Mechanisms of disease: Peripheral mechanisms in irritable bowel syndrome

New England Journal of Medicine

Volumn 367, Issue 17, 2012, Pages 1626-1635

  Camilleri, Michael ^a  

^a Clinical Enteric Neuroscience Translational and Epidemiological Research Mayo Clinic   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIBIOTIC AGENT; ANTIINFLAMMATORY AGENT; BILE ACID; BILE ACID SEQUESTRANT; CARBOXYLIC ACID; CYTOKINE; LARAZOTIDE; LINACLOTIDE; LUBIPROSTONE; NEUROTRANSMITTER; PROBIOTIC AGENT; PROKINETIC AGENT; SEROTONIN 3 ANTAGONIST; TEGASEROD;

ABDOMINAL DISCOMFORT; ABDOMINAL PAIN; BILE ACID SYNTHESIS; CELIAC DISEASE; CONSTIPATION; DIARRHEA; DIGESTIVE SYSTEM FUNCTION DISORDER; DISEASE PREDISPOSITION; ENTEROENDOCRINE CELL; FECES MICROFLORA; GASTROINTESTINAL IRRITATION; GENE MUTATION; GENETIC VARIABILITY; HEREDITY; HUMAN; INFLAMMATION; INTESTINAL DYSMOTILITY; INTESTINE MUCOSA; IRRITABLE COLON; MALABSORPTION; MOTOR DYSFUNCTION; PATHOPHYSIOLOGY; PRIORITY JOURNAL; REVIEW; SENSORY DYSFUNCTION; SIGNAL TRANSDUCTION; SYMPTOM; GASTROINTESTINAL MOTILITY; GASTROINTESTINAL TRANSIT; INTESTINE; METAGENOME; MICROBIOLOGY; PERMEABILITY; PHYSIOLOGY;

GASTROINTESTINAL MOTILITY; GASTROINTESTINAL TRANSIT; HUMANS; INTESTINES; IRRITABLE BOWEL SYNDROME; METAGENOME; PERMEABILITY;

EID: 84867828617     PISSN: 00284793     EISSN: 15334406     Source Type: Journal    
DOI: 10.1056/NEJMra1207068     Document Type: Review

References (101)

1. Lynn RB, Friedman LS. Irritable bowel syndrome. N Engl J Med 1993;329:1940-5. [Erratum, N Engl J Med 1994;330:228.]
2. Horwitz BJ, Fisher RS. The irritable bowel syndrome. N Engl J Med 2001;344:1846-50.
3. Mayer EA. Irritable bowel syndrome. N Engl J Med 2008;358:1692-9.
4. Barbara G, Cremon C, De Giorgio R, et al. Mechanisms underlying visceral hypersensitivity in irritable bowel syndrome. Curr Gastroenterol Rep 2011;13:308-15.
5. Camilleri M, McKinzie S, Busciglio I, et al. Prospective study of motor, sensory, psychologic, and autonomic functions in patients with irritable bowel syndrome. Clin Gastroenterol Hepatol 2008;6:772-81.
6. 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.
7. Zhou Q, Verne GN. New insights into visceral hypersensitivity - clinical implications in IBS. Nat Rev Gastroenterol Hepatol 2011;8:349-55.
8. Halder SL, Locke GR III, Schleck CD, Zinsmeister AR, Melton LJ III, Talley NJ. Natural history of functional gastrointestinal disorders: a 12-year longitudinal population-based study. Gastroenterology 2007;133:799-807.
9. Bouchoucha M, Devroede G, Dorval E, Faye A, Arhan P, Arsac M. Different segmental transit times in patients with irritable bowel syndrome and "normal" colonic transit time: is there a correlation with symptoms? Tech Coloproctol 2006;10:287-96. [Erratum, Tech Coloproctol 2009;13:103.]
10. Törnblom H, Van Oudenhove L, Sadik R, Abrahamsson H, Tack J, Simrén M. Colonic transit time and IBS symptoms: what's the link? Am J Gastroenterol 2012;107:754-60.
