Skip to main content
Log in

Probiotics in the Management of Inflammatory Bowel Disease

A Systematic Review of Intervention Studies in Adult Patients

  • Systematic Review
  • Published:
Drugs Aims and scope Submit manuscript

Abstract

Introduction: Mounting evidence suggests an important role for the intestinal microbiota in the chronic mucosal inflammation that occurs in inflammatory bowel disease (IBD), and novel molecular approaches have further identified a dysbiosis in these patients. Several mechanisms of action of probiotic products that may interfere with possible aetiological factors in IBD have been postulated.

Objective: Our objective was to discuss the rationale for probiotics in IBD and to systematically review clinical intervention studies with probiotics in the management of IBD in adults.

Methods: A systematic search was performed in PubMed up to 1 October 2011, using defined keywords. Only full-text papers in the English language addressing clinical outcomes in adult patients were included. The 41 eligible studies were categorized on disease type (ulcerative colitis [UC] with/without an ileo-anal pouch and Crohn’s disease [CD]) and disease activity. Pooled odds ratios were only calculated per probiotic for a specific patient group when more than one randomized controlled trial was available.

Results: Well designed randomized controlled trials supporting the application of probiotics in the management of IBD are still limited. Meta-analyses could only be performed for a limited number of studies revealing overall risk ratios of 2.70 (95% CI 0.47, 15.33) for inducing remission in active UC with Bifido-fermented milk versus placebo or no additive treatment (n = 2); 1.88 (95% CI 0.96, 3.67) for inducing remission in active UC with VSL#3 versus placebo (n = 2); 1.08 (95% CI 0.86, 1.37) for preventing relapses in inactive UC with Escherichia coli Nissle 1917 versus standard treatment (n= 3); 0.17 (95% CI 0.09,0.33) for preventing relapses in inactive UC/ileo-anal pouch anastomosis(IPAA) patients with VSL#3 versus placebo; 1.21 (95% CI 0.57, 2.57) for preventing endoscopic recurrences in inactive CD with Lactobacillus rhamnosus GG versus placebo (n=2); and 0.93 (95% CI 0.63, 1.38) for preventing endoscopic recurrences in inactive CD with Lactobacillus johnsonii versus placebo (n = 2).

Conclusion: Further well designed studies based on intention-to-treat analyses by several independent research groups are still warranted to support the promising results for E. coli Nissle in inactive UC and the multispecies product VSL#3 in active UC and inactive pouch patients. So far, no evidence is available to support the use of probiotics in CD. Future studies should focus on specific disease subtypes and disease location. Further insight into the aetiology of IBD and the mechanisms of probiotic strains will aid in selecting probiotic strains for specific disease entities and disease locations.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Table I
Table I
Table II
Table III
Table IV
a
a
a

Similar content being viewed by others

References

  1. Zoetendal EG, Akkermans ADL, Akkermans-van Vliet WM, et al. The host genotype affects the bacterial community in the human gastrointestinal tract. Microb Ecol Health Dis 2001; 13: 129–34

    Google Scholar 

  2. Eckburg PB, Bik EM, Bernstein CN, et al. Diversity of the human intestinal microbial flora. Science 2005 Jun 10; 308(5728): 1635–8

    PubMed  Google Scholar 

  3. Frank DN, St Amand AL, Feldman RA, et al. Molecular-phylogenetic characterization of microbial community imbalances in human inflammatory bowel diseases. Proc Natl Acad Sci U S A 2007 Aug 21; 104(34): 13780–5

    PubMed  CAS  Google Scholar 

  4. Takaishi H, Matsuki T, Nakazawa A, et al. Imbalance in intestinal microflora constitution could be involved in the pathogenesis of inflammatory bowel disease. Int J Med Microbiol 2008 Jul; 298(5-6): 463–72

    PubMed  CAS  Google Scholar 

  5. Qin J, Li R, Raes J, et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature 2010 Mar 4; 464(7285): 59–65

    PubMed  CAS  Google Scholar 

  6. Arumugam M, Raes J, Pelletier E, et al. Enterotypes of the human gut microbiome. Nature 2011 May 12; 473(7346): 174–80

    PubMed  CAS  Google Scholar 

  7. Thompson-Chagoyan OC, Maldonado J, Gil A. Aetiology of inflammatory bowel disease (IBD): role of intestinal microbiota and gut-associated lymphoid tissue immune response. Clin Nutr 2005 Jun; 24(3): 339–52

    PubMed  CAS  Google Scholar 

  8. Hamer HM, Jonkers D, Venema K, et al. Review article: the role of butyrate on colonic function. Aliment Pharmacol Ther 2008 Jan 15; 27(2): 104–19

