Clinical Reviews in Allergy & Immunology

, Volume 22, Issue 3, pp 255–273 | Cite as

Probiotics in clinical conditions

  • Philippe R. Marteau


Probiotics are nonpathogenic microorganisms which, when ingested, exert a positive influence on the health or physiology of the host. Their mechanisms of action and effects are now studied using the same pharmacological approach as for drugs. This article summarizes and comments on evidence for the positive effects of probiotics in various clinical situations. Substantial evidence can be achieved when randomized controlled trials or meta-analyses show positive results. The clinical situations studied include prevention or treatment of antibiotic-associated disorders, gastroenteritis, and diarrhea, lactose intolerance, intestinal infections and colonization by pathogenic bacteria (including Helicobacter pylori and Clostridium difficile), traveler's diarrhea, irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), colonic cancer, urogenital infections and tumors, allergy (especially atopic eczema), vaccination, and cholesterol lowering. Current probiotics have an excellent safety record—another topic discussed in this article.

Probiotics can be defined as nonpathogenic microorganisms which, when ingested, exert a positive influence on host health or physiology (1). They consist of either bacteria, especially lactic-acid bacteria (LAB), or yeast (Saccharomyces), and are increasingly used in foods—especially fermented milks—and pharmaceutical products. Physicians have long been skeptical about their “real” efficacy (2,3), and have raised three basic questions: are probiotic products stable, do they survive in the gastrointestinal tract, and what is the level of evidence for their efficacy? A pharmacological approach was used to assess the positive effects and potential side effects of the products as well as their pharmacokinetics (2,4). The level of evidence for efficacy can be assessed with the rules of evidence-based medicine. We now know that the stability of many products (but not all) is good (5), that many strains (but not all) survive in the gastrointestinal tract (4), and that many double-blind randomized controlled trials (RCT) reported that some probiotics were more efficient than a placebo or a control treatment in specific clinical situations. The effects can be direct or indirect through modulation of the endogenous flora or of the immune system (2). Some effects have clearly been demonstrated, and the level of evidence is still lower for other effects. The article summarizes the present knowledge on the clinical applications of probiotics in humans.

Key words

Probiotics bifidobacterium lactobacillus intestinal infections antibiotic-associated diarrhea gastroenteritis traveler's diarrhea intestinal flora inflammatory bowel disease colonic cancer allergy atopic eczema oral vaccination safety of probiotics 