11. Camilleri M. Pharmacology of the new treatments for lower gastrointestinal motility disorders and irritable bowel syndrome. Clin Pharmacol Ther 2012;91:44-59.
12. Prott G, Shim L, Hansen R, Kellow J, Malcolm A. Relationships between pelvic floor symptoms and function in irritable bowel syndrome. Neurogastroenterol Motil 2010;22:764-9.
13. Chiarioni G, Salandini L, Whitehead WE. Biofeedback benefits only patients with outlet dysfunction, not patients with isolated slow transit constipation. Gastroenterology 2005;129:86-97.
14. Voderholzer WA, Schatke W, Mühldorfer BE, Klauser AG, Birkner B, Müller-Lissner SA. Clinical response to dietary fiber treatment of chronic constipation. Am J Gastroenterol 1997;92:95-8.
15. Spiller R, Camilleri M, Longstreth GF. Do the symptom-based, Rome criteria of irritable bowel syndrome lead to better diagnosis and treatment outcomes? Clin Gastroenterol Hepatol 2010;8:125-9.
16. Ragnarsson G, Bodemar G. Pain is temporally related to eating but not to defaecation in the irritable bowel syndrome (IBS): patients' description of diarrhea, constipation and symptom variation during a prospective 6-week study. Eur J Gastroenterol Hepatol 1998;10:415-21.
17. Chey WY, Jin HO, Lee MH, Sun SW, Lee KY. Colonic motility abnormality in patients with irritable bowel syndrome exhibiting abdominal pain and diarrhea. Am J Gastroenterol 2001;96:1499-506.
18. Deiteren A, Camilleri M, Burton D, McKinzie S, Rao A, Zinsmeister AR. Effect of meal ingestion on ileocolonic and colonic transit in health and irritable bowel syndrome. Dig Dis Sci 2010;55:384-91.
19. Ludidi S, Conchillo JM, Keszthelyi D, et al. Does meal ingestion enhance sensitivity of visceroperception assessment in irritable bowel syndrome? Neurogastroenterol Motil 2012;24:47-53.
20. Simrén M, Agerforz P, Björnsson ES, Abrahamsson H. Nutrient-dependent enhancement of rectal sensitivity in irritable bowel syndrome (IBS). Neurogastroenterol Motil 2007;19:20-9.
21. Farup PG, Monsbakken KW, Vandvik PO. Lactose malabsorption in a population with irritable bowel syndrome: prevalence and symptoms: a case-control study. Scand J Gastroenterol 2004;39:645-9.
22. Rumessen JJ, Gudmand-Høyer E. Functional bowel disease: malabsorption and abdominal distress after ingestion of fructose, sorbitol, and fructose-sorbitol mixtures. Gastroenterology 1988;95:694-700.
23. Nelis GF, Vermeeren MA, Jansen W. Role of fructose-sorbitol malabsorption in the irritable bowel syndrome. Gastroenterology 1990;99:1016-20.
24. Treem WR, Ahsan N, Kastoff G, Hyams JS. Fecal short-chain fatty acids in patients with diarrhea-predominant irritable bowel syndrome: in vitro studies of carbohydrate fermentation. J Pediatr Gastroenterol Nutr 1996;23:280-6.
25. Stephen AM, Haddad AC, Phillips SF. Passage of carbohydrate into the colon: direct measurements in humans. Gastroenterology 1983;85:589-95.
26. Karaki S, Mitsui R, Hayashi H, et al. Short-chain fatty acid receptor, GPR43, is expressed by enteroendocrine cells and mucosal mast cells in rat intestine. Cell Tissue Res 2006;324:353-60.
27. Fukumoto S, Tatewaki M, Yamada T, et al. Short-chain fatty acids stimulate colonic transit via intraluminal 5-HT release in rats. Am J Physiol Regul Integr Comp Physiol 2003;284:R1269-R1276.
28. Mitsui R, Ono S, Karaki S, Kuwahara A. Neural and non-neural mediation of propionate-induced contractile responses in the rat distal colon. Neurogastroenterol Motil 2005;17:585-94.
