Current Gastroenterology Reports

, Volume 14, Issue 4, pp 324–333 | Cite as

Probiotics for the Treatment of Inflammatory Bowel Disease

  • Ganesh R. Veerappan
  • John Betteridge
  • Patrick E. YoungEmail author
Gastrointestinal Infections (W Coyle, Section Editor)


Probiotics are organisms which provide a desired and beneficial effect on human health. With recent evidence implicating a disruption in the balance of the gastrointestinal microbiome and intestinal immunity as a potential trigger for inflammatory bowel disease (IBD), there has been growing interest in using probiotics as an adjunct to standard anti-inflammatory and immune suppressing therapy. Animal models describe potential and plausible mechanisms of action for probiotics to counter inflammation of colonic mucosa. Although there are insufficient data to recommend probiotics in ulcerative colitis or Crohn’s disease, good evidence supports the use of specific probiotics for maintenance of remission in pouchitis. Although there are limited regulatory standards for the agents, probiotics are relatively safe with minimal reported side effects or contraindications. More rigorous studies need to be published supporting efficacy and safety of these agents before they become a mainstay of IBD medical treatment.


Inflammatory bowel disease Probiotics Pouchitis Ulcerative colitis Crohn’s disease Efficacy Review VSL#3 Sacchromyces boullardi Pathophysiology Flora Commensal Microbiome Therapy Treatment Evidence Trials Bacteria Mechanism of action Bifidobacterium Lactobacillus Alternative therapy Recommendations Dysbiosis Studies 



No potential conflicts of interest relevant to this article were reported.

The opinions are solely those of the authors and do not represent an endorsement by the Department of Defense. This is a U.S. Government work. There are no restrictions on its use


