1. LongstrethGF, ThompsonWG, CheyWD, et al.Functional bowel disorders. Gastroenterology2006;130:1480. CrossRef

2. CamilleriM. Peripheral mechanisms in irritable bowel syndrome. N Engl J Med2012;367:1626. CrossRef

3. WhiteheadWE, PalssonOS, LevyRR, et al.Comorbidity in irritable bowel syndrome. Am J Gastroenterol2007;102:2767. CrossRef

4. LovellRM, FordAC. Global prevalence of and risk factors for irritable bowel syndrome: a meta‐analysis. Clin Gastroenterol Hepatol2012;10:712. CrossRef

5. ManningAP, ThompsonWG, HeatonKW, et al.Towards positive diagnosis of the irritable bowel. Br Med J1978;2:653. CrossRef

6. ThompsonWG, LongstrethGF, DrossmanDA, et al.Functional bowel disorders and functional abdominal pain. Gut1999;45:II43.

7. DrossmanDA, SandlerRS, MckeeDC, et al.Bowel patterns among subjects not seeking health care. Use of a questionnaire to identify a population with bowel dysfunction. Gastroenterology1982;83:529.

8. ThompsonWG, HeatonKW. Functional bowel disorders in apparently healthy people. Gastroenterology1980;79:283.

9. AndrewsEB, EatonSC, HollisKA, et al.Prevalence and demographics of irritable bowel syndrome: results from a large web‐based survey. Aliment Pharmacol Ther2005;22:935. CrossRef

10. HunginAP, ChangL, LockeGR, et al.Irritable bowel syndrome in the United States: prevalence, symptom patterns and impact. Aliment Pharmacol Ther2005;21:1365. CrossRef

11. MinochaA, JohnsonWD, AbellTL, et al.Prevalence, sociodemography, and quality of life of older versus younger patients with irritable bowel syndrome: a population‐based study. Dig Dis Sci2006;51:446. CrossRef

12. SaitoYA, TalleyNJ, MeltonJL, et al.The effect of new diagnostic criteria for irritable bowel syndrome on community prevalence estimates. Neurogastroenterol Motil2003;15:687. CrossRef

13. BrandtLJ, CheyWD, Foxx‐OrensteinAE, et al.An evidence‐based position statement on the management of irritable bowel syndrome. Am J Gastroenterol2009;104:S1. CrossRef

14. DrossmanDA, MckeeDC, SandlerRS, et al.Psychosocial factors in the irritable bowel syndrome. A multivariate study of patients and nonpatients with irritable bowel syndrome. Gastroenterology1988;95:701.

15. TalleyNJ, ZinsmeisterAR, Van DykeC, et al.Epidemiology of colonic symptoms and the irritable bowel syndrome. Gastroenterology1991;101:927.

16. SandlerRS, DrossmanDA, NathanHP, et al.Symptom complaints and health care seeking behavior in subjects with bowel dysfunction. Gastroenterology1984;87:314.

17. LevyRL, Von KorffM, WhiteheadWE, et al.Costs of care for irritable bowel syndrome patients in a health maintenance organization. Am J Gastroenterol2001;96:3122. CrossRef

18. DrossmanDA, LiZ, AndruzziE, et al.U.S. Householder survey of functional gastrointestinal disorders. Prevalence, sociodemography, and health impact. Dig Dis Sci1993;38:1569. CrossRef

19. GuileraM, BalboaA, MearinF. Bowel habit subtypes and temporal patterns in irritable bowel syndrome: systematic review. Am J Gastroenterol2005;100:1174. CrossRef

20. LovellRM, FordAC. Effect of gender on prevalence of irritable bowel syndrome in the community: systematic review and meta‐analysis. Am J Gastroenterol2012;107:991. CrossRef

21. SperberAD, DrossmanDA, QuigleyEM. The global perspective on irritable bowel syndrome: a Rome foundation‐world gastroenterology organisation symposium. Am J Gastroenterol2012;107:1602. CrossRef

22. QuigleyEM, Abdel‐HamidH, BarbaraG, et al.A global perspective on irritable bowel syndrome: a consensus statement of the world gastroenterology organisation summit task force on irritable bowel syndrome. J Clin Gastroenterol2012;46:356. CrossRef

23. GweeKA, LuCL, GhoshalUC. Epidemiology of irritable bowel syndrome in Asia: something old, something new, something borrowed. J Gastroenterol Hepatol2009;24:1601. CrossRef

24. GhoshalUC, AbrahamP, BhattC, et al.Epidemiological and clinical profile of irritable bowel syndrome in india: report of the Indian Society of Gastroenterology Task Force. Indian J Gastroenterol2008;27:22.

25. El‐SeragHB, OldenK, BjorkmanD. Health‐related quality of life among persons with irritable bowel syndrome: a systematic review. Aliment Pharmacol Ther2002;16:1171. CrossRef

26. GralnekIM, HaysRD, KilbourneA, et al.The impact of irritable bowel syndrome on health‐related quality of life. Gastroenterology2000;119:654. CrossRef

27. SaitoYA, SchoenfeldP, LockeGR3rd.The epidemiology of irritable bowel syndrome in North America: a systematic review. Am J Gastroenterol2002;97:1910.

28. MillerV, HopkinsL, WhorwellPJ. Suicidal ideation in patients with irritable bowel syndrome. Clin Gastroenterol Hepatol2004;2:1064. CrossRef

29. SpiegelB, SchoenfeldP, NaliboffB. Systematic review: the prevalence of suicidal behaviour in patients with chronic abdominal pain and irritable bowel syndrome. Aliment Pharmacol Ther2007;26:183. CrossRef

30. KoloskiNA, BoycePM, JonesMP, et al.What level of IBS symptoms drives impairment in health‐related quality of life in community subjects with irritable bowel syndrome? Are current IBS symptom thresholds clinically meaningful?Qual Life Res2012;21:829. CrossRef

31. CainKC, HeadstromP, JarrettME, et al.Abdominal pain impacts quality of life in women with irritable bowel syndrome. Am J Gastroenterol2006;101:124. CrossRef

32. NaliboffBD, KimSE, BolusR, et al.Gastrointestinal and psychological mediators of health‐related quality of life in IBS and IBD: a structural equation modeling analysis. Am J Gastroenterol2012;107:451. CrossRef

33. WareJEJr, SherbourneCD. The MOS 36‐item short‐form health survey (SF‐36). I. Conceptual framework and item selection. Med Care1992;30:473. CrossRef

34. SpiegelBM, GralnekIM, BolusR, et al.Clinical determinants of health‐related quality of life in patients with irritable bowel syndrome. Arch Intern Med2004;164:1773. CrossRef

35. PareP, GrayJ, LamS, et al.Health‐related quality of life, work productivity, and health care resource utilization of subjects with irritable bowel syndrome: baseline results from logic (longitudinal outcomes study of gastrointestinal symptoms in canada), a naturalistic study. Clin Ther2006;28:1726. CrossRef

36. DeanBB, AguilarD, BarghoutV, et al.Impairment in work productivity and health‐related quality of life in patients with IBS. Am J Manag Care2005;11:S17.

37. DibonaventuraM, SunSX, BolgeSC, et al.Health‐related quality of life, work productivity and health care resource use associated with constipation predominant irritable bowel syndrome. Curr Med Res Opin2011;27:2213. CrossRef

38. InadomiJM, FennertyMB, BjorkmanD. Systematic review: the economic impact of irritable bowel syndrome. Aliment Pharmacol Ther2003;18:671. CrossRef

39. LeongSA, BarghoutV, BirnbaumHG, et al.The economic consequences of irritable bowel syndrome: a US employer perspective. Arch Intern Med2003;163:929. CrossRef

40. SpiegelBM, HarrisLA, LucakSL, et al.Predictors of work productivity in irritable bowel syndrome (IBS): results from the proof cohort. Gastroenterology2008;134:A.

41. EverhartJE, RuhlCE. Burden of digestive diseases in the united states part ii: lower gastrointestinal diseases. Gastroenterology2009;136:741. CrossRef

42. EverhartJE. Functional intestinal disorders. Washington, DC: US Government Printing Office: US Department of Health and Human Services, Public Health Service, National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, 2008Contract No.: NIH Publication No. 09‐6443.

43. LadabaumU, BoydE, ZhaoWK, et al.Diagnosis, comorbidities, and management of irritable bowel syndrome in patients in a large health maintenance organization. Clin Gastroenterol Hepatol2012;10:37. CrossRef

44. CheyWD, NojkovB, RubensteinJH, et al.The yield of colonoscopy in patients with non‐constipated irritable bowel syndrome: results from a prospective, controlled us trial. Am J Gastroenterol2010;105:859. CrossRef

45. SpillerR, AzizQ, CreedF, et al.Guidelines on the irritable bowel syndrome: mechanisms and practical management. Gut2007;56:1770. CrossRef

46. SpiegelBM, GralnekIM, BolusR, et al.Is a negative colonoscopy associated with reassurance or improved health‐related quality of life in irritable bowel syndrome?Gastrointest Endosc2005;62:892. CrossRef

47. LongstrethGF, YaoJF. Irritable bowel syndrome and surgery: a multivariable analysis. Gastroenterology2004;126:1665. CrossRef

48. LuCL, LiuCC, FuhJL, et al.Irritable bowel syndrome and negative appendectomy: a prospective multivariable investigation. Gut2007;56:655. CrossRef

49. LiebermanDA, HolubJ, EisenG, et al.Utilization of colonoscopy in the United States: results from a national consortium. Gastrointest Endosc2005;62:875. CrossRef

50. LongstrethGF, WilsonA, KnightK, et al.Irritable bowel syndrome, health care use, and costs: a U.S. Managed care perspective. Am J Gastroenterol2003;98:600. CrossRef

51. RiedlA, SchmidtmannM, StengelA, et al.Somatic comorbidities of irritable bowel syndrome: a systematic analysis. J Psychosom Res2008;64:573. CrossRef

52. WhiteheadWE, PalssonO, JonesKR. Systematic review of the comorbidity of irritable bowel syndrome with other disorders: what are the causes and implications?Gastroenterology2002;122:1140. CrossRef

53. WalkerEA, KatonWJ, JemelkaRP, et al.Comorbidity of gastrointestinal complaints, depression, and anxiety in the epidemiologic catchment area (ECA) study. Am J Med1992;92:26S. CrossRef

54. DrossmanDA, CamilleriM, MayerEA, et al.AGA technical review on irritable bowel syndrome. Gastroenterology2002;123:2108. CrossRef

55. NorthCS, DownsD, ClouseRE, et al.The presentation of irritable bowel syndrome in the context of somatization disorder. Clin Gastroenterol Hepatol2004;2:787. CrossRef

56. SpiegelBM, KanwalF, NaliboffB, et al.The impact of somatization on the use of gastrointestinal health‐care resources in patients with irritable bowel syndrome. Am J Gastroenterol2005;100:2262. CrossRef

57. SaitoYA, PetersenGM, LarsonJJ, et al.Familial aggregation of irritable bowel syndrome: a family case‐control study. Am J Gastroenterol2010;105:833. CrossRef

58. SaitoYA, ZimmermanJM, HarmsenWS, et al.Irritable bowel syndrome aggregates strongly in families: a family‐based case‐control study. Neurogastroenterol Motil2008;20:790. CrossRef

59. LockeGR3rd, ZinsmeisterAR, TalleyNJ, et al.Familial association in adults with functional gastrointestinal disorders. Mayo Clin Proc2000;75:907. CrossRef

60. Morris‐YatesA, TalleyNJ, BoycePM, et al.Evidence of a genetic contribution to functional bowel disorder. Am J Gastroenterol1998;93:1311. CrossRef

61. BengtsonMB, RonningT, VatnMH, et al.Irritable bowel syndrome in twins: genes and environment. Gut2006;55:1754. CrossRef

62. MohammedI, CherkasLF, RileySA, et al.Genetic influences in irritable bowel syndrome: a twin study. Am J Gastroenterol2005;100:1340. CrossRef

63. LevyRL, JonesKR, WhiteheadWE, et al.Irritable bowel syndrome in twins: heredity and social learning both contribute to etiology. Gastroenterology2001;121:799. CrossRef

64. LevyRL. Exploring the intergenerational transmission of illness behavior: from observations to experimental intervention. Ann Behav Med2011;41:174. CrossRef

65. LevyRL, WhiteheadWE, Von KorffMR, et al.Intergenerational transmission of gastrointestinal illness behavior. Am J Gastroenterol2000;95:451. CrossRef

66. LevyRL, WhiteheadWE, WalkerLS, et al.Increased somatic complaints and health‐care utilization in children: effects of parent IBS status and parent response to gastrointestinal symptoms. Am J Gastroenterol2004;99:2442. CrossRef

67. WhiteheadWE, WingetC, FedoraviciusAS, et al.Learned illness behavior in patients with irritable bowel syndrome and peptic ulcer. Dig Dis Sci1982;27:202. CrossRef

