Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Probiotics and the gut microbiota in intestinal health and disease

Abstract

The use of probiotics is increasing in popularity for both the prevention and treatment of a variety of diseases. While a growing number of well-conducted, prospective, randomized, controlled, clinical trials are emerging and investigations of underlying mechanisms of action are being undertaken, questions remain with respect to the specific immune and physiological effects of probiotics in health and disease. This Review considers recent advances in clinical trials of probiotics for intestinal disorders in both adult and pediatric populations. An overview of recent in vitro and in vivo research related to potential mechanisms of action of various probiotic formulations is also considered.

Key Points

  • Probiotics are increasingly being used for various digestive diseases, including IBS, IBD, necrotizing enterocolitis, acute infectious diarrhea and antibiotic-associated diarrhea

  • Not all probiotic strains are appropriate for all ailments

  • Depending on the strain, probiotics have different underlying mechanisms of action to provide a beneficial effect

  • In addition to live organisms, probiotic-derived products, such as surface-layer proteins and bacteriocins may provide beneficial effects

  • Probiotics are contraindicated in certain patient populations, including those with severe immune deficiencies

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Potential mechanisms of action of probiotics.

Similar content being viewed by others

References

  1. Round, J. L. & Mazmanian, S. K. The gut microbiota shapes intestinal immune responses during health and disease. Nat. Rev. Immunol. 9, 313–323 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Eckburg, P. B. et al. Diversity of the human intestinal microbial flora. Science 308, 1635–1638 (2005).

    Article  PubMed  PubMed Central  Google Scholar 

  3. Forsythe, P., Sudo, N., Dinan, T., Taylor, V. H. & Bienenstock, J. Mood and gut feelings. Brain Behav. Immun. 24, 9–16 (2010).

    Article  PubMed  Google Scholar 

  4. Qin, J. et al. A human gut microbial gene catalogue established by metagenomic sequencing. Nature 464, 59–65 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Ley, R. E., Peterson, D. A. & Gordon, J. I. Ecological and evolutionary forces shaping microbial diversity in the human intestine. Cell 124, 837–848 (2006).

    Article  CAS  PubMed  Google Scholar 

  6. Chen, J., Cai, W. & Feng, Y. Development of intestinal bifidobacteria and lactobacilli in breast-fed neonates. Clin. Nutr. 26, 559–566 (2007).

    Article  CAS  PubMed  Google Scholar 

  7. Conroy, M. E., Shi, H. N. & Walker, W. A. The long-term health effects of neonatal microbial flora. Curr. Opin. Allergy Clin. Immunol. 9, 197–201 (2009).

    Article  PubMed  Google Scholar 

  8. Taylor, S. N., Basile, L. A., Ebeling, M. & Wagner, C. L. Intestinal permeability in preterm infants by feeding type: mother's milk versus formula. Breastfeed. Med. 4, 11–15 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  9. Martin, R. et al. Human milk is a source of lactic acid bacteria for the infant gut. J. Pediatr. 143, 754–758 (2003).

    Article  CAS  PubMed  Google Scholar 

  10. Rautava, S., Salminen, S. & Isolauri, E. Specific probiotics in reducing the risk of acute infections in infancy—a randomised, double-blind, placebo-controlled study. Br. J. Nutr. 101, 1722–1726 (2009).

    Article  CAS  PubMed  Google Scholar 

  11. Turnbaugh, P. J. & Gordon, J. I. The core gut microbiome, energy balance and obesity. J. Physiol. 587, 4153–4158 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Friswell, M. K. et al. Site and strain-specific variation in gut microbiota profiles and metabolism in experimental mice. PLoS ONE 5, e8584 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Mariat, D. et al. The Firmicutes/Bacteroidetes ratio of the human microbiota changes with age. BMC Microbiol. 9, 123 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Vael, C. & Desager, K. The importance of the development of the intestinal microbiota in infancy. Curr. Opin. Pediatr. 21, 794–800 (2009).

    Article  PubMed  Google Scholar 

  15. Hoffmann, C. et al. Community-wide response of the gut microbiota to enteropathogenic Citrobacter rodentium infection revealed by deep sequencing. Infect. Immun. 77, 4668–4678 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Hill, D. A. et al. Metagenomic analyses reveal antibiotic-induced temporal and spatial changes in intestinal microbiota with associated alterations in immune cell homeostasis. Mucosal Immunol. 3, 148–158 (2010).