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

  1. 1.
    Podolsky DK. Inflammatory bowel disease. N Engl J Med. 2002;347:417–29.PubMedCrossRefGoogle Scholar
  2. 2.
    Xavier RJ, Podolsky DK. Unravelling the pathogenesis of inflammatory bowel disease. Nature. 2007;448:427–34.PubMedCrossRefGoogle Scholar
  3. 3.
    Quigley EM: Prebiotics and probiotics: Their role in the management of gastrointestinal disorders in adults. Nutr Clin PractGoogle Scholar
  4. 4.
    Palmer C, Bik EM, DiGiulio DB, Relman DA, Brown PO. Development of the human infant intestinal microbiota. PLoS Biol. 2007;5:e177.PubMedCrossRefGoogle Scholar
  5. 5.
    Guarner F, Malagelada JR. Gut flora in health and disease. Lancet. 2003;361:512–9.PubMedCrossRefGoogle Scholar
  6. 6.
    Shanahan F. The host-microbe interface within the gut. Best Pract Res Clin Gastroenterol. 2002;16:915–31.PubMedCrossRefGoogle Scholar
  7. 7.
    Bhan AK, Mizoguchi E, Smith RN, Mizoguchi A. Colitis in transgenic and knockout animals as models of human inflammatory bowel disease. Immunol Rev. 1999;169:195–207.PubMedCrossRefGoogle Scholar
  8. 8.
    Bamias G, Nyce MR, De La Rue SA, Cominelli F. New concepts in the pathophysiology of inflammatory bowel disease. Ann Intern Med. 2005;143:895–904.PubMedGoogle Scholar
  9. 9.
    Onderdonk AB, Franklin ML, Cisneros RL. Production of experimental ulcerative colitis in gnotobiotic guinea pigs with simplified microflora. Infect Immun. 1981;32:225–31.PubMedGoogle Scholar
  10. 10.
    Sellon RK, Tonkonogy S, Schultz M, et al. Resident enteric bacteria are necessary for development of spontaneous colitis and immune system activation in interleukin-10-deficient mice. Infect Immun. 1998;66:5224–31.PubMedGoogle Scholar
  11. 11.
    Harper PH, Lee EC, Kettlewell MG, Bennett MK, Jewell DP. Role of the faecal stream in the maintenance of crohn's colitis. Gut. 1985;26:279–84.PubMedCrossRefGoogle Scholar
  12. 12.
    D'Haens GR, Geboes K, Peeters M, et al. P: Early lesions of recurrent crohn's disease caused by infusion of intestinal contents in excluded ileum. Gastroenterology. 1998;114:262–7.PubMedCrossRefGoogle Scholar
  13. 13.
    de Silva HJ, Millard PR, Soper N, et al. Effects of the faecal stream and stasis on the ileal pouch mucosa. Gut. 1991;32:1166–9.PubMedCrossRefGoogle Scholar
  14. 14.
    Ogura Y, Bonen DK, Inohara N, et al. A frameshift mutation in nod2 associated with susceptibility to crohn's disease. Nature. 2001;411:603–6.PubMedCrossRefGoogle Scholar
  15. 15.
    Swidsinski A, Ladhoff A, Pernthaler A, et al. Mucosal flora in inflammatory bowel disease. Gastroenterology. 2002;122:44–54.PubMedCrossRefGoogle Scholar
  16. 16.
    Seksik P, Rigottier-Gois L, Gramet G, et al. Alterations of the dominant faecal bacterial groups in patients with crohn's disease of the colon. Gut. 2003;52:237–42.PubMedCrossRefGoogle Scholar
  17. 17.
    Ruseler-van Embden JG, Schouten WR, van Lieshout LM. Pouchitis: result of microbial imbalance? Gut. 1994;35:658–64.PubMedCrossRefGoogle Scholar
  18. 18.
    Sartor RB. Mechanisms of disease: Pathogenesis of crohn's disease and ulcerative colitis. Nat Clin Pract Gastroenterol Hepatol. 2006;3:390–407.PubMedCrossRefGoogle Scholar
  19. 19.
    Clavel T, Haller D. Bacteria- and host-derived mechanisms to control intestinal epithelial cell homeostasis: Implications for chronic inflammation. Inflamm Bowel Dis. 2007;13:1153–64.PubMedCrossRefGoogle Scholar
  20. 20.
    Boyle RJ, Robins-Browne RM, Tang ML. Probiotic use in clinical practice: What are the risks? Am J Clin Nutr. 2006;83:1256–64. quiz 1446–1257.PubMedGoogle Scholar
  21. 21.
    Vanderpool C, Yan F, Polk DB. Mechanisms of probiotic action: Implications for therapeutic applications in inflammatory bowel diseases. Inflamm Bowel Dis. 2008;14:1585–96.PubMedCrossRefGoogle Scholar
  22. 22.
    Yoon SS, Sun J: Probiotics, nuclear receptor signaling, and anti-inflammatory pathways. Gastroenterol Res Pract; 2011:971938Google Scholar
  23. 23.
    Servin AL. Antagonistic activities of lactobacilli and bifidobacteria against microbial pathogens. FEMS Microbiol Rev. 2004;28:405–40.PubMedCrossRefGoogle Scholar
  24. 24.
    Collado MC, Surono IS, Meriluoto J, Salminen S. Potential probiotic characteristics of lactobacillus and enterococcus strains isolated from traditional dadih fermented milk against pathogen intestinal colonization. J Food Prot. 2007;70:700–5.PubMedGoogle Scholar