68. KalantarJS, LockeGR, ZinsmeisterAR, et al.Familial aggregation of irritable bowel syndrome: a prospective study. Gut2003;52:1703. CrossRef

69. LipowskiZJ. Somatization: the concept and its clinical application. Am J Psychiatry1988;145:1358. CrossRef

70. RuigomezA, Garcia RodriguezLA, PanesJ. Risk of irritable bowel syndrome after an episode of bacterial gastroenteritis in general practice: influence of comorbidities. Clin Gastroenterol Hepatol2007;5:465. CrossRef

71. NealKR, HebdenJ, SpillerR. Prevalence of gastrointestinal symptoms six months after bacterial gastroenteritis and risk factors for development of the irritable bowel syndrome: postal survey of patients. BMJ1997;314:779. CrossRef

72. WangLH, FangXC, PanGZ. Bacillary dysentery as a causative factor of irritable bowel syndrome and its pathogenesis. Gut2004;53:1096. CrossRef

73. SpillerR, GarsedK. Postinfectious irritable bowel syndrome. Gastroenterology2009;136:1979. CrossRef

74. MarshallJK, ThabaneM, BorgaonkarMR, et al.Postinfectious irritable bowel syndrome after a food‐borne outbreak of acute gastroenteritis attributed to a viral pathogen. Clin Gastroenterol Hepatol2007;5:457. CrossRef

75. ZaniniB, RicciC, BanderaF, et al.Incidence of post‐infectious irritable bowel syndrome and functional intestinal disorders following a water‐borne viral gastroenteritis outbreak. Am J Gastroenterol2012;107:891. CrossRef

76. DizdarV, GiljaOH, HauskenT. Increased visceral sensitivity in giardia‐induced postinfectious irritable bowel syndrome and functional dyspepsia. Effect of the 5HT3‐antagonist ondansetron. Neurogastroenterol Motil2007;19:977.

77. SoyturkM, AkpinarH, GurlerO, et al.Irritable bowel syndrome in persons who acquired trichinellosis. Am J Gastroenterol2007;102:1064. CrossRef

78. MarshallJK, ThabaneM, GargAX, et al.Incidence and epidemiology of irritable bowel syndrome after a large waterborne outbreak of bacterial dysentery. Gastroenterology2006;131:445. CrossRef

79. CohenE, FullerG, BolusR, et al.Increased risk for irritable bowel syndrome following acute diverticulitis. Clin Gastroenterol Hepatol2013;11:1614. CrossRef

80. WhiteheadWE, CrowellMD, RobinsonJC, et al.Effects of stressful life events on bowel symptoms: subjects with irritable bowel syndrome compared with subjects without bowel dysfunction. Gut1992;33:825. CrossRef

81. DunlopSP, JenkinsD, NealKR, et al.Relative importance of enterochromaffin cell hyperplasia, anxiety, and depression in postinfectious IBS. Gastroenterology2003;125:1651. CrossRef

82. ChitkaraDK, Van TilburgM, Blois‐MartinN, et al.Early life risk factors that contribute to irritable bowel syndrome in adults: a systematic review. Am J Gastroenterol2008;103:765. CrossRef

83. BradfordK, ShihW, VidelockEJ, et al.Association between early adverse life events and irritable bowel syndrome. Clin Gastroenterol Hepatol2012;10:385. CrossRef

84. AnandKJ, RunesonB, JacobsonB. Gastric suction at birth associated with long‐term risk for functional intestinal disorders in later life. J Pediatr2004;144:449. CrossRef

85. DrossmanDA, LesermanJ, NachmanG, et al.Sexual and physical abuse in women with functional or organic gastrointestinal disorders. Ann Intern Med1990;113:828. CrossRef

86. KlookerTK, BraakB, PainterRC, et al.Exposure to severe wartime conditions in early life is associated with an increased risk of irritable bowel syndrome: a population‐based cohort study. Am J Gastroenterol2009;104:2250. CrossRef

87. GrayGC, ReedRJ, KaiserKS, et al.Self‐reported symptoms and medical conditions among 11,868 Gulf War‐era veterans: the Seabee health study. Am J Epidemiol2002;155:1033. CrossRef

88. DunphyRC, BridgewaterL, PriceDD, et al.Visceral and cutaneous hypersensitivity in Persian Gulf War veterans with chronic gastrointestinal symptoms. Pain2003;102:79. CrossRef

89. CamilleriM. Scintigraphic biomarkers for colonic dysmotility. Clin Pharmacol Ther2010;87:748. CrossRef

90. MayerEA, TillischK. The brain‐gut axis in abdominal pain syndromes. Annu Rev Med2011;62:381. CrossRef

91. BlackshawLA, BrookesSJ, GrundyD, et al.Sensory transmission in the gastrointestinal tract. Neurogastroenterol Motil2007;19:1. CrossRef

92. KylohM, NicholasS, ZagorodnyukVP, et al.Identification of the visceral pain pathway activated by noxious colorectal distension in mice. Front Neurosci2011;5:16. CrossRef

93. LiuCN, DevorM, WaxmanSG, et al.Subthreshold oscillations induced by spinal nerve injury in dissociated muscle and cutaneous afferents of mouse DRG. J Neurophysiol2002;87:2009.

94. GrundyD, Al‐ChaerED, AzizQ, et al.Fundamentals of neurogastroenterology: basic science. Gastroenterology2006;130:1391. CrossRef

95. FengB, LaJH, SchwartzES, et al.Irritable bowel syndrome: methods, mechanisms, and pathophysiology. Neural and neuro‐immune mechanisms of visceral hypersensitivity in irritable bowel syndrome. Am J Physiol Gastrointest Liver Physiol2012;302:G1085. CrossRef

96. BerthoudHR, BlackshawLA, BrookesSJ, et al.Neuroanatomy of extrinsic afferents supplying the gastrointestinal tract. Neurogastroenterol Motil2004;16:28. CrossRef

97. WatkinsLR, MaierSF. Immune regulation of central nervous system functions: from sickness responses to pathological pain. J Intern Med2005;257:139. CrossRef

98. Al‐ChaerE, WestlundK, WillisW. Sensitization of postsynaptic dorsal column neuronal responses by colon inflammation. Neuroreport1997;8:3267. CrossRef

99. MayerEA. Spinal and supraspinal modulation of visceral sensation. Gut2000;47:69.

100. LudidiS, ConchilloJM, KeszthelyiD, et al.Rectal hypersensitivity as hallmark for irritable bowel syndrome: defining the optimal cutoff. Neurogastroenterol Motil2012;24:729. CrossRef

101. RitchieJ. Pain from distension of the pelvic colon by inflating a balloon in the irritable colon syndrome. Gut1973;14:125. CrossRef

102. WhiteheadWE, HoltkotterB, EnckP, et al.Tolerance for rectosigmoid distention in irritable bowel syndrome. Gastroenterology1990;98:1187.

103. MertzH, NaliboffB, MunakataJ, et al.Altered rectal perception is a biological marker of patients with irritable bowel syndrome. Gastroenterology1995;109:40. CrossRef

104. BouinM, PlourdeV, BoivinM, et al.Rectal distention testing in patients with irritable bowel syndrome: sensitivity, specificity, and predictive values of pain sensory thresholds. Gastroenterology2002;122:1771. CrossRef

105. ChangL, MayerEA, JohnsonT, et al.Differences in somatic perception in female patients with irritable bowel syndrome with and without fibromyalgia. Pain2000;84:297. CrossRef

106. PriceDD, CraggsJG, ZhouQ, et al.Widespread hyperalgesia in irritable bowel syndrome is dynamically maintained by tonic visceral impulse input and placebo/nocebo factors: evidence from human psychophysics, animal models, and neuroimaging. Neuroimage2009;47:995. CrossRef

107. Wilder‐SmithCH, Robert‐YapJ. Abnormal endogenous pain modulation and somatic and visceral hypersensitivity in female patients with irritable bowel syndrome. World J Gastroenterol2007;13:3699.

108. PosserudI, SyrousA, LindstromL, et al.Altered rectal perception in irritable bowel syndrome is associated with symptom severity. Gastroenterology2007;133:1113. CrossRef

109. CremoniniF, HoughtonLA, CamilleriM, et al.Barostat testing of rectal sensation and compliance in humans: comparison of results across two centres and overall reproducibility. Neurogastroenterol Motil2005;17:810. CrossRef

110. GonlachanvitS, MahayosnondA, KullavanijayaP. Effects of chili on postprandial gastrointestinal symptoms in diarrhoea predominant irritable bowel syndrome: evidence for capsaicin‐sensitive visceral nociception hypersensitivity. Neurogastroenterol Motil2009;21:23. CrossRef

111. CamilleriM, MckinzieS, BusciglioI, et al.Prospective study of motor, sensory, psychologic, and autonomic functions in patients with irritable bowel syndrome. Clin Gastroenterol Hepatol2008;6:772. CrossRef

112. PriorA, MaxtonDG, WhorwellPJ. Anorectal manometry in irritable bowel syndrome: differences between diarrhoea and constipation predominant subjects. Gut1990;31:458. CrossRef

113. MunakataJ, NaliboffB, HarrafF, et al.Repetitive sigmoid stimulation induces rectal hyperalgesia in patients with irritable bowel syndrome. Gastroenterology1997;112:55. CrossRef

114. PoitrasP, Riberdy PoitrasM, PlourdeV, et al.Evolution of visceral sensitivity in patients with irritable bowel syndrome. Dig Dis Sci2002;47:914. CrossRef

115. KuikenSD, TytgatGN, BoeckxstaensGE. The selective serotonin reuptake inhibitor fluoxetine does not change rectal sensitivity and symptoms in patients with irritable bowel syndrome: a double blind, randomized, placebo‐controlled study. Clin Gastroenterol Hepatol2003;1:219. CrossRef

116. CreedF, FernandesL, GuthrieE, et al.The cost‐effectiveness of psychotherapy and paroxetine for severe irritable bowel syndrome. Gastroenterology2003;124:303. CrossRef

117. TackJ, BroekaertD, FischlerB, et al.A controlled crossover study of the selective serotonin reuptake inhibitor citalopram in irritable bowel syndrome. Gut2006;55:1095. CrossRef

118. WiechK, PlonerM, TraceyI. Neurocognitive aspects of pain perception. Trends Cogn Sci2008;12:306. CrossRef

119. WiechK, TraceyI. The influence of negative emotions on pain: behavioral effects and neural mechanisms. Neuroimage2009;47:987. CrossRef

120. ElsenbruchS, RosenbergerC, EnckP, et al.Affective disturbances modulate the neural processing of visceral pain stimuli in irritable bowel syndrome: an fMRI study. Gut2010;59:489. CrossRef

121. WhiteheadWE, PalssonOS. Is rectal pain sensitivity a biological marker for irritable bowel syndrome: psychological influences on pain perception. Gastroenterology1998;115:1263. CrossRef

122. DornSD, PalssonOS, ThiwanSIM, et al.Increased colonic pain sensitivity in irritable bowel syndrome is the result of an increased tendency to report pain rather than increased neurosensory sensitivity. Gut2007;56:1202. CrossRef

123. LacknerJM, CoadML, MertzHR, et al.Cognitive therapy for irritable bowel syndrome is associated with reduced limbic activity, GI symptoms, and anxiety. Behav Res Ther2006;44:621. CrossRef

124. TillischK, MayerEA, LabusJS. Quantitative meta‐analysis identifies brain regions activated during rectal distension in irritable bowel syndrome. Gastroenterology2011;140:91. CrossRef

125. LarssonMB, TillischK, CraigAD, et al.Brain responses to visceral stimuli reflect visceral sensitivity thresholds in patients with irritable bowel syndrome. Gastroenterology2012;142:463. CrossRef

126. DavisKD, PopeG, ChenJ, et al.Cortical thinning in IBS: implications for homeostatic, attention, and pain processing. Neurology2008;70:153. CrossRef

127. SeminowiczDA, LabusJS, BuellerJA, et al.Regional gray matter density changes in brains of patients with irritable bowel syndrome. Gastroenterology2010;139:48. CrossRef

128. GibneySM, GosselinRD, DinanTG, et al.Colorectal distension‐induced prefrontal cortex activation in the Wistar‐Kyoto rat: implications for irritable bowel syndrome. Neuroscience2010;165:675. CrossRef

129. MayerEA, BermanS, SuyenobuB, et al.Differences in brain responses to visceral pain between patients with irritable bowel syndrome and ulcerative colitis. Pain2005;115:398. CrossRef

130. Wilder‐SmithCH, SchindlerD, LovbladK, et al.Brain functional magnetic resonance imaging of rectal pain and activation of endogenous inhibitory mechanisms in irritable bowel syndrome patient subgroups and healthy controls. Gut2004;53:1595. CrossRef