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  1. 1.
    Fuller, R. (1989). J. Appl. Bacteriol. 66,365–378.PubMedGoogle Scholar
  2. 2.
    Marteau, P., Pochart, P., Bouhnik, Y., and Rambaud, J. C. (1993). World Rev. Nutr. Diet 74,1–21.PubMedGoogle Scholar
  3. 3.
    Dunne, C., Murphy, L, Flynn, S., O'Mahony, L, O'Halloran, S., Feeney, M., et al. (1999). Antonie Leeuwenhoek 76,279–292.PubMedGoogle Scholar
  4. 4.
    Marteau, P. and Vesa, T. (1998). Bioscience Microflora 17,1–6.Google Scholar
  5. 5.
    Canganella, F., Paganini, S., Ovidi, M., Vettraino, A.M., Bevilacqua, L., Massa, S., et al. (1997). Microbiol. Res. 152,171–179.PubMedGoogle Scholar
  6. 6.
    Adam, J., Banet, A., and Banet-Bellet, C. (1977). Gaz. Méd. Fr. 84,2072–2078.Google Scholar
  7. 7.
    Surawicz, C.M., Elmer, G.W., Speelman, P., McFarland, L.V., Chinn, J., and van Belle, G. (1989). Gastroenterology 96, 981–988.PubMedGoogle Scholar
  8. 8.
    McFarland, L.V., Surawicz, C.M., Greenberg, R.N., Elmer, G.W., Moyer, K.A., and Melcher, S.A. (1995). Am. J. Gastroenterol. 90,439–448.PubMedGoogle Scholar
  9. 9.
    Lewis, S.J., Potts, L.F., and Barry, R.E. (1998). J. Infect. 36,171–174.PubMedGoogle Scholar
  10. 10.
    Ligny, G. (1975). Rev. Fr. Gastroentérologie 114,45–50.Google Scholar
  11. 11.
    Elmer, G.W., Surawicz, C.M., and McFarland, L.V. (1996). JAMA 275:870–876.PubMedGoogle Scholar
  12. 12.
    Qamar, A., Aboudola, S., Warny, M., Michetti, P., Pothoulakis, C., LaMont, J.T., et al. (2001). Infect. Immun. 69,2762–2765.PubMedGoogle Scholar
  13. 13.
    Vanderhoof, J.A., Whitney, D.B., Antonson, D.L., Hanner, T.L., Lupo, J.V., and Young, R.J. (1999). J. Pediatr. 135,564–568.PubMedGoogle Scholar
  14. 14.
    Arvola, T., Laiho, K., Torkkeli, S., Mykkanen, H., Salminen, S., Maunula, L., et al. (1999). Pediatrics 104,e64.PubMedGoogle Scholar
  15. 15.
    Borgia, M., Sepe, N., Brancato, V., and Borgia, R. (1982). Curr. Ther. Res. 31,265–271.Google Scholar
  16. 16.
    Wunderlich, P.F., Braun, L., Fumagalli, I., D'Apuzzo, V., Heim, F., Karly, M., et al. (1989). J. Int. Med. Res. 17,333–338.PubMedGoogle Scholar
  17. 17.
    Gotz, V., Romankiewicz, J.A., Moss, J., and Murray, H.W. (1979). Am. J. Hosp. Pharm. 36,754–757.PubMedGoogle Scholar
  18. 18.
    Clements, M.L., Levine, M.M., Ristiano, P.A., Daya, V.E., and Hughes, T.P. (1983). Prog. Food Nutr. Sci. 7,29–37.PubMedGoogle Scholar
  19. 19.
    Witsell, D.L., Garrett, C.G., Yarbrough, W.G., Dorrestein, S.P., Drake, A.F., and Weissler, M.C. (1995). J. Otolaryngol. 24,230–233.PubMedGoogle Scholar
  20. 20.
    Marteau, P. (1992). Ann. Gastroentérol. Hépatol. 28,181–184.Google Scholar
  21. 21.
    Isolauri, E., Juntunen, M., Rautanen, T., Sillanaukee, P., and Koivula, T. (1991). Pediatrics 88,90–97.PubMedGoogle Scholar
  22. 22.
    Kaila, M., Isolauri, E., Soppi, E., Virtanen, E., Laine, S., and Arvilommi, H. (1992). Pediatr. Res. 32,141–144.PubMedGoogle Scholar
  23. 23.
    Majamaa, H., Isolauri, E., Saxelin, M., and Vesikari, T. (1995). J. Pediatr. Gastroenterol. Nutr. 20,333–338.PubMedGoogle Scholar
  24. 24.
    Isolauri, E., Kaila, M., Mykkanen, H., Ling, W.H., and Salminen, S. (1994). Dig. Dis. Sci. 39,2595–2600.PubMedGoogle Scholar