29. Kamath PS, Hoepfner MT, Phillips SF. Short-chain fatty acids stimulate motility of the canine ileum. Am J Physiol 1987;253:G427-G433.
30. Karaki S, Kuwahara A. Propionateinduced epithelial K(+) and Cl(-)/HCO3(-) secretion and free fatty acid receptor 2 (FFA2, GPR43) expression in the guinea pig distal colon. Pflugers Arch 2011;461:141-52.
31. Shepherd SJ, Parker FC, Muir JG, Gibson PR. Dietary triggers of abdominal symptoms in patients with irritable bowel syndrome: randomized, placebo-controlled evidence. Clin Gastroenterol Hepatol 2008;6:765-71.
32. Ong DK, Mitchell SB, Barrett JS, et al. Manipulation of dietary short chain carbohydrates alters the pattern of gas production and genesis of symptoms in irritable bowel syndrome. J Gastroenterol Hepatol 2010;25:1366-73.
33. Cash BD, Rubenstein JH, Young PE, et al. The prevalence of celiac disease among patients with nonconstipated irritable bowel syndrome is similar to controls. Gastroenterology 2011;141:1187-93.
34. Wahnschaffe U, Schulzke JD, Zeitz M, Ullrich R. Predictors of clinical response to gluten-free diet in patients diagnosed with diarrhea-predominant irritable bowel syndrome. Clin Gastroenterol Hepatol 2007;5:844-50.
35. Biesiekierski JR, Newnham ED, Irving PM, et al. Gluten causes gastrointestinal symptoms in subjects without celiac disease: a double-blind randomized placebocontrolled trial. Am J Gastroenterol 2011;106:508-14.
36. Verdu EF, Huang X, Natividad J, et al. Gliadin-dependent neuromuscular and epithelial secretory responses in glutensensitive HLA-DQ8 transgenic mice. Am J Physiol Gastrointest Liver Physiol 2008;294:G217-G225.
37. Camilleri M, Vazquez-Roque M, Carlson P, et al. Randomized trial of glutenfree diet in IBS-diarrhea: effect on small bowel and colonic morphology and barrier function. Neurogastroenterol Motil 2012;24:23. abstract.
38. Oddsson E, Rask-Madsen J, Krag E. A secretory epithelium of the small intestine with increased sensitivity to bile acids in irritable bowel syndrome associated with diarrhoea. Scand J Gastroenterol 1978;13:409-41.
39. Wedlake L, A'Hern R, Russell D, Thomas K, Walters JR, Andreyev HJ. Systematic review: the prevalence of idiopathic bile acid malabsorption as diagnosed by SeHCAT scanning in patients with diarrhoea-predominant irritable bowel syndrome. Aliment Pharmacol Ther 2009;30:707-17.
40. Camilleri M, Nadeau A, Tremaine WJ, 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 Motil 2009;21(7):e734-e743.
41. Wong BS, Camilleri M, Carlson P, et al. Increased bile acid biosynthesis is associated with irritable bowel syndrome with diarrhea. Clin Gastroenterol Hepatol 2012;10:1009-15.
42. Johnston I, Nolan J, Pattni SS, Walters JR. New insights into bile acid malabsorption. Curr Gastroenterol Rep 2011;13:418-25.
43. Walters JR, Tasleem AM, Omer OS, Brydon WG, Dew T, le Roux CW. A new mechanism for bile acid diarrhea: defective feedback inhibition of bile acid biosynthesis. Clin Gastroenterol Hepatol 2009;7:1189-94.
44. Odunsi-Shiyanbade ST, Camilleri M, McKinzie S, et al. Effects of chenodeoxycholate and a bile acid sequestrant, colesevelam, on intestinal transit and bowel function. Clin Gastroenterol Hepatol 2010;8:159-65.
45. Rao AS, Wong BS, Camilleri M, et al. Chenodeoxycholate in females with irritable bowel syndrome-constipation: a pharmacodynamic and pharmacogenetic analysis. Gastroenterology 2010;139:1549-58.