131. KingCD, WongF, CurrieT, et al.Deficiency in endogenous modulation of prolonged heat pain in patients with irritable bowel syndrome and temporomandibular disorder. Pain2009;143:172. CrossRef

132. PicheM, ArsenaultM, PoitrasP, et al.Widespread hypersensitivity is related to altered pain inhibition processes in irritable bowel syndrome. Pain2010;148:49. CrossRef

133. PicheM, BouinM, ArsenaultM, et al.Decreased pain inhibition in irritable bowel syndrome depends on altered descending modulation and higher‐order brain processes. Neuroscience2011;195:166. CrossRef

134. BermanSM, NaliboffBD, SuyenobuB, et al.Reduced brainstem inhibition during anticipated pelvic visceral pain correlates with enhanced brain response to the visceral stimulus in women with irritable bowel syndrome. J Neurosci2008;28:349. CrossRef

135. WoolfCJ, SalterMW. Neuronal plasticity: increasing the gain in pain. Science2000;288:1765. CrossRef

136. VerneGN, RobinsonME, VaseL, et al.Reversal of visceral and cutaneous hyperalgesia by local rectal anesthesia in irritable bowel syndrome (IBS) patients. Pain2003;105:223. CrossRef

137. BouinM, DelvauxM, BlancC, et al.Intrarectal injection of glycerol induces hypersensitivity to rectal distension in healthy subjects without modifying rectal compliance. Eur J Gastroenterol Hepatol2001;13:573. CrossRef

138. AkbarA, YiangouY, FacerP, et al.Increased capsaicin receptor trpv1‐expressing sensory fibres in irritable bowel syndrome and their correlation with abdominal pain. Gut2008;57:923. CrossRef

139. CenacN, AltierC, MottaJP, et al.Potentiation of trpv4 signalling by histamine and serotonin: an important mechanism for visceral hypersensitivity. Gut2010;59:481. CrossRef

140. ZhaoJH, DongL, ShiHT, et al.The expression of protease‐activated receptor 2 and 4 in the colon of irritable bowel syndrome patients. Dig Dis Sci2012;57:58. CrossRef

141. VerneGN, HimesNC, RobinsonME, et al.Central representation of visceral and cutaneous hypersensitivity in the irritable bowel syndrome. Pain2003;103:99. CrossRef

142. VerneGN, PriceDD, CallamCS, et al.Viscerosomatic facilitation in a subset of IBS patients, an effect mediated by N‐methyl‐D‐aspartate receptors. J Pain2012;13:901. CrossRef

143. ZhouQQ, FillingimRB, RileyJL, et al.Central and peripheral hypersensitivity in the irritable bowel syndrome. Pain2010;148:454. CrossRef

144. RodriguesAC, VerneGN, SchmidtS, et al.Hypersensitivity to cutaneous thermal nociceptive stimuli in irritable bowel syndrome. Pain2005;115:5. CrossRef

145. VerneGN, RobinsonME, PriceDD. Hypersensitivity to visceral and cutaneous pain in the irritable bowel syndrome. Pain2001;93:7. CrossRef

146. AccarinoAM, AzpirozF, MalageladaJR. Selective dysfunction of mechanosensitive intestinal afferents in irritable bowel syndrome. Gastroenterology1995;108:636. CrossRef

147. CookIJ, Van EedenA, CollinsSM. Patients with irritable bowel syndrome have greater pain tolerance than normal subjects. Gastroenterology1987;93:727.

148. StabellN, StubhaugA, FlaegstadT, et al.Increased pain sensitivity among adults reporting irritable bowel syndrome symptoms in a large population‐based study. Pain2013;154:385. CrossRef

149. ChangL, BermanS, MayerEA, et al.Brain responses to visceral and somatic stimuli in patients with irritable bowel syndrome with and without fibromyalgia. Am J Gastroenterol2003;98:1354. CrossRef

150. SterlingP, EyerJ. Allostasis: a new paradigm to explain arousal pathology. In: FisherS, ReasonJ(eds). Handbook of Life Stress, Cognition and Health. New York: John Wiley & Sons, 1988: 629.

151. McewenBS. Protective and damaging effects of stress mediators. N Engl J Med1998;338:171. CrossRef

152. BennettEJ, TennantCC, PiesseC, et al.Level of chronic life stress predicts clinical outcome in irritable bowel syndrome. Gut1998;43:256. CrossRef

153. GweeKA, LeongYL, GrahamC, et al.The role of psychological and biological factors in postinfective gut dysfunction. Gut1999;44:400. CrossRef

154. PosserudI, AgerforzP, EkmanR, et al.Altered visceral perceptual and neuroendocrine response in patients with irritable bowel syndrome during mental stress. Gut2004;53:1102. CrossRef

155. DickhausB, MayerEA, FiroozN, et al.Irritable bowel syndrome patients show enhanced modulation of visceral perception by auditory stress. Am J Gastroenterol2003;98:135. CrossRef

156. WelganP, MeshkinpourH, HoehlerF. The effect of stress on colon motor and electrical activity in irritable bowel syndrome. Psychosom Med1985;47:139. CrossRef

157. AndaRF, FelittiVJ, BremnerJD, et al.The enduring effects of abuse and related adverse experiences in childhood. A convergence of evidence from neurobiology and epidemiology. Eur Arch Psychiatry Clin Neurosci2006;256:174. CrossRef

158. AndaRF, BrownDW, DubeSR, et al.Adverse childhood experiences and chronic obstructive pulmonary disease in adults. Am J Prev Med2008;34:396. CrossRef

159. HeimC, NemeroffCB. The role of childhood trauma in the neurobiology of mood and anxiety disorders: preclinical and clinical studies. Biol Psychiatry2001;49:1023. CrossRef

160. CoutinhoSV, PlotskyPM, SabladM, et al.Neonatal maternal separation alters stress‐induced responses to viscerosomatic nociceptive stimuli in rat. Am J Physiol Gastrointest Liver Physiol2002;282:G307. CrossRef

161. ChungEKY, ZhangXJ, LiZ, et al.Neonatal maternal separation enhances central sensitivity to noxious colorectal distention in rat. Brain Res2007;1153:68. CrossRef

162. O'mahonySM, MarchesiJR, ScullyP, et al.Early life stress alters behavior, immunity, and microbiota in rats: implications for irritable bowel syndrome and psychiatric illnesses. Biol Psychiatry2009;65:263.

163. SoderholmJD, YatesDA, GareauMG, et al.Neonatal maternal separation predisposes adult rats to colonic barrier dysfunction in response to mild stress. Am J Physiol Gastrointest Liver Physiol2002;283:G1257. CrossRef

164. O'MahonyS, ChuaAS, QuigleyEM, et al.Evidence of an enhanced central 5HT response in irritable bowel syndrome and in the rat maternal separation model. Neurogastroenterol Motil2008;20:680. CrossRef

165. RenTH, WuJ, YewD, et al.Effects of neonatal maternal separation on neurochemical and sensory response to colonic distension in a rat model of irritable bowel syndrome. Am J Physiol Gastrointest Liver Physiol2007;292:G849. CrossRef

166. TylerK, MoriceauS, SullivanRM, et al.Long‐term colonic hypersensitivity in adult rats induced by neonatal unpredictable vs predictable shock. Neurogastroenterol Motil2007;19:761. CrossRef

167. ElzingaBM, RoelofsK, TollenaarMS, et al.Diminished cortisol responses to psychosocial stress associated with lifetime adverse events a study among healthy young subjects. Psychoneuroendocrinology2008;33:227. CrossRef

168. RinneT, De KloetER, WoutersL, et al.Hyperresponsiveness of hypothalamic‐pituitary‐adrenal axis to combined dexamethasone/ corticotropin‐releasing hormone challenge in female borderline personality disorder subjects with a history of sustained childhood abuse. Biol Psychiatry2002;52:1102. CrossRef

169. CarpenterLL, CarvalhoJP, TyrkaAR, et al.Decreased adrenocorticotropic hormone and cortisol responses to stress in healthy adults reporting significant childhood maltreatment. Biol Psychiatry2007;62:1080. CrossRef

170. McgowanPO, SasakiA, D'AlessioAC, et al.Epigenetic regulation of the glucocorticoid receptor in human brain associates with childhood abuse. Nat Neurosci2009;12:342. CrossRef

171. LabonteB, YerkoV, GrossJ, et al.Differential glucocorticoid receptor exon 1(b), 1(c), and 1(h) expression and methylation in suicide completers with a history of childhood abuse. Biol Psychiatry2012;72:41. CrossRef

172. ChangL, IliopoulosD, PolytarchouC, et al.Glucocorticoid receptor gene methylation is a potential biomarker of irritable bowel syndrome. Gastroenterology2012;142:S176. CrossRef

173. FukudoS, NomuraT, HongoM. Impact of corticotropin‐releasing hormone on gastrointestinal motility and adrenocorticotropic hormone in normal controls and patients with irritable bowel syndrome. Gut1998;42:845. CrossRef

174. MyersB, Greenwood‐Van MeerveldB. Elevated corticosterone in the amygdala leads to persistent increases in anxiety‐like behavior and pain sensitivity. Behav Brain Res2010;214:465. CrossRef

175. IbeakanmaC, Ochoa‐CortesF, Miranda‐MoralesM, et al.Brain‐gut interactions increase peripheral nociceptive signaling in mice with postinfectious irritable bowel syndrome. Gastroenterology2011;141:2098. CrossRef

176. ChangL. The role of stress on physiologic responses and clinical symptoms in irritable bowel syndrome. Gastroenterology2011;140:761. CrossRef

177. VidelockEJ, AdeyemoM, LicudineA, et al.Childhood trauma is associated with hypothalamic‐pituitary‐adrenal axis responsiveness in irritable bowel syndrome. Gastroenterology2009;137:1954. CrossRef

178. AggarwalA, CuttsTF, AbellTL, et al.Predominant symptoms in irritable bowel syndrome correlate with specific autonomic nervous system abnormalities. Gastroenterology1994;106:945.

179. JarrettME, BurrRL, CainKC, et al.Autonomic nervous system function during sleep among women with irritable bowel syndrome. Dig Dis Sci2008;53:694. CrossRef

180. HeitkemperM, JarrettM, CainKC, et al.Autonomic nervous system function in women with irritable bowel syndrome. Dig Dis Sci2001;46:1276. CrossRef

181. HeitkemperM, BurrRL, JarrettM, et al.Evidence for autonomic nervous system imbalance in women with irritable bowel syndrome. Dig Dis Sci1998;43:2093. CrossRef

182. Alba‐DelgadoC, Llorca‐TorralbaM, HorrilloI, et al.Chronic pain leads to concomitant noradrenergic impairment and mood disorders. Biol Psychiatry2013;73:54. CrossRef

183. AlmyTP. Experimental studies on the irritable bowel syndrome. Am J Med1951;10:60. CrossRef

184. VassalloM, CamilleriM, PhillipsSF, et al.Transit through the proximal colon influences stool weight in the irritable‐bowel‐syndrome. Gastroenterology1992;102:102.

