Health benefits of probiotics: are mixtures more effective than single strains?

Abstract

Purpose

Most studies on probiotics utilise single strains, sometimes incorporated into yoghurts. There are fewer studies on efficacy of mixtures of probiotic strains. This review examines the evidence that (a) probiotic mixtures are beneficial for a range of health-related outcomes and (b) mixtures are more or less effective than their component strains administered separately.

Results

Mixtures of probiotics had beneficial effects on the end points including irritable bowel syndrome and gut function, diarrhoea, atopic disease, immune function and respiratory tract infections, gut microbiota modulation, inflammatory bowel disease and treatment of Helicobacter pylori infection. However, only 16 studies compared the effect of a mixture with that of its component strains separately, although in 12 cases (75%), the mixture was more effective.

Conclusion

Probiotic mixtures appear to be effective against a wide range of end points. Based on a limited number of studies, multi-strain probiotics appear to show greater efficacy than single strains, including strains that are components of the mixtures themselves. However, whether this is due to synergistic interactions between strains or a consequence of the higher probiotic dose used in some studies is at present unclear.

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

References

  1. 1.

    Joint FAO/WHO Expert Consultation on Evaluation of Health and Nutritional Properties of Probiotics in Food Including Powder Milk with Live Lactic Acid Bacteria (2001) Health and nutritional properties of probiotics in food including powder milk with live lactic acid bacteria. Food and Agriculture Organization of the United Nations, World Health Organization

  2. 2.

    McFarland LV (2007) Meta-analysis of probiotics for the prevention of traveler’s diarrhoea. Travel Med Infect Dis 5(2):97–105

    Article  Google Scholar 

  3. 3.

    Rowland IR, Capurso L, Collins K, Cummings J, Delzenne N, Goulet O, Guarner F, Marteau P, Meier R (2010) Consensus on probiotic science. Gut Microbes 1 (in press)

  4. 4.

    Shibolet O, Karmeli F, Eliakim R, Swennen E, Brigidi P, Gionchetti P, Campieri M, Morgenstern S, Rachmilewitz D (2002) Variable response to probiotics in two models of experimental colitis in rats. Inflamm Bowel Dis 8(6):399–406

    Article  Google Scholar 

  5. 5.

    Lema M, Williams L, Rao DR (2001) Reduction of fecal shedding of enterohemorrhagic Escherichia coli O157:H7 in lambs by feeding microbial feed supplement. Small Rumin Res 39(1):31–39

    Article  Google Scholar 

  6. 6.

    Paubert-Braquet M, Xiao-Hu G, Gaudichon C, Hedef N, Serikoff A, Bouley C, Braquet BBP (1995) Enhancement of the host resistance against Salmonella Typhimurium in mice fed a diet of supplemented yogurt or milks fermented with various Lactobacillus Caseu strains. Int J Immunother 11(4):153–161

    Google Scholar 

  7. 7.

    Perdigon G, Nader de Macias ME, Alvarez S, Oliver G, Pesce de Ruiz Holgado AA (1990) Prevention of gastrointestinal infection using immunobiological methods with milk fermented with Lactobacillus casei and Lactobacillus acidophilus. J Dairy Res 57(2):255–264

    CAS  Article  Google Scholar 

  8. 8.

    Haller D, Antoine JM, Bengmark S, Enck P, Rijkers GT, Lenoir-Wijnkoop I (2010) Guidance for substantiating the evidence for beneficial effects of probiotics: probiotics in chronic inflammatory bowel disease and the functional disorder irritable bowel syndrome. J Nutr 140(3):690S–697S

    CAS  Article  Google Scholar 

  9. 9.

    Brigidi P, Vitali B, Swennen E, Bazzocchi G, Matteuzzi D (2001) Effects of probiotic administration upon the composition and enzymatic activity of human fecal microbiota in patients with irritable bowel syndrome or functional diarrhoea. Res Microbiol 152(8):735–741

    CAS  Article  Google Scholar 

  10. 10.

    Kim HJ, Camilleri M, McKinzie S, Lempke MB, Burton DD, Thomforde GM, Zinsmeister AR (2003) A randomized controlled trial of a probiotic, VSL#3, on gut transit and symptoms in diarrhoea-predominant irritable bowel syndrome. Aliment Pharmacol Ther 17(7):895–904

    CAS  Article  Google Scholar 

  11. 11.

    Kim HJ, Vazquez Roque MI, Camilleri M, Stephens D, Burton DD, Baxter K, Thomforde G, Zinsmeister AR (2005) A randomized controlled trial of a probiotic combination VSL#3 and placebo in irritable bowel syndrome with bloating. Neurogastroenterol Motil 17(5):687–696

    CAS  Article  Google Scholar 

  12. 12.

