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Probiotics in respiratory virus infections

  • L. Lehtoranta
  • A. Pitkäranta
  • R. Korpela
Review

Abstract

Viral respiratory infections are the most common diseases in humans. A large range of etiologic agents challenge the development of efficient therapies. Research suggests that probiotics are able to decrease the risk or duration of respiratory infection symptoms. However, the antiviral mechanisms of probiotics are unclear. The purpose of this paper is to review the current knowledge on the effects of probiotics on respiratory virus infections and to provide insights on the possible antiviral mechanisms of probiotics. A PubMed and Scopus database search was performed up to January 2014 using appropriate search terms on probiotic and respiratory virus infections in cell models, in animal models, and in humans, and reviewed for their relevance. Altogether, thirty-three clinical trials were reviewed. The studies varied highly in study design, outcome measures, probiotics, dose, and matrices used. Twenty-eight trials reported that probiotics had beneficial effects in the outcome of respiratory tract infections (RTIs) and five showed no clear benefit. Only eight studies reported investigating viral etiology from the respiratory tract, and one of these reported a significant decrease in viral load. Based on experimental studies, probiotics may exert antiviral effects directly in probiotic–virus interaction or via stimulation of the immune system. Although probiotics seem to be beneficial in respiratory illnesses, the role of probiotics on specific viruses has not been investigated sufficiently. Due to the lack of confirmatory studies and varied data available, more randomized, double-blind, and placebo-controlled trials in different age populations investigating probiotic dose response, comparing probiotic strains/genera, and elucidating the antiviral effect mechanisms are necessary.

Keywords

Lactobacillus Influenza Virus Lactis Respiratory Syncytial Virus Acute Otitis Medium 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Conflict of interest

None.

References

  1. 1.
    Fendrick AM, Monto AS, Nightengale B, Sarnes M (2003) The economic burden of non-influenza-related viral respiratory tract infection in the United States. Arch Intern Med 163:487–494PubMedCrossRefGoogle Scholar
  2. 2.
    Tapparel C, Siegrist F, Petty TJ, Kaiser L (2013) Picornavirus and enterovirus diversity with associated human diseases. Infect Genet Evol 14:282–293PubMedCrossRefGoogle Scholar
  3. 3.
    Zambon MC (1999) Epidemiology and pathogenesis of influenza. J Antimicrob Chemother 44:3–9PubMedCrossRefGoogle Scholar
  4. 4.
    Langley GF, Anderson LJ (2011) Epidemiology and prevention of respiratory syncytial virus infections among infants and young children. Pediatr Infect Dis J 30:510–517PubMedGoogle Scholar
  5. 5.
    Robinson CM, Seto D, Jones MS, Dyer DW, Chodosh J (2011) Molecular evolution of human species D adenoviruses. Infect Genet Evol 11:1208–1217PubMedCentralPubMedCrossRefGoogle Scholar
  6. 6.
    Nichols WG, Peck Campbell AJ, Boeckh M (2008) Respiratory viruses other than influenza virus: impact and therapeutic advances. Clin Microbiol Rev 21:274–290PubMedCentralPubMedCrossRefGoogle Scholar
  7. 7.
    Jartti T, Jartti L, Ruuskanen O, Söderlund-Venermo M (2012) New respiratory viral infections. Curr Opin Pulm Med 18:271–278PubMedCrossRefGoogle Scholar
  8. 8.
    Food and Agriculture Organization of the United Nations/World Health Organization (FAO/WHO) (2002) Guidelines for the evaluation of probiotics in food. Report of a joint FAO/WHO working group on drafting guidelines for the evaluation of probiotics in foodGoogle Scholar
  9. 9.
    Food and Agriculture Organization of the United Nations/World Health Organization (FAO/WHO) (2001) Health and nutritional properties of probiotics in food including powder milk with live lactic acid bacteriaGoogle Scholar
  10. 10.
    Wolvers D, Antoine JM, Myllyluoma E, Schrezenmeir J, Szajewska H, Rijkers GT (2010) Guidance for substantiating the evidence for beneficial effects of probiotics: prevention and management of infections by probiotics. J Nutr 140:698S–712SPubMedCrossRefGoogle Scholar
  11. 11.
    Aureli P, Capurso L, Castellazzi AM, Clerici M, Giovannini M, Morelli L et al (2011) Probiotics and health: an evidence-based review. Pharmacol Res 63:366–376PubMedCrossRefGoogle Scholar
  12. 12.