46. Montagnani M, Love MW, Rössel P, Dawson PA, Qvist P. Absence of dysfunctional ileal sodium-bile acid cotransporter gene mutations in patients with adult-onset idiopathic bile acid malabsorption. Scand J Gastroenterol 2001;36:1077-80.
47. Montagnani M, Abrahamsson A, Gälman C, et al. Analysis of ileal sodium/bile acid cotransporter and related nuclear receptor genes in a family with multiple cases of idiopathic bile acid malabsorption. World J Gastroenterol 2006;12: 7710-4.
48. Kassinen A, Krogius-Kurikka L, Mäkivuokko H, et al. The fecal microbiota of irritable bowel syndrome patients differs significantly from that of healthy subjects. Gastroenterology 2007;133:24-33.
49. Tana C, Umesaki Y, Imaoka A, Handa T, Kanazawa M, Fukudo S. Altered profiles of intestinal microbiota and organic acids may be the origin of symptoms in irritable bowel syndrome. Neurogastroenterol Motil 2010;22:512-9.
50. Rajilić-Stojanović M, Biagi E, Heilig HG, et al. Global and deep molecular analysis of microbiota signatures in fecal samples from patients with irritable bowel syndrome. Gastroenterology 2011;141:1792-801.
51. Salonen A, de Vos WM, Palva A. Gastrointestinal microbiota in irritable bowel syndrome: present state and perspectives. Microbiology 2010;156:3205-15.
52. Jeffery IB, O'Toole PW, Öhman L, et al. An irritable bowel syndrome subtype defined by species-specific alterations in faecal microbiota. Gut 2012;61:997-1006.
53. Parkes GC, Rayment NB, Hudspith BN, et al. Distinct microbial populations exist in the mucosa-associated microbiota of sub-groups of irritable bowel syndrome. Neurogastroenterol Motil 2012;24:31-9.
54. Pimentel M, Lembo A, Chey WD, et al. Rifaximin therapy for patients with irritable bowel syndrome without constipation. N Engl J Med 2011;364:22-32.
55. Moayyedi P, Ford AC, Talley NJ, et al. The efficacy of probiotics in the treatment of irritable bowel syndrome: a systematic review. Gut 2010;59:325-32.
56. Kim HJ, Camilleri M, McKinzie S, et al. A randomized, controlled trial of a probiotic, VSL#3, on gut transit and symptoms in diarrhea-predominant irritable bowel syndrome. Aliment Pharmacol Ther 2003;17:895-904.
57. Duboc H, Rainteau D, Rajca S, et al. Increase in fecal primary bile acids and dysbiosis in patients with diarrhea-predominant irritable bowel syndrome. Neurogastroenterol Motil 2012;24:513-20.
58. Chadwick VS, Gaginella TS, Carlson GL, Debongnie JC, Phillips SF, Hofmann AF. Effect of molecular structure on bile acid-induced alterations in absorptive function, permeability, and morphology in the perfused rabbit colon. J Lab Clin Med 1979;94:661-74.
59. Keely SJ, Scharl MM, Bertelsen LS, Hagey LR, Barrett KE, Hofmann AF. Bile acid-induced secretion in polarized monolayers of T84 colonic epithelial cells: structure-activity relationships. Am J Physiol Gastrointest Liver Physiol 2007;292:G290-G297.
60. Bampton PA, Dinning PG, Kennedy ML, Lubowski DZ, Cook IJ. The proximal colonic motor response to rectal mechanical and chemical stimulation. Am J Physiol Gastrointest Liver Physiol 2002;282:G443-G449.
61. Traub RJ, Tang B, Ji Y, Pandya S, Yfantis H, Sun Y. A rat model of chronic postinflammatory visceral pain induced by deoxycholic acid. Gastroenterology 2008;135:2075-83.
62. Islam KB, Fukiya S, Hagio M, et al. Bile acid is a host factor that regulates the composition of the cecal microbiota in rats. Gastroenterology 2011;141:1773-81.
63. Kidd M, Modlin IM, Gustafsson BI, Drozdov I, Hauso O, Pfragner R. Luminal regulation of normal and neoplastic human EC cell serotonin release is mediated by bile salts, amines, tastants, and olfactants. Am J Physiol Gastrointest Liver Physiol 2008;295:G260-G272.
64. Peregrin AT, Ahlman H, Jodal M, Lundgren O. Involvement of serotonin and calcium channels in the intestinal fluid secretion evoked by bile salt and cholera toxin. Br J Pharmacol 1999;127:887-94.
65. Gershon MD, Tack J. The serotonin signaling system: from basic understanding to drug development for functional GI disorders. Gastroenterology 2007;132:397-414.
66. Hoffman JM, Tyler K, MacEachern SJ, et al. Activation of colonic mucosal 5-HT(4) receptors accelerates propulsive motility and inhibits visceral hypersensitivity. Gastroenterology 2012;142:844-54.
67. Montero-Hadjadje M, Elias S, Chevalier L, et al. Chromogranin A promotes peptide hormone sorting to mobile granules in constitutively and regulated secreting cells: role of conserved N- and C-terminal peptides. J Biol Chem 2009;284:12420-31.
68. Shooshtarizadeh P, Zhang D, Chich JF, et al. The antimicrobial peptides derived from chromogranin/secretogranin family, new actors of innate immunity. Regul Pept 2010;165:102-10.
69. Öhman L, Stridsberg M, Isaksson S, Jerlstad P, Simrén M. Altered levels of fecal chromogranins and secretogranins in IBS: relevance for pathophysiology and symptoms? Am J Gastroenterol 2012;107:440-7.
70. El-Salhy M, Lomholt-Beck B, Gundersen TD. High chromogranin A cell density in the colon of patients with lymphocytic colitis. Mol Med Report 2011;4:603-5.
71. Moyana TN, Shukoor S. Gastrointestinal endocrine cell hyperplasia in celiac disease: a selective proliferative process of serotonergic cells. Mod Pathol 1991;4:419-23.
72. Pietroletti R, Bishop AE, Carlei F, et al. Gut endocrine cell population in coeliac disease estimated by immunocytochemistry using a monoclonal antibody to chromogranin. Gut 1986;27:838-43.
73. Iacangelo AL, Eiden LE. Chromogranin A: current status as a precursor for bioactive peptides and a granulogenic/ sorting factor in the regulated secretory pathway. Regul Pept 1995;58:65-88.
74. Camilleri M. Editorial: fecal granins in IBS: cause or indicator of intestinal or colonic irritation? Am J Gastroenterol 2012;107:448-50.
75. Öhman L, Simrén M. Pathogenesis of IBS: role of inflammation, immunity and neuroimmune interactions. Nat Rev Gastroenterol Hepatol 2010;7:163-73.
76. Spiller RC, Jenkins D, Thornley JP, et al. Increased rectal mucosal enteroendocrine cells, T lymphocytes, and increased gut permeability following acute Campylobacter enteritis and in post-dysenteric irritable bowel syndrome. Gut 2000;47:804-11.
77. Halvorson HA, Schlett CD, Riddle MS. Postinfectious irritable bowel syndrome - a meta-analysis. Am J Gastroenterol 2006;101:1894-9.
78. Spiller R, Garsed K. Postinfectious irritable bowel syndrome. Gastroenterology 2009;136:1979-88.
79. Aerssens J, Camilleri M, Talloen W, et al. Alterations in mucosal immunity identified in the colon of patients with irritable bowel syndrome. Clin Gastroenterol Hepatol 2008;6:194-205.
80. Rao AS, Camilleri M, Eckert DJ, et al. Urine sugars for in vivo gut permeability: validation and comparisons in irritable bowel syndrome-diarrhea and controls. Am J Physiol Gastrointest Liver Physiol 2011;301:G919-G928.
81. Shulman RJ, Eakin MN, Czyzewski DI, Jarrett M, Ou CN. Increased gastrointestinal permeability and gut inflammation in children with functional abdominal pain and irritable bowel syndrome. J Pediatr 2008;153:646-50.