    PubMed  CAS  Google Scholar 

  9. Quigley EM. Gut microbiota and the role of probiotics in therapy. Curr Opin Pharmacol 2011 Oct 11; 11(6): 593–603

    PubMed  CAS  Google Scholar 

  10. Tilg H. Obesity, metabolic syndrome, and microbiota: multiple interactions. J Clin Gastroenterol 2010 Sep; 44 Suppl. 1: S16–8

    PubMed  CAS  Google Scholar 

  11. Talley NJ, Abreu MT, Achkar JP, et al. An evidence-based systematic review on medical therapies for inflammatory bowel disease. Am J Gastroenterol 2011 Apr; 106 Suppl. 1: S2–25; quiz S6

    PubMed  CAS  Google Scholar 

  12. Hugot JP, Chamaillard M, Zouali H, et al. Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn’s disease. Nature 2001 May31;411(6837): 599–603

    PubMed  CAS  Google Scholar 

  13. Cho JH, Brant SR. Recent insights into the genetics of in-flammatory bowel disease. Gastroenterology 2011 May; 140(6): 1704–12

    PubMed  CAS  Google Scholar 

  14. Thia KT, Loftus Jr EV, Sandborn WJ, et al. An update on the epidemiology of inflammatory bowel disease in Asia. Am J Gastroenterol 2008 Dec; 103(12): 3167–82

    PubMed  Google Scholar 

  15. Kawada M, Arihiro A, Mizoguchi E. Insights from advances in research of chemically induced experimental models of human inflammatory bowel disease. World J Gastroenterol 2007 Nov 14; 13(42): 5581–93

    PubMed  CAS  Google Scholar 

  16. Campieri M, Gionchetti P. Probiotics in inflammatory bowel disease: new insight to pathogenesis or a possible therapeutic alternative? Gastroenterology 1999 May; 116(5): 1246–9

    PubMed  CAS  Google Scholar 

  17. Swidsinski A, Ladhoff A, Pernthaler A, et al. Mucosal flora in inflammatory bowel disease. Gastroenterology 2002; 122(1): 44–54

    PubMed  Google Scholar 

  18. Schultsz C, Van Den Berg FM, Ten Kate FW, et al. The intestinal mucus layer from patients with inflammatory bowel disease harbors high numbers of bacteria compared with controls. Gastroenterology 1999; 117(5): 1089–97

    PubMed  CAS  Google Scholar 

  19. D’Haens GR, Geboes K, Peeters M, et al. Early lesions of recurrent Crohn’s disease caused by infusion of intestinal contents in excluded ileum. Gastroenterology 1998 Feb; 114(2): 262–7

    PubMed  Google Scholar 

  20. Janowitz HD, Croen EC, Sachar DB. The role of the fecal stream in Crohn’s disease: an historical and analytic review. Inflamm Bowel Dis 1998 Feb; 4(1): 29–39

    PubMed  CAS  Google Scholar 

  21. Rutgeerts P, Goboes K, Peeters M, et al. Effect of faecal stream diversion on recurrence of Crohn’s disease in the neoterminal ileum. Lancet 1991 Sep 28; 338(8770): 771–4

    PubMed  CAS  Google Scholar 

  22. Wellmann W, Fink PC, Benner F, et al. Endotoxaemia in active Crohn’s disease: treatment with whole gut irrigation and 5-aminosalicylic acid. Gut 1986 Jul; 27(7): 814–20

    PubMed  CAS  Google Scholar 

  23. Khan KJ, Ullman TA, Ford AC, et al. Antibiotic therapy in inflammatory bowel disease: a systematic review and meta-analysis. Am J Gastroenterol 2011 Apr; 106(4): 661–73

    PubMed  CAS  Google Scholar 

  24. Linskens RK, Huijsdens XW, Savelkoul PH, et al. The bacterial flora in inflammatory bowel disease: current insights in pathogenesis and the influence of antibiotics and probiotics. Scand J Gastroenterol Suppl 2001; (234): 29–40

  25. Dicksved J, Halfvarson J, Rosenquist M, et al. Molecular analysis of the gut microbiota of identical twins with Crohn’s disease. Isme J 2008 Jul; 2(7): 716–27

    PubMed  CAS  Google Scholar 

  26. Manichanh C, Rigottier-Gois L, Bonnaud E, et al. Reduced diversity of faecal microbiota in Crohn’s disease revealed by a metagenomic approach. Gut 2006 Feb; 55(2): 205–11

    PubMed  CAS  Google Scholar 

  27. Martinez C, Antolin M, Santos J, et al. Unstable composition of the fecal microbiota in ulcerative colitis during clinical remission. Am J Gastroenterol 2008 Mar; 103(3): 643–8

