Advertisement

Brain and Gut Interactions in Irritable Bowel Syndrome: New Paradigms and New Understandings

  • Enrique Coss-Adame
  • Satish S. C. RaoEmail author
Neurogastroenterology and Motility Disorders of the Gastrointestinal Tract (S Rao, Section Editor)
Part of the following topical collections:
  1. Topical Collection on Neurogastroenterology and Motility Disorders of the Gastrointestinal Tract

Abstract

Irritable bowel syndrome (IBS) is characterized by abdominal pain and altered bowel habits. Visceral hypersensitivity is believed to be a key underlying mechanism that causes pain. There is evidence that interactions within the brain and gut axis (BGA), that involves both the afferent-ascending and the efferent-descending pathways, as well as the somatosensory cortex, insula, amygdala, anterior cingulate cortex, and hippocampus, are deranged in IBS showing both the activation and inactivation. Clinical manifestations of IBS such as pain, altered gut motility, and psychological dysfunction may each be explained, in part, through the changes in the BGA, but there is conflicting information, and its precise role is not fully understood. A better understanding of the BGA may shed more knowledge regarding the pathophysiology of IBS that in turn may lead to the discovery of novel therapies for this common disorder.

Keywords

Irritable bowel syndrome Brain-gut axis Cortical-evoked potentials Stress CRF Serotonin 