  25. 25.
    Collado MC, Meriluoto J, Salminen S. Role of commercial probiotic strains against human pathogen adhesion to intestinal mucus. Lett Appl Microbiol. 2007;45:454–60.PubMedCrossRefGoogle Scholar
  26. 26.
    Candela M, Seibold G, Vitali B, et al. Real-time pcr quantification of bacterial adhesion to caco-2 cells: Competition between bifidobacteria and enteropathogens. Res Microbiol. 2005;156:887–95.PubMedCrossRefGoogle Scholar
  27. 27.
    Michail S, Sylvester F, Fuchs G, Issenman R. Clinical efficacy of probiotics: Review of the evidence with focus on children. J Pediatr Gastroenterol Nutr. 2006;43:550–7.PubMedCrossRefGoogle Scholar
  28. 28.
    Rioux KP, Madsen KL, Fedorak RN. The role of enteric microflora in inflammatory bowel disease: Human and animal studies with probiotics and prebiotics. Gastroenterol Clin North Am. 2005;34:465–82. ix.PubMedCrossRefGoogle Scholar
  29. 29.
    Madsen KL. Inflammatory bowel disease: Lessons from the il-10 gene-deficient mouse. Clin Invest Med. 2001;24:250–7.PubMedGoogle Scholar
  30. 30.
    Mack DR, Ahrne S, Hyde L, Wei S, Hollingsworth MA. Extracellular muc3 mucin secretion follows adherence of lactobacillus strains to intestinal epithelial cells in vitro. Gut. 2003;52:827–33.PubMedCrossRefGoogle Scholar
  31. 31.
    Sandborn WJ. Pouchitis following ileal pouch-anal anastomosis: Definition, pathogenesis, and treatment. Gastroenterology. 1994;107:1856–60.PubMedGoogle Scholar
  32. 32.
    Gosselink MP, Schouten WR, van Lieshout LM, et al. Delay of the first onset of pouchitis by oral intake of the probiotic strain lactobacillus rhamnosus gg. Dis Colon Rectum. 2004;47:876–84.PubMedCrossRefGoogle Scholar
  33. 33.
    Laake KO, Line PD, Aabakken L, et al. Assessment of mucosal inflammation and circulation in response to probiotics in patients operated with ileal pouch anal anastomosis for ulcerative colitis. Scand J Gastroenterol. 2003;38:409–14.PubMedCrossRefGoogle Scholar
  34. 34.
    Kuisma J, Mentula S, Jarvinen H, et al. Effect of lactobacillus rhamnosus gg on ileal pouch inflammation and microbial flora. Aliment Pharmacol Ther. 2003;17:509–15.PubMedCrossRefGoogle Scholar
  35. 35.
    Laake KO, Line PD, Grzyb K, et al. Assessment of mucosal inflammation and blood flow in response to four weeks' intervention with probiotics in patients operated with a j-configurated ileal-pouch-anal-anastomosis (ipaa). Scand J Gastroenterol. 2004;39:1228–35.PubMedCrossRefGoogle Scholar
  36. 36.
    Gionchetti P, Rizzello F, Helwig U, et al. Prophylaxis of pouchitis onset with probiotic therapy: A double-blind, placebo-controlled trial. Gastroenterology. 2003;124:1202–9.PubMedCrossRefGoogle Scholar
  37. 37.
    Shen B, Brzezinski A, Fazio VW, et al. Maintenance therapy with a probiotic in antibiotic-dependent pouchitis: Experience in clinical practice. Aliment Pharmacol Ther. 2005;22:721–8.PubMedCrossRefGoogle Scholar
  38. 38.
    Mimura T, Rizzello F, Helwig U, et al. Once daily high dose probiotic therapy (vsl#3) for maintaining remission in recurrent or refractory pouchitis. Gut. 2004;53:108–14.PubMedCrossRefGoogle Scholar
  39. 39.
    Gionchetti P, Rizzello F, Venturi A, et al. Oral bacteriotherapy as maintenance treatment in patients with chronic pouchitis: A double-blind, placebo-controlled trial. Gastroenterology. 2000;119:305–9.PubMedCrossRefGoogle Scholar
  40. 40.
    • McLaughlin SD, Walker AW, Churcher C, et al.: The bacteriology of pouchitis: A molecular phylogenetic analysis using 16s rrna gene cloning and sequencing. Ann Surg;252:90–98. This well done study demonstrates reduced bacterial diversity in the pouches of those with UC versus those with FAP. Pouchitis is associated with a further reduction in biodiversity. Google Scholar
  41. 41.
    Uronis JM, Arthur JC, Keku T, et al.: Gut microbial diversity is reduced by the probiotic vsl#3 and correlates with decreased tnbs-induced colitis. Inflamm Bowel Dis;17:289–297.Google Scholar
  42. 42.
    Pronio A, Montesani C, Butteroni C, et al. Probiotic administration in patients with ileal pouch-anal anastomosis for ulcerative colitis is associated with expansion of mucosal regulatory cells. Inflamm Bowel Dis. 2008;14:662–8. This.PubMedCrossRefGoogle Scholar
  43. 43.