185. CheyWY, JinHO, LeeMH, et al.Colonic motility abnormality in patients with irritable bowel syndrome exhibiting abdominal pain and diarrhea. Am J Gastroenterol2001;96:1499. CrossRef

186. ClemensCHM, SamsomM, Van Berge HenegouwenGP, et al.Abnormalities of left colonic motility in ambulant nonconstipated patients with irritable bowel syndrome. Dig Dis Sci2003;48:74. CrossRef

187. AgrawalA, HoughtonLA, ReillyB, et al.Bloating and distension in irritable bowel syndrome: the role of gastrointestinal transit. Am J Gastroenterol2009;104:1998. CrossRef

188. KanazawaM, PalssonOS, ThiwanSI, et al.Contributions of pain sensitivity and colonic motility to IBS symptom severity and predominant bowel habits. Am J Gastroenterol2008;103:2550. CrossRef

189. SuttorVP, ProttGM, HansenRD, et al.Evidence for pelvic floor dyssynergia in patients with irritable bowel syndrome. Dis Colon Rectum2010;53:156. CrossRef

190. ProttG, ShimL, HansenR, et al.Relationships between pelvic floor symptoms and function in irritable bowel syndrome. Neurogastroenterol Motil2010;22:764. CrossRef

191. GershonMD, TackJ. The serotonin signaling system: from basic understanding to drug development for functional GI disorders. Gastroenterology2007;132:397. CrossRef

192. AtkinsonW, LockhartS, WhorwellPJ, et al.Altered 5‐hydroxytryptamine signaling in patients with constipation‐ and diarrhea‐predominant irritable bowel syndrome. Gastroenterology2006;130:34. CrossRef

193. HoughtonLA, AtkinsonW, LockhartC, et al.Sigmoid‐colonic motility in health and irritable bowel syndrome: a role for 5‐hydroxytryptamine. Neurogastroenterol Motil2007;19:724. CrossRef

194. KilkensTO, HonigA, Van NieuwenhovenMA, et al.Acute tryptophan depletion affects brain‐gut responses in irritable bowel syndrome patients and controls. Gut2004;53:1794. CrossRef

195. LabusJS, MayerEA, JarchoJ, et al.Acute tryptophan depletion alters the effective connectivity of emotional arousal circuitry during visceral stimuli in healthy women. Gut2011;60:1196. CrossRef

196. GweeKA, CollinsSM, ReadNW, et al.Increased rectal mucosal expression of interleukin 1 beta in recently acquired post‐infectious irritable bowel syndrome. Gut2003;52:523. CrossRef

197. OhmanL, IsakssonS, LindmarkAC, et al.T‐cell activation in patients with irritable bowel syndrome. Am J Gastroenterol2009;104:1205. CrossRef

198. OhmanL, IsakssonS, LundgrenA, et al.A controlled study of colonic immune activity and beta7+ blood T lymphocytes in patients with irritable bowel syndrome. Clin Gastroenterol Hepatol2005;3:980. CrossRef

199. CremonC, GarganoL, Morselli‐LabateAM, et al.Mucosal immune activation in irritable bowel syndrome: gender‐dependence and association with digestive symptoms. Am J Gastroenterol2009;104:392. CrossRef

200. ChadwickVS, ChenW, ShuD, et al.Activation of the mucosal immune system in irritable bowel syndrome. Gastroenterology2002;122:1778. CrossRef

201. BarbaraG, StanghelliniV, De GiorgioR, et al.Activated mast cells in proximity to colonic nerves correlate with abdominal pain in irritable bowel syndrome. Gastroenterology2004;126:693. CrossRef

202. LeeKJ, KimYB, KimJH, 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 Hepatol2008;23:1689. CrossRef

203. Vivinus‐NebotM, DaineseR, AntyR, et al.Combination of allergic factors can worsen diarrheic irritable bowel syndrome: role of barrier defects and mast cells. Am J Gastroenterol2012;107:75. CrossRef

204. KlookerTK, BraakB, KoopmanKE, et al.The mast cell stabiliser ketotifen decreases visceral hypersensitivity and improves intestinal symptoms in patients with irritable bowel syndrome. Gut2010;59:1213. CrossRef

205. CenacN, AndrewsCN, HolzhausenM, et al.Role for protease activity in visceral pain in irritable bowel syndrome. J Clin Invest2007;117:636. CrossRef

206. ChangL, AdeyemoM, KaragiannidesI, et al.Serum and colonic mucosal immune markers in irritable bowel syndrome. Am J Gastroenterol2012;107:262. CrossRef

207. HolmenN, IsakssonS, SimrenM, et al.CD4+CD25+ regulatory T cells in irritable bowel syndrome patients. Neurogastroenterol Motil2007;19:119. CrossRef

208. BraakB, KlookerTK, WoutersMM, et al.Mucosal immune cell numbers and visceral sensitivity in patients with irritable bowel syndrome: is there any relationship?Am J Gastroenterol2012;107:715. CrossRef

209. SchmulsonM, Pulido‐LondonD, RodriguezO, et al.Lower serum IL‐10 is an independent predictor of IBS among volunteers in Mexico. Am J Gastroenterol2012;107:747. CrossRef

210. ScullyP, MckernanDP, KeohaneJ, et al.Plasma cytokine profiles in females with irritable bowel syndrome and extra‐intestinal co‐morbidity. Am J Gastroenterol2010;105:2235. CrossRef

211. HodK, DickmanR, SperberA, et al.Assessment of high‐sensitivity CRP as a marker of micro‐inflammation in irritable bowel syndrome. Neurogastroenterol Motil2011;23:1105. CrossRef

212. MckernanDP, GasznerG, QuigleyEM, et al.Altered peripheral toll‐like receptor responses in the irritable bowel syndrome. Aliment Pharmacol Ther2011;33:1045. CrossRef

213. BelmonteL, Beutheu YoumbaS, Bertiaux‐VandaeleN, et al.Role of toll like receptors in irritable bowel syndrome: differential mucosal immune activation according to the disease subtype. PLoS ONE2012;7:e42777. CrossRef

214. BrintEK, MacsharryJ, FanningA, et al.Differential expression of toll‐like receptors in patients with irritable bowel syndrome. Am J Gastroenterol2011;106:329. CrossRef

215. BarkhordariE, RezaeiN, AnsaripourB, et al.Proinflammatory cytokine gene polymorphisms in irritable bowel syndrome. J Clin Immunol2010;30:74. CrossRef

216. BarkhordariE, RezaeiN, MahmoudiM, et al.T‐helper 1, T‐helper 2, and T‐regulatory cytokines gene polymorphisms in irritable bowel syndrome. Inflammation2010;33:281. CrossRef

217. O'malleyD, ListonM, HylandNP, et al.Colonic soluble mediators from the maternal separation model of irritable bowel syndrome activate submucosal neurons via an interleukin‐6‐dependent mechanism. Am J Physiol Gastrointest Liver Physiol2011;300:G241. CrossRef

218. DinanTG, ClarkeG, QuigleyEM, et al.Enhanced cholinergic‐mediated increase in the pro‐inflammatory cytokine IL‐6 in irritable bowel syndrome: role of muscarinic receptors. Am J Gastroenterol2008;103:2570. CrossRef

219. DinanTG, QuigleyEM, AhmedSM, et al.Hypothalamic‐pituitary‐gut axis dysregulation in irritable bowel syndrome: plasma cytokines as a potential biomarker?Gastroenterology2006;130:304. CrossRef

220. CamilleriM, MadsenK, SpillerR, et al.Intestinal barrier function in health and gastrointestinal disease. Neurogastroenterol Motil2012;24:503. CrossRef

221. DunlopSP, HebdenJ, CampbellE, et al.Abnormal intestinal permeability in subgroups of diarrhea‐predominant irritable bowel syndromes. Am J Gastroenterol2006;101:1288. CrossRef

222. ZhouQQ, ZhangBY, VerneGN. Intestinal membrane permeability and hypersensitivity in the irritable bowel syndrome. Pain2009;146:41. CrossRef

223. MarshallJK, ThabaneM, GargAX, et al.Intestinal permeability in patients with irritable bowel syndrome after a waterborne outbreak of acute gastroenteritis in Walkerton, Ontario. Aliment Pharmacol Ther2004;20:1317. CrossRef

224. GecseK, RokaR, SeraT, et al.Leaky gut in patients with diarrhea‐predominant irritable bowel syndrome and inactive ulcerative colitis. Digestion2012;85:40. CrossRef

225. PicheT, BarbaraG, AubertP, et al.Impaired intestinal barrier integrity in the colon of patients with irritable bowel syndrome: involvement of soluble mediators. Gut2009;58:196. CrossRef

226. Bertiaux‐VandaeleN, YoumbaSB, BelmonteL, et al.The expression and the cellular distribution of the tight junction proteins are altered in irritable bowel syndrome patients with differences according to the disease subtype. Am J Gastroenterol2011;106:2165. CrossRef

227. SpillerRC, JenkinsD, ThornleyJP, et al.Increased rectal mucosal enteroendocrine cells, T lymphocytes, and increased gut permeability following acute campylobacter enteritis and in post‐dysenteric irritable bowel syndrome. Gut2000;47:804. CrossRef

228. ZhouQQ, SoubaWW, CroceCM, et al.Microrna‐29a regulates intestinal membrane permeability in patients with irritable bowel syndrome. Gut2010;59:775. CrossRef

229. Vazquez‐RoqueMI, CamilleriM, SmyrkT, et al.A controlled trial of gluten‐free diet in patients with irritable bowel syndrome‐diarrhea: effects on bowel frequency and intestinal function. Gastroenterology2013;144:903. CrossRef

230. SaundersPR, KoseckaU, MckayDM, et al.Acute stressors stimulate ion secretion and increase epithelial permeability in rat intestine. Am J Physiol1994;267:G794.

231. SantosJ, YangPC, SoderholmJD, et al.Role of mast cells in chronic stress induced colonic epithelial barrier dysfunction in the rat. Gut2001;48:630. CrossRef

232. SaundersPR, SantosJ, HanssenNP, et al.Physical and psychological stress in rats enhances colonic epithelial permeability via peripheral CRH. Dig Dis Sci2002;47:208. CrossRef

233. GareauMG, JuryJ, YangPC, et al.Neonatal maternal separation causes colonic dysfunction in rat pups including impaired host resistance. Pediatr Res2006;59:83. CrossRef

234. BuenoL, FioramontiJ. Protease‐activated receptor 2 and gut permeability: a review. Neurogastroenterol Motil2008;20:580. CrossRef

235. SekirovI, RussellSL, AntunesLC, et al.Gut microbiota in health and disease. Physiol Rev2010;90:859. CrossRef

236. SimrenM, BarbaraG, FlintHJ, et al.Intestinal microbiota in functional bowel disorders: a Rome Foundation Report. Gut2013;62:159. CrossRef

237. MalinenE, RinttilaT, KajanderK, et al.Analysis of the fecal microbiota of irritable bowel syndrome patients and healthy controls with real‐time PCR. Am J Gastroenterol2005;100:373. CrossRef

238. KerckhoffsAP, SamsomM, Van Der RestME, et al.Lower Bifidobacteria counts in both duodenal mucosa‐associated and fecal microbiota in irritable bowel syndrome patients. World J Gastroenterol2009;15:2887. CrossRef

239. RousseauxC, ThuruX, GelotA, et al.Lactobacillus acidophilus modulates intestinal pain and induces opioid and cannabinoid receptors. Nat Med2007;13:35. CrossRef

240. PimentelM, ParkS, MirochaJ, et al.The effect of a nonabsorbed oral antibiotic (rifaximin) on the symptoms of the irritable bowel syndrome: a randomized trial. Ann Intern Med2006;145:557. CrossRef

241. VillarrealAA, AbergerFJ, BenrudR, et al.Use of broad‐spectrum antibiotics and the development of irritable bowel syndrome. WMJ2012;111:17.

242. VerduEF, BercikP, Verma‐GandhuM, et al.Specific probiotic therapy attenuates antibiotic induced visceral hypersensitivity in mice. Gut2006;55:182. CrossRef

243. KimHJ, CamilleriM, MckinzieS, et al.A randomized controlled trial of a probiotic, vsl#3, on gut transit and symptoms in diarrhoea‐predominant irritable bowel syndrome. Aliment Pharmacol Ther2003;17:895. CrossRef

244. ZareieM, Johnson‐HenryK, JuryJ, et al.Probiotics prevent bacterial translocation and improve intestinal barrier function in rats following chronic psychological stress. Gut2006;55:1553. CrossRef

245. RoundJL, MazmanianSK. The gut microbiota shapes intestinal immune responses during health and disease. Nat Rev Immunol2009;9:313. CrossRef

246. O'MahonyL, McCarthyJ, KellyP, et al.Lactobacillus and bifidobacterium in irritable bowel syndrome: symptom responses and relationship to cytokine profiles. Gastroenterology2005;128:541. CrossRef

247. NandaR, JamesR, SmithH, et al.Food intolerance and the irritable bowel syndrome. Gut1989;30:1099. CrossRef

248. ShepherdSJ, ParkerFC, MuirJG, et al.Dietary triggers of abdominal symptoms in patients with irritable bowel syndrome: randomized placebo‐controlled evidence. Clin Gastroenterol Hepatol2008;6:765. CrossRef

249. HusebyeE, HellstromPM, SundlerF, et al.Influence of microbial species on small intestinal myoelectric activity and transit in germ‐free rats. Am J Physiol Gastrointest Liver Physiol2001;280:G368.

