Advertisement

Reproductive Sciences

, Volume 19, Issue 3, pp 235–242 | Cite as

Importance of Vaginal Microbes in Reproductive Health

  • Jingru Li
  • John McCormick
  • Alan Bocking
  • Gregor ReidEmail author
Review

Abstract

Over 250 species of bacteria have been detected in the vagina using genomic sequencing. Lactobacillus iners and L crispatus dominate in most women who have a clinically healthy status. Unfortunately, the abundance profiles can change dramatically with significant increases in pathogens associated with bacterial vaginosis (BV) and aerobic vaginitis (AV). The BV microbiota have at least 4 different abundance profiles, indicating this is a complex condition, yet one that is treated with essentially 2 antimicrobial agents which were never designed for eradicting these organisms in dense biofilms. Future studies will uncover which abundance profiles are particularly associated with a risk of preterm labor, and hopefully identify the mechanisms involved in the switch from healthy to a BV or AV state. The use of probiotic lactobacilli vaginally and orally has shown great promise in helping to restore and maintain a healthy vagina, and studies have shown that certain strains have the capacity to interfere with the inflammatory pathway leading to preterm delivery. There is enormous need for new diagnostic and therapeutic modalities, especially to save the lives of millions of babies in resource-disadvantaged countries.

Keywords

vaginal microbiota Lactobacillus bacterial vaginosis aerobic vaginitis probiotics 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Srinivasan S, Fredricks DN. The human vaginal bacterial biota and bacterial vaginosis. Interdiscip Perspect Infect Dis. 2008; 2008:479–750.CrossRefGoogle Scholar
  2. 2.
    Marrazzo JM, Martin DH, Watts DH, et al. Bacterial vaginosis: identifying research gaps proceedings of a workshop sponsored by DHHS/NIH/NIAID. Sex Transm Dis. 2010;37(12):732–744.PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Zodzika J, Rezeberga D, Jermakova I, Vasina O, Vedmedovska N, Donders G. Factors related to elevated vaginal pH in the first trimester of pregnancy. Acta Obstet Gynecol Scand. 2011;90(1): 41–46.PubMedCrossRefPubMedCentralGoogle Scholar
  4. 4.
    Donders GG, Vereecken A, Bosmans E, Dekeersmaecker A, Salembier G, Spitz B. Definition of a type of abnormal vaginal flora that is distinct from bacterial vaginosis: aerobic vaginitis. BJOG. 2002;109(1):34–43.PubMedCrossRefPubMedCentralGoogle Scholar
  5. 5.
    Soper DE. Pelvic inflammatory disease. Obstet Gynecol. 2010; 116(2 Pt 1):419–428.PubMedCrossRefPubMedCentralGoogle Scholar
  6. 6.
    Sha BE, Zariffard MR, Wang QJ, et al. Female genital-tract HIV load correlates inversely with Lactobacillus species but positively with bacterial vaginosis and Mycoplasma hominis. J Infect Dis. 2005;191(1):25–32.PubMedCrossRefPubMedCentralGoogle Scholar
  7. 7.
    Donders GG, Van Calsteren K, Bellen G, et al. Predictive value for preterm birth of abnormal vaginal flora, bacterial vaginosis and aerobic vaginitis during the first trimester of pregnancy. BJOG. 2009;116(10):1315–1324.PubMedCrossRefPubMedCentralGoogle Scholar
  8. 8.
    Burton JP, Reid G. Evaluation of the bacterial vaginal flora of 20 postmenopausal women by direct (Nugent score) and molecular (Polymerase chain reaction and denaturing gradient gel electrophoresis) techniques. J Infect Dis. 2002;186(12):1770–1780.PubMedCrossRefPubMedCentralGoogle Scholar
  9. 9.
    Burton JP, Devillard E, Cadieux PA, Hammond J-A, Reid G. Detection of Atopobium vaginae in post menopausal women by cultivation-independent methods warrants further investigation. J Clin Microbiol. 2004;42(4):1829–1831.PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Schellenberg J, Links MG, Hill JE, Pyrosequencing of the chaperonin-60 universal target as a tool for determining microbial community composition. Appl Environ Microbiol. 2009;75(9): 2889–2898.PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Ravel J, Gajer P, Abdo Z, et al. Vaginal microbiome of reproductive-age women. Proc Natl Acad Sci U S A. 2011; 108(suppl 1):4680–4687.PubMedCrossRefPubMedCentralGoogle Scholar
  12. 12.
    Hummelen R, Fernandes AD, Macklaim JM, et al. Deep sequencing of the vaginal microbiota of women with HIV. PLoS One. 2010;5(8):e12078.PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Zozaya-Hinchliffe M, Lillis R, Martin DH, Ferris MJ. Quantitative PCR assessments of bacterial species in women with and without bacterial vaginosis. J Clin Microbiol. 2010;48(5): 1812–1819.PubMedPubMedCentralCrossRefGoogle Scholar
  14. 14.
    Yamamoto T, Zhou X, Williams CJ, Hochwalt A, Forney LJ. Bacterial populations in the vaginas of healthy adolescent women. J Pediatr Adolesc Gynecol. 2009;22(1):11–18.PubMedCrossRefPubMedCentralGoogle Scholar
  15. 15.
    Ferris MJ, Norori J, Zozaya-Hinchliffe M, Martin DH. Cultivation-independent analysis of changes in bacterial vaginosis flora following metronidazole treatment. J Clin Microbiol. 2007;45(3):1016–1018.PubMedPubMedCentralCrossRefGoogle Scholar
  16. 16.
    Jakobsson T, Forsum U. Lactobacillus iners: a marker of changes in the vaginal flora? J Clin Microbiol. 2007;45(9):3145.PubMedPubMedCentralCrossRefGoogle Scholar
  17. 17.
    Macklaim JM, Gloor GB, Anukam KC, Cribby S, Reid G. Microbes and Health Sackler Colloquium: At the crossroads of vaginal health and disease, the genome sequence of Lactobacillus iners AB-1. Proc Natl Acad Sci U S A. 2011;108(suppl 1): 4688–4695.PubMedCrossRefPubMedCentralGoogle Scholar
  18. 18.
    Rampersaud R, Planet PJ, Randis TM, Inerolysin, a cholesteroldependent cytolysin produced by Lactobacillus iners. J Bacteriol. 2011; 193(5): 1034–1041.PubMedCrossRefPubMedCentralGoogle Scholar
  19. 19.
    Reid G, Younes JA, Van der Mei HC, Gloor GB, Knight R, Busscher HJ. Microbiota restoration: natural and supplemented recovery of human microbial communities. Nat Rev Microbiol. 2011;9(1):27–38.PubMedCrossRefPubMedCentralGoogle Scholar
  20. 20.
    Reid G, Dols J, Miller W. Targeting the vaginal microbiota with probiotics as a means to counteract infections. Curr Opin Clin Nutr Metab Care. 2009;12(6):583–587.PubMedCrossRefPubMedCentralGoogle Scholar
  21. 21.
    Zhou X, Brown CJ, Abdo Z, et al. Differences in the composition of vaginal microbial communities found in healthy Caucasian and black women. ISME J. 2007;1(2):121–133.PubMedCrossRefPubMedCentralGoogle Scholar
  22. 22.
    Swidsinski A, Mendling W, Loening-Baucke V, et al. Adherent biofilms in bacterial vaginosis. Obstet Gynecol. 2005;106(5 pt 1): 1013–1023.PubMedCrossRefPubMedCentralGoogle Scholar
  23. 23.
    Kirjavainen P, Pautler S, Baroja ML, et al. Aberrant vaginal microbiota and IL-12 skewed cytokine production by antigenpresenting cells are characteristic of women prone to urinary tract infections. Clin Vaccine Immunol. 2008;16(1):29–36.PubMedPubMedCentralCrossRefGoogle Scholar
  24. 24.
    Schwebke JR, Desmond RA. A randomized trial of the duration of therapy with metronidazole plus or minus azithromycin for treatment of symptomatic bacterial vaginosis. Clin Infect Dis. 2007; 44(2):213–219.PubMedCrossRefPubMedCentralGoogle Scholar
  25. 25.
    Anukam KC, Osazuwa E, Osemene GI, Ehigiagbe F, Bruce AW, Reid G. Clinical study comparing probiotic Lactobacillus GR-1 and RC-14 with metronidazole vaginal gel to treat symptomatic bacterial vaginosis. Microbes Infect. 2006;8(12–13): 2772–2776.PubMedCrossRefPubMedCentralGoogle Scholar
  26. 26.
    Sobel, J. Efficacy of clindamycin vaginal ovule (3-day treatment) vs. clindamycin vaginal cream (7-day treatment) in bacterial vaginosis. Infect Dis Obstet Gynecol. 2001;9(1):9–15.PubMedPubMedCentralCrossRefGoogle Scholar
  27. 27.
    Denney JM, Culhane JF, Goldenberg RL. Prevention of preterm birth. Womens Health (Lond Engl). 2008;4(6):625–638.CrossRefGoogle Scholar
  28. 28.
    Klebanoff MA, Carey JC, Hauth JC, et al. Failure of metronidazole to prevent preterm delivery among pregnant women with asymptomatic Trichomonas vaginalis infection. N Engl J Med. 2001;345(7):487–493.PubMedCrossRefPubMedCentralGoogle Scholar
  29. 29.
    Andrews WW, Sibai BM, Thom EA, et al. Randomized clinical trial of metronidazole plus erythromycin to prevent spontaneous preterm delivery in fetal fibronectin-positive women. Obstet Gynecol. 2003;101(5 pt 1):847–855.PubMedCrossRefPubMedCentralGoogle Scholar
  30. 30.
    Shennan A, et al., A randomised controlled trial of metronidazole for the prevention of preterm birth in women positive for cervicovaginal fetal fibronectin: the PREMET Study. BJOG. 2006; 113(1):65–74.PubMedCrossRefPubMedCentralGoogle Scholar
  31. 31.
    Goldenberg RL, Culhane JF, Iams JD, Romero R. Epidemiology and causes of preterm birth. Lancet. 2008;371(9606):75–84.PubMedPubMedCentralCrossRefGoogle Scholar
  32. 32.
    Lawn JE, Kerber K, Enweronu-Laryea C, Cousens S. 3.6 million neonatal deaths-what is progressing and what is not? Semin Perinatol. 2010;34(6):371–386.PubMedCrossRefPubMedCentralGoogle Scholar
  33. 33.
    Beck S, Wojdyla D, Say L, et al. The worldwide incidence of preterm birth: a systematic review of maternal mortality and morbidity. Bull World Health Organ. 2010;88(1):31–38.PubMedPubMedCentralCrossRefGoogle Scholar
  34. 34.
    Nugent RP, Krohn MA, Hillier SL. Reliability of diagnosing bacterial vaginosis is improved by a standardized method of gram stain preparation. J Clin Microbiol. 1991;29(2):297–301.PubMedPubMedCentralCrossRefGoogle Scholar
  35. 35.
    Amsel R, Totten PA, Spiegel CA, Chen KC, Eschenbach D, Holmes KK. Nonspecific vaginitis. Diagnostic criteria and microbial and epidemiological associations. Am J Med. 1983;74(1):14–22.PubMedCrossRefPubMedCentralGoogle Scholar
  36. 36.
    Reid G, Bocking A. The potential for probiotics to prevent bacterial vaginosis and preterm labor. Am J Obstet Gynecol. 2003; 189(4): 1202–1208.PubMedCrossRefPubMedCentralGoogle Scholar
  37. 37.
    Wilson JD, Ralph SG, Rutherford AJ. Rates of bacterial vaginosis in women undergoing in vitro fertilisation for different types of infertility. BJOG. 2002;109(6):714–717.PubMedCrossRefPubMedCentralGoogle Scholar
  38. 38.
    Eckert LO, Moore DE, Patton DL, Agnew KJ, Eschenbach DA. Relationship of vaginal bacteria and inflammation with conception and early pregnancy loss following in-vitro fertilization. Infect Dis Obstet Gynecol. 2003;11(1):11–17.PubMedPubMedCentralCrossRefGoogle Scholar
  39. 39.
    Salim R, Ben-Shlomo I, Colodner R, Keness Y, Shalev E. Bacterial colonization of the uterine cervix and success rate in assisted reproduction: results of a prospective survey. Hum Reprod. 2002;17(2):337–340.PubMedCrossRefPubMedCentralGoogle Scholar
  40. 40.
    Spandorfer SD, Neuer A, Giraldo PC, Rosenwaks Z, Witkin SS. Relationship of abnormal vaginal flora, proinflammatory cytokines and idiopathic infertility in women undergoing IVF. J Reprod Med. 2001;46(9):806–810.PubMedPubMedCentralGoogle Scholar
  41. 41.
    Hedges SR, Barrientes F, Desmond RA, Schwebke JR. Local and systemic cytokine levels in relation to changes in vaginal flora. J Infect Dis. 2006;193(4):556–562.PubMedCrossRefPubMedCentralGoogle Scholar
  42. 42.
    Cauci S, Driussi S, Guaschino S, Isola M, Quadrifoglio F. Correlation of local interleukin-1beta levels with specific IgA response against Gardnerella vaginalis cytolysin in women with bacterial vaginosis. Am J Reprod Immunol. 2002;47(5):257–264.PubMedCrossRefPubMedCentralGoogle Scholar
  43. 43.
    Cauci S, Guaschino S, Driussi S, De Santo D, Lanzafame P, Quadrifoglio F. Correlation of local interleukin-8 with immunoglobulin A against Gardnerella vaginalis hemolysin and with prolidase and sialidase levels in women with bacterial vaginosis. J Infect Dis. 2002;185(11):1614–1620.PubMedCrossRefPubMedCentralGoogle Scholar
  44. 44.
    Ryckman KK, Williams SM, Kalinka J. Correlations of selected vaginal cytokine levels with pregnancy-related traits in women with bacterial vaginosis and mycoplasmas. J Reprod Immunol. 2008;78(2):172–180.PubMedCrossRefPubMedCentralGoogle Scholar
  45. 45.
    Raghupathy R, Kalinka J. Cytokine imbalance in pregnancy complications and its modulation. Front Biosci. 2008;13:985–94.PubMedCrossRefPubMedCentralGoogle Scholar
  46. 46.
    Ledee-Bataille N, Bonnet-Chea K, Hosny G, Dubanchet S, Frydman R, Chaouat G. Role of the endometrial tripod interleukin-18, -15, and -12 in inadequate uterine receptivity in patients with a history of repeated in vitro fertilization-embryo transfer failure. Fertil Steril. 2005;83(3):598–605.PubMedCrossRefPubMedCentralGoogle Scholar
  47. 47.
    Dey SK, Lim H, Das SK, et al. Molecular cues to implantation. Endocr Rev. 2004;25(3):341–373.PubMedCrossRefPubMedCentralGoogle Scholar
  48. 48.
    Johri AK, Paoletti LC, Glaser P, et al., Group B Streptococcus: global incidence and vaccine development. Nat Rev Microbiol. 2006;4(12):932–942.PubMedPubMedCentralCrossRefGoogle Scholar
  49. 49.
    Ditina MA, Meringova LF, Leont’eva GF, et al.. Comparative study of experimental conjugated and combined vaccines against group B streptococci. Zh Mikrobiol Epidemiol Immunobiol. 2009; Jan-Feb(1):37–41.Google Scholar
  50. 50.
    Chambers HF, Deleo FR. Waves of resistance: Staphylococcus aureus in the antibiotic era. Nat Rev Microbiol. 2009;7(9): 629–641.PubMedPubMedCentralCrossRefGoogle Scholar
  51. 51.
    Andrews WW, Schelonka R, Waites K, Stamm A, Cliver SP, Moser S. Genital tract methicillin-resistant Staphylococcus aureus: risk of vertical transmission in pregnant women. Obstet Gynecol. 2008;111(1):113–118.PubMedCrossRefPubMedCentralGoogle Scholar
  52. 52.
    Laibl VR, Sheffield JS, Roberts S, McIntire DD, Trevino S, Wendel GD Jr. Clinical presentation of community-acquired methicillin-resistant Staphylococcus aureus in pregnancy. Obstet Gynecol. 2005;106(3):461–465.PubMedCrossRefPubMedCentralGoogle Scholar
  53. 53.
    Chen KT, Huard RC, Della-Latta P, Saiman L. Prevalence of methicillin-sensitive and methicillin-resistant Staphylococcus aureus in pregnant women. Obstet Gynecol. 2006;108(3 pt 1):482–487.PubMedCrossRefPubMedCentralGoogle Scholar
  54. 54.
    Voravuthikunchai SP, Bilasoi S, Supamala O. Antagonistic activity against pathogenic bacteria by human vaginal lactobacilli. Anaerobe. 2006;12(5–6):221–226.PubMedCrossRefPubMedCentralGoogle Scholar
  55. 55.
    Zarate G, Nader-Macias ME. Influence of probiotic vaginal lactobacilli on in vitro adhesion of urogenital pathogens to vaginal epithelial cells. Lett Appl Microbiol. 2006;43(2):174–180.PubMedCrossRefPubMedCentralGoogle Scholar
  56. 56.
    Zarate G, Santos V, Nader-Macias ME. Protective effect of vaginal Lactobacillus paracasei CRL 1289 against urogenital infection produced by Staphylococcus aureus in a mouse animal model. Infect Dis Obstet Gynecol. 2009;2009:48358.Google Scholar
  57. 57.
    FAO/WHO. Evaluation of health and nutritional properties of powder milk and live lactic acid bacteria. Food and Agriculture Organization of the United Nations and World Health Organization Expert Consultation Report; 2001. http://www.who.int/foodsafety/publications/fs_management/en/probiotics.pdf (accessed, October 31, 2011).
  58. 58.
    Reid G, Bruce AW, Taylor M. Instillation of Lactobacillus and stimulation of indigenous organisms to prevent recurrence of urinary tract infections. Microecol Ther. 1995;23:32–45.Google Scholar
  59. 59.
    Gardiner GE, Heinemann C, Bruce AW, Beuerman D, Reid G. Persistence of Lactobacillus fermentum RC-14 and Lactobacillus rhamnosus GR-1 but not L. rhamnosus GG in the human vagina as demonstrated by randomly amplified polymorphic DNA. Clin Diagn Lab Immunol. 2002;9(1):92–96.PubMedPubMedCentralGoogle Scholar
  60. 60.
    Anukam KC, Osazuwa E, Osemene GI, Ehigiagbe F, Bruce AW, Reid G. Clinical study comparing probiotic Lactobacillus GR-1 and RC-14 with metronidazole vaginal gel to treat symptomatic bacterial vaginosis. Microbes Infect. 2006;8(12–13):2772–2776.PubMedCrossRefPubMedCentralGoogle Scholar
  61. 61.
    Reid G, Beuerman D, Heinemann C, Bruce AW. Probiotic Lactobacillus dose required to restore and maintain a normal vaginal flora. FEMS Immunol Med Microbiol. 2001;32(1): 37–41.PubMedCrossRefPubMedCentralGoogle Scholar
  62. 62.
    Reid G, Bruce AW, Fraser N, Heinemann C, Owen J, Henning B. Oral probiotics can resolve urogenital infections. FEMS Immunol Med Microbiol. 2001;30(1):49–52.PubMedCrossRefPubMedCentralGoogle Scholar
  63. 63.
    Reid G, Charbonneau D, Erb J, Kochanowski B, Beuerman D, Poehner R, Bruce AW. Oral use of Lactobacillus rhamnosus GR-1 and L. fermentum RC-14 significantly alters vaginal flora: randomized, placebo-controlled trial in 64 healthy women. FEMS Immunol Med Microbiol. 2003;35(2):131–134.PubMedCrossRefPubMedCentralGoogle Scholar
  64. 64.
    Hummelen R, Changalucha J, Butamanya NL, Cook A, Habbema JD, Reid G. Lactobacillus rhamnosus GR-1 and L. reuteri RC-14 to prevent or cure bacterial vaginosis among women with HIV.Int J Gynaecol Obstet. 2010;111(3):245–248.PubMedPubMedCentralGoogle Scholar
  65. 65.
    Yeganegi M, Leung CG, Martins A, Kim SO, Reid G, Challis JR, Bocking AD. Lactobacillus rhamnosus GR-1-induced IL-10 production in human placental trophoblast cells involves activation of JAK/STAT and MAPK pathways. Reprod Sci. 2010; 17(11):1043–1051.PubMedCrossRefPubMedCentralGoogle Scholar
  66. 66.
    Yeganegi M, Leung CG, Martins A, Kim SO, Reid G, Challis JR, Bocking AD. Lactobacillus rhamnosus GR-1 stimulates colonystimulating factor 3 (granulocyte) (CSF3) output in placental trophoblast cells in a fetal sex-dependent manner. Biol Reprod. 2011;84(1):18–25.PubMedCrossRefPubMedCentralGoogle Scholar
  67. 67.
    Yeganegi M, Watson CS, Martins A, Kim SO, Reid G, Challis JR, Bocking AD. Effect of Lactobacillus rhamnosus GR-1 supernatant and fetal sex on lipopolysaccharide-induced cytokine and prostaglandin-regulating enzymes in human placental trophoblast cells: implications for treatment of bacterial vaginosis and prevention of preterm labor. Am J Obstet Gynecol. 2009;200(5):532e1–e8.CrossRefGoogle Scholar
  68. 68.
    Romero R, Chaiworapongsa T, Kuivaniemi H, Tromp G. Bacterial vaginosis, the inflammatory response and the risk of preterm birth: a role for genetic epidemiology in the prevention of preterm birth. Am J Obstet Gynecol. 2004;190(6):1509–1519.PubMedCrossRefPubMedCentralGoogle Scholar
  69. 69.
    Zaga V, Estrada-Gutierrez G, Beltran-Montoya J, Maida-Claros R, Lopez-Vancell R, Vadillo-Ortega F. Secretions of interleukin-1beta and tumor necrosis factor alpha by whole fetal membranes depend on initial interactions of amnion or choriodecidua with lipopolysaccharides or group B streptococci. Biol Reprod. 2004;71(4):1296–1302.PubMedCrossRefPubMedCentralGoogle Scholar
  70. 70.
    Challis JR, Lye SJ, Gibb W, Whittle W, Patel F, Alfaidy N. Understanding preterm labor. Ann N Y Acad Sci. 2001;943:225–234.PubMedCrossRefPubMedCentralGoogle Scholar
  71. 71.
    Challis JR, Sloboda DM, Alfaidy N, et al. Prostaglandins and mechanisms of preterm birth. Reproduction. 2002;124(1):1–17.PubMedCrossRefPubMedCentralGoogle Scholar
  72. 72.
    Xu P, Alfaidy N, Challis JR. Expression of matrix metalloproteinase (MMP)-2 and MMP-9 in human placenta and fetal membranes in relation to preterm and term labor. J Clin Endocrinol Metab. 2002;87(3):1353–1361.PubMedCrossRefPubMedCentralGoogle Scholar
  73. 73.
    Panopoulos AD, Watowich SS. Granulocyte colony-stimulating factor: molecular mechanisms of action during steady state and ‘emergency’ hematopoiesis. Cytokine. 2008;42(3):277–288.PubMedPubMedCentralCrossRefGoogle Scholar
  74. 74.
    Roth I, Corry DB, Locksley RM, Abrams JS, Litton MJ, Fisher SJ. Human placental cytotrophoblasts produce the immunosuppressive cytokine interleukin 10. J Exp Med. 1996;184(2):539–548.PubMedCrossRefPubMedCentralGoogle Scholar
  75. 75.
    Velraeds MC, van der Belt B, van der Mei HC, Reid G, Busscher HJ. Interference in initial adhesion of uropathogenic bacteria and yeasts silicone rubber by a Lactobacillus acidophilus biosurfactant. J Med Microbiol. 1998;49:790–794.Google Scholar
  76. 76.
    Doleyres Y, Beck P, Vollenweider S, Lacroix C. Production of 3-hydroxypropionaldehyde using a two-step process with Lactobacillus reuteri. Appl Microbiol Biotechnol. 2005;68(4): 467–474.PubMedCrossRefPubMedCentralGoogle Scholar
  77. 77.
    Cadieux P, Wind A, Sommer P, et al. Evaluation of reuterin production in urogenital probiotic Lactobacillus reuteri RC-14. Appl Environ Microbiol. 2008;74(15):4645–4649.PubMedPubMedCentralCrossRefGoogle Scholar
  78. 78.
    Gan BS, Kim J, Reid G, Cadieux P, Howard JC. Lactobacillus fermentum RC-14 inhibits Staphylococcus aureus infection of surgical implants in rats. J Infect Dis. 2002;185(9):1369–1372.PubMedCrossRefPubMedCentralGoogle Scholar
  79. 79.
    Heinemann C. van Hylckama Vlieg JE, Janssen DB, Busscher HJ, van der Mei HC, Reid G. Purification and characterization of a surface-binding protein from Lactobacillus fermentum RC-14 inhibiting Enterococcus faecalis 1131 adhesion. FEMS Microbiol Letts 2000;190(1):177–180.CrossRefGoogle Scholar
  80. 80.
    Li J, Wang W, Xu SX, Magarvey NA, McCormick JK. Lactobacillus reuteri-produced cyclic dipeptides quench agr-mediated expression of toxic shock syndrome toxin-1 in staphylococci. Proc Natl Acad Sci U S A. 2011;108(8):3360–3365PubMedPubMedCentralCrossRefGoogle Scholar
  81. 81.
    Laughton JM, Devillard E, Heinrichs DE, Reid G, McCormick JK. Inhibition of expression of a staphylococcal superantigenlike protein by a soluble factor from Lactobacillus reuteri. Microbiology. 2006;152(pt 4):1155–1167.PubMedCrossRefPubMedCentralGoogle Scholar
  82. 82.
    Clatworthy AE, Pierson E, Hung DT, Targeting virulence: a new paradigm for antimicrobial therapy. Nat Chem Biol. 2007;3(9): 541–548.PubMedCrossRefPubMedCentralGoogle Scholar
  83. 83.
    Cegelski L, Marshall GR, Eldridge GR, Hultgren SJ. The biology and future prospects of antivirulence therapies. Nat Rev Microbiol. 2008;6(1):17–27.PubMedPubMedCentralCrossRefGoogle Scholar
  84. 84.
    Gilboa Y, Bar-Hava I, Fisch B, et al. Does intravaginal probiotic supplementation increase the pregnancy rate in IVF-embryo transfer cycles? Reprod Biomed Online. 2005;11(1):71–75.PubMedCrossRefPubMedCentralGoogle Scholar
  85. 85.
    Verstraelen H, Senok AC. Vaginal lactobacilli, probiotics, and IVF. Reprod Biomed Online. 2005;11(6):674–675.PubMedCrossRefPubMedCentralGoogle Scholar
  86. 86.
    Kim TK, Thomas SM, Ho M, et al. Heterogeneity of vaginal microbial communities within individuals. J Clin Microbiol. 2009;47(4):1181–1189.PubMedPubMedCentralCrossRefGoogle Scholar
  87. 87.
    Roberfroid M, Gibson GR, Hoyles L, et al. Prebiotic effects: metabolic and health benefits. Br J Nutr. 2010;104(suppl 2):S1–S63.PubMedCrossRefPubMedCentralGoogle Scholar
  88. 88.
    Reid G, Bruce AW, Soboh F, Mittelman M. Effect of nutrient composition on the in vitro growth of urogenital Lactobacillus and uropathogens. Can J Microbiol. 1998;44(9):1–6.CrossRefGoogle Scholar
  89. 89.
    Fredricks DN, Fiedler TL, Marrazzo JM. Molecular identification of bacteria associated with bacterial vaginosis. N Engl J Med. 2005;353(18):1899–1911.PubMedCrossRefPubMedCentralGoogle Scholar
  90. 90.
    Tamrakar R, Yamada T, Furuta I, et al. Association between Lactobacillus species and bacterial vaginosis-related bacteria, and bacterial vaginosis scores in pregnant Japanese women. BMC Infect Dis. 2007;7:128.Google Scholar
  91. 91.
    Diao Y, Fang X, Xia Q, et al.. Organism diversity between women with and without bacterial vaginosis as determined by polymerase chain reaction denaturing gradient gel electrophoresis and 16S rRNA gene sequence. J Obstet Gynaecol Res. 2011; 37(10): 1438–1446.PubMedCrossRefPubMedCentralGoogle Scholar
  92. 92.
    Santiago GL, Deschaght P, El Aila N, et al. Gardnerella vaginalis comprises three distinct genotypes of which only two produce sialidase. Am J Obstet Gynecol. 2011; 204(5): 450.e1–7.PubMedPubMedCentralGoogle Scholar
  93. 93.
    Nikolaitchouk N, Andersch B, Falsen E, Strömbeck L, Mattsby-Baltzer I. The lower genital tract microbiota in relation to cytokine-, SLPI- and endotoxin levels: application of checkerboard DNA-DNA hybridization (CDH). APMIS. 2008;116(4):263–277.PubMedCrossRefPubMedCentralGoogle Scholar
  94. 94.
    Mirmonsef P, Gilbert D, Zariffard MR, et al. The effects of commensal bacteria on innate immune responses in the female genital tract. Am J Reprod Immunol. 2011;65(3): 190–195.PubMedCrossRefPubMedCentralGoogle Scholar
  95. 95.
    Irvine SL, Hummelen R, Hekmat S, et al. Probiotic yogurt consumption is associated with an increase of CD4 count among people living with HIV/AIDS. J Clin Gastroenterol. 2010;44(9): e201–e205.PubMedCrossRefPubMedCentralGoogle Scholar
  96. 96.
    Hummelen R, Changalucha J, Butamanya NL, et al. Effect of 25 weeks probiotic supplementation on immune function of HIV patients. Gut Microbes. 2011;2(2):80–85.PubMedCrossRefPubMedCentralGoogle Scholar
  97. 97.
    Hummelen R, et al. Lactobacillus rhamnosus GR-1 and L. reuteri RC-14 to prevent or cure bacterial vaginosis among women with HIV. Int J Gynaecol Obstet. 2010; 111(3):245–8.PubMedCrossRefPubMedCentralGoogle Scholar
  98. 98.
    Trois L, Cardoso EM, Miura E. Use of probiotics in HIV-infected children: a randomized double-blind controlled study. J Trop Pediatr. 2008;54(1):19–24.PubMedCrossRefPubMedCentralGoogle Scholar
  99. 99.
    Hemmerling A, Harrison W, Schroeder A, et al. Phase 2a study assessing colonization efficiency, safety, and acceptability of Lactobacillus crispatus CTV-05 in women with bacterial vaginosis. Sex Transm Dis. 2010;37(12):745–750.PubMedCrossRefPubMedCentralGoogle Scholar
  100. 100.
    Anukam KC, Osazuwa E, Osemene GI, Ehigiagbe F, Bruce AW, Reid G. Clinical study comparing probiotic Lactobacillus GR-1 and RC-14 with metronidazole vaginal gel to treat symptomatic bacterial vaginosis. Microbes Infect. 2006;8(12–13):2772–2776.PubMedCrossRefPubMedCentralGoogle Scholar

Copyright information

© Society for Reproductive Investigation 2012

Authors and Affiliations

  • Jingru Li
    • 1
  • John McCormick
    • 2
  • Alan Bocking
    • 3
  • Gregor Reid
    • 1
    • 2
    • 4
    Email author
  1. 1.Department of Microbiology and ImmunologyThe University of Western OntarioLondonCanada
  2. 2.Canadian Research & Development Centre for Probiotics F2-116Lawson Health Research InstituteLondonCanada
  3. 3.Department of Obstetrics and GynecologyUniversity of Toronto and Mt. Sinai HospitalTorontoCanada
  4. 4.Department of SurgeryThe University of Western OntarioLondonCanada

Personalised recommendations