Notes

Compliance with Ethics Guidelines

Conflict of Interest

Dr. Rao and Dr. Coss-Adame declare no conflict of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by the author.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    Talley NJ. Irritable bowel syndrome. Intern Med J. 2006;36:724–8.PubMedCentralPubMedCrossRefGoogle Scholar
  2. 2.
    Ringel Y, Sperber AD, Drossman DA. Irritable bowel syndrome. Annu Rev Med. 2001;52:319–38.PubMedCrossRefGoogle Scholar
  3. 3.
    Pae CU, Masand PS, Ajwani N, et al. Irritable bowel syndrome in psychiatric perspectives: a comprehensive review. Int J Clin Pract. 2007;61:1708–18.PubMedCrossRefGoogle Scholar
  4. 4.
    Masand PS, Kaplan DS, Gupta S, et al. Irritable bowel syndrome and dysthymia. Is there a relationship? Psychosomatics. 1997;38:63–9.PubMedCrossRefGoogle Scholar
  5. 5.
    Barbara G, Cremon C, De Giorgio R, et al. Mechanisms underlying visceral hypersensitivity in irritable bowel syndrome. Curr Gastroenterol Rep. 2011;13(4):308–15.PubMedCrossRefGoogle Scholar
  6. 6.
    Bouin M, Meunier P, RiberdyPoitras M, Poitras P. Pain hypersensitivity in patients with functional gastrointestinal disorders: a gastrointestinal specific defect or a general systemic condition? Dig Dis Sci. 2001;46:2542–8.PubMedCrossRefGoogle Scholar
  7. 7.
    Zhou Q, Fillingim RB, Riley JL, et al. Central and peripheral hypersensitivity in the irritable bowel syndrome. Pain. 2010;148:454–61.PubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.
    Mayer EA, Gebhart GF. Basic and clinical aspects of visceral hyperalgesia. Gastroenterology. 1994;107:271–93.PubMedGoogle Scholar
  9. 9.
    Dupont AW. Post-infectious irritable bowel syndrome. Curr Gastroenterol Rep. 2007;9:378–84.PubMedCrossRefGoogle Scholar
  10. 10.
    Mertz H, Morgan V, Tanner G, et al. Regional cerebral activation in irritable bowel syndrome and control subjects with painful and nonpainful rectal distention. Gastroenterology. 2000;118:842–8.PubMedCrossRefGoogle Scholar
  11. 11.
    Hobday DI, Aziz Q, Thacker N, et al. A study of the cortical processing of ano-rectal sensation using functional MRI. Brain. 2001;124:361–8.PubMedCrossRefGoogle Scholar
  12. 12.
    Ladabaum U, Minoshima S, Hasler WL, Cross D, et al. Gastric distention correlates with activation of multiple cortical and subcortical regions. Gastroenterology. 2001;120:369–76.PubMedCrossRefGoogle Scholar
  13. 13.
    Hansen MB. The enteric nervous system I: the organization and classification. Pharmacol Toxicol. 2003;92:105–13.PubMedCrossRefGoogle Scholar
  14. 14.
    Furness JB. Types of neurons in the enteric nervous system. J Auton Nerv Syst. 2000;81:87–96.PubMedCrossRefGoogle Scholar
  15. 15.
    Langley JN. The autonomic nervous system, part 1. Cambridge: W. Heffer; 1921.Google Scholar
  16. 16.
    Hansen MD. Neurohumoral control of gastrointestinal motility. Physiol Res. 2003;52(1):1–30.PubMedGoogle Scholar
  17. 17.
    Hansen MB. The enteric nervous system II: gastrointestinal functions. Pharmacol Toxicol. 2003;92:249–57.PubMedCrossRefGoogle Scholar
  18. 18.
    Aziz Q, Thompson DG. Brain-gut axis in health and disease. Gastroenterology. 1998;114:559–78.PubMedCrossRefGoogle Scholar
  19. 19.
    Gaman A, Kuo B. Neuromodulatory processes of the brain-gut axis. Neuromodulation. 2009;11(4):249–59.CrossRefGoogle Scholar
  20. 20.
    Mayer EA. The neurobiology of stress and gastrointestinal disease. Gut. 2000;47:861–9.PubMedCentralPubMedCrossRefGoogle Scholar
  21. 21.
    Straub RH, Herfarth H, Falk W, et al. Uncoupling of the sympathetic nervous system and the hypothalamic–pituitary–adrenal axis in inflammatory bowel disease? J Neuroimmunol. 2002;126:116–25.PubMedCrossRefGoogle Scholar
  22. 22.
    Drossman DA. The functional gastrointestinal disorders and the Rome III process. Gastroenterology. 2006;130:1377–90.PubMedCrossRefGoogle Scholar
  23. 23.
    Thijssen AY, Jonkers DM, Leue C, et al. Dysfunctional cognitions, anxiety and depression in irritable bowel syndrome. J Clin Gastroenterol. 2010;44:e236–41.PubMedCrossRefGoogle Scholar
  24. 24.