250. KashyapPC, MarcobalA, UrsellLK, et al.Complex interactions among diet, gastrointestinal transit, and gut microbiota in humanized mice. Gastroenterology2013;144:967. CrossRef

251. BaileyMT, LubachGR, CoeCL. Prenatal stress alters bacterial colonization of the gut in infant monkeys. J Pediatr Gastroenterol Nutr2004;38:414. CrossRef

252. BaileyMT, CoeCL. Maternal separation disrupts the integrity of the intestinal microflora in infant rhesus monkeys. Dev Psychobiol1999;35:146. CrossRef

253. RheeSH, PothoulakisC, MayerEA. Principles and clinical implications of the brain‐gut‐enteric microbiota axis. Nat Rev Gastroenterol Hepatol2009;6:306. CrossRef

254. BercikP, DenouE, CollinsJ, et al.The intestinal microbiota affect central levels of brain‐derived neurotropic factor and behavior in mice. Gastroenterology2011;141:599. CrossRef

255. CollinsSM, BercikP. The relationship between intestinal microbiota and the central nervous system in normal gastrointestinal function and disease. Gastroenterology2009;136:2003. CrossRef

256. GroverM, HerfarthH, DrossmanDA. The functional‐organic dichotomy: postinfectious irritable bowel syndrome and inflammatory bowel disease‐irritable bowel syndrome. Clin Gastroenterol Hepatol2009;7:48. CrossRef

257. KiankC, TacheY, LaraucheM. Stress‐related modulation of inflammation in experimental models of bowel disease and post‐infectious irritable bowel syndrome: role of corticotropin‐releasing factor receptors. Brain Behav Immun2010;24:41. CrossRef

258. SaitoYA. The role of genetics in IBS. Gastroenterol Clin North Am2011;40:45. CrossRef

259. SaitoYA, LarsonJJ, AtkinsonEJ, et al.The role of 5‐HTT LPR and GNbeta3 825C>T polymorphisms and gene‐environment interactions in irritable bowel syndrome (IBS). Dig Dis Sci2012;57:2650. CrossRef

260. Van KerkhovenLA, LaheijRJ, JansenJB. 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 Ther2007;26:979. CrossRef

261. WangYM, ChangY, ChangYY, et al.Serotonin transporter gene promoter region polymorphisms and serotonin transporter expression in the colonic mucosa of irritable bowel syndrome patients. Neurogastroenterol Motil2012;24:560. CrossRef

262. KohenR, JarrettME, CainKC, et al.The serotonin transporter polymorphism rs25531 is associated with irritable bowel syndrome. Dig Dis Sci2009;54:2663. CrossRef

263. KapellerJ, HoughtonLA, MonnikesH, et al.First evidence for an association of a functional variant in the microrna‐510 target site of the serotonin receptor‐type 3e gene with diarrhea predominant irritable bowel syndrome. Hum Mol Genet2008;17:2967. CrossRef

264. FukudoS, KanazawaM, MizunoT, et al.Impact of serotonin transporter gene polymorphism on brain activation by colorectal distention. Neuroimage2009;47:946. CrossRef

265. KilpatrickLA, LabusJS, CoveleskieK, et al.The HTR3a polymorphism c. ‐42C>T is associated with amygdala responsiveness in patients with irritable bowel syndrome. Gastroenterology2011;140:1943. CrossRef

266. SatoN, SuzukiN, SasakiA, et al.Corticotropin‐releasing hormone receptor 1 gene variants in irritable bowel syndrome. PLoS ONE2012;7:e42450. CrossRef

267. ParkJM, ChoiMG, ChoYK, et al.Cannabinoid receptor 1 gene polymorphism and irritable bowel syndrome in the Korean population: a hypothesis‐generating study. J Clin Gastroenterol2011;45:45. CrossRef

268. KarlingP, DanielssonA, WikgrenM, et al.The relationship between the val158met catechol‐o‐methyltransferase (COMT) polymorphism and irritable bowel syndrome. PLoS ONE2011;6:e18035. CrossRef

269. Romero‐ValdovinosM, Gudino‐RamirezA, Reyes‐GordilloJ, et al.Interleukin‐8 and ‐10 gene polymorphisms in irritable bowel syndrome. Mol Biol Rep2012;39:8837. CrossRef

270. Van Der VeekPP, Van Den BergM, De KroonYE, et al.Role of tumor necrosis factor‐alpha and interleukin‐10 gene polymorphisms in irritable bowel syndrome. Am J Gastroenterol2005;100:2510. CrossRef

271. SpillerR, SwanC, CampbellE. Identifying and testing candidate genes underlying the inflammatory basis of irritable bowel syndrome. Gut2011;60:A164. CrossRef

272. SaitoYA, StregePR, TesterDJ, et al.Sodium channel mutation in irritable bowel syndrome: evidence for an ion channelopathy. Am J Physiol Gastrointest Liver Physiol2009;296:G211. CrossRef

273. CamilleriM, AtanasovaE, CarlsonPJ, et al.Serotonin‐transporter polymorphism pharmacogenetics in diarrhea‐predominant irritable bowel syndrome. Gastroenterology2002;123:425. CrossRef

274. WongBS, CamilleriM, CarlsonPJ, et al.Pharmacogenetics of the effects of colesevelam on colonic transit in irritable bowel syndrome with diarrhea. Dig Dis Sci2012;57:1222. CrossRef

275. CamilleriM. Genetics of human gastrointestinal sensation. Neurogastroenterol Motil2013;25:458. CrossRef

276. KirwanWO, SmithAN, MitchellWD, et al.Bile acids and colonic motility in the rabbit and the human. Gut1975;16:894. CrossRef

277. EdwardsCA, BrownS, BaxterAJ, et al.Effect of bile acid on anorectal function in man. Gut1989;30:383. CrossRef

278. WedlakeL, A'HernR, RussellD, et al.Systematic review: the prevalence of idiopathic bile acid malabsorption as diagnosed by SEHCAT scanning in patients with diarrhoea‐predominant irritable bowel syndrome. Aliment Pharmacol Ther2009;30:707. CrossRef

279. FordAC. Applicability of the reported prevalence of bile salt malabsorption in irritable bowel. Aliment Pharmacol Ther2010;31:161. CrossRef

280. GracieDJ, KaneJS, MumtazS, et al.Prevalence of, and predictors of, bile acid malabsorption in outpatients with chronic diarrhea. Neurogastroenterol Motil2012;24:983. CrossRef

281. CamilleriM, NadeauA, TremaineWJ, et al.Measurement of serum 7alpha‐hydroxy‐4‐cholesten‐3‐one (or 7alphac4), a surrogate test for bile acid malabsorption in health, ileal disease and irritable bowel syndrome using liquid chromatography‐tandem mass spectrometry. Neurogastroenterol Motil2009;21:734. CrossRef

282. WongBS, CamilleriM, CarlsonP, et al.Increased bile acid biosynthesis is associated with irritable bowel syndrome with diarrhea. Clin Gastroenterol Hepatol2012;10:1009. CrossRef

283. FordAC, BercikP, MorganDG, et al.Validation of the Rome III criteria for the diagnosis of irritable bowel syndrome in secondary care. Gastroenterology2013;145:1262. CrossRef

284. PalssonOS, BaggishJS, TurnerMJ, et al.IBS patients show frequent fluctuations between loose/watery and hard/lumpy stools: implications for treatment. Am J Gastroenterol2012;107:286. CrossRef

285. GarriguesV, MearinF, BadiaX, et al.Change over time of bowel habit in irritable bowel syndrome: a prospective, observational, 1‐year follow‐up study (RITMO study). Aliment Pharmacol Ther2007;25:323. CrossRef

286. LemboT, NaliboffB, MunakataJ, et al.Symptoms and visceral perception in patients with pain‐predominant irritable bowel syndrome. Am J Gastroenterol1999;94:1320. CrossRef

287. ChaudharyNA, TrueloveSC. The irritable colon syndrome. A study of the clinical features, predisposing causes, and prognosis in 130 cases. Q J Med1962;31:307.

288. SimrenM, ManssonA, LangkildeAM, et al.Food‐related gastrointestinal symptoms in the irritable bowel syndrome. Digestion2001;63:108.

289. HellstromPM, SaitoYA, BytzerP, et al.Characteristics of acute pain attacks in patients with irritable bowel syndrome meeting Rome III criteria. Am J Gastroenterol2011;106:1299. CrossRef

290. TalleyNJ, DennisEH, Schettler‐DuncanVA, et al.Overlapping upper and lower gastrointestinal symptoms in irritable bowel syndrome patients with constipation or diarrhea. Am J Gastroenterol2003;98:2454. CrossRef

291. TangYR, YangWW, WangYL, et al.Sex differences in the symptoms and psychological factors that influence quality of life in patients with irritable bowel syndrome. Eur J Gastroenterol Hepatol2012;24:702. CrossRef

292. SchmulsonM, LeeOY, ChangL, et al.Symptom differences in moderate to severe IBS patients based on predominant bowel habit. Am J Gastroenterol1999;94:2929. CrossRef

293. CoffinB, DapoignyM, CloarecD, et al.Relationship between severity of symptoms and quality of life in 858 patients with irritable bowel syndrome. Gastroenterol Clin Biol2004;28:11. CrossRef

294. Van Der HorstHE, Van DulmenAM, SchellevisFG, et al.Do patients with irritable bowel syndrome in primary care really differ from outpatients with irritable bowel syndrome?Gut1997;41:669. CrossRef

295. ChangL, HeitkemperMM. Gender differences in irritable bowel syndrome. Gastroenterology2002;123:1686. CrossRef

296. LeeOY, MayerEA, SchmulsonM, et al.Gender‐related differences in IBS symptoms. Am J Gastroenterol2001;96:2184. CrossRef

297. SimrenM, AbrahamssonH, SvedlundJ, et al.Quality of life in patients with irritable bowel syndrome seen in referral centers versus primary care: the impact of gender and predominant bowel pattern. Scand J Gastroenterol2001;36:545. CrossRef

298. CorneyRH, StantonR. Physical symptom severity, psychological and social dysfunction in a series of outpatients with irritable bowel syndrome. J Psychosom Res1990;34:483. CrossRef

299. TalleyNJ, ZinsmeisterAR, MeltonLJ3rd.Irritable bowel syndrome in a community: symptom subgroups, risk factors, and health care utilization. Am J Epidemiol1995;142:76.

300. HeitkemperM, JarrettM, BondEF, et al.Impact of sex and gender on irritable bowel syndrome. Biol Res Nurs2003;5:56. CrossRef

301. AdeyemoMA, SpiegelBM, ChangL. Meta‐analysis: do irritable bowel syndrome symptoms vary between men and women?Aliment Pharmacol Ther2010;32:738. CrossRef

302. HoughtonLA, LeaR, JacksonN, et al.The menstrual cycle affects rectal sensitivity in patients with irritable bowel syndrome but not healthy volunteers. Gut2002;50:471. CrossRef

303. DrossmanDA, ChangL, BellamyN, et al.Severity in irritable bowel syndrome: a Rome Foundation Working Team Report. Am J Gastroenterol2011;106:1749. CrossRef

304. DrossmanD. What determines severity among patients with painful functional bowel disorders?Am J Gastroenterol2000;95:974. CrossRef

305. SpiegelB, StricklandA, NaliboffBD, et al.Predictors of patient‐assessed illness severity in irritable bowel syndrome. Am J Gastroenterol2008;103:2536. CrossRef

306. SpiegelBM, BolusR, HarrisLA, et al.Characterizing abdominal pain in IBS: guidance for study inclusion criteria, outcome measurement and clinical practice. Aliment Pharmacol Ther2010;32:1192. CrossRef

307. GuyattG, GuttermanD, BaumannMH, et al.Grading strength of recommendations and quality of evidence in clinical guidelines: report from an American College of Chest Physicians Task Force. Chest2006;129:174. CrossRef

308. ThompsonW, CreedF, DrossmanD. Functional bowel disease and functional abdominal pain. Gastroenterol Int1992;5:75.

309. TalleyNJ, BoyceP, JonesM. Identification of distinct upper and lower gastrointestinal symptom groupings in an urban population. Gut1998;42:690. CrossRef

310. KellowJE. The “pro” case. The Rome III criteria. Neurogastroenterol Motil2007;19:787. CrossRef

311. TytgatGN. Foreword ii. In: DrossmanD, CorazziariE, DelvauxM, et al. (eds). Rome III the Functional Gastrointestinal Disorders. McLean, VA: Degnon Associates, Inc; 2006: 639.

312. WhiteheadWE, DrossmanDA. Validation of symptom‐based diagnostic criteria for irritable bowel syndrome: a critical review. Am J Gastroenterol2010;105:814. CrossRef

313. FordAC, TalleyNJ, Veldhuyzen Van ZantenSJ, et al.Will the history and physical examination help establish that irritable bowel syndrome is causing this patient's lower gastrointestinal tract symptoms?JAMA2008;300:1793. CrossRef

314. EngsbroAL, BegtrupLM, KjeldsenJ, et al.Patients suspected of irritable bowel syndrome–cross‐sectional study exploring the sensitivity of Rome III criteria in primary care. Am J Gastroenterol2013;108:972. CrossRef

315. BellentaniS, BaldoniP, PetrellaS, et al.A simple score for the identification of patients at high risk of organic diseases of the colon in the family doctor consulting room. The local IBS study group. Fam Pract1990;7:307. CrossRef

316. KruisW, ThiemeC, WeinzierlM, et al.A diagnostic score for the irritable bowel syndrome. Its value in the exclusion of organic disease. Gastroenterology1984;87:1.