    PubMed  Google Scholar 

  28. Sokol H, Seksik P, Rigottier-Gois L, et al. Specificities of the fecal microbiota in inflammatory bowel disease. Inflamm Bowel Dis 2006 Feb; 12(2): 106–11

    PubMed  Google Scholar 

  29. Swidsinski A, Loening-Baucke V, Vaneechoutte M, et al. Active Crohn’s disease and ulcerative colitis can be specifically diagnosed and monitored based on the biostructure of the fecal flora. Inflamm Bowel Dis 2008 Feb; 14(2): 147–61

    PubMed  Google Scholar 

  30. Frank DN, Robertson CE, Hamm CM, et al. Disease phenotype and genotype are associated with shifts in intestinal-associated microbiota in inflammatory bowel diseases. Inflamm Bowel Dis 2011 Jan; 17(1): 179–84

    PubMed  Google Scholar 

  31. Ott SJ, Musfeldt M, Timmis KN, et al. In vitro alterations of intestinal bacterial microbiota in fecal samples during storage. Diagn Microbiol Infect Dis 2004 Dec; 50(4): 237–45

    PubMed  CAS  Google Scholar 

  32. Kleessen B, Kroesen AJ, Buhr HJ, et al. Mucosal and invading bacteria in patients with inflammatory bowel disease compared with controls. Scand J Gastroenterol 2002 Sep; 37(9): 1034–41

    PubMed  CAS  Google Scholar 

  33. Swidsinski A, Weber J, Loening-Baucke V, et al. Spatial organization and composition of the mucosal flora in patients with inflammatory bowel disease. J Clin Microbiol 2005 Jul; 43(7): 3380–9

    PubMed  Google Scholar 

  34. Rehman A, Lepage P, Nolte A, et al. Transcriptional activity of the dominant gut mucosal microbiota in chronic inflammatory bowel disease patients. J Med Microbiol 2010 Sep; 59 (Pt 9): 1114–22

    PubMed  CAS  Google Scholar 

  35. Walker AW, Sanderson JD, Churcher C, et al. High-throughput clone library analysis of the mucosa-associated microbiota reveals dysbiosis and differences between inflamed and non-inflamed regions of the intestine in inflammatory bowel disease. BMC Microbiol 2011 Jan 10; 11: 7

    PubMed  Google Scholar 

  36. Sokol H, Seksik P, Furet JP, et al. Low counts of Faecali-bacterium prausnitzii in colitis microbiota. Inflamm Bowel Dis 2009 Aug; 15(8): 1183–9

    PubMed  CAS  Google Scholar 

  37. Gueimonde M, Ouwehand A, Huhtinen H, et al. Qualitative and quantitative analyses of the bifidobacterial microbiota in the colonic mucosa of patients with colorectal cancer, diverticulitis and inflammatory bowel disease. World J Gastroenterol 2007 Aug 7; 13(29): 3985–9

    PubMed  Google Scholar 

  38. Macfarlane S, Furrie E, Kennedy A, et al. Mucosal bacteria in ulcerative colitis. Br J Nutr 2005 Apr; 93 Suppl. 1: S67–72

    PubMed  CAS  Google Scholar 

  39. Mylonaki M, Rayment NB, Rampton DS, et al. Molecular characterization of rectal mucosa-associated bacterial flora in inflammatory bowel disease. Inflamm Bowel Dis 2005 May; 11(5): 481–7

    PubMed  Google Scholar 

  40. Thomazini CM, Samegima DA, Rodrigues MA, et al. High prevalence of aggregative adherent Escherichia coli strains in the mucosa-associated microbiota of patients with inflammatory bowel diseases. Int J Med Microbiol 2011 Aug; 301(6): 475–9

    PubMed  CAS  Google Scholar 

  41. Vernia P, Gnaedinger A, Hauck W, et al. Organic anions and the diarrhea of inflammatory bowel disease. Dig Dis Sci 1988 Nov; 33(11): 1353–8

    PubMed  CAS  Google Scholar 

  42. Sepehri S, Kotlowski R, Bernstein CN, et al. Microbial diversity of inflamed and noninflamed gut biopsy tissues in inflammatory bowel disease. Inflamm Bowel Dis 2007 Jun; 13(6): 675–83

    PubMed  Google Scholar 

  43. Willing BP, Dicksved J, Halfvarson J, et al. A pyrosequencing study in twins shows that gastrointestinal microbial profiles vary with inflammatory bowel disease phenotypes. Gastroenterology 2010 Dec; 139(6): 1844–54.e1

    PubMed  Google Scholar 

  44. Abraham C, Medzhitov R. Interactions between the host innate immune system and microbes in inflammatory bowel disease. Gastroenterology 2011 May; 140(6): 1729–37