    Servin AL (2004) Antagonistic activities of lactobacilli and bifidobacteria against microbial pathogens. FEMS Microbiol Rev 28:405–440PubMedCrossRefGoogle Scholar
  13. 13.
    Bodera P, Chcialowski A (2009) Immunomodulatory effect of probiotic bacteria. Recent Pat Inflamm Allergy Drug Discov 3:58–64PubMedCrossRefGoogle Scholar
  14. 14.
    Guarino A, Lo Vecchio A, Canani RB (2009) Probiotics as prevention and treatment for diarrhea. Curr Opin Gastroenterol 25:18–23PubMedCrossRefGoogle Scholar
  15. 15.
    Hao Q, Lu Z, Dong BR, Huang CQ, Wu T (2011) Probiotics for preventing acute upper respiratory tract infections. Cochrane Database Syst Rev (9):CD006895Google Scholar
  16. 16.
    Hori T, Kiyoshima J, Shida K, Yasui H (2001) Effect of intranasal administration of Lactobacillus casei Shirota on influenza virus infection of upper respiratory tract in mice. Clin Diagn Lab Immunol 8:593–597PubMedCentralPubMedGoogle Scholar
  17. 17.
    Yasui H, Kiyoshima J, Hori T (2004) Reduction of influenza virus titer and protection against influenza virus infection in infant mice fed Lactobacillus casei shirota. Clin Diagn Lab Immunol 11:675–679PubMedCentralPubMedGoogle Scholar
  18. 18.
    Maeda N, Nakamura R, Hirose Y, Murosaki S, Yamamoto Y, Kase T et al (2009) Oral administration of heat-killed Lactobacillus plantarum L-137 enhances protection against influenza virus infection by stimulation of type I interferon production in mice. Int Immunopharmacol 9:1122–1125PubMedCrossRefGoogle Scholar
  19. 19.
    Takeda S, Takeshita M, Kikuchi Y, Dashnyam B, Kawahara S, Yoshida H et al (2011) Efficacy of oral administration of heat-killed probiotics from Mongolian dairy products against influenza infection in mice: alleviation of influenza infection by its immunomodulatory activity through intestinal immunity. Int Immunopharmacol 11:1976–1983PubMedCrossRefGoogle Scholar
  20. 20.
    Park MK, Ngo V, Kwon YM, Lee YT, Yoo S, Cho YH et al (2013) Lactobacillus plantarum DK119 as a probiotic confers protection against influenza virus by modulating innate immunity. PLoS One 8:e75368PubMedCentralPubMedCrossRefGoogle Scholar
  21. 21.
    Kawase M, He F, Kubota A, Harata G, Hiramatsu M (2010) Oral administration of lactobacilli from human intestinal tract protects mice against influenza virus infection. Lett Appl Microbiol 51:6–10PubMedGoogle Scholar
  22. 22.
    Kawase M, He F, Kubota A, Yoda K, Miyazawa K, Hiramatsu M (2012) Heat-killed Lactobacillus gasseri TMC0356 protects mice against influenza virus infection by stimulating gut and respiratory immune responses. FEMS Immunol Med Microbiol 64:280–288PubMedCrossRefGoogle Scholar
  23. 23.
    Harata G, He F, Hiruta N, Kawase M, Kubota A, Hiramatsu M et al (2010) Intranasal administration of Lactobacillus rhamnosus GG protects mice from H1N1 influenza virus infection by regulating respiratory immune responses. Lett Appl Microbiol 50:597–602PubMedCrossRefGoogle Scholar
  24. 24.
    Harata G, He F, Hiruta N, Kawase M, Kubota A, Hiramatsu M et al (2011) Intranasally administered Lactobacillus gasseri TMC0356 protects mice from H1N1 influenza virus infection by stimulating respiratory immune responses. World J Microbiol Biotechnol 27:411–416CrossRefGoogle Scholar
  25. 25.
    Lee YN, Youn HN, Kwon JH, Lee DH, Park JK, Yuk SS et al (2013) Sublingual administration of Lactobacillus rhamnosus affects respiratory immune responses and facilitates protection against influenza virus infection in mice. Antiviral Res 98:284–290PubMedCrossRefGoogle Scholar
  26. 26.
    Youn HN, Lee DH, Lee YN, Park JK, Yuk SS, Yang SY et al (2012) Intranasal administration of live Lactobacillus species facilitates protection against influenza virus infection in mice. Antiviral Res 93:138–143PubMedCrossRefGoogle Scholar
  27. 27.