317. WhiteheadWE, PalssonOS, FeldAD, et al.Utility of red flag symptom exclusions in the diagnosis of irritable bowel syndrome. Aliment Pharmacol Ther2006;24:137. CrossRef

318. HammerJ, EslickGD, HowellSC, et al.Diagnostic yield of alarm features in irritable bowel syndrome and functional dyspepsia. Gut2004;53:666. CrossRef

319. LacyBE, RosemoreJ, RobertsonD, et al.Physicians' attitudes and practices in the evaluation and treatment of irritable bowel syndrome. Scand J Gastroenterol2006;41:892. CrossRef

320. SpiegelBM, FaridM, EsrailianE, et al.Is irritable bowel syndrome a diagnosis of exclusion?: A survey of primary care providers, gastroenterologists, and IBS experts. Am J Gastroenterol2010;105:848. CrossRef

321. PorterCK, CashBD, PimentelM, et al.Risk of inflammatory bowel disease following a diagnosis of irritable bowel syndrome. BMC Gastroenterol2012;12:55. CrossRef

322. CashBD, SchoenfeldP, CheyWD. The utility of diagnostic tests in irritable bowel syndrome patients: a systematic review. Am J Gastroenterol2002;97:2812. CrossRef

323. TolliverBA, HerreraJL, DipalmaJA. Evaluation of patients who meet clinical criteria for irritable bowel syndrome. Am J Gastroenterol1994;89:176.

324. KaneSV, SandbornWJ, RufoPA, et al.Fecal lactoferrin is a sensitive and specific marker in identifying intestinal inflammation. Am J Gastroenterol2003;98:1309. CrossRef

325. JonefjallB, StridH, OhmanL, et al.Characterization of IBS‐like symptoms in patients with ulcerative colitis in clinical remission. Neurogastroenterol Motil2013;25:756. CrossRef

326. WaughN, CumminsE, RoyleP, et al.Faecal calprotectin testing for differentiating amongst inflammatory and non‐inflammatory bowel diseases: systematic review and economic evaluation. Health Technol Assess2013;17:1.

327. FasanoA, BertiI, GerarduzziT, et al.Prevalence of celiac disease in at‐risk and not‐at‐risk groups in the united states: a large multicenter study. Arch Intern Med2003;163:286. CrossRef

328. CashBD, RubensteinJH, YoungPE, et al.The prevalence of celiac disease among patients with nonconstipated irritable bowel syndrome is similar to controls. Gastroenterology2011;141:1187. CrossRef

329. MeinSM, LadabaumU. Serological testing for coeliac disease in patients with symptoms of irritable bowel syndrome: a cost‐effectiveness analysis. Aliment Pharmacol Ther2004;19:1199. CrossRef

330. SpiegelBMR, DerosaVP, GralnekIM, et al.Testing for celiac sprue in irritable bowel syndrome with predominant diarrhea: a cost‐effectiveness analysis. Gastroenterology2004;126:1721. CrossRef

331. PimentelM, ChowEJ, LinHC. Normalization of lactulose breath testing correlates with symptom improvement in irritable bowel syndrome. A double‐blind, randomized, placebo‐controlled study. Am J Gastroenterol2003;98:412.

332. WaltersB, VannerSJ. Detection of bacterial overgrowth in IBS using the lactulose H2 breath test: comparison with 14C‐D‐xylose and healthy controls. Am J Gastroenterol2005;100:1566. CrossRef

333. BrattenJR, SpanierJ, JonesMP. Lactulose breath testing does not discriminate patients with irritable bowel syndrome from healthy controls. Am J Gastroenterol2008;103:958. CrossRef

334. YuD, CheesemanF, VannerS. Combined oro‐caecal scintigraphy and lactulose hydrogen breath testing demonstrate that breath testing detects oro‐caecal transit, not small intestinal bacterial overgrowth in patients with IBS. Gut2011;60:334. CrossRef

335. PosserudI, StotzerPO, BjornssonES, et al.Small intestinal bacterial overgrowth in patients with irritable bowel syndrome. Gut2007;56:802. CrossRef

336. PylerisE, Giamarellos‐BourboulisEJ, TzivrasD, et al.The prevalence of overgrowth by aerobic bacteria in the small intestine by small bowel culture: relationship with irritable bowel syndrome. Dig Dis Sci2012;57:1321. CrossRef

337. JacobsC, Coss AdameE, AttaluriA, et al.Dysmotility and proton pump inhibitor use are independent risk factors for small intestinal bacterial and/or fungal overgrowth. Aliment Pharmacol Ther2013;37:1103. CrossRef

338. WilliamsC, MccollKE. Review article: proton pump inhibitors and bacterial overgrowth. Aliment Pharmacol Ther2006;23:3. CrossRef

339. LovellRM, FordAC. Prevalence of gastro‐esophageal reflux‐type symptoms in individuals with irritable bowel syndrome in the community: a meta‐analysis. Am J Gastroenterol2012;107:1793. CrossRef

340. SpiegelBM, CheyWD, ChangL. Bacterial overgrowth and irritable bowel syndrome: unifying hypothesis or a spurious consequence of proton pump inhibitors?Am J Gastroenterol2008;103:2972. CrossRef

341. VesaTH, MarteauP, KorpelaR. Lactose intolerance. J Am Coll Nutr2000;19:165S. CrossRef

342. CasellasF, ApariciA, CasausM, et al.Subjective perception of lactose intolerance does not always indicate lactose malabsorption. Clin Gastroenterol Hepatol2010;8:581. CrossRef

343. LomerMCE, ParkesGC, SandersonJD. Review article: lactose intolerance in clinical practice – myths and realities. Aliment Pharmacol Ther2008;27:93. CrossRef

344. MonsbakkenKW, VandvikPO, FarupPG. Perceived food intolerance in subjects with irritable bowel syndrome–etiology, prevalence and consequences. Eur J Clin Nutr2006;60:667. CrossRef

345. KuikenSD, LindeboomR, TytgatGN, et al.Relationship between symptoms and hypersensitivity to rectal distension in patients with irritable bowel syndrome. Aliment Pharmacol Ther2005;22:157. CrossRef

346. SchmulsonM, ChangL, NaliboffB, et al.Correlation of symptom criteria with perception thresholds during rectosigmoid distension in irritable bowel syndrome patients. Am J Gastroenterol2000;95:152. CrossRef

347. SabateJM, VeyracM, MionF, et al.Relationship between rectal sensitivity, symptoms intensity and quality of life in patients with irritable bowel syndrome. Aliment Pharmacol Ther2008;28:484. CrossRef

348. MayerEA, BradesiS, ChangL, et al.Functional GI disorders: from animal models to drug development. Gut2008;57. CrossRef

349. TornblomH, Van OudenhoveL, SadikR, et al.Colonic transit time and IBS symptoms: what's the link?Am J Gastroenterol2012;107:754. CrossRef

350. BharuchaAE, DornSD, LemboA, et al.American gastroenterological association medical position statement on constipation. Gastroenterology2013;144:211. CrossRef

351. CamilleriM, ChangL. Challenges to the therapeutic pipeline for irritable bowel syndrome: end points and regulatory hurdles. Gastroenterology2008;135:1877. CrossRef

352. StewartM, BrownJB, DonnerA, et al.The impact of patient‐centered care on outcomes. J Fam Pract2000;49:796.

353. KaptchukTJ, KelleyJM, ConboyLA, et al.Components of placebo effect: randomised controlled trial in patients with irritable bowel syndrome. BMJ2008;336:999. CrossRef

354. ChangL, DrossmanD. Optimizing patient care: the psychological interview in irritable bowel syndrome. Clin Perspect2002;5:336.

355. RingstromG, StorsrudS, PosserudI, et al.Structured patient education is superior to written information in the management of patients with irritable bowel syndrome: a randomized controlled study. Eur J Gastroenterol Hepatol2010;22:420. CrossRef

356. RingstromG, StorsrudS, SimrenM. A comparison of a short nurse‐based and a long multidisciplinary version of structured patient education in irritable bowel syndrome. Eur J Gastroenterol Hepatol2012;24:950. CrossRef

357. BiesiekierskiJR, NewnhamED, IrvingPM, et al.Gluten causes gastrointestinal symptoms in subjects without celiac disease: a double‐blind randomized placebo‐controlled trial. Am J Gastroenterol2011;106:508. CrossRef

358. AtkinsonW, SheldonTA, ShaathN, et al.Food elimination based on IgG antibodies in irritable bowel syndrome: a randomised controlled trial. Gut2004;53:1459. CrossRef

359. WahnschaffeU, SchulzkeJD, ZeitzM, et al.Predictors of clinical response to gluten‐free diet in patients diagnosed with diarrhea‐predominant irritable bowel syndrome. Clin Gastroenterol Hepatol2007;5:844. CrossRef

360. OngDK, MitchellSB, BarrettJS, et al.Manipulation of dietary short chain carbohydrates alters the pattern of gas production and genesis of symptoms in irritable bowel syndrome. J Gastroenterol Hepatol2010;25:1366. CrossRef

361. BuschAJ, SchachterCL, OverendTJ, et al.Exercise for fibromyalgia: a systematic review. J Rheumatol2008;35:1130.

362. VilloriaA, SerraJ, AzpirozF, et al.Physical activity and intestinal gas clearance in patients with bloating. Am J Gastroenterol2006;101:2552. CrossRef

363. JohannessonE, SimrenM, StridH, et al.Physical activity improves symptoms in irritable bowel syndrome: a randomized controlled trial. Am J Gastroenterol2011;106:915. CrossRef

364. RuepertL, QuarteroAO, De WitNJ, et al.Bulking agents, antispasmodics and antidepressants for the treatment of irritable bowel syndrome. Cochrane Database Syst Rev2011;(8):CD003460.

365. FordAC, TalleyNJ, SpiegelBM, et al.Effect of fibre, antispasmodics, and peppermint oil in the treatment of irritable bowel syndrome: systematic review and meta‐analysis. BMJ2008;337:a2313. CrossRef

366. BijkerkCJ, De WitNJ, MurisJW, et al.Soluble or insoluble fibre in irritable bowel syndrome in primary care? Randomised placebo controlled trial. BMJ2009;339:b3154. CrossRef

367. The Cochrane Collaboration. Review manager (RevMan) [computer program]. Copenhagen: The Nordic Cochrane Centre; 2011.

368. ToskesPP, ConneryKL, RitcheyTW. Calcium polycarbophil compared with placebo in irritable bowel syndrome. Aliment Pharmacol Ther1993;7:87. CrossRef

369. KhoshooV, ArmsteadC, LandryL. Effect of a laxative with and without tegaserod in adolescents with constipation predominant irritable bowel syndrome. Aliment Pharmacol Ther2006;23:191. CrossRef

370. ChapmanRW, StanghelliniV, GeraintM, et al.Randomized clinical trial: macrogol/peg 3350 plus electrolytes for treatment of patients with constipation associated with irritable bowel syndrome. Am J Gastroenterol2013;108:1508. CrossRef

371. BharuchaAE, PembertonJH, LockeGR3rd.American gastroenterological association technical review on constipation. Gastroenterology2013;144:218. CrossRef

372. Muller‐LissnerSA, FumagalliI, BardhanKD, et al.Tegaserod, a 5‐HT(4) receptor partial agonist, relieves symptoms in irritable bowel syndrome patients with abdominal pain, bloating and constipation. Aliment Pharmacol Ther2001;15:1655. CrossRef

373. NovickJ, MinerP, KrauseR, et al.A randomized, double‐blind, placebo‐controlled trial of tegaserod in female patients suffering from irritable bowel syndrome with constipation. Aliment Pharmacol Ther2002;16:1877. CrossRef

374. CheyWD, PareP, ViegasA, et al.Tegaserod for female patients suffering from IBS with mixed bowel habits or constipation: a randomized controlled trial. Am J Gastroenterol2008;103:1217. CrossRef

375. CamilleriM, KerstensR, RykxA, et al.A placebo‐controlled trial of prucalopride for severe chronic constipation. N Engl J Med2008;358:2344. CrossRef

376. DrossmanDA, CheyWD, JohansonJF, et al.Clinical trial: lubiprostone in patients with constipation‐associated irritable bowel syndrome–results of two randomized, placebo‐controlled studies. Aliment Pharmacol Ther2009;29:329. CrossRef

377. US Food and Drug Administration. Detailed view: safety and labeling changes approved by FDA center for drug evaluation and research (CDER)—November 2012. Accessed March 2013. Available at: http://www.accessdata.fda.gov/drugsatfda_docs/label/2012/021908s010lbl.pdf.

