bowel severity scoring system: a simple method of monitoring irritable bowel syndrome and its progress. Aliment Pharmacol Ther 1997;11(2):395–402.
42. Hyland NP, Quigley EM, Brint E. Microbiota-host interactions in irritable bowel syndrome: epithelial barrier, immune regulation and brain-gut inter- actions. World J Gastroenterol 2014;20(27):8859–66.
43. Rajilic-Stojanovic M, Smidt H, de Vos WM. Diversity of the human gastrointestinal tract microbiota revisited. Environ Microbiol. 2007;9(9):2125-36.
44. Faith JJ, Guruge JL, Charbonneau M, Subramanian S, Seedorf H, Goodman AL, Clemente JC, Knight R, Heath AC, Leibel RL, Rosenbaum M, Gordon JI. The long-term stability of the human gut microbiota. Science. 2013;341(6141):1237439.
45. Sommer F, Backhed F. The gut microbiota--masters of host development and physiology. Nat Rev Microbiol. 2013;11(4):227-38.
46. Helgeland L, Dissen E, Dai KZ, Midtvedt T, Brandtzaeg P, Vaage JT. Microbial colonization induces oligoclonal expansions of intraepithelial CD8 T cells in the gut. Eur J Immunol. 2004;34(12):3389-400.
47. Sundin J, Rangel I, Fuentes S, Heikamp-de Jong I, Hultgren-Hörnquist E, de Vos WM, Brummer RJ. Altered faecal and mucosal microbial composition in post-infectious irritable bowel syndrome patients correlates with mucosal lymphocyte phenotypes and psychological distress. Aliment Pharmacol Ther. 2015;41(4):342-51.
48. Carroll IM, Ringel-Kulka T, Keku TO, Chang YH, Packey CD, Sartor RB, Ringel Y. Molecular analysis of the luminal- and mucosal-associated intestinal microbiota in diarrhea-predominant irritable bowel syndrome. Am J Physiol Gastrointest Liver Physiol. 2011;301(5):G799-807.
49. Giamarellos-Bourboulis E, Tang J, Pyleris E, Pistiki A, Barbatzas C, Brown J, Lee CC, Harkins TT, Kim G, Weitsman S, Barlow GM, Funari VA, Pimentel M. Molecular assessment of differences in the duodenal microbiome in subjects with irritable bowel syndrome. Scand J Gastroenterol. 2015;50(9):1076-87.
50. Lee YJ, Park KS. Irritable bowel syndrome: emerging paradigm in pathophys- iology. World J Gastroenterol 2014;20(10):2456–69.
51. Spiller R, Lam C. An Update on Post-infectious Irritable Bowel Syndrome: Role of Genetics, Immune Activation, Serotonin and Altered Microbiome. J Neurogastroenterol Motil. 2012;18(3):258-68.
52. Brint EK, MacSharry J, Fanning A, Shanahan F, Quigley EM. Differential expression of toll-like receptors in patients with irritable bowel syndrom. Am J Gastroenterol. 2011;106(2):329-36.
53. Schoepfer AM, Schaffer T, Seibold-Schmid B, Müller S, Seibold F. Antibodies to flagellin indicate reactivity to bacterial antigens in IBS patients. Neurogastroenterol Motil. 2008;20(10):1110-8.
54. Souza EL, Elian SD, Paula LM, Garcia CC, Vieira AT, Teixeira MM, Arantes RM, Nicoli JR, Martins FS. Escherichia coli strain Nissle 1917 ameliorates experimental colitis by modulating intestinal permeability, the inflammatory response and clinical signs in a faecal transplantation model. J Med Microbiol. 2016;65(3):201-10.
55. Rogers GB, Keating DJ, Young RL, Wong ML, Licinio J, Wesselingh S. From gut dysbiosis to altered brain function and mental illness: mechanisms and pathways. Mol Psychiatry. 2016.
56. Cossais F, Durand T, Chevalier J, Boudaud M, Kermarrec L, Aubert P, Neveu I, Naveilhan P, Neunlist M. Postnatal development of the myenteric glial network and its modulation by butyrate. Am J Physiol Gastrointest Liver Physiol. 2016:ajpgi 00232 2015.
57. Robinette ML, Colonna M. GI motility: microbiota and macrophages join forces. Cell. 2014;158(2):239-40.
58. Moloney RD, Johnson AC, O'Mahony SM, Dinan TG, Greenwood-Van Meerveld B, Cryan JF. Stress and the Microbiota-Gut-Brain Axis in Visceral Pain: Relevance to Irritable Bowel Syndrome. CNS Neurosci Ther. 2016;22(2):102-17.
59. Parkes GC, Brostoff J, Whelan K, Sanderson JD. Gastrointestinal microbiota in irritable bowel syndrome: their role in its pathogenesis and treatment. Am J Gastroenterol. 2008;103(6):1557-67.
60. Di Nicolantonio JJ, Lucan SC. Is fructose malabsorption a cause of irritable bowel syndrome? Med. Hypotheses 2015;85:295-297.
61. Niec AM, Frankum B, Talley NJ. Are adverse food reactions linked to irritable bowel syndrome? Am J Gastroenterol 1998;93(11):2184–90.
62. Heizer WD, Southern S, McGovern S. The role of diet in symptoms of irritable bowel syndrome in adults: a narrative review. J Am Diet Assoc 2009;109(7):1204–14.
63. El-Salhy M, Ostgaard H, Gundersen D, Hatlebakk JG, Hausken T. The role of diet in the pathogenesis and management of irritable bowel syndrome (Review). Int J Mol Med 2012;29(5):723–31.
64. Savaiano DA, Levitt MD. Milk intolerance and microbe-containing dairy foods. J Dairy Sci 1987;70(2):397–406.
65. Lomer MC, Parkes GC, Sanderson JD. Review article: lactose intolerance in clinical practice – myths and realities. Aliment Pharmacol Ther 2008;27(2): 93–103.
66. Catassi C, Elli L, Bonaz B, Bouma G, Carroccio A, Castillejo G, et al. Diagnosis of non-celiac gluten sensitivity (NCGS): the Salerno Experts’ Criteria. Nutrients 2015;7(6):4966–77.
67. Pimentel M, Chatterjee S, Chang C, Low K, Song Y, Liu C, et al. A new rat model links two contemporary theories in irritable bowel syndrome. Dig Dis Sci 2008;53(4):982–9.
68. Saha L. Irritable bowel syndrome: pathogenesis, diagnosis, treatment, and evidence-based medicine. World J Gastroenterol 2014;20(22):6759–73.
69. Camilleri M. Evolving concepts of the pathogenesis of irritable bowel syn- drome: to treat the brain or the gut? J Pediatr Gastroenterol Nutr 2009;48(Suppl. 2):S46–8.
70. El-Salhy M. Recent developments in the pathophysiology of irritable bowel syndrome. World J Gastroenterol 2015;21(25):7621–36.
71. Saps M, Pensabene L, Turco R, Staiano A, Cupuro D, Di Lorenzo C. Rotavirus gastroenteritis: precursor of functional gastrointestinal disorders? J Pediatr Gastroenterol Nutr 2009;49(5):580–3.ü
72. Henderson P, Casey A, Lawrence SJ, Kennedy NA, Kingstone K, Rogers P, et al. The diagnostic accuracy of fecal calprotectin during the investigation of suspected pediatric inflammatory bowel disease. Am J Gastroenterol 2012;107(6):941–9.