  25. 25.
    Raza, S., Graham, S.M., Allen, S.J., Sultana, S., Cuevas, L., and Hart, C.A. (1995). Pediatr. Infect. Dis. J. 14,107–111.PubMedGoogle Scholar
  26. 26.
    Pant, A.R., Graham, S.M., Allen, S.J., Harikul, S., Sabchareon, A., Cuevas, L., et al. (1996). J. Tropic. Pediatr. 42,162–165.Google Scholar
  27. 27.
    Guarino, A., Canani, R.B., Spagnuolo, M.I., Albano, F., and Di Benedetto, L. (1997). J. Pediatr. Gastroenterol. Nutr. 25,516–519.PubMedGoogle Scholar
  28. 28.
    Shornikova, A.V., Isolauri, E., Burkanova, L., Lukovnikova, S., and Vesikari, T. (1997). Acta Paediatr. 86,460–465.PubMedGoogle Scholar
  29. 29.
    Guandalini, S., Pensabene, L., Zikri, M.A., Dias, J.A., Casali, L.G., Hoekstra, H., et al. (2000). J. Ped. Gastroenterol. Nutr. 30,54–60.Google Scholar
  30. 30.
    Bellomo, G., Mangiagle, A., Nicastro, L., et al. (1980). Curr. Ther. Res. 28,927–936.Google Scholar
  31. 31.
    Camarri, E., Belvisi, A., Guidoni, G., Marini, G., and Frigerio, G. (1981). Chemotherapy 27,466–470.PubMedGoogle Scholar
  32. 32.
    Buydens, P. and Debeuckelaere, S. (1996). Scand. J. Gastroenterol. 31,887–891.PubMedGoogle Scholar
  33. 33.
    Chapoy, P. (1985). Ann. Pediatr. 32:1–3.Google Scholar
  34. 34.
    Sugita, T. and Togawa, M. (1994). Jap. J. Pediatry 47:2755–2762.Google Scholar
  35. 35.
    Shornikova, A.V., Casas, I.A., Mykkanen, H., Salo, E., and Vesikari, T. (1997). Pediatr. Infect. Dis. J. 16,1103–1107.PubMedGoogle Scholar
  36. 36.
    Kaila, M., Isolauri, E., Saxelin, M., Arvilommi, H., and Vesikari, T. (1995). Arch. Dis. Child. 72,51–53.PubMedGoogle Scholar
  37. 37.
    Bodilis, J.Y. (1983). Méd. Actu. 10,232–235.Google Scholar
  38. 38.
    Saavedra, J.M., Bauman, N.A., Oung, I., Perman, J.A., and Yolken, R.H. (1994). Lancet 344,1046–1049.PubMedGoogle Scholar
  39. 39.
    Szajewska, H., Kotowska, M., Mrukowicz, J.Z., Armanska, M., and Mikolajczyk, W. (2001). J. Pediatr. 138,361–365.PubMedGoogle Scholar
  40. 40.
    Mastretta, E., Longo, P., Laccisaglia, A., Balbo, L., Russo, R., Muzzaccara, A., gianino, P. J. Verrdiate. Gastroentrol, Nutr., in press.Google Scholar
  41. 41.
    Oberhelman, R.A., Gilman, R.H., Sheen, P., Taylor, D.N., Black, R.E., Cabrera, L., et al. (1999). J. Pediatr. 134,15–20.PubMedGoogle Scholar
  42. 42.
    Marteau, P., Flourié, B., Pochart, P., Chastang, C., Desjeux, J.F., and Rambaud, J.C., Br. J. Nutr. 64,71–79.Google Scholar
  43. 43.
    Marteau, P., Vesa, T., and Rambaud, J.C. (1997), Lactose maldigestion, in Probiotics, Fuller, R., ed., Chapman & Hall, pp. 65–88.Google Scholar
  44. 44.
    Marteau, P., Messing, B., Arrigoni, E., Briet, F., Flourié, B., Morin, M.C., et al. (1997). Nutrition 13,13–16.PubMedGoogle Scholar
  45. 45.
    Harms, H.K., Bertele-Harms, R.M., and Bruer-Kleis, D. (1987). N. Engl. J. Med. 316,1306–1309.PubMedGoogle Scholar
  46. 46.
    Drouault, S., Juste, C., Marteau, P., Renault, P., and Corthier, G. (2001). Gastroenterology. 20,A3642.Google Scholar
  47. 47.
    Huber, J.T. (1997), Probiotics in cattle, in Probiotics, Fuller, R., ed., Chapman & Hall, London, pp. 162–185.Google Scholar
  48. 48.