    Yeo JM, Lee HJ, Kim JW, Lee JB, Park SY, Choi IS et al (2014) Lactobacillus fermentum CJL-112 protects mice against influenza virus infection by activating T-helper 1 and eliciting a protective immune response. Int Immunopharmacol 18:50–54PubMedCrossRefGoogle Scholar
  28. 28.
    Waki N, Yajima N, Suganuma H, Buddle BM, Luo D, Heiser A et al (2014) Oral administration of Lactobacillus brevis KB290 to mice alleviates clinical symptoms following influenza virus infection. Lett Appl Microbiol 58:87–93PubMedCrossRefGoogle Scholar
  29. 29.
    Izumo T, Maekawa T, Ida M, Noguchi A, Kitagawa Y, Shibata H et al (2010) Effect of intranasal administration of Lactobacillus pentosus S-PT84 on influenza virus infection in mice. Int Immunopharmacol 10:1101–1106PubMedCrossRefGoogle Scholar
  30. 30.
    Kobayashi N, Saito T, Uematsu T, Kishi K, Toba M, Kohda N et al (2011) Oral administration of heat-killed Lactobacillus pentosus strain b240 augments protection against influenza virus infection in mice. Int Immunopharmacol 11:199–203PubMedCrossRefGoogle Scholar
  31. 31.
    Kiso M, Takano R, Sakabe S, Katsura H, Shinya K, Uraki R et al (2013) Protective efficacy of orally administered, heat-killed Lactobacillus pentosus b240 against influenza A virus. Sci Rep 3:1–8CrossRefGoogle Scholar
  32. 32.
    Goto H, Sagitani A, Ashida N, Kato S, Hirota T, Shinoda T et al (2013) Anti-influenza virus effects of both live and non-live Lactobacillus acidophilus L-92 accompanied by the activation of innate immunity. Br J Nutr 110:1810–1818PubMedCrossRefGoogle Scholar
  33. 33.
    Iwabuchi N, Xiao JZ, Yaeshima T, Iwatsuki K (2011) Oral administration of Bifidobacterium longum ameliorates influenza virus infection in mice. Biol Pharm Bull 34:1352–1355PubMedCrossRefGoogle Scholar
  34. 34.
    Wu S, Jiang ZY, Sun YF, Yu B, Chen J, Dai CQ et al (2013) Microbiota regulates the TLR7 signaling pathway against respiratory tract influenza a virus infection. Curr Microbiol 67:414–422PubMedCrossRefGoogle Scholar
  35. 35.
    Gabryszewski SJ, Bachar O, Dyer KD, Percopo CM, Killoran KE, Domachowske JB et al (2011) Lactobacillus-mediated priming of the respiratory mucosa protects against lethal pneumovirus infection. J Immunol 186:1151–1161PubMedCentralPubMedCrossRefGoogle Scholar
  36. 36.
    Garcia-Crespo KE, Chan CC, Gabryszewski SJ, Percopo CM, Rigaux P, Dyer KD et al (2013) Lactobacillus priming of the respiratory tract: heterologous immunity and protection against lethal pneumovirus infection. Antiviral Res 97:270–279PubMedCentralPubMedCrossRefGoogle Scholar
  37. 37.
    Tomosada Y, Chiba E, Zelaya H, Takahashi T, Tsukida K, Kitazawa H et al (2013) Nasally administered Lactobacillus rhamnosus strains differentially modulate respiratory antiviral immune responses and induce protection against respiratory syncytial virus infection. BMC Immunol 14:40PubMedCentralPubMedCrossRefGoogle Scholar
  38. 38.
    Kechaou N, Chain F, Gratadoux JJ, Blugeon S, Bertho N, Chevalier C et al (2013) Identification of one novel candidate probiotic lactobacillus plantarum strain active against influenza virus infection in mice by a large-scale screening. Appl Environ Microbiol 79:1491–1499PubMedCentralPubMedCrossRefGoogle Scholar
  39. 39.
    Nagai T, Makino S, Ikegami S, Itoh H, Yamada H (2011) Effects of oral administration of yogurt fermented with Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1 and its exopolysaccharides against influenza virus infection in mice. Int Immunopharmacol 11:2246–2250PubMedCrossRefGoogle Scholar
  40. 40.