    Article  CAS  PubMed  Google Scholar 

  17. De Palma, G. et al. Intestinal dysbiosis and reduced immunoglobulin-coated bacteria associated with coeliac disease in children. BMC Microbiol. 10, 63 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  18. Larsen, N. et al. Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults. PLoS ONE 5, e9085 (2010).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Turnbaugh, P. J. et al. A core gut microbiome in obese and lean twins. Nature 457, 480–484 (2009).

    Article  CAS  PubMed  Google Scholar 

  20. Tannock, G. W. Molecular analysis of the intestinal microflora in IBD. Mucosal Immunol. 1 (Suppl. 1), S15–S18 (2008).

    Article  CAS  PubMed  Google Scholar 

  21. Swidsinski, A., Loening-Baucke, V., Verstraelen, H., Osowska, S. & Doerffel, Y. Biostructure of fecal microbiota in healthy subjects and patients with chronic idiopathic diarrhea. Gastroenterology 135, 568–579 (2008).

    Article  PubMed  Google Scholar 

  22. Willing, B. et al. Twin studies reveal specific imbalances in the mucosa-associated microbiota of patients with ileal Crohn's disease. Inflamm. Bowel Dis. 15, 653–660 (2009).

    Article  PubMed  Google Scholar 

  23. Seksik, P. et al. Search for localized dysbiosis in Crohn's disease ulcerations by temporal temperature gradient gel electrophoresis of 16S rRNA. J. Clin. Microbiol. 43, 4654–4658 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. FAO/WHO. Joint FAO/WHO Working Group Report on Drafting Guidelines for the Evaluation of Probiotics in Food (FAO/WHO, London, Canada, 2002).

  25. Mileti, E., Matteoli, G., Iliev, I. D. & Rescigno, M. Comparison of the immunomodulatory properties of three probiotic strains of Lactobacilli using complex culture systems: prediction for in vivo efficacy. PLoS ONE 4, e7056 (2009).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  26. Sherman, P. M., Ossa, J. C. & Johnson-Henry, K. Unraveling mechanisms of action of probiotics. Nutr. Clin. Pract. 24, 10–14 (2009).

    Article  PubMed  Google Scholar 

  27. Ford, A. C., Talley, N. J., Schoenfeld, P. S., Quigley, E. M. & Moayyedi, P. Efficacy of antidepressants and psychological therapies in irritable bowel syndrome: systematic review and meta-analysis. Gut 58, 367–378 (2009).

    Article  CAS  PubMed  Google Scholar 

  28. Spiller, R. & Garsed, K. Postinfectious irritable bowel syndrome. Gastroenterology 136, 1979–1988 (2009).

    Article  PubMed  Google Scholar 

  29. O'Mahony, L. et al. Lactobacillus and Bifidobacterium in irritable bowel syndrome: symptom responses and relationship to cytokine profiles. Gastroenterology 128, 541–551 (2005).

    Article  PubMed  Google Scholar 

  30. Whorwell, P. J. et al. Efficacy of an encapsulated probiotic Bifidobacterium infantis 35624 in women with irritable bowel syndrome. Am. J. Gastroenterol. 101, 1581–1590 (2006).

    Article  PubMed  Google Scholar 

  31. Agrawal, A. et al. Clinical trial: the effects of a fermented milk product containing Bifidobacterium lactis DN-173-010 on abdominal distension and gastrointestinal transit in irritable bowel syndrome with constipation. Aliment. Pharmacol. Ther. 29, 104–114 (2008).

    Article  PubMed  Google Scholar 

  32. Guyonnet, D. et al. Effect of a fermented milk containing Bifidobacterium animalis DN-173 010 on the health-related quality of life and symptoms in irritable bowel syndrome in adults in primary care: a multicentre, randomized, double-blind, controlled trial. Aliment. Pharmacol. Ther. 26, 475–486 (2007).

    Article  CAS  PubMed  Google Scholar 

  33. Moayyedi, P. et al. The efficacy of probiotics in the treatment of irritable bowel syndrome: a systematic review. Gut 59, 325–332 (2010).

    Article  CAS  PubMed  Google Scholar 

  34. Brenner, D. M., Moeller, M. J., Chey, W. D. & Schoenfeld, P. S. The utility of probiotics in the treatment of irritable bowel syndrome: a systematic review. Am. J. Gastroenterol. 104, 1033–1049 (2009).