    Patel SM, Stason WB, Legedza A, Ock SM, Kaptchuk TJ, Conboy L, Canenguez K, Park JK, Kelly E, Jacobson E, Kerr CE, Lembo AJ (2005) The placebo effect in irritable bowel syndrome trials: a meta-analysis. Neurogastroenterol Motil 17(3):332–340

    CAS  Article  Google Scholar 

  13. 13.

    Kajander K, Hatakka K, Poussa T, Farkkila M, Korpela R (2005) A probiotic mixture alleviates symptoms in irritable bowel syndrome patients: a controlled 6-month intervention. Aliment Pharmacol Ther 22(5):387–394

    CAS  Article  Google Scholar 

  14. 14.

    Kajander K, Krogius-Kurikka L, Rinttila T, Karjalainen H, Palva A, Korpela R (2007) Effects of multispecies probiotic supplementation on intestinal microbiota in irritable bowel syndrome. Aliment Pharmacol Ther 26(3):463–473

    CAS  Article  Google Scholar 

  15. 15.

    Kajander K, Myllyluoma E, Rajilic-Stojanovic M, Kyronpalo S, Rasmussen M, Jarvenpaa S, Zoetendal EG, de Vos WM, Vapaatalo H, Korpela R (2008) Clinical trial: multispecies probiotic supplementation alleviates the symptoms of irritable bowel syndrome and stabilizes intestinal microbiota. Aliment Pharmacol Ther 27(1):48–57

    CAS  Article  Google Scholar 

  16. 16.

    O’Sullivan MA, O’Morain CA (2000) Bacterial supplementation in the irritable bowel syndrome. A randomised double-blind placebo-controlled crossover study. Dig Liver Dis 32(4):294–301

    Article  Google Scholar 

  17. 17.

    Ouwehand AC, Lagstrom H, Suomalainen T, Salminen S (2002) Effect of probiotics on constipation, fecal azoreductase activity and fecal mucin content in the elderly. Ann Nutr Metab 46(3–4):159–162

    CAS  Article  Google Scholar 

  18. 18.

    Olivares M, Diaz-Ropero MA, Gomez N, Lara-Villoslada F, Sierra S, Maldonado JA, Martin R, Lopez-Huertas E, Rodriguez JM, Xaus J (2006) Oral administration of two probiotic strains, Lactobacillus gasseri CECT5714 and Lactobacillus coryniformis CECT5711, enhances the intestinal function of healthy adults. Int J Food Microbiol 107(2):104–111

    Article  Google Scholar 

  19. 19.

    Fabia R, Ar’Rajab A, Johansson ML, Willen R, Andersson R, Molin G, Bengmark S (1993) The effect of exogenous administration of Lactobacillus reuteri R2LC and oat fiber on acetic acid-induced colitis in the rat. Scand J Gastroenterol 28(2):155–162

    CAS  Article  Google Scholar 

  20. 20.

    Favier C, Neut C, Mizon C, Cortot A, Colombel JF, Mizon J (1997) Fecal beta-d-galactosidase production and Bifidobacteria are decreased in Crohn’s disease. Dig Dis Sci 42(4):817–822

    CAS  Article  Google Scholar 

  21. 21.

    Bibiloni R, Fedorak RN, Tannock GW, Madsen KL, Gionchetti P, Campieri M, De Simone C, Sartor RB (2005) VSL#3 probiotic-mixture induces remission in patients with active ulcerative colitis. Am J Gastroenterol 100(7):1539–1546

    Article  Google Scholar 

  22. 22.

    Venturi A, Gionchetti P, Rizzello F, Johansson R, Zucconi E, Brigidi P, Matteuzzi D, Campieri M (1999) 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 13(8):1103–1108

    CAS  Article  Google Scholar 

  23. 23.

    Cui HH, Chen CL, Wang JD, Yang YJ, Cun Y, Wu JB, Liu YH, Dan HL, Jian YT, Chen XQ (2004) Effects of probiotic on intestinal mucosa of patients with ulcerative colitis. World J Gastroenterol 10(10):1521–1525

    CAS  Google Scholar 

  24. 24.

    Sandborn WJ (1994) Pouchitis following ileal pouch-anal anastomosis: definition, pathogenesis, and treatment. Gastroenterology 107(6):1856–1860

    CAS  Google Scholar 

  25. 25.