378. CheyWD, DrossmanDA, JohansonJF, et al.Safety and patient outcomes with lubiprostone for up to 52 weeks in patients with irritable bowel syndrome with constipation. Aliment Pharmacol Ther2012;35:587. CrossRef

379. EutameneH, BradesiS, LaraucheM, et al.Guanylate cyclase c‐mediated antinociceptive effects of linaclotide in rodent models of visceral pain. Neurogastroenterol Motil2010;22:312. CrossRef

380. BryantAP, BusbyRW, BartoliniWP, et al.Linaclotide is a potent and selective guanylate cyclase c agonist that elicits pharmacological effects locally in the gastrointestinal tract. Life Sci2010;86:760. CrossRef

381. LemboAJ, SchneierHA, ShiffSJ, et al.Two randomized trials of linaclotide for chronic constipation. N Engl J Med2011;365:527. CrossRef

382. CheyWD, LemboAJ, LavinsBJ, et al.Linaclotide for irritable bowel syndrome with constipation: a 26‐week, randomized, double‐blind, placebo‐controlled trial to evaluate efficacy and safety. Am J Gastroenterol2012;107:1702. CrossRef

383. VidelockEJ, ChengV, CremoniniF. Effects of linaclotide in patients with irritable bowel syndrome with constipation or chronic constipation: a meta‐analysis. Clin Gastroenterol Hepatol2013;11:1084. CrossRef

384. LemboA, CarsonR, ShiffSJ, et al.Factors contributing to treatment satisfaction in patients with irritable bowel syndrome with constipation (IBS‐C) treated with linaclotide vs placebo. Gastroenterology2012;142:S822. CrossRef

385. SchoenfeldPS, ChangL, CarsonR, et al.Do baseline factors contribute to treatment satisfaction in patients with chronic constipation treated with linaclotide vs placebo?Gastroenterology2012;142:S737. CrossRef

386. PimentelM, LemboA, CheyWD, et al.Rifaximin therapy for patients with irritable bowel syndrome without constipation. N Engl J Med2011;364:22. CrossRef

387. MeneesSB, ManeerattannapornM, KimHM, et al.The efficacy and safety of rifaximin for the irritable bowel syndrome: a systematic review and meta‐analysis. Am J Gastroenterol2012;107:28. CrossRef

388. DelvauxM, LouvelD, MametJP, et al.Effect of alosetron on responses to colonic distension in patients with irritable bowel syndrome. Aliment Pharmacol Ther1998;12:849. CrossRef

389. HoughtonLA, FosterJM, WhorwellPJ. Alosetron, a 5‐HT3 receptor antagonist, delays colonic transit in patients with irritable bowel syndrome and healthy volunteers. Aliment Pharmacol Ther2000;14:775. CrossRef

390. CremoniniF, NicandroJP, AtkinsonV, et al.Randomised clinical trial: alosetron improves quality of life and reduces restriction of daily activities in women with severe diarrhoea‐predominant IBS. Aliment Pharmacol Ther2012;36:437. CrossRef

391. ChangL, AmeenVZ, DukesGE, et al.A dose‐ranging, phase II study of the efficacy and safety of alosetron in men with diarrhea‐predominant IBS. Am J Gastroenterol2005;100:115. CrossRef

392. LemboT, WrightRA, BagbyB, et al.Alosetron controls bowel urgency and provides global symptom improvement in women with diarrhea‐predominant irritable bowel syndrome. Am J Gastroenterol2001;96:2662. CrossRef

393. CamilleriM, CheyWY, MayerEA, et al.A randomized controlled clinical trial of the serotonin type 3 receptor antagonist alosetron in women with diarrhea‐predominant irritable bowel syndrome. Arch Intern Med2001;161:1733. CrossRef

394. CamilleriM, NorthcuttAR, KongS, et al.Efficacy and safety of alosetron in women with irritable bowel syndrome: a randomised, placebo‐controlled trial. Lancet2000;355:1035. CrossRef

395. CheyWD, CheyWY, HeathAT, et al.Long‐term safety and efficacy of alosetron in women with severe diarrhea‐predominant irritable bowel syndrome. Am J Gastroenterol2004;99:2195. CrossRef

396. ChangL, CheyWD, HarrisL, et al.Incidence of ischemic colitis and serious complications of constipation among patients using alosetron: systematic review of clinical trials and post‐marketing surveillance data. Am J Gastroenterol2006;101:1069. CrossRef

397. ChangL, TongK, AmeenV. Ischemic colitis and complications of constipation associated with the use of alosetron under a risk management plan: clinical characteristics, outcomes, and incidences. Am J Gastroenterol2010;105:866. CrossRef

398. TongK, NicandroJP, ShringarpureR, et al.A 9‐year evaluation of temporal trends in alosetron post‐marketing safety under the risk management program. Therap Adv Gastroenterol2013;6:344. CrossRef

399. MatsuedaK, HarasawaS, HongoM, et al.A phase II trial of the novel serotonin type 3 receptor antagonist ramosetron in Japanese male and female patients with diarrhea‐predominant irritable bowel syndrome. Digestion2008;77:225. CrossRef

400. LeeKJ, KimNY, KwonJK, et al.Efficacy of ramosetron in the treatment of male patients with irritable bowel syndrome with diarrhea: a multicenter, randomized clinical trial, compared with mebeverine. Neurogastroenterol Motil2011;23:1098. CrossRef

401. JonesRH, HoltmannG, RodrigoL, et al.Alosetron relieves pain and improves bowel function compared with mebeverine in female nonconstipated irritable bowel syndrome patients. Aliment Pharmacol Ther1999;13:1419. CrossRef

402. ShaheenNJ, RobertsonDJ, CrosbyMA, et al.Hyoscyamine as a pharmacological adjunct in colonoscopy: a randomized, double blinded, placebo‐controlled trial. Am J Gastroenterol1999;94:2905. CrossRef

403. KruegerD, MichelK, AllamS, et al.Effect of hyoscinebutylbromide (Buscopan) oncholinergic pathways in the human intestine. Neurogastroenterol Motil2013;25:e530. CrossRef

404. EvangelistaS. Quaternary ammonium derivatives as spasmolytics for irritable bowel syndrome. Curr Pharm Des2004;10:3561. CrossRef

405. RomanFJ, LanetS, HamonJ, et al.Pharmacological properties of trimebutine and N‐monodesmethyltrimebutine. J Pharmacol Exp Ther1999;289:1391.

406. AbysiqueA, LucchiniS, OrsoniP, et al.Effects of alverine citrate on cat intestinal mechanoreceptor responses to chemical and mechanical stimuli. Aliment Pharmacol Ther1999;13:561. CrossRef

407. CoelhoAM, JacobL, FioramontiJ, et al.Rectal antinociceptive properties of alverine citrate are linked to antagonism at the 5‐HT1a receptor subtype. J Pharm Pharmacol2001;53:1419. CrossRef

408. TackJ, FriedM, HoughtonLA, et al.Systematic review: the efficacy of treatments for irritable bowel syndrome–a European perspective. Aliment Pharmacol Ther2006;24:183. CrossRef

409. WittmannT, ParadowskiL, DucrotteP, et al.Clinical trial: the efficacy of alverine citrate/simeticone combination on abdominal pain/discomfort in irritable bowel syndrome–a randomized, double‐blind, placebo‐controlled study. Aliment Pharmacol Ther2010;31:615. CrossRef

410. ClaveP, AcalovschiM, TriantafillidisJK, et al.Randomised clinical trial: otilonium bromide improves frequency of abdominal pain, severity of distention and time to relapse in patients with irritable bowel syndrome. Aliment Pharmacol Ther2011;34:432. CrossRef

411. ChangFY, LuCL, LuoJC, et al.The evaluation of otilonium bromide treatment in Asian patients with irritable bowel syndrome. J Neurogastroenterol Motil2011;17:402. CrossRef

412. GuarnerF, RequenaT, MarcosA. Consensus statements from the workshop “probiotics and health: scientific evidence”. Nutr Hosp2010;25:700.

413. KamiyaT, WangL, ForsytheP, et al.Inhibitory effects of Lactobacillus reuteri on visceral pain induced by colorectal distension in Sprague‐Dawley rats. Gut2006;55:191. CrossRef

414. AgrawalA, HoughtonLA, MorrisJ, et al.Clinical trial: the effects of a fermented milk product containing Bifidobacterium lactis DN‐173 010 on abdominal distension and gastrointestinal transit in irritable bowel syndrome with constipation. Aliment Pharmacol Ther2009;29:104. CrossRef

415. KimHJ, Vazquez RoqueMI, CamilleriM, et al.A randomized controlled trial of a probiotic combination vsl# 3 and placebo in irritable bowel syndrome with bloating. Neurogastroenterol Motil2005;17:687. CrossRef

416. AgostiniS, GoubernM, TondereauV, et al.A marketed fermented dairy product containing Bifidobacterium lactis CNCM I‐2494 suppresses gut hypersensitivity and colonic barrier disruption induced by acute stress in rats. Neurogastroenterol Motil2012;24:376. CrossRef

417. KajanderK, MyllyluomaE, Rajilic‐StojanovicM, et al.Clinical trial: multispecies probiotic supplementation alleviates the symptoms of irritable bowel syndrome and stabilizes intestinal microbiota. Aliment Pharmacol Ther2008;27:48. CrossRef

418. MccarthyJ, O'mahonyL, O'CallaghanL, et al.Double blind, placebo controlled trial of two probiotic strains in interleukin 10 knockout mice and mechanistic link with cytokine balance. Gut2003;52:975. CrossRef

419. KoniecznaP, GroegerD, ZieglerM, et al.Bifidobacterium infantis 35624 administration induces Foxp3 T regulatory cells in human peripheral blood: potential role for myeloid and plasmacytoid dendritic cells. Gut2012;61:354. CrossRef

420. WhorwellPJ, AltringerL, MorelJ, et al.Efficacy of an encapsulated probiotic Bifidobacterium infantis 35624 in women with irritable bowel syndrome. Am J Gastroenterol2006;101:1581. CrossRef

421. KajanderK, HatakkaK, PoussaT, et al.A probiotic mixture alleviates symptoms in irritable bowel syndrome patients: a controlled 6‐month intervention. Aliment Pharmacol Ther2005;22:387. CrossRef

422. GuyonnetD, ChassanyO, DucrotteP, et al.Effect of a fermented milk containing Bifidobacterium animalis dn‐173 010 on the health‐related quality of life and symptoms in irritable bowel syndrome in adults in primary care: a multicentre, randomized, double‐blind, controlled trial. Aliment Pharmacol Ther2007;26:475. CrossRef

423. MoayyediP, FordAC, TalleyNJ, et al.The efficacy of probiotics in the treatment of irritable bowel syndrome: a systematic review. Gut2010;59:325. CrossRef

424. BrennerDM, MoellerMJ, CheyWD, et al.The utility of probiotics in the treatment of irritable bowel syndrome: a systematic review. Am J Gastroenterol2009;104:1033. CrossRef

425. McfarlandLV, DublinS. Meta‐analysis of probiotics for the treatment of irritable bowel syndrome. World J Gastroenterol2008;14:2650. CrossRef

426. HunginAP, MulliganC, PotB, et al.Systematic review: probiotics in the management of lower gastrointestinal symptoms in clinical practice – an evidence‐based international guide. Aliment Pharmacol Ther2013;38:864. CrossRef

427. GorardDA, LibbyGW, FarthingMJ. Influence of antidepressants on whole gut and orocaecal transit times in health and irritable bowel syndrome. Aliment Pharmacol Ther1994;8:159. CrossRef

428. ChoungRS, CremoniniF, ThapaP, et al.The effect of short‐term, low‐dose tricyclic and tetracyclic antidepressant treatment on satiation, postnutrient load gastrointestinal symptoms and gastric emptying: a double‐blind, randomized, placebo‐controlled trial. Neurogastroenterol Motil2008;20:220. CrossRef

429. ChialHJ, CamilleriM, FerberI, et al.Effects of venlafaxine, buspirone, and placebo on colonic sensorimotor functions in healthy humans. Clin Gastroenterol Hepatol2003;1:211. CrossRef

430. MorganV, PickensD, GautamS, et al.Amitriptyline reduces rectal pain related activation of the anterior cingulate cortex in patients with irritable bowel syndrome. Gut2005;54:601. CrossRef

431. FordAC, TalleyNJ, SchoenfeldPS, et al.Efficacy of antidepressants and psychological therapies in irritable bowel syndrome: systematic review and meta‐analysis. Gut2009;58:367. CrossRef

432. DrossmanDA, TonerBB, WhiteheadWE, et al.Cognitive‐behavioral therapy versus education and desipramine versus placebo for moderate to severe functional bowel disorders. Gastroenterology2003;125:19. CrossRef

433. CamilleriM, MayerEA. Developing irritable bowel syndrome guidelines through meta‐analyses: does the emperor really have new clothes?Gastroenterology2009;137:766. CrossRef

434. HalpertA, DaltonCB, DiamantNE, et al.Clinical response to tricyclic antidepressants in functional bowel disorders is not related to dosage. Am J Gastroenterol2005;100:664. CrossRef

435. ThiwanS, DrossmanDA, MorrisCB, et al.Not all side effects associated with tricyclic antidepressant therapy are true side effects. Clin Gastroenterol Hepatol2009;7:446. CrossRef

436. BrennanBP, FogartyKV, RobertsJL, et al.Duloxetine in the treatment of irritable bowel syndrome: an open‐label pilot study. Hum Psychopharmacol2009;24:423. CrossRef