    Article  CAS  PubMed  Google Scholar 

  35. Soderholm, J. D. et al. Neonatal maternal separation predisposes adult rats to colonic barrier dysfunction in response to mild stress. Am. J. Physiol. Gastrointest. Liver Physiol. 283, G1257–G1263 (2002).

    Article  CAS  PubMed  Google Scholar 

  36. Gareau, M. G., Jury, J., MacQueen, G., Sherman, P. M. & Perdue, M. H. Probiotic treatment of rat pups normalises corticosterone release and ameliorates colonic dysfunction induced by maternal separation. Gut 56, 1522–1528 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. O'Mahony, S. M. et al. Early life stress alters behavior, immunity, and microbiota in rats: implications for irritable bowel syndrome and psychiatric illnesses. Biol. Psychiatry 65, 263–267 (2009).

    Article  PubMed  Google Scholar 

  38. Soderholm, J. D. et al. Chronic stress induces mast cell-dependent bacterial adherence and initiates mucosal inflammation in rat intestine. Gastroenterology 123, 1099–1108 (2002).

    Article  PubMed  Google Scholar 

  39. Zareie, M. et al. Probiotics prevent bacterial translocation and improve intestinal barrier function in rats following chronic psychological stress. Gut 55, 1553–1560 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Rousseaux, C. et al. Lactobacillus acidophilus modulates intestinal pain and induces opioid and cannabinoid receptors. Nat. Med. 13, 35–37 (2007).

    Article  CAS  PubMed  Google Scholar 

  41. Verdu, E. F. et al. Specific probiotic therapy attenuates antibiotic induced visceral hypersensitivity in mice. Gut 55, 182–190 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Verdu, E. F. et al. Lactobacillus paracasei normalizes muscle hypercontractility in a murine model of postinfective gut dysfunction. Gastroenterology 127, 826–837 (2004).

    Article  CAS  PubMed  Google Scholar 

  43. Kamiya, T. et al. Inhibitory effects of Lactobacillus reuteri on visceral pain induced by colorectal distension in Sprague-Dawley rats. Gut 55, 191–196 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Ait-Belgnaoui, A. et al. Lactobacillus farciminis treatment attenuates stress-induced overexpression of Fos protein in spinal and supraspinal sites after colorectal distension in rats. Neurogastroenterol. Motil. 21, 567–569 (2009).

    Article  CAS  PubMed  Google Scholar 

  45. Mankertz, J. & Schulzke, J. D. Altered permeability in inflammatory bowel disease: pathophysiology and clinical implications. Curr. Opin. Gastroenterol. 23, 379–383 (2007).

    Article  CAS  PubMed  Google Scholar 

  46. Shanahan, F. & Bernstein, C. N. The evolving epidemiology of inflammatory bowel disease. Curr. Opin. Gastroenterol. 25, 301–305 (2009).

    Article  PubMed  Google Scholar 

  47. Sokol, H. et al. Faecalibacterium prausnitzii is an anti-inflammatory commensal bacterium identified by gut microbiota analysis of Crohn disease patients. Proc. Natl Acad. Sci. USA 105, 16731–16736 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Darfeuille-Michaud, A. et al. High prevalence of adherent-invasive Escherichia coli associated with ileal mucosa in Crohn's disease. Gastroenterology 127, 412–421 (2004).

    Article  PubMed  Google Scholar 

  49. Barnich, N. et al. CEACAM6 acts as a receptor for adherent-invasive E. coli, supporting ileal mucosa colonization in Crohn disease. J. Clin. Invest. 117, 1566–1574 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Isaacs, K. & Herfarth, H. Role of probiotic therapy in IBD. Inflamm. Bowel Dis. 14, 1597–1605 (2008).

    Article  PubMed  Google Scholar 

  51. Pronio, A. 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. 14, 662–668 (2008).

    Article  PubMed  Google Scholar 

  52. Bibiloni, R. et al. VSL#3 probiotic-mixture induces remission in patients with active ulcerative colitis. Am. J. Gastroenterol. 100, 1539–1546 (2005).

    Article  PubMed  Google Scholar 

  53. Hansen, R., Thomson, J. M., El Omar, E. M. & Hold, G. L. The role of infection in the aetiology of inflammatory bowel disease. J. Gastroenterol. 45, 266–276 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  54. Marteau, P. Bacterial flora in inflammatory bowel disease. Dig. Dis. 27 (Suppl. 1), 99–103 (2009).