    Delvaux M, Denis P, Allemand H. Sexual abuse is more frequently reported by IBS patients than by patients with organic digestive diseases or controls. Results of a multicentre inquiry. French club of digestive motility. Eur J Gastroenterol Hepatol. 1997;9:345–52.PubMedCrossRefGoogle Scholar
  25. 25.
    Drossman DA, Leserman J, Nachman G, et al. Sexual and physical abuse in women with functional or organic gastrointestinal disorders. Ann Intern Med. 1990;113:828–33.PubMedCrossRefGoogle Scholar
  26. 26.
    Ren TH, Wu J, Yew D, 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 Physiol. 2007;292:G849–56.PubMedCrossRefGoogle Scholar
  27. 27.
    Fukudo S, Kanazawa M, Kano M, et al. Exaggerated motility of the descending colon with repetitive distention of the sigmoid colon in patients with irritable bowel syndrome. J Gastroenterol. 2002;37:145–50.PubMedCrossRefGoogle Scholar
  28. 28.
    Bennett EJ, Tennant CC, Piesse C, Badcock CA, Kellow JE. Level of chronic life stress predicts clinical outcome in irritable bowel syndrome. Gut. 1998;43:256–61.PubMedCentralPubMedCrossRefGoogle Scholar
  29. 29.
    Sternberg EM, Chrousos GP, Wilder RL, Gold PW. The stress response and the regulation of inflammatory disease. Ann Intern Med. 1992;117:854–66.PubMedCrossRefGoogle Scholar
  30. 30.
    Sajdyk TJ, Shekhar A, Gehlert DR. Interactions between NPY and CRF in the amygdala to regulate emotionality. Neuropeptides. 2004;38:225–34.PubMedCrossRefGoogle Scholar
  31. 31.
    Swanson LW, Sawchenko PE, Rivier J, Vale WW. Organization of ovine corticotropin-releasing factor immunoreactive cells and fibers in the rat brain: an immunohistochemical study. Neuroendocrinology. 1983;36:165–86.PubMedCrossRefGoogle Scholar
  32. 32.
    Creed F. The relationship between psychosocial parameters and outcome in the irritable bowel syndrome. Am J Med. 1999;107:74–80.CrossRefGoogle Scholar
  33. 33.
    Gwee KA, Leong YL, Graham C, et al. The role of psychological and biological factors in postinfective gut dysfunction. Gut. 1999;44:400–6.PubMedCentralPubMedCrossRefGoogle Scholar
  34. 34.
    Aggarwal A, Cutts TF, et al. Predominant symptoms in irritable bowel syndrome correlate with specific autonomic nervous system abnormalities. Gastroenterology. 1994;106:945–50.PubMedGoogle Scholar
  35. 35.
    Heitkemper M, Jarret M, Cain KC, et al. Autonomic nervous system in women with irritable bowel syndrome. Dig Dis Sci. 2001;46:1276–84.PubMedCrossRefGoogle Scholar
  36. 36.
    Dunn AJ, Berridge CW. Physiological and behavioral responses to corticotropin-releasing factor administration: is CRF a mediator of anxiety or stress responses? Brain Res Rev. 1990;15:71–100.PubMedCrossRefGoogle Scholar
  37. 37.
    Taché Y, Kiank C, Stengel A. A role for corticotropin-releasing factor in functional gastrointestinal disorders. Curr Gastroenterol Rep. 2009;11:270–7.PubMedCrossRefGoogle Scholar
  38. 38.
    Million M, Grigoriadis DE, Sullivan S, et al. A novel watersoluble selective CRF1 receptor antagonist, NBI 35965, blunts stressinduced visceral hyperalgesia and colonic motor function in rats. Brain Res. 2003;985:32–42.PubMedCrossRefGoogle Scholar
  39. 39.
    Trimble N, Johnson AC, Foster A, Greenwood-van Meerveld B. Corticotropin-releasing factor receptor 1-deficient mice show decreased anxiety and colonic sensitivity. Neurogastroenterol Motil. 2007;19:754–60.PubMedCrossRefGoogle Scholar
  40. 40.
    Lembo T, Plourde V, Shui Z, et al. Effects of the corticotropin-releasing factor (CRF) on rectal afferent nerves in humans. Neurogastroenterol Motil. 1996;8:9–18.PubMedCrossRefGoogle Scholar
  41. 41.
    Sagami Y, Shimada Y, Tayama J, et al. Effect of a corticotropin releasing hormone receptor antagonist on colonic sensory and motor function in patients with irritable bowel syndrome. Gut. 2004;53:958–64.PubMedCentralPubMedCrossRefGoogle Scholar
  42. 42.
    Hubbard CS, Labus JS, Bueller J, et al. Corticotropin-releasing factor receptor 1 antagonist alters regional activation and effective connectivity in an emotional–arousal circuit during expectation of abdominal pain. J Neurosci. 2011;31(35):12491–500.PubMedCentralPubMedCrossRefGoogle Scholar