437. Van KerkhovenLA, LaheijRJ, AparicioN, et al.Effect of the antidepressant venlafaxine in functional dyspepsia: a randomized, double‐blind, placebo‐controlled trial. Clin Gastroenterol Hepatol2008;6:746. CrossRef

438. HamnerMB, DeitschSE, BrodrickPS, et al.Quetiapine treatment in patients with posttraumatic stress disorder: an open trial of adjunctive therapy. J Clin Psychopharmacol2003;23:15. CrossRef

439. PalssonOS, WhiteheadWE. Psychological treatments in functional gastrointestinal disorders: a primer for the gastroenterologist. Clin Gastroenterol Hepatol2013;11:208. CrossRef

440. CraskeMG, Wolitzky‐TaylorKB, LabusJ, et al.A cognitive‐behavioral treatment for irritable bowel syndrome using interoceptive exposure to visceral sensations. Behav Res Ther2011;49:413. CrossRef

441. KennedyT, JonesR, DarnleyS, et al.Cognitive behaviour therapy in addition to antispasmodic treatment for irritable bowel syndrome in primary care: randomised controlled trial. BMJ2005;331:435. CrossRef

442. LjotssonB, HedmanE, AnderssonE, et al.Internet‐delivered exposure‐based treatment vs. Stress management for irritable bowel syndrome: a randomized trial. Am J Gastroenterol2011;106:1481. CrossRef

443. HuntMG, MoshierS, MilonovaM. Brief cognitive‐behavioral internet therapy for irritable bowel syndrome. Behav Res Ther2009;47:797. CrossRef

444. Moss‐MorrisR, McalpineL, DidsburyLP, et al.A randomized controlled trial of a cognitive behavioural therapy‐based self‐management intervention for irritable bowel syndrome in primary care. Psychol Med2010;40:85. CrossRef

445. LjotssonB, AnderssonG, AnderssonE, et al.Acceptability, effectiveness, and cost‐effectiveness of internet‐based exposure treatment for irritable bowel syndrome in a clinical sample: a randomized controlled trial. BMC Gastroenterol2011;11:110. CrossRef

446. VandulmenAM, FennisJFM, BleijenbergG. Cognitive‐behavioral group therapy for irritable bowel syndrome: effects and long‐term follow‐up. Psychosom Med1996;58:508. CrossRef

447. WhorwellPJ, PriorA, FaragherEB. Controlled trial of hypnotherapy in the treatment of severe refractory irritable‐bowel syndrome. Lancet1984;2:1232. CrossRef

448. LindforsP, UngeP, ArvidssonP, et al.Effects of gut‐directed hypnotherapy on IBS in different clinical settings‐results from two randomized, controlled trials. Am J Gastroenterol2012;107:276. CrossRef

449. ForbesA, MacauleyS, Chiotakakou‐FaliakouE. Hypnotherapy and therapeutic audiotape: effective in previously unsuccessfully treated irritable bowel syndrome?Int J Colorectal Dis2000;15:328. CrossRef

450. GalovskiTE, BlanchardEB. The treatment of irritable bowel syndrome with hypnotherapy. Appl Psychophysiol Biofeedback1998;23:219. CrossRef

451. PalssonOS, TurnerMJ, JohnsonDA, et al.Hypnosis treatment for severe irritable bowel syndrome: investigation of mechanism and effects on symptoms. Dig Dis Sci2002;47:2605. CrossRef

452. RobertsL, WilsonS, SinghS, et al.Gut‐directed hypnotherapy for irritable bowel syndrome: piloting a primary care‐based randomised controlled trial. Br J Gen Pract2006;56:115.

453. LindforsP, UngeP, NyhlinH, et al.Long‐term effects of hypnotherapy in patients with refractory irritable bowel syndrome. Scand J Gastroenterol2012;47:414. CrossRef

454. FernandezC, PerezM, AmigoI, et al.Stress and contingency management in the treatment of irritable bowel syndrome. Stress Health1998;14:31.

455. Van Der VeekPP, Van RoodYR, MascleeAA. Clinical trial: short‐ and long‐term benefit of relaxation training for irritable bowel syndrome. Aliment Pharmacol Ther2007;26:943. CrossRef

456. BoycePM, TalleyNJ, BalaamB, et al.A randomized controlled trial of cognitive behavior therapy, relaxation training, and routine clinical care for the irritable bowel syndrome. Am J Gastroenterol2003;98:2209. CrossRef

457. GaylordSA, PalssonOS, GarlandEL, et al.Mindfulness training reduces the severity of irritable bowel syndrome in women: results of a randomized controlled trial. Am J Gastroenterol2011;106:1678. CrossRef

458. PatcharatrakulT, GonlachanvitS. Outcome of biofeedback therapy in dyssynergic defecation patients with and without irritable bowel syndrome. J Clin Gastroenterol2011;45:593. CrossRef

459. BrownPM, DrossmanDA, WoodAJ, et al.The tryptophan hydroxylase inhibitor lx1031 shows clinical benefit in patients with nonconstipating irritable bowel syndrome. Gastroenterology2011;141:507. CrossRef

460. SohnW, LeeOY, KwonJG, et al.Tianeptine vs amitriptyline for the treatment of irritable bowel syndrome with diarrhea: a multicenter, open‐label, non‐inferiority, randomized controlled study. Neurogastroenterol Motil2012;24:860. CrossRef

461. DrossmanDA, DanilewitzM, NaesdalJ, et al.Randomized, double‐blind, placebo‐controlled trial of the 5‐HT1a receptor antagonist azd7371 tartrate monohydrate (robalzotan tartrate monohydrate) in patients with irritable bowel syndrome. Am J Gastroenterol2008;103:2562. CrossRef

462. RaoAS, WongBS, CamilleriM, et al.Chenodeoxycholate in females with irritable bowel syndrome‐constipation: a pharmacodynamic and pharmacogenetic analysis. Gastroenterology2010;139:1549. CrossRef

463. WongBS, CamilleriM, MckinzieS, et al.Effects of a3309, an ileal bile acid transporter inhibitor, on colonic transit and symptoms in females with functional constipation. Am J Gastroenterol2011;106:2154. CrossRef

464. CheyWD, CamilleriM, ChangL, et al.A randomized placebo‐controlled phase IIb trial of A3309, a bile acid transporter inhibitor, for chronic idiopathic constipation. Am J Gastroenterol2011;106:1803. CrossRef

465. SimrenM, BajorA, GillbergPG, et al.Randomised clinical trial: the ileal bile acid transporter inhibitor A3309 vs. placebo in patients with chronic idiopathic constipation–a double‐blind study. Aliment Pharmacol Ther2011;34:41. CrossRef

466. CorinaldesiR, StanghelliniV, CremonC, et al.Effect of mesalazine on mucosal immune biomarkers in irritable bowel syndrome: a randomized controlled proof‐of‐concept study. Aliment Pharmacol Ther2009;30:245. CrossRef

467. DunlopSP, JenkinsD, NealKR, et al.Randomized, double‐blind, placebo‐controlled trial of prednisolone in post‐infectious irritable bowel syndrome. Aliment Pharmacol Ther2003;18:77. CrossRef

468. TackJF, DochevYS, BochenekA, et al.Efficacy of ibodutant, a selective antagonist of neurokinin 2 receptors, in irritable bowel syndrome with diarrhoea (IBS‐D): the results of a double‐ blind, randomised, placebo‐controlled, parallel‐group phase II study (the IRIS‐2). Gastroenterology2013;144:S92. CrossRef

469. CamilleriM. Novel pharmacology: asimadoline, a kappa‐opioid agonist, and visceral sensation. Neurogastroenterol Motil2008;20:971. CrossRef

470. MangelAW, BornsteinJD, HammLR, et al.Clinical trial: asimadoline in the treatment of patients with irritable bowel syndrome. Aliment Pharmacol Ther2008;28:239. CrossRef

471. SzarkaLA, CamilleriM, BurtonD, et al.Efficacy of on‐demand asimadoline, a peripheral kappa‐opioid agonist, in females with irritable bowel syndrome. Clin Gastroenterol Hepatol2007;5:1268. CrossRef

472. KelleherDL, HicksKJ, CoxDS, et al.Randomized, double‐blind, placebo‐controlled, crossover study to evaluate efficacy and safety of the beta 3‐adrenergic receptor agonist solabegron in patients with irritable bowel syndrome. Neurogastroenterol Motil2008;20:131.

473. AltheRx Pharmaceuticals. Altherx Development Program, 2011. Accessed March 2013. Available at: http://www.altherx.com/development_program/default.asp.

474. MangelAW, ChaturvediP. Evaluation of crofelemer in the treatment of diarrhea‐predominant irritable bowel syndrome patients. Digestion2008;78:180. CrossRef

475. ManheimerE, ChengK, WielandLS, et al.Acupuncture for treatment of irritable bowel syndrome. Cochrane Database Syst Rev2012;(5):CD005111.

476. BensoussanA, TalleyNJ, HingM, et al.Treatment of irritable bowel syndrome with Chinese herbal medicine: a randomized controlled trial. JAMA1998;280:1585. CrossRef

477. BundyR, WalkerAF, MiddletonRW, et al.Artichoke leaf extract reduces symptoms of irritable bowel syndrome and improves quality of life in otherwise healthy volunteers suffering from concomitant dyspepsia: a subset analysis. J Altern Complement Med2004;10:667. CrossRef

478. VejdaniR, ShalmaniHR, Mir‐FattahiM, et al.The efficacy of an herbal medicine, carmint, on the relief of abdominal pain and bloating in patients with irritable bowel syndrome: a pilot study. Dig Dis Sci2006;51:1501. CrossRef

479. MadischA, HoltmannG, PleinK, et al.Treatment of irritable bowel syndrome with herbal preparations: results of a double‐blind, randomized, placebo‐controlled, multi‐centre trial. Aliment Pharmacol Ther2004;19:271. CrossRef

480. LuWZ, GweeKA, MoochhallaS, et al.Melatonin improves bowel symptoms in female patients with irritable bowel syndrome: a double‐blind placebo‐controlled study. Aliment Pharmacol Ther2005;22:927. CrossRef

481. SongGH, LengPH, GweeKA, et al.Melatonin improves abdominal pain in irritable bowel syndrome patients who have sleep disturbances: a randomised, double blind, placebo controlled study. Gut2005;54:1402. CrossRef

482. SpenceMJ, Moss‐MorrisR. The cognitive behavioural model of irritable bowel syndrome: a prospective investigation of patients with gastroenteritis. Gut2007;56:1066. CrossRef

483. NichollBI, HalderSL, MacfarlaneGJ, et al.Psychosocial risk markers for new onset irritable bowel syndrome – results of a large prospective population‐based study. Pain2008;137:147. CrossRef

484. HalderSL, McbethJ, SilmanAJ, et al.Psychosocial risk factors for the onset of abdominal pain. Results from a large prospective population‐based study. Int J Epidemiol2002;31:1219. CrossRef

485. LacknerJM, BraselAM, QuigleyBM, et al.The ties that bind: perceived social support, stress, and IBS in severely affected patients. Neurogastroenterol Motil2010;22:893. CrossRef

486. OlafsdottirLB, GudjonssonH, JonsdottirHH, et al.Stability of the irritable bowel syndrome and subgroups as measured by three diagnostic criteria – a 10‐year follow‐up study. Aliment Pharmacol Ther2010;32:670.

487. El‐SeragHB, PilgrimP, SchoenfeldP. Systemic review: natural history of irritable bowel syndrome. Aliment Pharmacol Ther2004;19:861. CrossRef

488. HalderSLS, LockeGR, SchleckCD, et al.Natural history of functional gastrointestinal disorders: a 12‐year longitudinal population‐based study. Gastroenterology2007;133:799. CrossRef

489. MarshallJK, ThabaneM, GargAX, et al.Eight year prognosis of postinfectious irritable bowel syndrome following waterborne bacterial dysentery. Gut2010;59:605. CrossRef

490. FordAC, BrandtLJ, YoungC, et al.Efficacy of 5‐HT3 antagonists and 5‐HT4 agonists in irritable bowel syndrome: systematic review and meta‐analysis. Am J Gastroenterol2009;104:1831. CrossRef

491. KennedyPJ, ClarkeG, QuigleyEM, et al.Gut memories: towards a cognitive neurobiology of irritable bowel syndrome. Neurosci Biobehav Rev2012;36:310. CrossRef

492. MearinF, LacyBE. Diagnostic criteria in IBS: useful or not?Neurogastroenterol Motil2012;24:791. CrossRef

493. VidelockEJ, ChangL. Irritable bowel syndrome. In: TalleyN(ed). Practical Gastroenterology and Hepatology: Small and Large Intestine and Pancreas. Oxford, United Kingdom: Wiley Blackwell; 2010.