    Article  PubMed  Google Scholar 

  55. Ingrassia, I., Leplingard, A. & Darfeuille-Michaud, A. Lactobacillus casei DN-114 001 inhibits the ability of adherent-invasive Escherichia coli isolated from Crohn's disease patients to adhere to and to invade intestinal epithelial cells. Appl. Environ. Microbiol. 71, 2880–2887 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Johnson-Henry, K. C. et al. Amelioration of the effects of Citrobacter rodentium infection in mice by pretreatment with probiotics. J. Infect. Dis. 191, 2106–2117 (2005).

    Article  PubMed  Google Scholar 

  57. Wu, X. et al. Saccharomyces boulardii ameliorates Citrobacter rodentium-induced colitis through actions on bacterial virulence factors. Am. J. Physiol. Gastrointest. Liver Physiol. 294, G295–G306 (2008).

    Article  CAS  PubMed  Google Scholar 

  58. Ewaschuk, J. B. et al. Secreted bioactive factors from Bifidobacterium infantis enhance epithelial cell barrier function. Am. J. Physiol. Gastrointest. Liver Physiol. 295, G1025–G1034 (2008).

    Article  CAS  PubMed  Google Scholar 

  59. Ukena, S. N. et al. Probiotic Escherichia coli Nissle 1917 inhibits leaky gut by enhancing mucosal integrity. PLos ONE 2, e1308 (2007).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  60. Mennigen, R. et al. Probiotic mixture VSL#3 protects the epithelial barrier by maintaining tight junction protein expression and preventing apoptosis in a murine model of colitis. Am. J. Physiol. Gastrointest. Liver Physiol. 296, G1140–G1149 (2009).

    Article  CAS  PubMed  Google Scholar 

  61. Miyauchi, E., Morita, H. & Tanabe, S. Lactobacillus rhamnosus alleviates intestinal barrier dysfunction in part by increasing expression of zonula occludens-1 and myosin light-chain kinase in vivo. J. Dairy Sci. 92, 2400–2408 (2009).

    Article  CAS  PubMed  Google Scholar 

  62. Tien, M. T. et al. Anti-inflammatory effect of Lactobacillus casei on Shigella-infected human intestinal epithelial cells. J. Immunol. 176, 1228–1237 (2006).

    Article  CAS  PubMed  Google Scholar 

  63. Kamada, N. et al. Nonpathogenic Escherichia coli strain Nissle 1917 inhibits signal transduction in intestinal epithelial cells. Infect. Immun. 76, 214–220 (2008).

    Article  CAS  PubMed  Google Scholar 

  64. Roselli, M. et al. Prevention of TNBS-induced colitis by different Lactobacillus and Bifidobacterium strains is associated with an expansion of gammadeltaT and regulatory T cells of intestinal intraepithelial lymphocytes. Inflamm. Bowel Dis. 15, 1526–1536 (2009).

    Article  PubMed  Google Scholar 

  65. Hacini-Rachinel, F. et al. CD4+ T cells and Lactobacillus casei control relapsing colitis mediated by CD8+ T cells. J. Immunol. 183, 5477–5486 (2009).

    Article  CAS  PubMed  Google Scholar 

  66. Kwon, H. K. et al. Generation of regulatory dendritic cells and CD4+Foxp3+ T cells by probiotics administration suppresses immune disorders. Proc. Natl Acad. Sci. USA 107, 2159–2164 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Chen, C. C., Louie, S., Shi, H. N. & Walker, W. A. Preinoculation with the probiotic Lactobacillus acidophilus early in life effectively inhibits murine Citrobacter rodentium colitis. Pediatr. Res. 58, 1185–1191 (2005).

    Article  PubMed  Google Scholar 

  68. Im, E., Choi, Y. J., Pothoulakis, C. & Rhee, S. H. Bacillus polyfermenticus ameliorates colonic inflammation by promoting cytoprotective effects in colitic mice. J. Nutr. 139, 1848–1854 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Carol, M. et al. Modulation of apoptosis in intestinal lymphocytes by a probiotic bacteria in Crohn's disease. J. Leukoc. Biol. 79, 917–922 (2006).

    Article  CAS  PubMed  Google Scholar 

  70. Llopis, M. et al. Lactobacillus casei downregulates commensals' inflammatory signals in Crohn's disease mucosa. Inflamm. Bowel Dis. 15, 275–283 (2009).