    Madden MV, McIntyre AS, Nicholls RJ (1994) Double-blind crossover trial of metronidazole versus placebo in chronic unremitting pouchitis. Dig Dis Sci 39(6):1193–1196

    CAS  Article  Google Scholar 

  26. 26.

    Gionchetti P, Rizzello F, Helwig U, Venturi A, Lammers KM, Brigidi P, Vitali B, Poggioli G, Miglioli M, Campieri M (2003) Prophylaxis of pouchitis onset with probiotic therapy: a double-blind, placebo-controlled trial. Gastroenterology 124(5):1202–1209

    Article  Google Scholar 

  27. 27.

    Gionchetti P, Rizzello F, Venturi A, Brigidi P, Matteuzzi D, Bazzocchi G, Poggioli G, Miglioli M, Campieri M (2000) Oral bacteriotherapy as maintenance treatment in patients with chronic pouchitis: a double-blind, placebo-controlled trial. Gastroenterology 119(2):305–309

    CAS  Article  Google Scholar 

  28. 28.

    Mimura T, Rizzello F, Helwig U, Poggioli G, Schreiber S, Talbot IC, Nicholls RJ, Gionchetti P, Campieri M, Kamm MA (2004) Once daily high dose probiotic therapy (VSL#3) for maintaining remission in recurrent or refractory pouchitis. Gut 53(1):108–114

    CAS  Article  Google Scholar 

  29. 29.

    Bergogne-Berezin E (2000) Treatment and prevention of antibiotic associated diarrhoea. Int J Antimicrob Agents 16(4):521–526

    CAS  Article  Google Scholar 

  30. 30.

    Williams C, McColl KE (2006) Review article: proton pump inhibitors and bacterial overgrowth. Aliment Pharmacol Ther 23(1):3–10

    CAS  Article  Google Scholar 

  31. 31.

    Cremonini F, Di Caro S, Covino M, Armuzzi A, Gabrielli M, Santarelli L, Nista EC, Cammarota G, Gasbarrini G, Gasbarrini A (2002) Effect of different probiotic preparations on anti-helicobacter pylori therapy-related side effects: a parallel group, triple blind, placebo-controlled study. Am J Gastroenterol 97(11):2744–2749

    Article  Google Scholar 

  32. 32.

    Myllyluoma E, Veijola L, Ahlroos T, Tynkkynen S, Kankuri E, Vapaatalo H, Rautelin H, Korpela R (2005) Probiotic supplementation improves tolerance to Helicobacter pylori eradication therapy—a placebo-controlled, double-blind randomized pilot study. Aliment Pharmacol Ther 21(10):1263–1272

    CAS  Article  Google Scholar 

  33. 33.

    Finegold SM (1970) Interaction of antimicrobial therapy and intestinal flora. Am J Clin Nutr 23(11):1466–1471

    CAS  Google Scholar 

  34. 34.

    Nord CE, Lidbeck A, Orrhage K, Sjostedt S (1997) Oral supplementation with lactic acid-producing bacteria during intake of clindamycin. Clin Microbiol Infect 3(1):124–132

    CAS  Article  Google Scholar 

  35. 35.

    Orrhage K, Sjostedt S, Nord CE (2000) Effect of supplements with lactic acid bacteria and oligofructose on the intestinal microflora during administration of cefpodoxime proxetil. J Antimicrob Chemother 46(4):603–612

    CAS  Article  Google Scholar 

  36. 36.

    Zoppi G, Cinquetti M, Benini A, Bonamini E, Minelli EB (2001) Modulation of the intestinal ecosystem by probiotics in children during treatment with Cefratriaxone. Current Therapeutic Research 62(5):418–435

    CAS  Article  Google Scholar 

  37. 37.

    Rosenfeldt V, Benfeldt E, Nielsen SD, Michaelsen KF, Jeppesen DL, Valerius NH, Paerregaard A (2003) Effect of probiotic Lactobacillus strains in children with atopic dermatitis. J Allergy Clin Immunol 111(2):389–395

    Article  Google Scholar 

  38. 38.

    Viljanen M, Kuitunen M, Haahtela T, Juntunen-Backman K, Korpela R, Savilahti E (2005) Probiotic effects on faecal inflammatory markers and on faecal IgA in food allergic atopic eczema/dermatitis syndrome infants. Pediatr Allergy Immunol 16(1):65–71

    Article  Google Scholar 

  39. 39.

    Viljanen M, Savilahti E, Haahtela T, Juntunen-Backman K, Korpela R, Poussa T, Tuure T, Kuitunen M (2005) Probiotics in the treatment of atopic eczema/dermatitis syndrome in infants: a double-blind placebo-controlled trial. Allergy 60(4):494–500

    CAS  Article  Google Scholar 

  40. 40.