    Maruo T, Gotoh Y, Nishimura H, Ohashi S, Toda T, Takahashi K (2012) Oral administration of milk fermented with Lactococcus lactis subsp. cremoris FC protects mice against influenza virus infection. Lett Appl Microbiol 55:135–140PubMedCrossRefGoogle Scholar
  41. 41.
    Yasui H, Kiyoshima J, Hori T, Shida K (1999) Protection against influenza virus infection of mice fed Bifidobacterium breve YIT4064. Clin Diagn Lab Immunol 6:186–192PubMedCentralPubMedGoogle Scholar
  42. 42.
    Hatakka K, Savilahti E, Pönkä A, Meurman JH, Poussa T, Näse L et al (2001) Effect of long term consumption of probiotic milk on infections in children attending day care centres: double blind, randomised trial. Br Med J 322:1327–1329CrossRefGoogle Scholar
  43. 43.
    Hojsak I, Snovak N, Abdović S, Szajewska H, Misak Z, Kolacek S (2010) Lactobacillus GG in the prevention of gastrointestinal and respiratory tract infections in children who attend day care centers: a randomized, double-blind, placebo-controlled trial. Clin Nutr 29:312–316PubMedCrossRefGoogle Scholar
  44. 44.
    Hojsak I, Abdović S, Szajewska H, Milošević M, Krznarić Ž, Kolaček S (2010) Lactobacillus GG in the prevention of nosocomial gastrointestinal and respiratory tract infections. Pediatrics 125:e1171–e1177PubMedCrossRefGoogle Scholar
  45. 45.
    Kumpu M, Kekkonen RA, Kautiainen H, Järvenpää S, Kristo A, Huovinen P et al (2012) Milk containing probiotic Lactobacillus rhamnosus GG and respiratory illness in children: a randomized, double-blind, placebo-controlled trial. Eur J Clin Nutr 66:1020–1023PubMedCrossRefGoogle Scholar
  46. 46.
    Luoto R, Ruuskanen O, Waris M, Kalliomäki M, Salminen S, Isolauri E (2013) Prebiotic and probiotic supplementation prevents rhinovirus infections in preterm infants: a randomized, placebo-controlled trial. J Allergy Clin Immunol pii: S0091-6749(13)01307-9Google Scholar
  47. 47.
    Kumpu M, Lehtoranta L, Roivainen M, Rönkkö E, Ziegler T, Söderlund-Venermo M et al (2013) The use of the probiotic Lactobacillus rhamnosus GG and viral findings in the nasopharynx of children attending day care. J Med Virol 85:1652–1658CrossRefGoogle Scholar
  48. 48.
    Liu S, Hu P, Du X, Zhou T, Pei X (2013) Lactobacillus rhamnosus GG supplementation for preventing respiratory infections in children: a meta-analysis of randomized, placebo-controlled trials. Indian Pediatr 50:377–381PubMedCrossRefGoogle Scholar
  49. 49.
    Lin JS, Chiu YH, Lin NT, Chu CH, Huang KC, Liao KW et al (2009) Different effects of probiotic species/strains on infections in preschool children: a double-blind, randomized, controlled study. Vaccine 27:1073–1079PubMedCrossRefGoogle Scholar
  50. 50.
    Cobo Sanz JM, Mateos JA, Muñoz Conejo A (2006) Effect of Lactobacillus casei on the incidence of infectious conditions in children. Nutr Hosp 21:547–551PubMedGoogle Scholar
  51. 51.
    Maldonado J, Cañabate F, Sempere L, Vela F, Sánchez AR, Narbona E et al (2012) Human milk probiotic lactobacillus fermentum CECT5716 reduces the incidence of gastrointestinal and upper respiratory tract infections in infants. J Pediatr Gastroenterol Nutr 54:55–61PubMedCrossRefGoogle Scholar
  52. 52.
    Taipale T, Pienihäkkinen K, Isolauri E, Larsen C, Brockmann E, Alanen P et al (2011) Bifidobacterium animalis subsp. lactis BB-12 in reducing the risk of infections in infancy. Br J Nutr 105:409–416PubMedCrossRefGoogle Scholar
  53. 53.
    Weizman Z, Asli G, Alsheikh A (2005) Effect of a probiotic infant formula on infections in child care centers: comparison of two probiotic agents. Pediatrics 115:5–9PubMedGoogle Scholar
  54. 54.