    Article  PubMed  Google Scholar 

  71. Schultz, M. et al. Lactobacillus plantarum 299V in the treatment and prevention of spontaneous colitis in interleukin-10-deficient mice. Inflamm. Bowel Dis. 8, 71–80 (2002).

    Article  PubMed  Google Scholar 

  72. Jijon, H. et al. DNA from probiotic bacteria modulates murine and human epithelial and immune function. Gastroenterology 126, 1358–1373 (2004).

    Article  CAS  PubMed  Google Scholar 

  73. Pagnini, C. et al. Probiotics promote gut health through stimulation of epithelial innate immunity. Proc. Natl Acad. Sci. USA 107, 454–459 (2010).

    Article  CAS  PubMed  Google Scholar 

  74. Madsen, K. et al. Probiotic bacteria enhance murine and human intestinal epithelial barrier function. Gastroenterology 121, 580–591 (2001).

    Article  CAS  PubMed  Google Scholar 

  75. Conte, M. P. et al. Gut-associated bacterial microbiota in paediatric patients with inflammatory bowel disease. Gut 55, 1760–1767 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  76. Miele, E. et al. Effect of a probiotic preparation (VSL#3) on induction and maintenance of remission in children with ulcerative colitis. Am. J. Gastroenterol. 104, 437–443 (2009).

    Article  CAS  PubMed  Google Scholar 

  77. Huynh, H. Q. et al. Probiotic preparation VSL#3 induces remission in children with mild to moderate acute ulcerative colitis: a pilot study. Inflamm. Bowel Dis. 15, 760–768 (2009).

    Article  PubMed  Google Scholar 

  78. Guandalini, S. et al. VSL#3 improves symptoms in children with irritable bowel syndrome: a multicenter, randomized, placebo-controlled, double-blind, crossover study. J. Pediatr. Gastroenterol. Nutr. 51, 24–30 (2010).

    Article  PubMed  Google Scholar 

  79. Fedorak, R. N. Understanding why probiotic therapies can be effective in treating IBD. J. Clin. Gastroenterol. 42 (Suppl. 3), S111–S115 (2008).

    Article  PubMed  Google Scholar 

  80. Petrosyan, M., Guner, Y. S., Williams, M., Grishin, A. & Ford, H. R. Current concepts regarding the pathogenesis of necrotizing enterocolitis. Pediatr. Surg. Int. 25, 309–318 (2009).

    Article  PubMed  Google Scholar 

  81. Morowitz, M. J., Poroyko, V., Caplan, M., Alverdy, J. & Liu, D. C. Redefining the role of intestinal microbes in the pathogenesis of necrotizing enterocolitis. Pediatrics 125, 777–785 (2010).

    Article  PubMed  Google Scholar 

  82. Cotten, C. M. et al. Prolonged duration of initial empirical antibiotic treatment is associated with increased rates of necrotizing enterocolitis and death for extremely low birth weight infants. Pediatrics 123, 58–66 (2009).

    Article  PubMed  Google Scholar 

  83. Wang, Y. et al. 16S rRNA gene-based analysis of fecal microbiota from preterm infants with and without necrotizing enterocolitis. ISME J. 3, 944–954 (2009).

    Article  CAS  PubMed  Google Scholar 

  84. Alfaleh, K., Anabrees, J. & Bassler, D. Probiotics reduce the risk of necrotizing enterocolitis in preterm infants: a meta-analysis. Neonatology 97, 93–99 (2009).

    Article  PubMed  Google Scholar 

  85. Deshpande, G., Rao, S., Patole, S. & Bulsara, M. Updated meta-analysis of probiotics for preventing necrotizing enterocolitis in preterm neonates. Pediatrics 125, 921–930 (2010).

    Article  PubMed  Google Scholar 

  86. Chou, I. C. et al. Lack of effects of oral probiotics on growth and neurodevelopmental outcomes in preterm very low birth weight infants. J. Pediatr. 156, 393–396 (2010).

    Article  PubMed  Google Scholar 

  87. Lin, H. C. et al. Oral probiotics prevent necrotizing enterocolitis in very low birth weight preterm infants: a multicenter, randomized, controlled trial. Pediatrics 122, 693–700 (2008).

    Article  PubMed  Google Scholar 

  88. Manzoni, P. et al. Bovine lactoferrin supplementation for prevention of late-onset sepsis in very low-birth-weight neonates: a randomized trial. JAMA 302, 1421–1428 (2009).