    Klüken H, Wienker T, Bieber T (2003) Atopic eczema/dermatitis syndrome—a genetically complex disease. New advances in discovering the genetic contribution. Allergy 58(1):5–12

    Article  Google Scholar 

  41. 41.

    Kane EM, Turcios RM, Arvay ML, Garcia S, Bresee JS, Glass RI (2004) The epidemiology of rotavirus diarrhoea in Latin America. Anticipating rotavirus vaccines. Rev Panam Salud Publica 16(6):371–377

    Article  Google Scholar 

  42. 42.

    Samadi AR, Islam R, Huq MI (1983) Replacement of intravenous therapy by oral rehydration solution in a large treatment centre for diarrhoea with dehydration. Bull World Health Organ 61(3):471–476

    CAS  Google Scholar 

  43. 43.

    Boirivant M, Strober W (2007) The mechanism of action of probiotics. Curr Opin Gastroenterol 23(6):679–692

    Article  Google Scholar 

  44. 44.

    Barone C, Pettinato R, Avola E, Alberti A, Greco D, Failla P, Romano C (2000) Comparison of three probiotics in the treatment of acute diarrhoea in mentally retarded children. Minerva Pediatr 52(3):161–165

    CAS  Google Scholar 

  45. 45.

    Rosenfeldt V, Michaelsen KF, Jakobsen M, Larsen CN, Moller PL, Pedersen P, Tvede M, Weyrehter H, Valerius NH, Paerregaard A (2002) Effect of probiotic Lactobacillus strains in young children hospitalized with acute diarrhoea. Pediatr Infect Dis J 21(5):411–416

    Article  Google Scholar 

  46. 46.

    Saavedra JM, Bauman NA, Oung I, Perman JA, Yolken RH (1994) Feeding of Bifidobacterium bifidum and Streptococcus thermophilus to infants in hospital for prevention of diarrhoea and shedding of rotavirus. Lancet 344(8929):1046–1049

    CAS  Article  Google Scholar 

  47. 47.

    Grandy G, Medina M, Soria R, Teran CG, Araya M (2010) Probiotics in the treatment of acute rotavirus diarrhoea. A randomized, double-blind, controlled trial using two different probiotic preparations in Bolivian children. BMC Infect Dis 10(1):253

    Article  Google Scholar 

  48. 48.

    Barbut F, Petit JC (2001) Epidemiology of Clostridium difficile-associated infections. Clin Microbiol Infect 7(8):405–410

    CAS  Article  Google Scholar 

  49. 49.

    Gotz V, Romankiewicz JA, Moss J, Murray HW (1979) Prophylaxis against ampicillin-associated diarrhoea with a lactobacillus preparation. Am J Hosp Pharm 36(6):754–757

    CAS  Google Scholar 

  50. 50.

    Hickson M, D’Souza AL, Muthu N, Rogers TR, Want S, Rajkumar C, Bulpitt CJ (2007) Use of probiotic Lactobacillus preparation to prevent diarrhoea associated with antibiotics: randomised double blind placebo controlled trial. BMJ 335(7610):80

    Article  Google Scholar 

  51. 51.

    Plummer S, Weaver MA, Harris JC, Dee P, Hunter J (2004) Clostridium difficile pilot study: effects of probiotic supplementation on the incidence of C. difficile diarrhoea. Int Microbiol 7(1):59–62

    Google Scholar 

  52. 52.

    de Vrese M, Winkler P, Rautenberg P, Harder T, Noah C, Laue C, Ott S, Hampe J, Schreiber S, Heller K, Schrezenmeir J (2006) Probiotic bacteria reduced duration and severity but not the incidence of common cold episodes in a double blind, randomized, controlled trial. Vaccine 24(44–46):6670–6674

    Google Scholar 

  53. 53.

    Winkler P, de Vrese M, Laue C, Schrezenmeir J (2005) Effect of a dietary supplement containing probiotic bacteria plus vitamins and minerals on common cold infections and cellular immune parameters. Int J Clin Pharmacol Ther 43(7):318–326

    CAS  Google Scholar 

  54. 54.

    Olivares M, Diaz-Ropero MP, Gomez N, Lara-Villoslada F, Sierra S, Maldonado JA, Martin R, Rodriguez JM, Xaus J (2006) The consumption of two new probiotic strains, Lactobacillus gasseri CECT 5714 and Lactobacillus coryniformis CECT 5711, boosts the immune system of healthy humans. Int Microbiol 9(1):47–52

    CAS  Google Scholar 

  55. 55.