    Niittynen L, Pitkäranta A, Korpela R (2012) Probiotics and otitis media in children. Int J Pediatr Otorhinolaryngol 76:465–470PubMedCrossRefGoogle Scholar
  55. 55.
    Agustina R, Kok FJ, Van De Rest O, Fahmida U, Firmansyah A, Lukito W et al (2012) Randomized trial of probiotics and calcium on diarrhea and respiratory tract infections in Indonesian children. Pediatrics 129(5):e1155–e1164PubMedCrossRefGoogle Scholar
  56. 56.
    Hatakka K, Blomgren K, Pohjavuori S, Kaijalainen T, Poussa T, Leinonen M et al (2007) Treatment of acute otitis media with probiotics in otitis-prone children—a double-blind, placebo-controlled randomised study. Clin Nutr 26:314–321PubMedCrossRefGoogle Scholar
  57. 57.
    Rautava S, Salminen S, Isolauri E (2009) Specific probiotics in reducing the risk of acute infections in infancy—a randomised, double-blind, placebo-controlled study. Br J Nutr 101:1722–1726PubMedCrossRefGoogle Scholar
  58. 58.
    Rerksuppaphol S, Rerksuppaphol L (2012) Randomized controlled trial of probiotics to reduce common cold in schoolchildren. Pediatr Int 54:682–687PubMedCrossRefGoogle Scholar
  59. 59.
    Lehtoranta L, Söderlund-Venermo M, Nokso-Koivisto J, Toivola H, Blomgren K, Hatakka K et al (2012) Human bocavirus in the nasopharynx of otitis-prone children. Int J Pediatr Otorhinolaryngol 76:206–211PubMedCrossRefGoogle Scholar
  60. 60.
    Hatakka K (2007) Probiotics in the prevention of clinical manifestations of common infectious diseases in children and in the elderly. Dissertation, University of HelsinkiGoogle Scholar
  61. 61.
    Olivares M, Díaz-Ropero MP, Sierra S, Lara-Villoslada F, Fonollá J, Navas M et al (2007) Oral intake of Lactobacillus fermentum CECT5716 enhances the effects of influenza vaccination. Nutrition 23:254–260PubMedCrossRefGoogle Scholar
  62. 62.
    Winkler P, de Vrese M, Laue Ch, 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 43:318–326PubMedCrossRefGoogle Scholar
  63. 63.
    de Vrese M, Winkler P, Rautenberg P, Harder T, Noah C, Laue C et al (2005) Effect of Lactobacillus gasseri PA 16/8, Bifidobacterium longum SP 07/3, B. bifidum MF 20/5 on common cold episodes: a double blind, randomized, controlled trial. Clin Nutr 24:481–491PubMedCrossRefGoogle Scholar
  64. 64.
    de Vrese M, Winkler P, Rautenberg P, Harder T, Noah C, Laue C et al (2006) Probiotic bacteria reduced duration and severity but not the incidence of common cold episodes in a double blind, randomized, controlled trial. Vaccine 24:6670–6674PubMedCrossRefGoogle Scholar
  65. 65.
    West NP, Horn PL, Pyne DB, Gebski VJ, Lahtinen SJ, Fricker PA et al (2013) Probiotic supplementation for respiratory and gastrointestinal illness symptoms in healthy physically active individuals. Clin Nutr pii: S0261-5614(13)00261-6Google Scholar
  66. 66.
    Smith TJ, Rigassio-Radler D, Denmark R, Haley T, Touger-Decker R (2013) Effect of Lactobacillus rhamnosus LGG® and Bifidobacterium animalis ssp. lactis BB-12® on health-related quality of life in college students affected by upper respiratory infections. Br J Nutr 109:1999–2007PubMedCrossRefGoogle Scholar
  67. 67.
    Cox AJ, Pyne DB, Saunders PU, Fricker PA (2010) Oral administration of the probiotic Lactobacillus fermentum VRI-003 and mucosal immunity in endurance athletes. Br J Sports Med 44:222–226PubMedCrossRefGoogle Scholar
  68. 68.
    West NP, Pyne DB, Cripps AW, Hopkins WG, Eskesen DC, Jairath A et al (2011) Lactobacillus fermentum (PCC®) supplementation and gastrointestinal and respiratory-tract illness symptoms: a randomised control trial in athletes. Nutr J 10:30PubMedCentralPubMedCrossRefGoogle Scholar
  69. 69.