    Article  CAS  PubMed  Google Scholar 

  89. Rouge, C. et al. Oral supplementation with probiotics in very-low-birth-weight preterm infants: a randomized, double-blind, placebo-controlled trial. Am. J. Clin. Nutr. 89, 1828–1835 (2009).

    Article  CAS  PubMed  Google Scholar 

  90. Luoto, R., Matomaki, J., Isolauri, E. & Lehtonen, L. Incidence of necrotizing enterocolitis in very-low-birth-weight infants related to the use of Lactobacillus GG. Acta Paediatr. 99, 1135–1138 (2010).

    Article  CAS  PubMed  Google Scholar 

  91. Khailova, L. et al. Bifidobacterium bifidum improves intestinal integrity in a rat model of necrotizing enterocolitis. Am. J. Physiol. Gastrointest. Liver Physiol. 297, G940–G949 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  92. Lin, P. W., Nasr, T. R., Berardinelli, A. J., Kumar, A. & Neish, A. S. The probiotic Lactobacillus GG may augment intestinal host defense by regulating apoptosis and promoting cytoprotective responses in the developing murine gut. Pediatr. Res. 64, 511–516 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  93. McFarland, L. V. Update on the changing epidemiology of Clostridium difficile-associated disease. Nat. Clin. Pract. Gastroenterol. Hepatol. 5, 40–48 (2008).

    Article  PubMed  Google Scholar 

  94. Leffler, D. A. & Lamont, J. T. Treatment of Clostridium difficile-associated disease. Gastroenterology 136, 1899–1912 (2009).

    Article  CAS  PubMed  Google Scholar 

  95. McFarland, L. V. Meta-analysis of probiotics for the prevention of antibiotic associated diarrhea and the treatment of Clostridium difficile disease. Am. J. Gastroenterol. 101, 812–822 (2006).

    Article  PubMed  Google Scholar 

  96. Pillai, A. & Nelson, R. Probiotics for treatment of Clostridium difficile-associated colitis in adults. Cochrane Database of Systematic Reviews, Issue 1. Art no.: CD004611. doi:10.1002/14651858.CD004611.pub2. (2008).

    Google Scholar 

  97. Miller, M. The fascination with probiotics for Clostridium difficile infection: lack of evidence for prophylactic or therapeutic efficacy. Anaerobe 15, 281–284 (2009).

    Article  PubMed  Google Scholar 

  98. Tung, J. M., Dolovich, L. R. & Lee, C. H. Prevention of Clostridium difficile infection with Saccharomyces boulardii: A systematic review. Can. J. Gastroenterol. 23, 817–821 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  99. McFarland, L. V. Antibiotic-associated diarrhea: epidemiology, trends and treatment. Future Microbiol. 3, 563–578 (2008).

    Article  PubMed  Google Scholar 

  100. Lonnermark, E. et al. Intake of Lactobacillus plantarum reduces certain gastrointestinal symptoms during treatment with antibiotics. J. Clin. Gastroenterol. 44, 106–112 (2010).

    Article  PubMed  Google Scholar 

  101. Ruszczynski, M., Radzikowski, A. & Szajewska, H. Clinical trial: effectiveness of Lactobacillus rhamnosus (strains E/N, Oxy and Pen) in the prevention of antibiotic-associated diarrhoea in children. Aliment. Pharmacol. Ther. 28, 154–161 (2008).

    Article  CAS  PubMed  Google Scholar 

  102. McFarland, L. V. Systematic review and meta-analysis of Saccharomyces boulardii in adult patients. World J. Gastroenterol. 16, 2202–2222 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  103. Chen, C. C. et al. Probiotics have clinical, microbiologic, and immunologic efficacy in acute infectious diarrhea. Pediatr. Infect. Dis. J. 29, 135–138 (2010).

    Article  PubMed  Google Scholar 

  104. Pedone, C. A., Arnaud, C. C., Postaire, E. R., Bouley, C. F. & Reinert, P. Multicentric study of the effect of milk fermented by Lactobacillus casei on the incidence of diarrhoea. Int. J. Clin. Pract. 54, 568–571 (2000).

    CAS  PubMed  Google Scholar 

  105. Pedone, C. A., Bernabeu, A. O., Postaire, E. R., Bouley, C. F. & Reinert, P. The effect of supplementation with milk fermented by Lactobacillus casei (strain DN-114 001) on acute diarrhoea in children attending day care centres. Int. J. Clin. Pract. 53, 179–184 (1999).