82. Saps M, Pensabene L, Di Martino L, et al. Post-infectious functional gastrointestinal disorders in children. J Pediatr 2008;152:812-6.
83. Saps M, Lu P, Bonilla S. Cow's-milk allergy is a risk factor for the development of FGIDs in children. J Pediatr Gastroenterol Nutr 2011;52:166-9.
84. Lillestøl K, Helgeland L, Arslan Lied G, et al. Indications of 'atopic bowel' in patients with self-reported food hypersensitivity. Aliment Pharmacol Ther 2010;31:1112-22.
85. Wallon C, Yang PC, Keita AV, et al. Corticotropin-releasing hormone (CRH) regulates macromolecular permeability via mast cells in normal human colonic biopsies in vitro. Gut 2008;57:50-8.
86. Alonso C, Guilarte M, Vicario M, et al. Acute experimental stress evokes a differential gender-determined increase in human intestinal macromolecular permeability. Neurogastroenterol Motil 2012;24:740-6.
87. Pendyala S, Walker JM, Holt PR. A high-fat diet is associated with endotoxemia that originates from the gut. Gastroenterology 2012;142:1100-1.
88. Laugerette F, Vors C, Géloën A, et al. Emulsified lipids increase endotoxemia: possible role in early postprandial lowgrade inflammation. J Nutr Biochem 2011;22:53-9.
89. Camilleri M, Katzka DA. Genetic epidemiology and pharmacogenetics in irritable bowel syndrome. Am J Physiol 2012;302:G1075-G1084.
90. Zucchelli M, Camilleri M, Andreasson AN, et al. Association of TNFSF15 polymorphism with irritable bowel syndrome. Gut 2011;60:1671-7.
91. Swan C, Duroudier NP, Campbell E, et al. Identifying and testing candidate genetic polymorphisms in the irritable bowel syndrome (IBS): association with TNFSF15 and TNFα. Gut 2012 June 8 (Epub ahead of print).
92. Villani AC, Lemire M, Thabane M, et al. Genetic risk factors for post-infectious irritable bowel syndrome following a waterborne outbreak of gastroenteritis. Gastroenterology 2010;138:1502-13.
93. Camilleri M, Carlson P, McKinzie S, et al. Genetic susceptibility to inflammation and colonic transit in lower functional gastrointestinal disorders: preliminary analysis. Neurogastroenterol Motil 2011;23:935-43.
94. Wong BS, Camilleri M, Carlson PJ, et al. A Klothoß variant mediates protein stability and associates with colon transit in irritable bowel syndrome with diarrhea. Gastroenterology 2011;140:1934-42.
95. Camilleri M, Vazquez-Roque MI, Carlson P, Burton D, Wong BS, Zinsmeister AR. Association of bile acid receptor TGR5 variation and transit in health and lower functional gastrointestinal disorders. Neurogastroenterol Motil 2011;23:995-9.
96. Camilleri M, Carlson P, Zinsmeister AR, et al. Neuropeptide S receptor induces neuropeptide expression and associates with intermediate phenotypes of functional gastrointestinal disorders. Gastroenterology 2010;138:98-107.
97. Camilleri M, Carlson P, McKinzie S, et al. Genetic variation in endocannabinoid metabolism, gastrointestinal motility, and sensation. Am J Physiol Gastrointest Liver Physiol 2008;294:G13-G19.
98. Camilleri M, Busciglio I, Carlson P, et al. Candidate genes and sensory functions in health and irritable bowel syndrome. Am J Physiol Gastrointest Liver Physiol 2008;295:G219-G225.
99. Fukudo S, Kanazawa M, Mizuno T, et al. Impact of serotonin transporter gene polymorphism on brain activation by colorectal distention. Neuroimage 2009;47:946-51.
100. Fiskerstrand T, Arshad N, Haukanes BI, et al. Familial diarrhea syndrome caused by an activating GUCY2C mutation. N Engl J Med 2012;366:1586-95.
101. Rosenstiel P, Sina C, Franke A, Schreiber S. Towards a molecular risk map - recent advances on the etiology of inflammatory bowel disease. Semin Immunol 2009;21:334-45.