    Haywood BA, Black KE, Baker D, McGarvey J, Healey P, Brown RC (2013) Probiotic supplementation reduces the duration and incidence of infections but not severity in elite rugby union players. J Sci Med Sport pii: S1440-2440(13)00190-4Google Scholar
  70. 70.
    Kekkonen RA, Vasankari TJ, Vuorimaa T, Haahtela T, Julkunen I, Korpela R (2007) The effect of probiotics on respiratory infections and gastrointestinal symptoms during training in marathon runners. Int J Sport Nutr Exerc Metab 17:352–363PubMedGoogle Scholar
  71. 71.
    Tiollier E, Chennaoui M, Gomez-Merino D, Drogou C, Filaire E, Guezennec CY (2007) Effect of a probiotics supplementation on respiratory infections and immune and hormonal parameters during intense military training. Mil Med 172:1006–1011PubMedGoogle Scholar
  72. 72.
    Gleeson M, Bishop NC, Oliveira M, McCauley T, Tauler P, Lawrence C (2012) Effects of a Lactobacillus salivarius probiotic intervention on infection, cold symptom duration and severity, and mucosal immunity in endurance athletes. Int J Sport Nutr Exerc Metab 22:235–242PubMedGoogle Scholar
  73. 73.
    Guillemard E, Tanguy J, Flavigny A, de la Motte S, Schrezenmeir J (2010) Effects of consumption of a fermented dairy product containing the probiotic Lactobacillus casei DN-114 001 on common respiratory and gastrointestinal infections in shift workers in a randomized controlled trial. J Am Coll Nutr 29:455–468PubMedCrossRefGoogle Scholar
  74. 74.
    Turchet P, Laurenzano M, Auboiron S, Antoine JM (2003) Effect of fermented milk containing the probiotic Lactobacillus casei DN-114001 on winter infections in free-living elderly subjects: a randomised, controlled pilot study. J Nutr Health Aging 7:75–77PubMedGoogle Scholar
  75. 75.
    Guillemard E, Tondu F, Lacoin F, Schrezenmeir J (2010) Consumption of a fermented dairy product containing the probiotic Lactobacillus casei DN-114001 reduces the duration of respiratory infections in the elderly in a randomised controlled trial. Br J Nutr 103:58–68PubMedCrossRefGoogle Scholar
  76. 76.
    Fujita R, Iimuro S, Shinozaki T, Sakamaki K, Uemura Y, Takeuchi A et al (2013) Decreased duration of acute upper respiratory tract infections with daily intake of fermented milk: a multicenter, double-blinded, randomized comparative study in users of day care facilities for the elderly population. Am J Infect Control 41:1231–1235PubMedCrossRefGoogle Scholar
  77. 77.
    Van Puyenbroeck K, Hens N, Coenen S, Michiels B, Beunckens C, Molenberghs G et al (2012) Efficacy of daily intake of Lactobacillus casei Shirota on respiratory symptoms and influenza vaccination immune response: a randomized, double-blind, placebo-controlled trial in healthy elderly nursing home residents. Am J Clin Nutr 95:1165–1171PubMedCrossRefGoogle Scholar
  78. 78.
    Merenstein D, Murphy M, Fokar A, Hernandez RK, Park H, Nsouli H et al (2010) Use of a fermented dairy probiotic drink containing Lactobacillus casei (DN-114 001) to decrease the rate of illness in kids: the DRINK study. A patient-oriented, double-blind, cluster-randomized, placebo-controlled, clinical trial. Eur J Clin Nutr 64:669–677PubMedCentralPubMedCrossRefGoogle Scholar
  79. 79.
    Agarwal S, Busse PJ (2010) Innate and adaptive immunosenescence. Ann Allergy Asthma Immunol 104:183–190PubMedCrossRefGoogle Scholar
  80. 80.
    Lehtoranta L (2012) Probiotics and virus infections: the effects of Lactobacillus rhamnosus GG on respiratory and gastrointestinal virus infections. Dissertation, University of HelsinkiGoogle Scholar
  81. 81.
    Botić T, Klingberg TD, Weingartl H, Cencic A (2007) A novel eukaryotic cell culture model to study antiviral activity of potential probiotic bacteria. Int J Food Microbiol 115:227–234PubMedCrossRefGoogle Scholar
  82. 82.
    Choi H-J, Song J-H, Ahn Y-J, Baek S-H, Kwon D-H (2009) Antiviral activities of cell-free supernatants of yogurts metabolites against some RNA viruses. Eur Food Res Technol 228:945–950CrossRefGoogle Scholar
  83. 83.
    Ivec M, Botić T, Koren S, Jakobsen M, Weingartl H, Cencic A (2007) Interactions of macrophages with probiotic bacteria lead to increased antiviral response against vesicular stomatitis virus. Antiviral Res 75:266–274PubMedCrossRefGoogle Scholar
  84. 84.
    Pipenbaher N, Moeller PL, Dolinšek J, Jakobsen M, Weingartl H, Cencič A (2009) Nitric oxide (NO) production in mammalian non-tumorigenic epithelial cells of the small intestine and macrophages induced by individual strains of lactobacilli and bifidobacteria. Int Dairy J 19:166–171CrossRefGoogle Scholar
  85. 85.
    Miettinen M, Matikainen S, Vuopio-Varkila J, Pirhonen J, Varkila K, Kurimoto M et al (1998) Lactobacilli and streptococci induce interleukin-12 (IL-12), IL-18, and gamma interferon production in human peripheral blood mononuclear cells. Infect Immun 66:6058–6062PubMedCentralPubMedGoogle Scholar
  86. 86.
    Vinderola G, Matar C, Perdigon G (2005) Role of intestinal epithelial cells in immune effects mediated by gram-positive probiotic bacteria: Involvement of Toll-like receptors. Clin Diagn Lab Immunol 12:1075–1084PubMedCentralPubMedGoogle Scholar
  87. 87.
    Foligne B, Nutten S, Grangette C, Dennin V, Goudercourt D, Poiret S et al (2007) Correlation between in vitro and in vivo immunomodulatory properties of lactic acid bacteria. World J Gastroenterol 13:236–243PubMedCrossRefGoogle Scholar
  88. 88.
    Miettinen M, Veckman V, Latvala S, Sareneva T, Matikainen S, Julkunen I (2008) Live Lactobacillus rhamnosus and Streptococcus pyogenes differentially regulate Toll-like receptor (TLR) gene expression in human primary macrophages. J Leukoc Biol 84:1092–1100PubMedCrossRefGoogle Scholar
  89. 89.
    O’Hara AM, O’Regan P, Fanning A, O’Mahony C, MacSharry J, Lyons A et al (2006) Functional modulation of human intestinal epithelial cell responses by Bifidobacterium infantis and Lactobacillus salivarius. Immunology 118:202–215PubMedCentralPubMedCrossRefGoogle Scholar
  90. 90.
    Latvala S, Miettinen M, Kekkonen R, Korpela R, Julkunen I (2009) Potentially probiotic bacteria induce cytokine production and suppressor of cytokine signaling 3 gene expression in human monocyte-derived macrophages. Cytokine 48:100–101CrossRefGoogle Scholar
  91. 91.
    Miettinen M, Lehtonen A, Julkunen I, Matikainen S (2000) Lactobacilli and streptococci activate NF-kappa B and STAT signaling pathways in human macrophages. J Immunol 164:3733–3740PubMedCrossRefGoogle Scholar
  92. 92.
    Veckman V, Miettinen M, Matikainen S, Lande R, Giacomini E, Coccia EM et al (2003) Lactobacilli and streptococci induce inflammatory chemokine production in human macrophages that stimulates Th1 cell chemotaxis. J Leukoc Biol 74:395–402PubMedCrossRefGoogle Scholar
  93. 93.
    Veckman V, Miettinen M, Pirhonen J, Sirén J, Matikainen S, Julkunen I (2004) Streptococcus pyogenes and Lactobacillus rhamnosus differentially induce maturation and production of Th1-type cytokines and chemokines in human monocyte-derived dendritic cells. J Leukoc Biol 75:764–771PubMedCrossRefGoogle Scholar
  94. 94.
    Latvala S, Miettinen M, Kekkonen RA, Korpela R, Julkunen I (2011) Lactobacillus rhamnosus GG and Streptococcus thermophilus induce suppressor of cytokine signalling 3 (SOCS3) gene expression directly and indirectly via interleukin-10 in human primary macrophages. Clin Exp Immunol 165:94–103PubMedCentralPubMedCrossRefGoogle Scholar
  95. 95.
    Weiss G, Rasmussen S, Zeuthen LH, Nielsen BN, Jarmer H, Jespersen L et al (2010) Lactobacillus acidophilus induces virus immune defence genes in murine dendritic cells by a Toll-like receptor-2-dependent mechanism. Immunology 131:268–281PubMedCentralPubMedCrossRefGoogle Scholar
  96. 96.
    Weiss G, Christensen HR, Zeuthen LH, Vogensen FK, Jakobsen M, Frøkiær H (2011) Lactobacilli and bifidobacteria induce differential interferon-beta profiles in dendritic cells. Cytokine 56:520–530PubMedCrossRefGoogle Scholar
  97. 97.
    Miettinen M, Pietilä TE, Kekkonen RA, Kankainen M, Latvala S, Pirhonen J et al (2012) Nonpathogenic Lactobacillus rhamnosus activates the inflammasome and antiviral responses in human macrophages. Gut Microbes 3:510–522PubMedCentralPubMedCrossRefGoogle Scholar
  98. 98.
    Hori T, Kiyoshima J, Shida K, Yasui H (2002) Augmentation of cellular immunity and reduction of influenza virus titer in aged mice fed Lactobacillus casei strain Shirota. Clin Diagn Lab Immunol 9:105–108PubMedCentralPubMedGoogle Scholar
  99. 99.
    Davidson LE, Fiorino AM, Snydman DR, Hibberd PL (2011) Lactobacillus GG as an immune adjuvant for live-attenuated influenza vaccine in healthy adults: a randomized double-blind placebo-controlled trial. Eur J Clin Nutr 65:501–507PubMedCentralPubMedCrossRefGoogle Scholar
  100. 100.
    Rizzardini G, Eskesen D, Calder PC, Capetti A, Jespersen L, Clerici M (2011) Evaluation of the immune benefits of two probiotic strains Bifidobacterium animalis ssp. lactis, BB-12® and Lactobacillus paracasei ssp. paracasei, L. casei 431® in an influenza vaccination model: a randomised, double-blind, placebo-controlled study. Br J Nutr 107:876–884PubMedCrossRefGoogle Scholar
  101. 101.
    Boge T, Rémigy M, Vaudaine S, Tanguy J, Bourdet-Sicard R, van der Werf S (2009) A probiotic fermented dairy drink improves antibody response to influenza vaccination in the elderly in two randomised controlled trials. Vaccine 27:5677–5684PubMedCrossRefGoogle Scholar
  102. 102.
    Boyle RJ, Robins-Browne RM, Tang MLK (2006) Probiotic use in clinical practice: what are the risks? Am J Clin Nutr 83:1256–1264PubMedGoogle Scholar
  103. 103.
    Sanders ME, Akkermans LM, Haller D, Hammerman C, Heimbach J, Hörmannsperger G et al (2010) Safety assessment of probiotics for human use. Gut Microbes 1:164–185PubMedCentralPubMedCrossRefGoogle Scholar
  104. 104.
    Land MH, Rouster-Stevens K, Woods CR, Cannon ML, Cnota J, Shetty AK (2005) Lactobacillus sepsis associated with probiotic therapy. Pediatrics 115:178–181PubMedGoogle Scholar
  105. 105.
    Kalima P, Masterton RG, Roddie PH, Thomas AE (1996) Lactobacillus rhamnosus infection in a child following bone marrow transplant. J Infect 32:165–167PubMedCrossRefGoogle Scholar
  106. 106.
    Besselink MG, van Santvoort HC, Buskens E, Boermeester MA, van Goor H, Timmerman HM et al (2008) Probiotic prophylaxis in predicted severe acute pancreatitis: a randomised, double-blind, placebo-controlled trial. Lancet 371:651–659PubMedCrossRefGoogle Scholar
  107. 107.
    European Food Safety Authority (EFSA) (2011) Scientific Opinion on the maintenance of the list of QPS biological agents intentionally added to food and feed (2011 update). EFSA J 9:2497, 82 ppGoogle Scholar
  108. 108.
    Salminen MK, Tynkkynen S, Rautelin H, Saxelin M, Vaara M, Ruutu P et al (2002) Lactobacillus bacteremia during a rapid increase in probiotic use of Lactobacillus rhamnosus GG in Finland. Clin Infect Dis 35:1155–1160PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  1. 1.Institute of Biomedicine, PharmacologyUniversity of HelsinkiHelsinkiFinland
  2. 2.Institute of Clinical Medicine, OtorhinolaryngologyUniversity of HelsinkiHelsinkiFinland
  3. 3.Department of Otorhinolaryngology—Head and Neck SurgeryHelsinki University Central HospitalHelsinkiFinland

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