    CAS  PubMed  Google Scholar 

  106. Szajewska, H. & Mrukowicz, J. Z. Probiotics in the treatment and prevention of acute infectious diarrhea in infants and children: a systematic review of published randomized, double-blind, placebo-controlled trials. J. Pediatr. Gastroenterol. Nutr. 33 (Suppl. 2), S17–S25 (2001).

    Article  CAS  PubMed  Google Scholar 

  107. Van Niel, C. W., Feudtner, C., Garrison, M. M. & Christakis, D. A. Lactobacillus therapy for acute infectious diarrhea in children: a meta-analysis. Pediatrics 109, 678–684 (2002).

    Article  PubMed  Google Scholar 

  108. Huang, J. S., Bousvaros, A., Lee, J. W., Diaz, A. & Davidson, E. J. Efficacy of probiotic use in acute diarrhea in children: a meta-analysis. Dig. Dis. Sci. 47, 2625–2634 (2002).

    Article  CAS  PubMed  Google Scholar 

  109. Szajewska, H., Skorka, A. & Dylag, M. Meta-analysis: Saccharomyces boulardii for treating acute diarrhoea in children. Aliment. Pharmacol. Ther. 25, 257–264 (2007).

    Article  CAS  PubMed  Google Scholar 

  110. Szajewska, H., Skorka, A., Ruszczynski, M. & Gieruszczak-Bialek, D. Meta-analysis: Lactobacillus GG for treating acute diarrhoea in children. Aliment. Pharmacol. Ther. 25, 871–881 (2007).

    Article  CAS  PubMed  Google Scholar 

  111. Wine, E., Gareau, M. G., Johnson-Henry, K. & Sherman, P. M. Strain-specific probiotic (Lactobacillus helveticus) inhibition of Campylobacter jejuni invasion of human intestinal epithelial cells. FEMS Microbiol. Lett. 300, 146–152 (2009).

    Article  CAS  PubMed  Google Scholar 

  112. Corr, S. C. et al. Bacteriocin production as a mechanism for the antiinfective activity of Lactobacillus salivarius UCC118. Proc. Natl Acad. Sci. USA 104, 7617–7621 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Konstantinov, S. R. et al. S layer protein A of Lactobacillus acidophilus NCFM regulates immature dendritic cell and T cell functions. Proc. Natl Acad. Sci. USA 105, 19474–19479 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  114. Johnson-Henry, K. C., Hagen, K. E., Gordonpour, M., Tompkins, T. A. & Sherman, P. M. Surface-layer protein extracts from Lactobacillus helveticus inhibit enterohaemorrhagic Escherichia coli O157:H7 adhesion to epithelial cells. Cell Microbiol. 9, 356–367 (2007).

    Article  CAS  PubMed  Google Scholar 

  115. Mondel, M. et al. Probiotic E. coli treatment mediates antimicrobial human beta-defensin synthesis and fecal excretion in humans. Mucosal Immunol. 2, 166–172 (2009).

    Article  CAS  PubMed  Google Scholar 

  116. Sherman, P. M. et al. Probiotics reduce enterohemorrhagic Escherichia coli O157:H7- and enteropathogenic E. coli O127:H6-induced changes in polarized T84 epithelial cell monolayers by reducing bacterial adhesion and cytoskeletal rearrangements. Infect. Immun. 73, 5183–5188 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Johnson-Henry, K. C., Donato, K. A., Shen-Tu, G., Gordanpour, M. & Sherman, P. M. Lactobacillus rhamnosus strain GG prevents enterohemorrhagic Escherichia coli O157:H7-induced changes in epithelial barrier function. Infect. Immun. 76, 1340–1348 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. Gareau, M. G., Wine, E., Reardon, C. & Sherman, P. M. Probiotics prevent death caused by Citrobacter rodentium infection in neonatal mice. J. Infect. Dis. 201, 81–91 (2010).

    Article  PubMed  Google Scholar 

  119. O'Mahony, C. et al. Commensal-induced regulatory T cells mediate protection against pathogen-stimulated NF-kappaB activation. PLoS Pathog. 4, e1000112 (2008).

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  120. Steidler, L. et al. Treatment of murine colitis by Lactococcus lactis secreting interleukin-10. Science 289, 1352–1355 (2000).