    Mulder, R., Havenaar, R., and Huis in't Veld, J. (1997), Intervention strategies: the use of probiotics and competitive exclusion microfloras against contamination with pathogens in pigs and poultry, in Probiotics, Fuller, R., ed., Chapman & Hall, London, pp. 186–208.Google Scholar
  49. 49.
    McFarland, L.V., Surawicz, C.M., Greenberg, R.N., Fekety, R., Elmer, G.W., Moyer, K.A., et al. (1994). JAMA 271,1913–1918.PubMedGoogle Scholar
  50. 50.
    Surawicz, C.M., McFarland, L.V., Greenberg, R.N., Rubin, M., Fekety, R., Mulligan, M.E., et al. (2000). Clin. Infect. Dis. 31,1012–1017.PubMedGoogle Scholar
  51. 51.
    Coconnier, M.H., Lievin, V., Hemery, E., and Servin, A.L. (1998). Appl. Environ. Microbiol. 64,4573–4580.PubMedGoogle Scholar
  52. 52.
    Michetti, P., Dorta, G., Wiesel, P.H., Brassart, D., Verdu, E., Herranz, M., et al. (1999). Digestion 60,203–209.PubMedGoogle Scholar
  53. 53.
    Canducci, F., Armuzzi, A., Cremonini, F., Cammarota, G., Bartolozzi, F., Pola, P., et al. (2000). Alim. Pharmacol. Ther. 14,1625–1629.Google Scholar
  54. 54.
    Felley, C.P., Corthesy-Theulaz, I., Rivero, J.L., Sipponen, P., Kaufmann, M., Bauerfeind, P., et al. (2001). Eur. J. Gastroenteroly Hepatol. 13:25–29.Google Scholar
  55. 55.
    Armuzzi, A., Cremonini, F., Bartolozzi, F., Canducci, F., Candelli, M., Ojetti, V., et al. (2001). Aliment. Pharmacol. Ther. 15,163–169.PubMedGoogle Scholar
  56. 56.
    DuPont, H.L. and the Practice Parameters Committee of the American College of Gastroenterology. (1997). Am. J. Gastroenterol. 92,1962–1975.PubMedGoogle Scholar
  57. 57.
    Kollaritsch von, H., Holst, H, Grobara, P., and Wiedermann, G. (1993). Fortschr Med 111,153–156.Google Scholar
  58. 58.
    Oksanen, P.J., Salminen, S., Saxelin, M., Hamalainen, P., Ihantola-Vormisto, A., Muurasniemi-Isoviita, L., et al. (1990). Ann. Med. 22,53–56.PubMedGoogle Scholar
  59. 59.
    Hilton, E., Kolakowski, P., Singer, C., and Smith, M. (1997). J. Travel Med. 4,41–43.PubMedGoogle Scholar
  60. 60.
    Bouglé, D., Roland, N., Lebeurrier, F., and Arhan, P. (1999). Scand. J. Gastroenterol. 34,144–148.PubMedGoogle Scholar
  61. 61.
    Marteau, P., Cuillerier, E., Gerhardt, M.F., Myara, A., Bouvier, M., Bouley, C., et al. (2001). Gastroenterol. Clin. Biol. 25,A122.Google Scholar
  62. 62.
    Maupas, J.L., Champemont, P., and Delforge, M. (1983), Méd. Chir. Dig. 12,77–79.Google Scholar
  63. 63.
    Halpern, G.M., Prindiville, T., Blanckenburg, M., Hsia, T., and Gerschwin, M.E. (1996). Am. J. Gastroenterol. 91,1579–1585.PubMedGoogle Scholar
  64. 64.
    Hentschel, C., Bauer, J., Dill, N., et al. (1997). Gastroenterology 112,A146.Google Scholar
  65. 65.
    Tempé, J.D., Steidel, A.L., Bléhaut, H., Hasselmann, M., Lutun, P., and Maurier, F. (1983). Sem. Hôp Paris 59,1409–1412.PubMedGoogle Scholar
  66. 66.
    Schlotterer, M., Bernasconi, P., Lebreton, F., and Wassermann, D. (1987). Nutr. Clin. Métab. 1:31–34.Google Scholar
  67. 67.
    Bleichner, G., Bléhaut, H., Mentec, H., and Moyse, D. (1997). Intensive Care Med. 23,517–523.PubMedGoogle Scholar
  68. 68.
    Simenhoff, M.L., Dunn, S.R., Zollner, G.P., Fitzpatrick, M.E., Emery, S.M., and Sandine, W.E. (1996). Miner. Electrolyte Metab. 22,92–96.PubMedGoogle Scholar