    PubMed  CAS  Google Scholar 

  45. Danese S. Immune and nonimmune components orchestrate the pathogenesis of inflammatory bowel disease. Am J Physiol Gastrointest Liver Physiol 2011 May; 300(5): G716–22

    PubMed  CAS  Google Scholar 

  46. Abraham C, Cho JH. IL-23 and autoimmunity: new insights into the pathogenesis of inflammatory bowel disease. Annu Rev Med 2009; 60: 97–110

    PubMed  CAS  Google Scholar 

  47. Korzenik JR, Podolsky DK. Evolving knowledge and therapy of inflammatory bowel disease. Nat Rev Drug Discov 2006 Mar; 5(3): 197–209

    PubMed  CAS  Google Scholar 

  48. Cario E. Toll-like receptors in inflammatory bowel diseases: a decade later. Inflamm Bowel Dis 2010 Sep; 16(9): 1583–97

    PubMed  Google Scholar 

  49. Cario E. Bacterial interactions with cells of the intestinal mucosa: Toll-like receptors and NOD2. Gut 2005 Aug; 54(8): 1182–93

    PubMed  CAS  Google Scholar 

  50. Roda G, Sartini A, Zambon E, et al. Intestinal epithelial cells in inflammatory bowel diseases. World J Gastroenterol 2010 Sep 14; 16(34): 4264–71

    PubMed  Google Scholar 

  51. Elinav E, Strowig T, Kau AL, et al. NLRP6 inflammasome regulates colonic microbial ecology and risk for colitis. Cell 2011 May 27; 145(5): 745–57

    PubMed  CAS  Google Scholar 

  52. Lees CW, Barrett JC, Parkes M, et al. New IBD genetics: common pathways with other diseases. Gut 2011 Feb 7; 60(12): 1739–53

    PubMed  CAS  Google Scholar 

  53. Wehkamp J, Harder J, Weichenthal M, et al. NOD2 (CARD 15) mutations in Crohn’s disease are associated with diminished mucosal alpha-defensin expression. Gut 2004 Nov; 53(11): 1658–64

    PubMed  CAS  Google Scholar 

  54. Wehkamp J, Salzman NH, Porter E, et al. Reduced Paneth cell alpha-defensins in ileal Crohn’s disease. Proc Natl Acad Sci U S A 2005 Dec 13; 102(50): 18129–34

    PubMed  CAS  Google Scholar 

  55. Dignass A, Van Assche G, Lindsay JO, et al. The second European evidence-based consensus on the diagnosis and management of Crohn’s disease: current management. J Crohns Colitis 2010 Feb; 4(1): 28–62

    PubMed  CAS  Google Scholar 

  56. Herrinton LJ, Liu L, Weng X, et al. Role of thiopurine and anti-TNF therapy in lymphoma in inflammatory bowel disease. Am J Gastroenterol 2011 Dec; 106(12): 2146–53

    PubMed  CAS  Google Scholar 

  57. Kelsen J, Dige A, Schwindt H, et al. Infliximab induces clonal expansion of gammadelta-T cells in Crohn’s disease: a predictor of lymphoma risk? PLoS One 2011 Mar 31; 6(3): e17890

    PubMed  CAS  Google Scholar 

  58. Food and Agriculture Organization of the United Nations, WHO. Joint FAO/WHO expert consultation on evaluation of health and nutritional properties of probiotics in food including powder milk with live lactic acid bacteria. Cordoba: 2001 Oct [online]. Available from URL: http://www.who.int/foodsafety/publications/fs_management/en/probiotics.pdf [Accessed 2012 Apr 2]

  59. Timmerman HM, Koning CJ, Mulder L, et al. Monostrain, multistrain and multispecies probiotics: a comparison of functionality and efficacy. Int J Food Microbiol 2004 Nov 15; 96(3): 219–33

    PubMed  CAS  Google Scholar 

  60. Lebeer S, Vanderleyden J, De Keersmaecker SC. Genes and molecules of lactobacilli supporting probiotic action. Microbiol Mol Biol Rev 2008 Dec; 72(4): 728–64

    PubMed  CAS  Google Scholar 

  61. Sherman PM, Ossa JC, Johnson-Henry K. Unraveling mechanisms of action of probiotics. Nutr Clin Pract 2009 Feb-Mar; 24(1): 10–4

    PubMed  Google Scholar 

  62. Oelschlaeger TA. Mechanisms of probiotic actions: a review. Int J Med Microbiol 2010 Jan; 300(1): 57–62

    PubMed  CAS  Google Scholar 

  63. Borchers AT, Selmi C, Meyers FJ, et al. Probiotics and immunity. J Gastroenterol 2009; 44(1): 26–46

    PubMed  Google Scholar 

  64. Caballero-Franco C, Keller K, De Simone C, et al. The VSL#3 probiotic formula induces mucin gene expression and secretion in colonic epithelial cells. Am J Physiol Gastrointest Liver Physiol 2007 Jan; 292(1): G315–22

    PubMed  CAS  Google Scholar 

  65. Karczewski J, Troost FJ, Konings I, et al. Regulation of human epithelial tight junction proteins by Lactobacillus plantarum in vivo and protective effects on the epithelial barrier. Am J Physiol Gastrointest Liver Physiol 2010 Jun; 298(6): G851–9

    PubMed  CAS  Google Scholar 

  66. Mattar AF, Teitelbaum DH, Drongowski RA, et al. Probiotics up-regulate MUC-2 mucin gene expression in a Caco-2 cell-culture model. Pediatr Surg Int 2002 Oct; 18(7): 586–90

    PubMed  CAS  Google Scholar 

  67. Ukena SN, Singh A, Dringenberg U, et al. Probiotic Escherichia coli Nissle 1917 inhibits leaky gut by enhancing mucosal integrity. PLoS One 2007; 2(12): e1308

    PubMed  Google Scholar 

  68. Claes IJ, De Keersmaecker SC, Vanderleyden J, et al. Lessons from probiotic-host interaction studies in murine models of experimental colitis. Mol Nutr Food Res 2011 Oct; 55(10): 1441–53

    PubMed  CAS  Google Scholar 

  69. Karimi O, Pena AS, van Bodegraven AA. Probiotics (VSL#3) in arthralgia in patients with ulcerative colitis and Crohn’s disease: a pilot study. Drugs Today (Barc) 2005 Jul; 41(7): 453–9

    CAS  Google Scholar 

  70. Lorea Baroja M, Kirjavainen PV, Hekmat S, et al. Anti-inflammatory effects of probiotic yogurt in inflammatory bowel disease patients. Clin Exp Immunol 2007 Sep; 149(3): 470–9

    PubMed  CAS  Google Scholar 

  71. Guslandi M, Giollo P, Testoni PA. A pilot trial of Sac-charomyces boulardii in ulcerative colitis. Eur J Gastroenterol Hepatol 2003 Jun; 15(6): 697–8

    PubMed  Google Scholar 

  72. Ishikawa H, Akedo I, Umesaki Y, et al. Randomized controlled trial of the effect of bifidobacteria-fermented milk on ulcerative colitis. J Am Coll Nutr 2003 Feb; 22(1): 56–63

    PubMed  Google Scholar 

  73. 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 Nov 15; 20(10): 1133–41

    PubMed  CAS  Google Scholar 

  74. 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 Nov; 10(11): PI126–31

    PubMed  CAS  Google Scholar 

  75. Bibiloni R, Fedorak RN, Tannock GW, et al. VSL#3 probiotic-mixture induces remission in patients with active ulcerative colitis. Am J Gastroenterol 2005 Jul; 100(7): 1539–46

    PubMed  Google Scholar 

  76. Tsuda Y, Yoshimatsu Y, Aoki H, et al. Clinical effectiveness of probiotics therapy (BIO-THREE) in patients with ulcerative colitis refractory to conventional therapy. Scand J Gastroenterol 2007 Nov; 42(11): 1306–11

    PubMed  Google Scholar 

  77. Soo I, Madsen KL, Tejpar Q, et al. VSL#3 probiotic up-regulates intestinal mucosal alkaline sphingomyelinase and reduces inflammation. Can J Gastroenterol 2008 Mar; 22(3): 237–42

    PubMed  CAS  Google Scholar 

  78. Takeda Y, Nakase H, Namba K, et al. Upregulation of T-bet and tight junction molecules by Bifidobactrium longum improves colonic inflammation of ulcerative colitis. Inflamm Bowel Dis 2009 Nov; 15(11): 1617–8

    PubMed  Google Scholar 

  79. 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 Nov; 7(11): 1202–9, 9 e1

    PubMed  Google Scholar 

  80. Matthes H, Krummenerl T, Giensch M, et al. Clinical trial: probiotic treatment of acute distal ulcerative colitis with rectally administered Escherichia coli Nissle 1917 (EcN). BMC Complement Altern Med 2010 Apr 15; 10: 13

    PubMed  Google Scholar 

  81. 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 2010 Oct; 105(10): 2218–27

    PubMed  Google Scholar 

  82. Nagasaki A, Takahashi H, Iinuma M, et al. Ulcerative colitis with multidrug-resistant Pseudomonas aeruginosa infection successfully treated with bifidobacterium. Digestion 2010; 81(3): 204–5

