The Role of Pathogenic Microbes and Commensal Bacteria in Irritable Bowel SyndromeCollins S. · Verdu E. · Denou E. · Bercik P.
The Farncombe Family Digestive Health Institute, Faculty of Health Sciences, McMaster University, Hamilton, Ont., Canada
Do you have an account?
- Rent for 48h to view
- Buy Cloud Access for unlimited viewing via different devices
- Synchronizing in the ReadCube Cloud
- Printing and saving restrictions apply
Rental: USD 8.50
Cloud: USD 20.00
Background: Irritable bowel syndrome (IBS) reflects several pathogenetic entities including a subgroup with low-grade colonic inflammation. We propose that pathogenic bacteria act as triggers and that disturbances of commensal bacteria maintain low-grade inflammation, that in turn leads to dysfunction in the gut or brain. Methods: Studies were performed in mice under specific pathogen-free conditions. Visceral pain was assessed by the visceromotor response and motility was assessed by in vivo fluoroscopy and in vitro by muscle contractility. Brain chemistry was assessed by in situ hybridization and behavior by standard tests. The microbiota was monitored using 16s-based RT-PCR and DGGE. Results: Mice transiently infected with the nematode Trichinella spiralis exhibited changes in motility and in visceral perception that persisted for up to 6 weeks post-infection. This was accompanied by alterations in the microbiota and an upregulation of cyclooxygenase-2 which could be reversed by treatment with anti-inflammatory agents or selected probiotics. To investigate the contribution of the microbiota, we treated mice with oral antibiotics and monitored visceral perception and behavior. Antibiotic therapy produced substantial changes in the microbiota, a small increment in inflammatory activity and an increase in substance P or pain perception. Oral, but not systemic antibiotic treatment, produced changes in brain chemistry and an increase in anxiety-like behavior. Conclusion: These studies provide proof of concept that pathogenic microbes can induce persistent gut dysfunction and that changes in microbial composition of the gut can maintain gut dysfunction as well as induce behavioral changes reminiscent of the psychiatric comorbidity that occurs in up to 60% of irritable bowel syndrome patients.
© 2010 S. Karger AG, Basel
- Bentkover JD, Field C, Greene EM, Plourde V, Casciano JP: The economic burden of irritable bowel syndrome in Canada. Can J Gastroenterol 1999;13(suppl A):89A–96A.
- Boivin M: Socioeconomic impact of irritable bowel syndrome in Canada. Can J Gastroenterol 2001;15(suppl B):8B–11B.
- Hillila MT, Siivola MT, Farkkila MA: Comorbidity and use of health-care services among irritable bowel syndrome sufferers. Scand J Gastroenterol 2007;42:799–806.
- Whitehead WE, Palsson OS, Levy RR, Feld AD, Turner M, Von Korff M: Comorbidity in irritable bowel syndrome. Am J Gastroenterol 2007;102:2767–2776.
- Spiller RC: Postinfectious irritable bowel syndrome. Gastroenterology 2003;124:1662–1671.
- Marshall JK, Thabane M, Garg AX, Clark WF, Salvadori M, Collins SM: Incidence and epidemiology of irritable bowel syndrome after a large waterborne outbreak of bacterial dysentery. Gastroenterology 2006;131:445–450.
- Marchesi J, Shanahan F: The normal intestinal microbiota. Curr Opin Infect Dis 2007;20:508–513.
- Abrams GD, Bishop JE: Effect of the normal microbial flora on gastrointestinal motility. Proc Soc Exp Biol Med 1967;126:301–304.
- Vallance BA, Collins SM: The effect of nematode infection upon intestinal smooth muscle function. Parasite Immunol 1998;20:249–253.
- Barbara G, Vallance BA, Collins SM: Persistent intestinal neuromuscular dysfunction after acute nematode infection in mice. Gastroenterology 1997;113:1224–1232.
- Bercik P, Wang L, Verdu EF, Mao YK, Blennerhassett P, Khan WI, et al: Visceral hyperalgesia and intestinal dysmotility in a mouse model of postinfective gut dysfunction. Gastroenterology 2004;127:179–187.
- Verdu EF, Bercik P, Bergonzelli GE, Huang XX, Blennerhasset P, Rochat F, et al: Lactobacillus paracasei normalizes muscle hypercontractility in a murine model of postinfective gut dysfunction. Gastroenterology 2004;127:826–837.
- Husebye E, Hellstrom PM, Sundler F, Chen J, Midtvedt T: Influence of microbial species on small intestinal myoelectric activity and transit in germ-free rats. Am J Physiol Gastrointest Liver Physiol 2001;280:G368–G380.
- Scott LD, Cahall DL: Influence of the interdigestive myoelectrical complex on enteric flora in the rat. Gastroenterology 1982;82:737–745.
- Verdu EF, Bercik P, Verma-Gandhu M, Huang XX, Blennerhassett P, Jackson W, et al: Specific probiotic therapy attenuates antibiotic induced visceral hypersensitivity in mice. Gut 2006;55:182–190.
- Collins SM, Bercik P: The relationship between intestinal microbiota and the central nervous system in normal gastrointestinal function and disease. Gastroenterology 2009;136:2003–2014.
- Kassinen A, Krogius-Kurikka L, Makivuokko H, Rinttila T, Paulin L, Corander J, et al: The fecal microbiota of irritable bowel syndrome patients differs significantly from that of healthy subjects. Gastroenterology 2007;133:24–33.
- Malinen E, Rinttila T, Kajander K, Matto J, Kassinen A, Krogius L, et al: Analysis of the fecal microbiota of irritable bowel syndrome patients and healthy controls with real-time PCR. Am J Gastroenterol 2005;100:373–382.
- Maukonen J, Satokari R, Matto J, Soderlund H, Mattila-Sandholm T, Saarela M: Prevalence and temporal stability of selected clostridial groups in irritable bowel syndrome in relation to predominant faecal bacteria. J Med Microbiol 2006;55:625–633.
- Quigley EM: The efficacy of probiotics in IBS. J Clin Gastroenterol 2008;42(suppl 2):S85–S90.
- O’Mahony L, McCarthy J, Kelly P, Hurley G, Luo F, Chen K, et al: Lactobacillus and bifidobacterium in irritable bowel syndrome: symptom responses and relationship to cytokine profiles. Gastroenterology 2005;128:541–551.
Article / Publication Details
Copyright / Drug Dosage / DisclaimerCopyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.