  69. 69.
    Vanderhoof, J.A., Young, R.J., Murray, N., and Kaufman, S.S. (1998). Gastroenterol. Nutr. 27,155–160.Google Scholar
  70. 70.
    Attar, A., Flourié, B., Rambaud, J.C, Franchisseur, C., Ruszniewski, P., and Bouhnik, Y. (1999). Gastroenterology 117,794–797.PubMedGoogle Scholar
  71. 71.
    Salminen, E., Elomaa, I., Minkkinen, J., Vapaatalo, H., and Salminen, S. (1988). Clin. Radiol. 39,4357.Google Scholar
  72. 72.
    Shanahan, F. (2001). Gastroenterology 120,622–635.PubMedGoogle Scholar
  73. 73.
    Marteau, P. and Shanahan, F. (2001), Role of antibiotics and probiotics in the management of inflammatory bowel disease, in Inflammatory Bowel Disease: From Bench to Bedside, 2nd ed., in press.Google Scholar
  74. 74.
    Kruis, W., Schütz, E., Fric, P., Fixa, B., Judmaier, G., and Stolte, M. (1997). Aliment. Pharmacol. Ther. 11,853–858.PubMedGoogle Scholar
  75. 75.
    Rembacken, B.J., Snelling, A.M., Hawkey, P.M., Chalmers, D.M., and Axon, A.T. (1999). Lancet 354,635–639.PubMedGoogle Scholar
  76. 76.
    Malchow, H.A. (1997). J. Clin. Gastroenterol. 25,653–658.PubMedGoogle Scholar
  77. 77.
    Gionchetti, P., Rizzello, F., Venturi, A., Brigidi, P., Matteuzzi, D., Bazzocchi, G., et al. (2000). Gastroenterology 119,305–309.PubMedGoogle Scholar
  78. 78.
    Gionchetti, P., Rizzello, F., Venturi, A., Helwig, U., Amadini, C., Lammers, K.M., et al. Gastroenterology 118,G1214.Google Scholar
  79. 79.
    Campieri, M., Rizzello, F., Venturi, A., et al. (2000). Gastroenterology 118,G4179.Google Scholar
  80. 80.
    Copaci, I., Micu, L., Chira, C., and Rovinaru, I. (2000). Gut 47(suppl III),A240-P929.Google Scholar
  81. 81.
    Guslandi, M., Mezzi, G., Sorghi, M., and Testoni, PA. (2000). Dig. Dis. Sci. 45,1462–1464.PubMedGoogle Scholar
  82. 82.
    Ishikawa, H., Imaoka, A., Umesaki, Y., Tanaka, R., and Ohtani, T. (2000). Gastroenterology 118,A4171.Google Scholar
  83. 83.
    Ruseler van Embden, J.G.H., Schouten, W.R., and van Lieshout, L.M.C. (1994). Gut 35,658–664.PubMedGoogle Scholar
  84. 84.
    Gionchetti, P., Orsla, O., Rizzello, F., Cifone, G., Benturi, A., D'Alo, S., et al. (1999). Gastroenterology 116,A723.Google Scholar
  85. 85.
    Plein, K. and Hotz, J. (1993). Z. Gastroenterol. 31,129–134.PubMedGoogle Scholar
  86. 86.
    Hirayama, K. and Rafter, J. (2000). Microbes Infect. 2,681–686.PubMedGoogle Scholar
  87. 87.
    Wollowski, I., Rechkemmer, G., and Pool-Zobel, B.L. (2001). Am. J. Clin. Nutr. 73(2 Suppl),451S-455S.PubMedGoogle Scholar
  88. 88.
    Boutron, M.C., Faivre, J., Marteau, P., Couillault, C., Senesse, P., and Quipourt, V. (1996). Br. J. Cancer 74,145–151.PubMedGoogle Scholar
  89. 89.
    Drutz, D.J. (1992). Ann. Intern. Med. 116,419–420.PubMedGoogle Scholar
  90. 90.
    Reid, G., Bruce, A.W., Fraser, N., Heinemann, C., Owen, J., and Henning, B. (2001). FEMS Immunol. Med. Microbiol. 30,49–52.PubMedGoogle Scholar
  91. 91.
    Reid, G. (2001). Am. J. Clin. Nutr. 73(2 Suppl),437S-443S.PubMedGoogle Scholar
  92. 92.
    Hilton, E., Isenberg, H.D., Alperstein, P., France, and Borenstein, M.T. (1992). Ann. Intern. Med. 116,353–357.PubMedGoogle Scholar