    Gluck U, Gebbers JO (2003) Ingested probiotics reduce nasal colonization with pathogenic bacteria (Staphylococcus aureus, Streptococcus pneumoniae, and beta-hemolytic streptococci). Am J Clin Nutr 77(2):517–520

    CAS  Google Scholar 

  56. 56.

    Hatakka K, Blomgren K, Pohjavuori S, Kaijalainen T, Poussa T, Leinonen M, Korpela R, Pitkaranta A (2007) Treatment of acute otitis media with probiotics in otitis-prone children-a double-blind, placebo-controlled randomised study. Clin Nutr 26(3):314–321

    Article  Google Scholar 

  57. 57.

    Lin JS, Chiu YH, Lin NT, Chu CH, Huang KC, Liao KW, Peng KC (2009) Different effects of probiotic species/strains on infections in preschool children: A double-blind, randomized, controlled study. Vaccine 27(7):1073–1079

    Article  Google Scholar 

  58. 58.

    Yao-Zong Y, Shi-Rong L, Delvaux M (2004) Comparative efficacy of dioctahedral smectite (Smecta) and a probiotic preparation in chronic functional diarrhoea. Dig Liver Dis 36(12):824–828

    CAS  Article  Google Scholar 

  59. 59.

    Collado MC, Isolauri E, Salminen S (2008) Specific probiotic strains and their combinations counteract adhesion of Enterobacter sakazakii to intestinal mucus. FEMS Microbiol Lett 285(1):58–64

    CAS  Article  Google Scholar 

  60. 60.

    Collado MC, Jalonen L, Meriluoto J, Salminen S (2006) Protection mechanism of probiotic combination against human pathogens: in vitro adhesion to human intestinal mucus. Asia Pac J Clin Nutr 15(4):570–575

    Google Scholar 

  61. 61.

    Myllyluoma E, Ahonen AM, Korpela R, Vapaatalo H, Kankuri E (2008) Effects of multispecies probiotic combination on helicobacter pylori infection in vitro. Clin Vaccine Immunol 15(9):1472–1482

    CAS  Article  Google Scholar 

  62. 62.

    Roselli M, Finamore A, Britti MS, Mengheri E (2006) Probiotic bacteria Bifidobacterium animalis MB5 and Lactobacillus rhamnosus GG protect intestinal Caco-2 cells from the inflammation-associated response induced by enterotoxigenic Escherichia coli K88. Br J Nutr 95(6):1177–1184

    CAS  Article  Google Scholar 

  63. 63.

    Collado MC, Meriluoto J, Salminen S (2007) Development of new probiotics by strain combinations: is it possible to improve the adhesion to intestinal mucus? J Dairy Sci 90(6):2710–2716

    CAS  Article  Google Scholar 

  64. 64.

    Ouwehand AC, Tuomola EM, Tolkko S, Salminen S (2001) Assessment of adhesion properties of novel probiotic strains to human intestinal mucus. Int J Food Microbiol 64(1–2):119–126

    CAS  Article  Google Scholar 

  65. 65.

    Apella MC, Gonzalez SN, Nader de Macias ME, Romero N, Oliver G (1992) In vitro studies on the growth of Shigella sonnei by Lactobacillus casei and Lact. acidophilus. J Appl Bacteriol 73(6):480–483

    CAS  Google Scholar 

  66. 66.

    Drago L, Gismondo MR, Lombardi A, de Haen C, Gozzini L (1997) Inhibition of in vitro growth of enteropathogens by new Lactobacillus isolates of human intestinal origin. FEMS Microbiol Lett 153(2):455–463

    CAS  Article  Google Scholar 

  67. 67.

    Ridwan BU, Koning CJ, Besselink MG, Timmerman HM, Brouwer EC, Verhoef J, Gooszen HG, Akkermans LM (2008) Antimicrobial activity of a multispecies probiotic (Ecologic 641) against pathogens isolated from infected pancreatic necrosis. Lett Appl Microbiol 46(1):61–67

    CAS  Google Scholar 

Download references

Acknowledgments

This work forms part of a PhD project funded by Probiotics International, Somerset, UK.

Author information

Affiliations

Authors

Corresponding author

Correspondence to C. M. C. Chapman.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Chapman, C.M.C., Gibson, G.R. & Rowland, I. Health benefits of probiotics: are mixtures more effective than single strains?. Eur J Nutr 50, 1–17 (2011). https://doi.org/10.1007/s00394-010-0166-z

Download citation

Keywords

  • Multi-strain probiotics
  • Health benefits
  • Synergy
  • Probiotic efficacy