    PubMed  Google Scholar 

  83. D’Inca R, Barollo M, Scarpa M, et al. Rectal administra-tion of Lactobacillus casei DG modifies flora composition and Toll-like receptor expression in colonic mucosa of patients with mild ulcerative colitis. Dig Dis Sci 2011 Apr; 56(4): 1178–87

    PubMed  Google Scholar 

  84. 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 Oct; 11(5): 853–8

    PubMed  CAS  Google Scholar 

  85. Rembacken BJ, Snelling AM, Hawkey PM, et al. Non-pathogenic Escherichia coli versus mesalazine for the treatment of ulcerative colitis: a randomised trial. Lancet 1999; 354(9179): 635–9

    PubMed  CAS  Google Scholar 

  86. Venturi A, Gionchetti P, Rizzello F, et al. Impact on the composition of the faecal flora by a new probiotic preparation: preliminary data on maintenance treatment of patients with ulcerative colitis. Aliment Pharmacol Ther 1999; 13(8): 1103–8

    PubMed  CAS  Google Scholar 

  87. Cui HH, Chen CL, Wang JD, et al. Effects of probiotic on intestinal mucosa of patients with ulcerative colitis. World J Gastroenterol 2004 May 15; 10(10): 1521–5

    PubMed  CAS  Google Scholar 

  88. 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 Nov; 53(11): 1617–23

    PubMed  CAS  Google Scholar 

  89. Zocco MA, dal Verme LZ, Cremonini F, et al. Efficacy of Lactobacillus GG in maintaining remission of ulcerative colitis. Aliment Pharmacol Ther 2006 Jun 1; 23(11): 1567–74

    PubMed  CAS  Google Scholar 

  90. Guslandi M. Saccharomyces boulardii plus rifaximin in mesalamine-intolerant ulcerative colitis. J Clin Gastro-enterol 2010 May–Jun; 44(5): 385

    Google Scholar 

  91. Wildt S, Nordgaard I, Hansen U, et al. A randomised double-blind placebo-controlled trial with Lactobacillus acidophilus La-5 and Bifidobacterium animalis subsp. lactis BB-12 for maintenance of remission in ulcerative colitis. J Crohns Colitis 2011 Apr; 5(2): 115–21

    Google Scholar 

  92. Kuzela L, Kascak M, Vavrecka A. Induction and maintenance of remission with nonpathogenic Escherichia coli in patients with pouchitis. Am J Gastroenterol 2001 Nov; 96(11): 3218–9

    PubMed  CAS  Google Scholar 

  93. Gionchetti P, Rizzello F, Morselli C, et al. High-dose probiotics for the treatment of active pouchitis. Dis Colon Rectum 2007 Dec; 50(12): 2075–82; discussion 82-4

    PubMed  Google Scholar 

  94. 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 Aug; 119(2): 305–9

    PubMed  CAS  Google Scholar 

  95. Kuisma J, Mentula S, Jarvinen H, et al. Effect of Lacto-bacillus rhamnosus GG on ileal pouch inflammation and microbial flora. Aliment Pharmacol Ther 2003 Feb 15; 17(4): 509–15

    PubMed  CAS  Google Scholar 

  96. Gionchetti P, Rizzello F, Helwig U, et al. Prophylaxis of pouchitis onset with probiotic therapy: a double-blind, placebo-controlled trial. Gastroenterology 2003 May; 124(5): 1202–9

    PubMed  Google Scholar 

  97. 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 Apr; 38(4): 409–14

    PubMed  CAS  Google Scholar 

  98. Laake KO, Line PD, Grzyb K, et al. Assessment of mu-cosal 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 Dec; 39(12): 1228–35

    PubMed  CAS  Google Scholar 

  99. 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 Jan; 53(1): 108–14

    PubMed  CAS  Google Scholar 

  100. 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 Jun; 47(6): 876–84

    PubMed  Google Scholar 

  101. Laake KO, Bjorneklett A, Aamodt G, et al. Outcome of four weeks’ intervention with probiotics on symptoms and endoscopic appearance after surgical reconstruction with a J-configurated ileal-pouch-anal-anastomosis in ulcerative colitis. Scand J Gastroenterol 2005 Jan; 40(1): 43–51

    PubMed  CAS  Google Scholar 

  102. 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 Oct 15; 22(8): 721–8

    PubMed  CAS  Google Scholar 

  103. 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 May; 14(5): 662–8

    PubMed  Google Scholar 

  104. 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(4): 653–8

    PubMed  CAS  Google Scholar 

  105. Mattila-Sandholm T, Blum S, Collins JK, et al. Probiotics: towards demonstrating efficacy. Trends Food Sci Technol 1999; 10: 393–9

    CAS  Google Scholar 

  106. Doman DB, Goldberg HJ, Golding MI. “Ecologic niche” therapy for Crohn’s disease with adjunctive rifaximin antibiotic treatment followed by Flora-Q probiotic maintenance therapy. Am J Gastroenterol 2008 Jan; 103(1): 251–2

    PubMed  Google Scholar 

  107. Guslandi M, Mezzi G, Sorghi M, et al. Saccharomyces boulardii in maintenance treatment of Crohn’s disease. Dig Dis Sci 2000 Jul; 45(7): 1462–4

    PubMed  CAS  Google Scholar 

  108. Prantera C, Scribano ML, Falasco G, et al. Ineffectiveness of probiotics in preventing recurrence after curative resection for Crohn’s disease: a randomised controlled trial with Lactobacillus GG. Gut 2002; 51(3): 405–9

    PubMed  CAS  Google Scholar 

  109. Marteau P, Lemann M, Seksik P, et al. Ineffectiveness of Lactobacillus johnsonii LA1 for prophylaxis of post-operative recurrence in Crohn’s disease: a randomised, double blind, placebo controlled GET AID trial. Gut 2006 Jun; 55(6): 842–7

    PubMed  CAS  Google Scholar 

  110. Schultz M, Timmer A, Herfarth HH, et al. Lactobacillus GG in inducing and maintaining remission of Crohn’s disease. BMC Gastroenterol 2004 Mar 15; 4: 5

    PubMed  Google Scholar 

  111. Van Gossum A, Dewit O, Louis E, et al. Multicenter ran-domized-controlled clinical trial of probiotics (Lactobacillus johnsonii, LA1) on early endoscopic recurrence of Crohn’s disease after lleo-caecal resection. Inflamm Bowel Dis 2007 Feb; 13(2): 135–42

    PubMed  Google Scholar 

  112. Huedo-Medina TB, Sanchez-Meca J, Marin-Martinez F, et al. Assessing heterogeneity in meta-analysis: Q statistic or I2 index? Psychol Methods 2006 Jun; 11(2): 193–206

    PubMed  Google Scholar 

  113. Bennet JD, Brinkman M. Treatment of ulcerative colitis by implantation of normal colonic flora. Lancet 1989 Jan 21; 1(8630): 164

    PubMed  CAS  Google Scholar 

  114. Borody TJ, Warren EF, Leis S, et al. Treatment of ulcerative colitis using fecal bacteriotherapy. J Clin Gastroenterol 2003 Jul; 37(1): 42–7

    PubMed  Google Scholar 

  115. Mallon P, McKay D, Kirk S, et al. Probiotics for induction of remission in ulcerative colitis. Cochrane Database Syst Rev 2007; (4): CD005573

  116. Uronis JM, Arthur JC, Keku T, et al. Gut microbial diersity is reduced by the probiotic VSL#3 and correlates with decreased TNBS-induced colitis. Inflamm Bowel Dis 2011 Jan; 17(1): 289–97

    PubMed  Google Scholar 

  117. Di Giacinto C, Marinaro M, Sanchez M, et al. Probiotics ameliorate recurrent Th1-mediated murine colitis by inducing IL-10 and IL-10-dependent TGF-beta-bearing regulatory cells. J Immunol 2005 Mar 15; 174(6): 3237–46

    PubMed  Google Scholar 

  118. Mennigen R, Bruewer M. Effect of probiotics on intestinal barrier function. Ann N Y Acad Sci 2009 May; 1165: 183–9

    PubMed  Google Scholar 

  119. Grabig A, Paclik D, Guzy C, et al. Escherichia coli strain Nissle 1917 ameliorates experimental colitis via toll-like receptor 2-and toll-like receptor 4-dependent pathways. Infect Immun 2006 Jul; 74(7): 4075–82

    PubMed  CAS  Google Scholar 

  120. Schultz M, Strauch UG, Linde HJ, et al. Preventive effects of Escherichia coli strain Nissle 1917 on acute and chronic intestinal inflammation in two different murine models of colitis. Clin Diagn Lab Immunol 2004 Mar; 11(2): 372–8

    PubMed  Google Scholar 

  121. Claes IJ, Lebeer S, Shen C, et al. Impact of lipoteichoic acid modification on the performance of the probiotic Lactobacillus rhamnosus GG in experimental colitis. Clin Exp Immunol 2010 Nov; 162(2): 306–14

    PubMed  CAS  Google Scholar 

  122. Penna C, Dozois R, Tremaine W, et al. Pouchitis after ileal pouch-anal anastomosis for ulcerative colitis occurs with increased frequency in patients with associated primary sclerosing cholangitis. Gut 1996 Feb; 38(2): 234–9

    PubMed  CAS  Google Scholar 

  123. Sandborn WJ. Pouchitis following ileal pouch-anal anastomosis: definition, pathogenesis, and treatment. Gastroenterology 1994; 107(6): 1856–60

    PubMed  CAS  Google Scholar 

  124. Landy J, Al-Hassi HO, McLaughlin SD, et al. Etiology of pouchitis. Inflamm Bowel Dis. Epub 2011 Oct 21

  125. Navaneethan U, Shen B. Secondary pouchitis: those with identifiable etiopathogenetic or triggering factors. Am J Gastroenterol 2010 Jan; 105(1): 51–64

    PubMed  Google Scholar 

  126. Shebani KO, Stucchi AF, McClung JP, et al. Role of stasis and oxidative stress in ileal pouch inflammation. J Surg Res 2000 May 1; 90(1): 67–75

    PubMed  CAS  Google Scholar 

  127. Kühbacher T, Ott SJ, Helwig U, et al. Bacterial and fungal microbiota in relation to probiotic therapy (VSL#3) in pouchitis. Gut 2006 Jun; 55(6): 833–41

    PubMed  Google Scholar 

  128. Ulisse S, Gionchetti P, D’Alo S, et al. Expression of cytokines, inducible nitric oxide synthase, and matrix metalloproteinases in pouchitis: effects of probiotic treatment. Am J Gastroenterol 2001 Sep; 96(9): 2691–9

    PubMed  CAS  Google Scholar 

  129. Lammers KM, Vergopoulos A, Babel N, et al. Probiotic therapy in the prevention of pouchitis onset: decreased interleukin-1beta, interleukin-8, and interferon-gamma gene expression. Inflamm Bowel Dis 2005 May; 11(5): 447–54

    PubMed  Google Scholar 

  130. Mattila-Sandholm T. The probdemo project: demonstration of the nutritional functionality of probiotic foods. Trends Food Sci Technol 1999; 10(12): 385–6

    CAS  Google Scholar 

  131. Garcia Vilela E, De Lourdes De Abreu Ferrari M, Oswaldo Da Gama Torres H, et al. Influence of Saccharomyces boulardii on the intestinal permeability of patients with Crohn’s disease in remission. Scand J Gastroenterol 2008; 43(7): 842–8

    PubMed  Google Scholar 

  132. Joossens S, Suenaert P, Noman M, et al. Saccharomyces boulardii in Crohn’s disease: effect on anti-Saccharomyces cerevisiae antibodies and intestinal permeability. Inflamm Bowel Dis 2005 Sep; 11(9): 863–4

    PubMed  CAS  Google Scholar 

  133. Guarner F, Schaafsma GJ. Probiotics. Int J Food Microbiol 1998 Feb 17; 39(3): 237–8

    PubMed  CAS  Google Scholar 

  134. Havenaar R, Ten Brink B, Huis in’t Veld HJ. Selection of strains for probiotic use. In: Fuller R, editor. Probiotics: the scientific basis. London: Chapman & Hall, 1992: 209–24

    Google Scholar 

  135. Adams MR. Safety of industrial lactic acid bacteria. J Biotechnol 1999; 68(2-3): 171–8

    PubMed  CAS  Google Scholar 

  136. Liong MT. Safety of probiotics: translocation and infection. Nutr Rev 2008 Apr; 66(4): 192–202

    PubMed  Google Scholar 

  137. Cukovic-Cavka S, Likic R, Francetic I, et al. Lactobacillus acidophilus as a cause of liver abscess in a NOD2/ CARD15-positive patient with Crohn’s disease. Digestion 2006; 73(2-3): 107–10

    PubMed  CAS  Google Scholar 

  138. Farina C, Arosio M, Mangia M, et al. Lactobacillus casei subsp. rhamnosus sepsis in a patient with ulcerative colitis. J Clin Gastroenterol 2001 Sep; 33(3): 251–2

    CAS  Google Scholar 

  139. Besselink MG, van Santvoort HC, Buskens E, et al. Probiotic prophylaxis in predicted severe acute pancreatitis: a randomised, double-blind, placebo-controlled trial. Lancet 2008 Feb 23; 371(9613): 651–9

    PubMed  Google Scholar 

Download references

Acknowledgements

No sources of funding were used to conduct this study or prepare this manuscript. The authors have no conflicts of interest that are directly relevant to the content of this review.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Daisy Jonkers PhD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jonkers, D., Penders, J., Masclee, A. et al. Probiotics in the Management of Inflammatory Bowel Disease. Drugs 72, 803–823 (2012). https://doi.org/10.2165/11632710-000000000-00000

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/11632710-000000000-00000

Keywords

Navigation