    O'Mahony L, McCarthy J, Kelly P, et al. Lactobacillus and bifidobacterium in irritable bowel syndrome: Symptom responses and relationship to cytokine profiles. Gastroenterology. 2005;128:541–51.PubMedCrossRefGoogle Scholar
  44. 44.
    Turroni S, Vitali B, Candela M, et al. Antibiotics and probiotics in chronic pouchitis: A comparative proteomic approach. World J Gastroenterol. 2010;16:30–41.PubMedGoogle Scholar
  45. 45.
    Tursi A, Brandimarte G, Giorgetti GM, et al. Low-dose balsalazide plus a high-potency probiotic preparation is more effective than balsalazide alone or mesalazine in the treatment of acute mild-to-moderate ulcerative colitis. Med Sci Monit. 2004;10:PI126–31.PubMedGoogle Scholar
  46. 46.
    Matthes H, Krummenerl T, Giensch M, Wolff C, Schulze J: Clinical trial: Probiotic treatment of acute distal ulcerative colitis with rectally administered escherichia coli nissle 1917 (ecn). BMC Complement Altern Med. 10:13.Google Scholar
  47. 47.
    Rembacken BJ, Snelling AM, Hawkey PM, Chalmers DM, Axon AT. Non-pathogenic escherichia coli versus mesalazine for the treatment of ulcerative colitis: A randomised trial. Lancet. 1999;354:635–9.PubMedCrossRefGoogle Scholar
  48. 48.
    Kato K, Mizuno S, Umesaki Y, et al. Randomized placebo-controlled trial assessing the effect of bifidobacteria-fermented milk on active ulcerative colitis. Aliment Pharmacol Ther. 2004;20:1133–41.PubMedCrossRefGoogle Scholar
  49. 49.
    Guslandi M, Giollo P, Testoni PA. A pilot trial of saccharomyces boulardii in ulcerative colitis. Eur J Gastroenterol Hepatol. 2003;15:697–8.PubMedCrossRefGoogle Scholar
  50. 50.
    Bibiloni R, Fedorak RN, Tannock GW, et al. Vsl#3 probiotic-mixture induces remission in patients with active ulcerative colitis. Am J Gastroenterol. 2005;100:1539–46.PubMedCrossRefGoogle Scholar
  51. 51.
    • Sood A, Midha V, Makharia GK, et al.: The probiotic preparation, vsl#3 induces remission in patients with mild-to-moderately active ulcerative colitis. Clin Gastroenterol Hepatol 2009;7:1202–1209, 1209 e1201. This recent large double blind, placebo controlled study of VSL #3 is one of the more recent positive studies that may suggest that this will be a useful adjunct to our current medical therapies for induction of remission in mild to moderate ulcerative colitis. As mentioned more studies with more robust outcomes and longer follow up are necessary before these agents can be used routinely. PubMedCrossRefGoogle Scholar
  52. 52.
    Tursi A, Brandimarte G, Papa A, et al.: Treatment of relapsing mild-to-moderate ulcerative colitis with the probiotic vsl#3 as adjunctive to a standard pharmaceutical treatment: A double-blind, randomized, placebo-controlled study. Am J Gastroenterol;105:2218–2227.Google Scholar
  53. 53.
    Miele E, Pascarella F, Giannetti E, et al. Effect of a probiotic preparation (vsl#3) on induction and maintenance of remission in children with ulcerative colitis. Am J Gastroenterol. 2009;104:437–43.PubMedCrossRefGoogle Scholar
  54. 54.
    Mallon P, McKay D, Kirk S, Gardiner K: Probiotics for induction of remission in ulcerative colitis. Cochrane Database Syst Rev. 2007;CD005573.Google Scholar
  55. 55.
    Zigra PI, Maipa VE, Alamanos YP. Probiotics and remission of ulcerative colitis: A systematic review. Neth J Med. 2007;65:411–8.PubMedGoogle Scholar
  56. 56.
    Kruis W, Schutz E, Fric P, et al. Double-blind comparison of an oral escherichia coli preparation and mesalazine in maintaining remission of ulcerative colitis. Aliment Pharmacol Ther. 1997;11:853–8.PubMedCrossRefGoogle Scholar
  57. 57.
    Kruis W, Fric P, Pokrotnieks J, et al. Maintaining remission of ulcerative colitis with the probiotic escherichia coli nissle 1917 is as effective as with standard mesalazine. Gut. 2004;53:1617–23.PubMedCrossRefGoogle Scholar
  58. 58.
    Zocco MA, dal Verme LZ, Cremonini F, et al. Efficacy of lactobacillus gg in maintaining remission of ulcerative colitis. Aliment Pharmacol Ther. 2006;23:1567–74.PubMedCrossRefGoogle Scholar
  59. 59.
    Huynh HQ, deBruyn J, Guan L, et al. Probiotic preparation vsl#3 induces remission in children with mild to moderate acute ulcerative colitis: A pilot study. Inflamm Bowel Dis. 2009;15:760–8.PubMedCrossRefGoogle Scholar
  60. 60.
    Naidoo K, Gordon M, Fagbemi AO, Thomas AG, Akobeng AK. Probiotics for maintenance of remission in ulcerative colitis. Cochrane Database Syst Rev. 2011;12:CD007443.PubMedGoogle Scholar
  61. 61.