  43. 43.
    Dukes GE, Mayer EA, Kelleher DL, et al. A randomised, double blind, placebo (PLA) controlled, crossover study to evaluate the efficacy and safety of the corticotrophin releasing factor 1 (CRF1) receptor antagonist (RA) GW876008 in irritable bowel syndrome (IBS) patients. Neurogastroenterol Motil. 2009;21:84. Suppl.Google Scholar
  44. 44.
    Thoua NM, Hobson AR, Dukes GE, et al. The selective CRF-1 receptor antagonist GW876008 attenuates stress induced rectal hypersensitivity in patients with irritable bowel syndrome (IBS). Neurogastroenterol Motil. 2009;21:85. Suppl.CrossRefGoogle Scholar
  45. 45.
    Drossman DA, Li Z, Andruzzi E, Temple R, et al. U.S. Householder survey of functional gastrointestinal disorders. Prevalence, sociodemography and health impact. Dig Dis Sci. 1993;38:1569–80.PubMedCrossRefGoogle Scholar
  46. 46.
    Camilleri M. Management of the irritable bowel syndrome. Gastroenterology. 2001;120:652–68.PubMedCrossRefGoogle Scholar
  47. 47.
    Viramontes BE, Camilleri M, McKinzie, et al. Gender-related differences in slowing colonic transit by a 5-HT3 antagonist in subjects with diarrhea-predominant irritable bowel syndrome. Am J Gastroenterol. 2001;96:2671–9.PubMedCrossRefGoogle Scholar
  48. 48.
    Talley NJ. Serotoninergic neuroenteric modulators. Lancet. 2001;358:2061–8.PubMedCrossRefGoogle Scholar
  49. 49.
    Nakai A, Kumakura K, Boivin M, et al. Sex differences of brain serotonin synthesis in patients with irritable bowel syndrome using α [11C] methyl-L-tryptophan, positron emission tomography and statistical parametric mapping. Can J Gastroenterol. 2003;17(3):191–6.PubMedGoogle Scholar
  50. 50.
    Naliboff BD, Berman S, Chang L, et al. Sex-related differences in IBS patients: central processing of visceral stimuli. Gastroenterology. 2003;124:1738–47.PubMedCrossRefGoogle Scholar
  51. 51.
    Labus JS, Naliboff BN, Fallon J, et al. Sex differences in brain activity during aversive visceral stimulation and its expectation in patients with chronic abdominal pain: a network analysis. NeuroImage. 2008;41:1032–43.PubMedCentralPubMedCrossRefGoogle Scholar
  52. 52.
    Jiang Z, Dinov ID, Labus J, et al. Sex-related differences of cortical thickness in patients with chronic abdominal pain) and correlate with symptom severity in IBS female patients. PLoS ONE. 2013;8(9):e73932.PubMedCentralPubMedCrossRefGoogle Scholar
  53. 53.
    Dekel R, Drossman DA, Sperber AD. The use of psychotropic drugs in irritable bowel syndrome. Expert Opin Investig Drugs. 2013;22(3):329–39.PubMedCrossRefGoogle Scholar
  54. 54.
    Labus JS, Mayer EA, Jarcho J, et al. Acute tryptophan depletion alters the effective connectivity of emotional arousal circuitry during visceral stimuli in healthy women. Gut. 2011;60(9):1196–203.PubMedCrossRefGoogle Scholar
  55. 55.
    Morgan P, Pickens D, Gautam S, et al. Amitriptyline reduces rectal pain related activation of the anterior cingulate cortex in patients with irritable bowel syndrome. Gut. 2005;54:601–7.PubMedCentralPubMedCrossRefGoogle Scholar
  56. 56.
    Tillisch K, Labus J, Nam B, et al. Neurokinin-1-receptor antagonism decreases anxiety and emotional arousal circuit response to noxious visceral distension in women with irritable bowel syndrome: a pilot study. Aliment Pharmacol Ther. 2012;35(3):360–7.PubMedCrossRefGoogle Scholar
  57. 57.
    Silverman DH, Munakata JA, Ennes H, et al. Regional cerebral activity in normal and pathological perception of visceral pain. Gastroenterology. 1997;112:64–72.PubMedCrossRefGoogle Scholar
  58. 58.
    Drossman DA, Ringel Y, Vogt BA, et al. Alterations of brain activity associated with resolution of emotional distress and pain in a case of severe irritable bowel syndrome. Gastroenterology. 2003;124:754–61.PubMedCrossRefGoogle Scholar
  59. 59.•
    Keszthelyi D, Troost FJ, Masclee AA. Irritable bowel syndrome: methods, mechanisms, and pathophysiology. Methods to assess visceral hypersensitivity in irritable bowel syndrome. Am J Physiol Gastrointest Liver Physiol. 2012;303:G141–54. This metaanalysis points out the relevance of the several ways of studying patients with IBS accordingly to its pathophysiology, more specifically in regards to visceral hypersensitivity.PubMedCrossRefGoogle Scholar