  93. 93.
    Hallen, A., Jarstrand, C., and Pahlson, C. (1992). Sex Transm. Dis. 19,146–148.PubMedGoogle Scholar
  94. 94.
    Aso, Y. and Akazan, H. (1992). Urol. Int. 49,125–129.PubMedGoogle Scholar
  95. 95.
    Aso, Y., Akaza, H., Kotake, T., Tsukamoto, T., Imai, K., Naito, S., and the BLP study group. (1995). Eur. Urol. 27,104–109.PubMedGoogle Scholar
  96. 96.
    Isolauri, E., Arvola, T., Sutas, Y, Moilanen, E., and Salminen, S. (2000). Clin. Exp. Allergy 30,1604–1610.PubMedGoogle Scholar
  97. 97.
    Kalliomaki, M., Salminen, S., Arvilommi, H., Kero, P., Koskinen, P., and Isolauri, E. (2001). Lancet 357,1076–1079.PubMedGoogle Scholar
  98. 98.
    Murch, S. (2000). Curr. Opin. Gastroenterol. 16,552–557.PubMedGoogle Scholar
  99. 99.
    Marteau, P. and Cellier, C. (1998), Immunological effects of biotherapeutic agents, in Biotherapeutic Agents, Humana Press, pp. 121–144.Google Scholar
  100. 100.
    Link-Amster, H., Rochat, F., Saudan, K.Y., Saudan, K.Y., Mignot, O., and Aeschlimann, J.M. (1994). FEMS Immunol. Med. Microbiol. 10,55–64.PubMedGoogle Scholar
  101. 101.
    Fang, H., Elina, T., Heikki, A., and Salminen, S.. FEMS Immunol. Med. Microbiol. 29,47–52.Google Scholar
  102. 102.
    Isolauri, E., Joensuu, J., Suomalainen, H., Luomala, M., and Vesikari, T. (1995). Vaccine 13,310–312.PubMedGoogle Scholar
  103. 103.
    Grangette, C., Muller-Alouf, H., Goudercourt, D., Geoffroy, M.C., Turneer, M., and Mercenier, A. (2001). Infect. Immun. 69,1547–1553.PubMedGoogle Scholar
  104. 104.
    St-Onge, M.P., Farnworth, E.R., and Jones, P.J. (2000). Am. J. Clin. Nutr. 71,674–681.PubMedGoogle Scholar
  105. 105.
    Klaver, F.A. and van der Meer, R.. Appl. Environ. Microbiol. 59,1120–1124.Google Scholar
  106. 106.
    Marteau, P., Gerhardt, M.F., Myara, A., Bouvier, E., Trivin, F., and Rambaud, J.C. (1995). Microbiol. Ecol. Health Dis. 8,151–157.Google Scholar
  107. 107.
    Marteau, P. (2001). Scand. J. Nutr. 45,22–24.Google Scholar
  108. 108.
    Hennequin, C., Kauffmann-Lacroix, C., Jobert, A., Viard, J.P., Ricour, C., Jacquemin, J.L, et al. (2000). Eur. J. Clin. Microbiol. Infect. Dis. 19,16–20.PubMedGoogle Scholar
  109. 109.
    Rautio, M., Jousimies-Somer, H., Kauma, H., Pietarinen, I., Saxelin, M., Tynkkynen, S., et al. (1999). Clin. Infect. Dis 28,1159–1160.PubMedGoogle Scholar
  110. 110.
    MacKay, A., Taylor, M., Kibbler, C., and Hamilton Miller, J. (1999). Clin. Microbiol. Infect. 5,290–292.PubMedGoogle Scholar
  111. 111.
    Saxelin, M., Chuang, N.H., Chassy, B., Rautelin, H., Mäkelä, P.H., Salminen, S., et al. (1996). Clin. Infect. Dis. 22,564–566.PubMedGoogle Scholar
  112. 112.
    Saxelin, M., Rautelin, H., Salminen, S., and Mäkelä, P.H. (1996). Infect. Dis. Clin. Pract. 5,331–335.Google Scholar

Copyright information

© Humana Press Inc 2002

Authors and Affiliations

  • Philippe R. Marteau
    • 1
    • 2
    • 3
  1. 1.Gastroenterology Department, Hôpital Européen Georges PompidouAssistance Publique des Hôpitaux de ParisParis CEDEX 15France
  2. 2.ISTNA (INSERM U557-INRA U1125-EA CNAM 3200)France
  3. 3.Paris V UniversityFrance

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