    Gupta P, Andrew H, Kirschner BS, Guandalini S. Is lactobacillus gg helpful in children with crohn's disease? Results of a preliminary, open-label study. J Pediatr Gastroenterol Nutr. 2000;31:453–7.PubMedCrossRefGoogle Scholar
  62. 62.
    Fujimori S, Tatsuguchi A, Gudis K, et al. High dose probiotic and prebiotic cotherapy for remission induction of active crohn's disease. J Gastroenterol Hepatol. 2007;22:1199–204.PubMedCrossRefGoogle Scholar
  63. 63.
    Schultz M, Timmer A, Herfarth HH, et al. Lactobacillus gg in inducing and maintaining remission of crohn's disease. BMC Gastroenterol. 2004;4:5.PubMedCrossRefGoogle Scholar
  64. 64.
    Butterworth AD, Thomas AG, Akobeng AK: Probiotics for induction of remission in crohn's disease. Cochrane Database Syst Rev 2008;CD006634.Google Scholar
  65. 65.
    Bousvaros A, Guandalini S, Baldassano RN, et al. A randomized, double-blind trial of lactobacillus gg versus placebo in addition to standard maintenance therapy for children with crohn's disease. Inflamm Bowel Dis. 2005;11:833–9.PubMedCrossRefGoogle Scholar
  66. 66.
    Guslandi M, Mezzi G, Sorghi M, Testoni PA. Saccharomyces boulardii in maintenance treatment of crohn's disease. Dig Dis Sci. 2000;45:1462–4.PubMedCrossRefGoogle Scholar
  67. 67.
    Malchow HA. Crohn's disease and escherichia coli. A new approach in therapy to maintain remission of colonic crohn's disease? J Clin Gastroenterol. 1997;25:653–8.PubMedCrossRefGoogle Scholar
  68. 68.
    Rolfe VE, Fortun PJ, Hawkey CJ, Bath-Hextall F: Probiotics for maintenance of remission in crohn's disease. Cochrane Database Syst Rev 2006;CD004826.Google Scholar
  69. 69.
    • Rahimi R, Nikfar S, Rahimi F, et al.: A meta-analysis on the efficacy of probiotics for maintenance of remission and prevention of clinical and endoscopic relapse in crohn's disease. Dig Dis Sci 2008;53:2524–2531. This is the most recent meta-analysis on the role of probiotics to maintain remission in Crohn’s disease, which had a similar negative results to a Cochrane Review performed a few years prior. A total of 8 randomized controlled studies were included in study. Clinical relapse yielded odds ratio of 0.92 (0.52-1.62) and endoscopic relapse was 0.97 (0.54 = 1.78). PubMedCrossRefGoogle Scholar
  70. 70.
    Marteau P, Lemann M, Seksik P, et al. Ineffectiveness of lactobacillus johnsonii la1 for prophylaxis of postoperative recurrence in crohn's disease: A randomised, double blind, placebo controlled getaid trial. Gut. 2006;55:842–7.PubMedCrossRefGoogle Scholar
  71. 71.
    Prantera C, Scribano ML, Falasco G, Andreoli A, Luzi C. Ineffectiveness of probiotics in preventing recurrence after curative resection for crohn's disease: A randomised controlled trial with lactobacillus gg. Gut. 2002;51:405–9.PubMedCrossRefGoogle Scholar
  72. 72.
    Van Gossum A, Dewit O, Louis E, et al. Multicenter randomized-controlled clinical trial of probiotics (lactobacillus johnsonii, la1) on early endoscopic recurrence of crohn's disease after lleo-caecal resection. Inflamm Bowel Dis. 2007;13:135–42.PubMedCrossRefGoogle Scholar
  73. 73.
    Chermesh I, Tamir A, Reshef R, et al. Failure of synbiotic 2000 to prevent postoperative recurrence of crohn's disease. Dig Dis Sci. 2007;52:385–9.PubMedCrossRefGoogle Scholar
  74. 74.
    Doherty G, Bennett G, Patil S, Cheifetz A, Moss AC: Interventions for prevention of post-operative recurrence of crohn's disease. Cochrane Database Syst Rev 2009;CD006873.Google Scholar
  75. 75.
    Meijer BJ, Dieleman LA: Probiotics in the treatment of human inflammatory bowel diseases: Update 2011. J Clin Gastroenterol. 45 Suppl:S139-144.Google Scholar
  76. 76.
    Bensoussan M, Jovenin N, Garcia B, et al. Complementary and alternative medicine use by patients with inflammatory bowel disease: Results from a postal survey. Gastroenterol Clin Biol. 2006;30:14–23.PubMedCrossRefGoogle Scholar
  77. 77.
    Floch MH, Walker WA, Madsen K, et al.: Recommendations for probiotic use-2011 update. J Clin Gastroenterol. 45 Suppl:S168-171.Google Scholar

Copyright information

© Springer Science+Business Media, LLC (outside the USA) 2012

Authors and Affiliations

  • Ganesh R. Veerappan
    • 1
  • John Betteridge
    • 1
  • Patrick E. Young
    • 1
    Email author
  1. 1.Gastroenterology Service, Department of MedicineWalter Reed National Military Medical CenterBethesdaUSA

Personalised recommendations