  60. 60.
    Ammons WS, Girardot MN, Foreman RD. T2-T5 spinothalamic neurons projecting to medial thalamus with viscerosomatic input. J Neurophysiol. 1985;54:73–89.PubMedGoogle Scholar
  61. 61.•
    Tillisch K, Mayer EA, Labus JS. Quantitative meta-analysis identifies brain regions activated during rectal distension in irritable bowel syndrome. Gastroenterology. 2011;140:91–100. In this meta-analysis, the authors review the different areas that have been reported to be activated or inhibited in IBS patients. IBS have greater engagement of regions associated with emotional arousal and endogenous pain modulation when compared to controls.PubMedCentralPubMedCrossRefGoogle Scholar
  62. 62.••
    Larsson MB, Tillisch K, Craig AD, et al. Brain responses to visceral stimuli reflect visceral sensitivity thresholds in patients with irritable bowel syndrome. Gastroenterology. 2012;142:463–72. In this study, 44 IBS female patients were compared with 20 healthy age-paired women. They found that hyper- and normosensitive patients with IBS differ in cerebral responses to rectal distensions, consistent with differences in ascending visceral afferent input.PubMedCentralPubMedCrossRefGoogle Scholar
  63. 63.
    Arebi N, Bullas DC, Dukes GE, et al. Distinct neurophysiological profiles in irritable bowel syndrome. Am J Physiol Gastrointest Liver Physiol. 2011;300:G1086–93. By using cortical-evoked potentials, this authors showed four different neurophysiological patterns in IBS patients.PubMedCrossRefGoogle Scholar
  64. 64.
    Chan YK, Herkes GK, Badcock C, et al. Alterations in cerebral potentials evoked by rectal distension in irritable bowel syndrome. Am J Gastroenterol. 2001;96:2413–7.PubMedCrossRefGoogle Scholar
  65. 65.
    Loening-Baucke V, Read NW, Yamada T. Cerebral evoked potentials after rectal stimulation. Electroencephalogr Clin Neurophysiol. 1991;80:490–5.PubMedCrossRefGoogle Scholar
  66. 66.
    Sinhamahapatra P, Saha SP, Chowdhury A, et al. Visceral afferent hypersensitivity in irritable bowel syndrome evaluation by cerebral evoked potential after rectal stimulation. Am J Gastroenterol. 2001;96:2150–7.PubMedGoogle Scholar
  67. 67.
    Zuo XL, Li YQ, Huang KM, et al. Alterations in cerebral potentials evoked by rectal distention and drinking ice water in patients with irritable bowel syndrome. J Gastroenterol Hepatol. 2006;21:1844–9.PubMedCrossRefGoogle Scholar
  68. 68.•
    Remes-Troche JM, Tantiphlachiva K, Attaluri A, Rao SS, et al. A bi-directional assessment of the human brain-anorectal axis. Neurogastroenterol Motil. 2011;23:240–8. This study provides evidence about the feasibility, reproducibility and normal values for bi-directional assessment of brain–gut axis in healthy subjects. Assessment of the afferent pathway was performed with cortical-evoked potentials and motor-evoked potentials for the efferent pathway using transcranial and translumbosacral magnetic stimulation.PubMedCentralPubMedCrossRefGoogle Scholar
  69. 69.
    Coss-Adame E, Valestin J, Bradley C, et al. Investigation of the afferent anorectal-brain neuromuscular axis in irritable bowel syndrome (IBS) and interstitial cystitis (IC). Neurogastroenterol Motil. 2012;24 Suppl 2:24.Google Scholar
  70. 70.
    Coss-Adame E, Valestin J, Bradley C, et al. Investigation of the efferent spinofugal axis by translumbar and trans-sacral magnetic stimulation in irritable bowel syndrome (IBS) and interstitial cystitis (IC). Neurogastroenterol Motil. 2012;24 Suppl 2:175.Google Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Section of Gastroenterology and Hepatology, Medical College of GeorgiaGeorgia Regents UniversityAugustaUSA
  2. 2.Section of Neurogastroenterology and MotilityAugustaUSA
  3. 3.Department of Gastroenterology, Neurgastroenterology and MotilityInstituto Nacional de Ciencias Médicas y Nutrición “Salvador Zubirán”México CityMéxico

Personalised recommendations