    Article  CAS  PubMed  Google Scholar 

  121. Braat, H. et al. A phase I trial with transgenic bacteria expressing interleukin-10 in Crohn's disease. Clin. Gastroenterol. Hepatol. 4, 754–759 (2006).

    Article  CAS  PubMed  Google Scholar 

  122. Sturm, A. & Dignass, A. U. Epithelial restitution and wound healing in inflammatory bowel disease. World J. Gastroenterol. 14, 348–353 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  123. Vandenbroucke, K. et al. Active delivery of trefoil factors by genetically modified Lactococcus lactis prevents and heals acute colitis in mice. Gastroenterology 127, 502–513 (2004).

    Article  CAS  PubMed  Google Scholar 

  124. Lih-Brody, L. et al. Increased oxidative stress and decreased antioxidant defenses in mucosa of inflammatory bowel disease. Dig. Dis. Sci. 41, 2078–2086 (1996).

    Article  CAS  PubMed  Google Scholar 

  125. Carroll, I. M. et al. Anti-inflammatory properties of Lactobacillus gasseri expressing manganese superoxide dismutase using the interleukin 10-deficient mouse model of colitis. Am. J. Physiol. Gastrointest. Liver Physiol. 293, G729–G738 (2007).

    Article  CAS  PubMed  Google Scholar 

  126. Hamady, Z. Z. et al. Xylan-regulated delivery of human keratinocyte growth factor-2 to the inflamed colon by the human anaerobic commensal bacterium Bacteroides ovatus. Gut 59, 461–469 (2010).

    Article  CAS  PubMed  Google Scholar 

  127. De Groote, M. A., Frank, D. N., Dowell, E., Glode, M. P. & Pace, N. R. Lactobacillus rhamnosus GG bacteremia associated with probiotic use in a child with short gut syndrome. Pediatr. Infect. Dis. J. 24, 278–280 (2005).

    Article  PubMed  Google Scholar 

  128. Land, M. H. et al. Lactobacillus sepsis associated with probiotic therapy. Pediatrics 115, 178–181 (2005).

    Article  PubMed  Google Scholar 

  129. Barton, L. L., Rider, E. D. & Coen, R. W. Bacteremic infection with Pediococcus: vancomycin-resistant opportunist. Pediatrics 107, 775–776 (2001).

    Article  CAS  PubMed  Google Scholar 

  130. van Minnen, L. P. et al. Modification of intestinal flora with multispecies probiotics reduces bacterial translocation and improves clinical course in a rat model of acute pancreatitis. Surgery 141, 470–480 (2007).

    Article  PubMed  Google Scholar 

  131. Besselink, M. G. et al. Probiotic prophylaxis in predicted severe acute pancreatitis: a randomised, double-blind, placebo-controlled trial. Lancet 371, 651–659 (2008).

    Article  PubMed  Google Scholar 

  132. Sorokulova, I. Preclinical testing in the development of probiotics: a regulatory perspective with Bacillus strains as an example. Clin. Infect. Dis. 46 (Suppl. 2), S92–S95 (2008).

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

Work in the authors' laboratories is supported by grants from the National Institutes of Health (WAW: R01 HD012437, R01 DK070260, P01 DK033506 and P30 DK040561), the Canadian Institutes of Health Research (PMS), and a Fay Shapiro-Cutler grant-in-aid from the Crohn's and Colitis Foundation of Canada (MGG & PMS). MGG is the recipient of a CIHR/CCFC/Canadian Association of Gastroenterology fellowship. PMS is the recipient of a Canada Research Chair in Gastrointestinal Disease.

Author information

Authors and Affiliations

Authors

Contributions

M. G. Gareau researched data for the article and wrote the article. All three authors contributed equally to discussions of the content of the article and to review/editing of the manuscript before submission.

Corresponding author

Correspondence to Philip M. Sherman.

Ethics declarations

Competing interests

M. G. Gareau declares no competing interests. P. M. Sherman has received grant/research support from the Institut Rosell Lallemand and is a Consultant for Mead Johnson, Abbott, and Nestle. W. A. Walker is a Consultant for Dannon and Mead Johnson.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gareau, M., Sherman, P. & Walker, W. Probiotics and the gut microbiota in intestinal health and disease. Nat Rev Gastroenterol Hepatol 7, 503–514 (2010). https://doi.org/10.1038/nrgastro.2010.117

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrgastro.2010.117

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing