CoChat
Sign Up
Cited by 557Reproductive tract infections researchProbiotics and Fermented FoodsGut microbiota and health

The role of lactic acid production by probiotic Lactobacillus species in vaginal health

Open access
Tachedjian, Gilda, Aldunate, Muriel, Bradshaw, Catronia S., Cone, Richard A.·2017·Research in Microbiology
DOI 10.1016/j.resmic.2017.04.001
Open this paper in CoChat — free accountOpen PDF

Abstract

Vaginal eubiosis is characterised by beneficial lactobacillus-dominated microbiota. In contrast, vaginal dysbiosis (e.g. bacterial vaginosis, BV), characterised by an overgrowth of multiple anaerobes, is associated with an increased risk of adverse urogenital and reproductive health outcomes. A major distinguishing feature between the vaginal environment in states of eubiosis and dysbiosis is a high concentration of lactic acid, produced by lactobacilli, that acidifies the vagina in eubiosis versus a sharp drop in lactic acid and an increase in pH in dysbiosis. Here we review the antimicrobial, antiviral and immunomodulatory properties of lactic acid and the use of lactic acid and lactobacilli probiotics in preventing or treating BV.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.resmic.2017.04.001

Cites

8 of 8 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 123

  1. Aroutcheva A, Gariti D, Simon M, Shott S, Faro J, Simoes JA, et al. Defense factors of vaginal lactobacilli. Am J Obstet Gynecol 2001;185: 375e9.
  2. Selle K, Klaenhammer TR. Genomic and phenotypic evidence for probiotic influences of Lactobacillus gasseri on human health. FEMS Microbiol Rev 2013;37:915e35.
  3. Gong Z, Luna Y, Yu P, Fan H. Lactobacilli inactivate Chlamydia trachomatis through lactic acid but not H 2 O 2 . PLoS One 2014;9: e107758.
  4. Verhelst R, Verstraelen H, Claeys G, Verschraegen G, Delanghe J, Van Simaey L, et al. Cloning of 16S rRNA genes amplified from normal and disturbed vaginal microflora suggests a strong association between Atopobium vaginae, Gardnerella vaginalis and bacterial vaginosis. BMC Microbiol 2004;4:16.
  5. Nugent RP, Krohn MA, Hillier SL. Reliability of diagnosing bacterial vaginosis is improved by a standardized method of gram stain inter- pretation. J Clin Microbiol 1991;29:297e301.
  6. Ling Z, Kong J, Liu F, Zhu H, Chen X, Wang Y, et al. Molecular analysis of the diversity of vaginal microbiota associated with bacterial vaginosis. BMC Genomics 2010;11:488.
  7. Brotman RM. Vaginal microbiome and sexually transmitted infections: an epidemiologic perspective. J Clin Invest 2011;121:4610e7.
  8. Amsel R, Totten PA, Spiegel CA, Chen KC, Eschenbach D, Holmes KK. Nonspecific vaginitis. Diagnostic criteria and microbial and epidemiologic associations. Am J Med 1983;74:14e22.
  9. Zhou X, Brown CJ, Abdo Z, Davis CC, Hansmann MA, Joyce P, et al. Differences in the composition of vaginal microbial communities found in healthy Caucasian and black women. ISME J 2007;1:121e33.
  10. Verstraelen H, Verhelst R, Claeys G, De Backer E, Temmerman M, Vaneechoutte M. Longitudinal analysis of the vaginal microflora in pregnancy suggests that L. crispatus promotes the stability of the normal vaginal microflora and that L. gasseri and/or L. iners are more conducive to the occurrence of abnormal vaginal microflora. BMC Microbiol 2009;9:116.
  11. Aldunate M, Srbinovski D, Hearps AC, Latham CF, Ramsland PA, Gugasyan R, et al. Antimicrobial and immune modulatory effects of lactic acid and short chain fatty acids produced by vaginal micro- biota associated with eubiosis and bacterial vaginosis. Front Physiol 2015;6:164.
  12. Al-Mushrif S, Eley A, Jones BM. Inhibition of chemotaxis by organic acids from anaerobes may prevent a purulent response in bacterial vaginosis. J Med Microbiol 2000;49:1023e30.
  13. Mirmonsef P, Gilbert D, Zariffard MR, Hamaker BR, Kaur A, Landay AL, et al. The effects of commensal bacteria on innate immune responses in the female genital tract. Am J Reprod Immunol 2011;65: 190e5.
  14. Wilson WA, Roach PJ, Montero M, Baroja-Fernandez E, Munoz FJ, Eydallin G, et al. Regulation of glycogen metabolism in yeast and bacteria. FEMS Microbiol Rev 2010;34:952e85.
  15. O'Hanlon DE, Moench TR, Cone RA. Vaginal pH and microbicidal lactic acid when lactobacilli dominate the microbiota. PLoS One 2013; 8:e80074.
  16. Owen DH, Katz DF. A vaginal fluid simulant. Contraception 1999;59: 91e5.
  17. Boskey ER, Cone RA, Whaley KJ, Moench TR. Origins of vaginal acidity: high D/L lactate ratio is consistent with bacteria being the primary source. Hum Reprod 2001;16:1809e13.
  18. Boskey ER, Telsch KM, Whaley KJ, Moench TR, Cone RA. Acid production by vaginal flora in vitro is consistent with the rate and extent of vaginal acidification. Infect Immun 1999;67:5170e5.
  19. Borgdorff H, Tsivtsivadze E, Verhelst R, Marzorati M, Jurriaans S, Ndayisaba GF, et al. Lactobacillus-dominated cervicovaginal micro- biota associated with reduced HIV/STI prevalence and genital HIV viral load in African women. ISME J 2014;8:1781e93.
  20. van de Wijgert JH, Borgdorff H, Verhelst R, Crucitti T, Francis S, Verstraelen H, et al. The vaginal microbiota: what have we learned after a decade of molecular characterization? PLoS One 2014;9: e105998.
  21. Kindinger LM, Bennett PR, Lee YS, Marchesi JR, Smith A, Cacciatore S, et al. The interaction between vaginal microbiota, cervical length, and vaginal progesterone treatment for preterm birth risk. Microbiome 2017;5:6.
  22. Aldunate M, Tyssen D, Johnson A, Zakir T, Sonza S, Moench T, et al. Vaginal concentrations of lactic acid potently inactivate HIV. J Antimicrob Chemother 2013;68:2015e25.
  23. Ahmed K, Tunaru S, Offermanns S. GPR109A, GPR109B and GPR81, a family of hydroxy-carboxylic acid receptors. Trends Pharmacol Sci 2009;30:557e62.
  24. Kuchiiwa T, Nio-Kobayashi J, Takahashi-Iwanaga H, Yajima T, Iwanaga T. Cellular expression of monocarboxylate transporters in the female reproductive organ of mice: implications for the genital lactate shuttle. Histochem Cell Biol 2011;135:351e60.
  25. Kashet ER. Bioenergetics of lactic acid bacteria: cytoplasmic pH and osmotolerance. FEMS Microbiol Lett 1987;46:233e44.
  26. Alakomi HL, Skytta E, Saarela M, Mattila-Sandholm T, Latva-Kala K, Helander IM. Lactic acid permeabilizes gram-negative bacteria by disrupting the outer membrane. Appl Environ Microbiol 2000;66: 2001e5.
  27. Klebanoff SJ, Coombs RW. Viricidal effect of Lactobacillus acidophi- lus on human immunodeficiency virus type 1: possible role in hetero- sexual transmission. J Exp Med 1991;174:289e92.
  28. Klebanoff SJ, Hillier SL, Eschenbach DA, Waltersdorph AM. Control of the microbial flora of the vagina by H 2 O 2 -generating lactobacilli. J Infect Dis 1991;164:94e100.
  29. Ocana VS, Pesce de Ruiz Holgado AA, Nader-Macias ME. Selection of vaginal H 2 O 2 -generating Lactobacillus species for probiotic use. Curr Microbiol 1999;38:279e84.
  30. O'Hanlon DE, Lanier BR, Moench TR, Cone RA. Cervicovaginal fluid and semen block the microbicidal activity of hydrogen peroxide pro- duced by vaginal lactobacilli. BMC Infect Dis 2010;10:120.
  31. Nardini P, Nahui Palomino RA, Parolin C, Laghi L, Foschi C, Cevenini R, et al. Lactobacillus crispatus inhibits the infectivity of Chlamydia trachomatis elementary bodies, in vitro study. Sci Rep 2016; 6:29024.
  32. Graver MA, Wade JJ. The role of acidification in the inhibition of Neisseria gonorrhoeae by vaginal lactobacilli during anaerobic growth. Ann Clin Microbiol Antimicrob 2011;10:8.
  33. Valore EV, Park CH, Igreti SL, Ganz T. Antimicrobial components of vaginal fluid. Am J Obstet Gynecol 2002;187:561e8.
  34. Maisey HC, Doran KS, Nizet V. Recent advances in understanding the molecular basis of group B Streptococcus virulence. Expert Rev Mol Med 2008;10:e27.
  35. Goncalves B, Ferreira C, Alves CT, Henriques M, Azeredo J, Silva S. Vulvovaginal candidiasis: epidemiology, microbiology and risk factors. Crit Rev Microbiol 2016;42:905e27.
  36. Kling DE, Cavicchio AJ, Sollinger CA, Madoff LC, Schnitzer JJ, Kinane TB. Lactic acid is a potential virulence factor for group B Streptococcus. Microb Pathog 2009;46:43e52.
  37. De Gregorio PR, Juarez Tomas MS, Leccese Terraf MC, Nader- Macias ME. In vitro and in vivo effects of beneficial vaginal lactobacilli on pathogens responsible for urogenital tract infections. J Med Micro- biol 2014;63:685e96.
  38. Bodaszewska M, Brzychczy-Wloch M, Gosiewski T, Adamski P, Strus M, Heczko PB. Evaluation of group B Streptococcus suscepti- bility to lactic acid bacteria strains. Med Dosw Mikrobiol 2010;62: 153e61.
  39. Juarez Tomas MS, Saralegui Duhart CI, De Gregorio PR, Vera Pingitore E, Nader-Macias ME. Urogenital pathogen inhibition and compatibility between vaginal Lactobacillus strains to be considered as probiotic candidates. Eur J Obstet Gynecol Reprod Biol 2011;159: 399e406.
  40. Ho M, Chang YY, Chang WC, Lin HC, Wang MH, Lin WC, et al. Oral Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 to reduce Group B Streptococcus colonization in pregnant women: a randomized controlled trial. Taiwan J Obstet Gynecol 2016;55:515e8.
  41. Morales DK, Hogan DA. Candida albicans interactions with bacteria in the context of human health and disease. PLoS Pathog 2010;6: e1000886.
  42. Krasner RI, Young G, Yudkofsky PL. Interactions of oral strains of Candida albicans and lactobacilli. J Bacteriol 1956;72:525e9.
  43. Cunha DV, Salazar SB, Lopes MM, Mira NP. Mechanistic insights underlying tolerance to acetic acid stress in vaginal Candida glabrata clinical isolates. Front Microbiol 2017;8:259.
  44. McClelland RS, Richardson BA, Hassan WM, Graham SM, Kiarie J, Baeten JM, et al. Prospective study of vaginal bacterial flora and other risk factors for vulvovaginal candidiasis. J Infect Dis 2009;199: 1883e90.
  45. De Seta F, Parazzini F, De Leo R, Banco R, Maso GP, De Santo D, et al. Lactobacillus plantarum P17630 for preventing Candida vaginitis recurrence: a retrospective comparative study. Eur J Obstet Gynecol Reprod Biol 2014;182:136e9.
  46. Taha TE, Hoover DR, Dallabetta GA, Kumwenda NI, Mtimavalye LA, Yang LP, et al. Bacterial vaginosis and disturbances of vaginal flora: association with increased acquisition of HIV. AIDS 1998;12: 1699e706.
  47. Sha BE, Zariffard MR, Wang QJ, Chen HY, Bremer J, Cohen MH, et al. Female genital-tract HIV load correlates inversely with Lactobacillus species but positively with bacterial vaginosis and Mycoplasma homi- nis. J Infect Dis 2005;191:25e32.
  48. Mitchell C, Balkus JE, Fredricks D, Liu C, McKernan-Mullin J, Frenkel LM, et al. Interaction between lactobacilli, bacterial vaginosis-associated bacteria, and HIV type 1 RNA and DNA genital shedding in U.S. and Kenyan women. AIDS Res Hum Retrovir 2013; 29:13e9.
  49. Aldunate M, Tyssen D, Latham C, Ramsland P, Permutter P, Moench T, et al. Vaginal concentrations of lactic acid potently inactivate HIV-1 compared to short chain fatty acids present during bacterial vaginosis. AIDS Res Hum Retrovir 2014;30:A228.
  50. Lai SK, Hida K, Shukair S, Wang YY, Figueiredo A, Cone R, et al. Human immunodeficiency virus type 1 is trapped by acidic but not by neutralized human cervicovaginal mucus. J Virol 2009;83:11196e200.
  51. Olmsted SS, Khanna KV, Ng EM, Whitten ST, Johnson 3rd ON, Markham RB, et al. Low pH immobilizes and kills human leukocytes and prevents transmission of cell-associated HIV in a mouse model. BMC Infect Dis 2005;5:79.
  52. Shukair SA, Allen SA, Cianci GC, Stieh DJ, Anderson MR, Baig SM, et al. Human cervicovaginal mucus contains an activity that hinders HIV-1 movement. Mucosal Immunol 2013;6:427e34.
  53. Cherpes TL, Melan MA, Kant JA, Cosentino LA, Meyn LA, Hillier SL. Genital tract shedding of herpes simplex virus type 2 in women: effects of hormonal contraception, bacterial vaginosis, and vaginal group B Streptococcus colonization. Clin Infect Dis 2005;40:1422e8.
  54. Dimitonova SP, Danova ST, Serkedjieva JP, Bakalov BV. Antimicrobial activity and protective properties of vaginal lactobacilli from healthy Bulgarian women. Anaerobe 2007;13:178e84.
  55. Isaacs CE, Xu W. Theaflavin-3,3'-digallate and lactic acid combinations reduce herpes simplex virus infectivity. Antimicrob Agents Chemother 2013;57:3806e14.
  56. Sakai M, Ishiyama A, Tabata M, Sasaki Y, Yoneda S, Shiozaki A, et al. Relationship between cervical mucus interleukin-8 concentra- tions and vaginal bacteria in pregnancy. Am J Reprod Immunol 2004; 52:106e12.
  57. Nikolaitchouk N, Andersch B, Falsen E, Strombeck L, Mattsby- Baltzer I. The lower genital tract microbiota in relation to cytokine-, SLPI-and endotoxin levels: application of checkerboard DNA-DNA hybridization. APMIS 2008;116:263e77.
  58. Kyongo JK, Jespers V, Goovaerts O, Michiels J, Menten J, Fichorova RN, et al. Searching for lower female genital tract soluble and cellular biomarkers: defining levels and predictors in a cohort of healthy Caucasian women. PLoS One 2012;7:e43951.
  59. Passmore JA, Jaspan HB, Masson L. Genital inflammation, immune activation and risk of sexual HIV acquisition. Curr Opin HIV AIDS 2016;11:156e62.
  60. Gosmann C, Anahtar MN, Handley SA, Farcasanu M, Abu-Ali G, Bowman BA, et al. Lactobacillus-deficient cervicovaginal bacterial communities are associated with increased HIV acquisition in young South African women. Immunity 2017;46:29e37.
  61. Arnold KB, Burgener A, Birse K, Romas L, Dunphy LJ, Shahabi K, et al. Increased levels of inflammatory cytokines in the female repro- ductive tract are associated with altered expression of proteases, mucosal barrier proteins, and an influx of HIV-susceptible target cells. Mucosal Immunol 2016;9:194e205.
  62. Zevin AS, Xie IY, Birse K, Arnold K, Romas L, Westmacott G, et al. Microbiome Composition and function drives wound-healing impair- ment in the female genital tract. PLoS Pathog 2016;12:e1005889.
  63. Libby EK, Pascal KE, Mordechai E, Adelson ME, Trama JP. Atopobium vaginae triggers an innate immune response in an in vitro model of bacterial vaginosis. Microbes Infect 2008;10:439e46.
  64. Yamamoto HS, Xu Q, Fichorova RN. Homeostatic properties of Lactobacillus jensenii engineered as a live vaginal anti-HIV microbi- cide. BMC Microbiol 2013;13:4.
  65. Eade CR, Diaz C, Wood MP, Anastos K, Patterson BK, Gupta P, et al. Identification and characterization of bacterial vaginosis-associated pathogens using a comprehensive cervical-vaginal epithelial coculture assay. PLoS One 2012;7:e50106.
  66. Rose 2nd WA, McGowin CL, Spagnuolo RA, Eaves-Pyles TD, Popov VL, Pyles RB. Commensal bacteria modulate innate immune responses of vaginal epithelial cell multilayer cultures. PLoS One 2012; 7:e32728.
  67. Doerflinger SY, Throop AL, Herbst-Kralovetz MM. Bacteria in the vaginal microbiome alter the innate immune response and barrier properties of the human vaginal epithelia in a species-specific manner. J Infect Dis 2014;209:1989e99.
  68. Hearps A, Gugasyan R, Srbinovski D, Tyssen D, Aldunate M, Anderson DJ, et al. Lactic acid, a vaginal microbiota metabolite, elicits an anti-inflammatory response from vaginal and cervical epithelial cells. AIDS Res Hum Retroviruses 2014;30:A238e9.
  69. Hearps AC, Tyssen D, Srbinovski D, Bayigga L, Delgado DJD, Aldunate M, et al. Vaginal lactic acid elicits an anti-inflammatory response from human cervicovaginal epithelial cells and inhibits pro- duction of pro-inflammatory mediators associated with HIV acquisition. Mucosal Immunol 2017 Apr 12. http://dx.doi.org/10.1038/mi2017.27 [Epub ahead of print]. · DOI
  70. Nazli A, Kafka JK, Ferreira VH, Anipindi V, Mueller K, Osborne BJ, et al. HIV-1 gp120 induces TLR2-and TLR4-mediated innate immune activa- tion in human female genital epithelium. J Immunol 2013;191:4246e58.
  71. Mares D, Simoes JA, Novak RM, Spear GT. TLR2-mediated cell stimulation in bacterial vaginosis. J Reprod Immunol 2008;77:91e9.
  72. Witkin SS, Alvi S, Bongiovanni AM, Linhares IM, Ledger WJ. Lactic acid stimulates interleukin-23 production by peripheral blood mono- nuclear cells exposed to bacterial lipopolysaccharide. FEMS Immunol Med Microbiol 2011;61:153e8.
  73. Mossop H, Linhares IM, Bongiovanni AM, Ledger WJ, Witkin SS. Influence of lactic acid on endogenous and viral RNA-induced immune mediator production by vaginal epithelial cells. Obstet Gynecol 2011; 118:840e6.
  74. Rahkonen L, Rutanen EM, Unkila-Kallio L, Nuutila M, Nieminen P, Sorsa T, et al. Factors affecting matrix metalloproteinase-8 levels in the vaginal and cervical fluids in the first and second trimester of pregnancy. Hum Reprod 2009;24:2693e702.
  75. Beghini J, Linhares IM, Giraldo PC, Ledger WJ, Witkin SS. Differential expression of lactic acid isomers, extracellular matrix metalloproteinase inducer, and matrix metalloproteinase-8 in vaginal fluid from women with vaginal disorders. BJOG 2015;122:1580e5.
  76. Cruickshank R, Sharman A. The biology of the vagina in the human subject. BJOG 1934;41:190e207.
  77. Rampersaud R, Planet PJ, Randis TM, Kulkarni R, Aguilar JL, Lehrer RI, et al. Inerolysin, a cholesterol-dependent cytolysin produced by Lactobacillus iners. J Bacteriol 2011;193:1034e41.
  78. Yildirim S, Yeoman CJ, Janga SC, Thomas SM, Ho M, Leigh SR, et al. Primate vaginal microbiomes exhibit species specificity without uni- versal Lactobacillus dominance. ISME J 2014;8:2431e44.
  79. Mirmonsef P, Hotton AL, Gilbert D, Burgad D, Landay A, Weber KM, et al. Free glycogen in vaginal fluids is associated with Lactobacillus colonization and low vaginal pH. PLoS One 2014;9:e102467.
  80. Mirmonsef P, Hotton AL, Gilbert D, Gioia CJ, Maric D, Hope TJ, et al. Glycogen levels in undiluted genital fluid and their relationship to vaginal pH, estrogen, and progesterone. PLoS One 2016;11:e0153553.
  81. Stewart-Tull DES. Evidence that vaginal lactobacilli do not ferment glycogen. Am J Obstet Gynecol 1964;88:676e9.
  82. Spear GT, French AL, Gilbert D, Zariffard MR, Mirmonsef P, Sullivan TH, et al. Human alpha-amylase present in lower-genital-tract mucosal fluid processes glycogen to support vaginal colonization by Lactobacillus. J Infect Dis 2014;210:1019e28.
  83. Nasioudis D, Beghini J, Bongiovanni AM, Giraldo PC, Linhares IM, Witkin SS. alpha-amylase in vaginal fluid: association with conditions favorable to dominance of Lactobacillus. Reprod Sci 2015;22:1393e8.
  84. Hickey M, Marino JL, Tachedjian G. Critical review: mechanisms of HIV transmission in Depo-Provera users: the likely role of hypo- estrogenism. J Acquir Immune Defic Syndr 2016;71:1e7.
  85. Mirmonsef P, Modur S, Burgad D, Gilbert D, Golub ET, French AL, et al. Exploratory comparison of vaginal glycogen and Lactobacillus levels in premenopausal and postmenopausal women. Menopause 2015; 22:702e9.
  86. Macklaim JM, Fernandes AD, Di Bella JM, Hammond JA, Reid G, Gloor GB. Comparative meta-RNA-seq of the vaginal microbiota and differential expression by Lactobacillus iners in health and dysbiosis. Microbiome 2013;1:12.
  87. Ozkinay E, Terek MC, Yayci M, Kaiser R, Grob P, Tuncay G. The effectiveness of live lactobacilli in combination with low dose oestriol (Gynoflor) to restore the vaginal flora after treatment of vaginal in- fections. BJOG 2005;112:234e40.
  88. MacPhee RA, Hummelen R, Bisanz JE, Miller WL, Reid G. Probiotic strategies for the treatment and prevention of bacterial vaginosis. Expert Opin Pharmacother 2010;11:2985e95.
  89. Hutt P, Lapp E, Stsepetova J, Smidt I, Taelma H, Borovkova N, et al. Characterisation of probiotic properties in human vaginal lactobacilli strains. Microb Ecol Health Dis 2016;27:30484.
  90. Borges S, Silva J, Teixeira P. The role of lactobacilli and probiotics in maintaining vaginal health. Arch Gynecol Obstet 2014;289:479e89.
  91. Hallen A, Jarstrand C, Pahlson C. Treatment of bacterial vaginosis with lactobacilli. Sex Transm Dis 1992;19:146e8.
  92. Parent D, Bossens M, Bayot D, Kirkpatrick C, Graf F, Wilkinson FE, et al. Therapy of bacterial vaginosis using exogenously-applied Lacto- bacilli acidophili and a low dose of estriol: a placebo-controlled mul- ticentric clinical trial. Arzneimittel-Forschung 1996;46:68e73.
  93. Eriksson K, Carlsson B, Forsum U, Larsson PG. A double-blind treat- ment study of bacterial vaginosis with normal vaginal lactobacilli after an open treatment with vaginal clindamycin ovules. Acta Dermato- Venereologica 2005;85:42e6.
  94. Anukam K, Osazuwa E, Ahonkhai I, Ngwu M, Osemene G, Bruce AW, et al. Augmentation of antimicrobial metronidazole therapy of bacterial vaginosis with oral probiotic Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14: randomized, double-blind, placebo controlled trial. Microbes Infect 2006;8:1450e4.
  95. Larsson PG, Stray-Pedersen B, Ryttig KR, Larsen S. Human lactobacilli as supplementation of clindamycin to patients with bacterial vaginosis reduce the recurrence rate; a 6-month, double-blind, randomized, placebo-controlled study. BMC Womens Health 2008;8:3.
  96. Marcone V, Calzolari E, Bertini M. Effectiveness of vaginal adminis- tration of Lactobacillus rhamnosus following conventional metronida- zole therapy: how to lower the rate of bacterial vaginosis recurrences. New Microbiol 2008;31:429e33.
  97. Petricevic L, Witt A. The role of Lactobacillus casei rhamnosus Lcr35 in restoring the normal vaginal flora after antibiotic treatment of bac- terial vaginosis. BJOG 2008;115:1369e74.
  98. Martinez RC, Franceschini SA, Patta MC, Quintana SM, Gomes BC, De Martinis EC, et al. Improved cure of bacterial vaginosis with single dose of tinidazole (2 g), Lactobacillus rhamnosus GR-1, and Lacto- bacillus reuteri RC-14: a randomized, double-blind, placebo-controlled trial. Can J Microbiol 2009;55:133e8.
  99. Mastromarino P, Macchia S, Meggiorini L, Trinchieri V, Mosca L, Perluigi M, et al. Effectiveness of Lactobacillus-containing vaginal tablets in the treatment of symptomatic bacterial vaginosis. Clin Microbiol Infect 2009;15:67e74.
  100. Marcone V, Rocca G, Lichtner M, Calzolari E. Long-term vaginal administration of Lactobacillus rhamnosus as a complementary approach to management of bacterial vaginosis. Int J Gynaecol Obstet 2010;110:223e6.
  101. Bradshaw CS, Pirotta M, De Guingand D, Hocking JS, Morton AN, Garland SM, et al. Efficacy of oral metronidazole with vaginal clin- damycin or vaginal probiotic for bacterial vaginosis: randomised placebo-controlled double-blind trial. PLoS One 2012;7:e34540.
  102. Ya W, Reifer C, Miller LE. Efficacy of vaginal probiotic capsules for recurrent bacterial vaginosis: a double-blind, randomized, placebo- controlled study. Am J Obstet Gynecol 2010;203(120):e1e6.
  103. Ehrstrom S, Daroczy K, Rylander E, Samuelsson C, Johannesson U, Anzen B, et al. Lactic acid bacteria colonization and clinical outcome after probiotic supplementation in conventionally treated bacterial vagi- nosis and vulvovaginal candidiasis. Microbes Infect 2010;12:691e9.
  104. Vujic G, Jajac Knez A, Despot Stefanovic V, Kuzmic Vrbanovic V. Efficacy of orally applied probiotic capsules for bacterial vaginosis and other vaginal infections: a double-blind, randomized, placebo- controlled study. Eur J Obstet Gynecol Reprod Biol 2013;168:75e9.
  105. 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;111:245e8.
  106. Tomusiak A, Strus M, Heczko PB, Adamski P, Stefanski G, Miko- lajczyk-Cichonska A, et al. Efficacy and safety of a vaginal medicinal product containing three strains of probiotic bacteria: a multicenter, randomized, double-blind, and placebo-controlled trial. Drug Des Devel Ther 2015;9:5345e54.
  107. Heczko PB, Tomusiak A, Adamski P, Jakimiuk AJ, Stefanski G, Mikolajczyk-Cichonska A, et al. Supplementation of standard antibiotic therapy with oral probiotics for bacterial vaginosis and aerobic vagi- nitis: a randomised, double-blind, placebo-controlled trial. BMC Womens Health 2015;15:115.
  108. Recine N, Palma E, Domenici L, Giorgini M, Imperiale L, Sassu C, et al. Restoring vaginal microbiota: biological control of bacterial vaginosis. A prospective case-control study using Lactobacillus rham- nosus BMX 54 as adjuvant treatment against bacterial vaginosis. Arch Gynecol Obstet 2016;293:101e7.
  109. Macklaim JM, Clemente JC, Knight R, Gloor GB, Reid G. Changes in vaginal microbiota following antimicrobial and probiotic therapy. Microb Ecol Health Dis 2015;26:27799.
  110. Ling Z, Liu X, Chen W, Luo Y, Yuan L, Xia Y, et al. The restoration of the vaginal microbiota after treatment for bacterial vaginosis with metronidazole or probiotics. Microb Ecol 2013;65:773e80.
  111. Verdenelli MC, Cecchini C, Coman MM, Silvi S, Orpianesi C, Coata G, et al. Impact of probiotic SYNBIO((R)) administered by vaginal sup- positories in promoting vaginal health of apparently healthy women. Curr Microbiol 2016;73:483e90.
  112. Ngugi BM, Hemmerling A, Bukusi EA, Kikuvi G, Gikunju J, Shiboski S, et al. Effects of bacterial vaginosis-associated bacteria and sexual intercourse on vaginal colonization with the probiotic Lactoba- cillus crispatus CTV-05. Sex Transm Dis 2011;38:1020e7.
  113. Antonio MA, Meyn LA, Murray PJ, Busse B, Hillier SL. Vaginal colonization by probiotic Lactobacillus crispatus CTV-05 is decreased by sexual activity and endogenous Lactobacilli. J Infect Dis 2009;199: 1506e13.
  114. Mastromarino P, Brigidi P, Macchia S, Maggi L, Pirovano F, Trinchieri V, et al. Characterization and selection of vaginal Lactoba- cillus strains for the preparation of vaginal tablets. J Appl Microbiol 2002;93:884e93.
  115. Mastromarino P, Vitali B, Mosca L. Bacterial vaginosis: a review on clinical trials with probiotics. New Microbiol 2013;36:229e38.
  116. Andersch B, Forssman L, Lincoln K, Torstensson P. Treatment of bacterial vaginosis with an acid cream: a comparison between the effect of lactate-gel and metronidazole. Gynecol Obstet Invest 1986;21: 19e25.
  117. Andersch B, Lindell D, Dahlen I, Brandberg A. Bacterial vaginosis and the effect of intermittent prophylactic treatment with an acid lactate gel. Gynecol Obstet Invest 1990;30:114e9.
  118. Decena DC, Co JT, Manalastas Jr RM, Palaypayon EP, Padolina CS, Sison JM, et al. Metronidazole with Lactacyd vaginal gel in bacterial vaginosis. J Obstet Gynaecol Res 2006;32:243e51.
  119. Bahamondes MV, Portugal PM, Brolazo EM, Simoes JA, Bahamondes L. Use of a lactic acid plus lactoserum intimate liquid soap for external hygiene in the prevention of bacterial vaginosis recurrence after metronidazole oral treatment. Rev Assoc Med Bras 2011;57: 415e20.
  120. Holst E, Brandberg A. Treatment of bacterial vaginosis in pregnancy with a lactate gel. Scand J Infect Dis 1990;22:625e6.
  121. Braga PC, Dal Sasso M, Culici M, Spallino A. Inhibitory activity of thymol on native and mature Gardnerella vaginalis biofilms: in vitro study. Arzneimittelforschung 2010;60:675e81.
  122. Sundara Rajan S, Turovskiy Y, Singh Y, Chikindas ML, Sinko PJ. Poly(ethylene glycol) (PEG)-lactic acid nanocarrier-based degradable hydrogels for restoring the vaginal microenvironment. J Control Release 2014;194:301e9.
  123. Verstraelen H, Vervaet C, Remon JP. Rationale and safety assessment of a novel intravaginal drug-delivery system with sustained DL-Lactic acid release, intended for long-term protection of the vaginal microbiome. PLoS One 2016;11:e0153441.

Cited by

Sorted by citations

Authors
Tachedjian, G., Aldunate, M., Bradshaw, C. S., & Cone, R. A.
Affiliations
  • Burnet Institute (AU)
  • Johns Hopkins University (US)
Corresponding author
Tachedjian, Gilda
ORCID
Tachedjian, Gilda
Venue
Research in Microbiology
Publisher
Elsevier BV
Published
2017-11
Volume
168
Issue
9-10
Pages
782-792
ISSN
  • 0769-2609 (ISSN-L)
  • 0923-2508
DOI
10.1016/j.resmic.2017.04.001
OpenAlex
W2606807087
Cited by
557
References
8
Citations by year
2026: 74 · 2025: 78 · 2024: 67 · 2023: 68 · 2022: 75 · 2021: 60 · 2020: 50 · 2019: 50 · 2018: 28 · 2017: 6
FWCI
5.14
Type
journal article
Language
en
Open access
Licence
Locations
  • Research in Microbiology (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • RMIT Research Repository (RMIT University Library) (submittedVersion, other-oa)
  • Figshare (submittedVersion, cc-by)
Funders
  • National Health and Medical Research Council (NHMRC) (1055564, 1117748)
  • Monash University
  • NIAID
  • Burnet Institute
Topics
  • Life Sciences › Immunology and Microbiology › Microbiology › Reproductive tract infections research
  • Life Sciences › Agricultural and Biological Sciences › Food Science › Probiotics and Fermented Foods
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
Keywords
lactic acid, Lactobacillus, probiotics, vaginal microbiota, vaginal dysbiosis, bacterial vaginosis, vaginal pH, antimicrobial activity, antiviral activity, immunomodulation, probiotic therapy
MeSH terms
Female, Humans, Lactobacillus, Vagina, Vaginosis, Bacterial, Lactic Acid, Probiotics, Microbiota, Dysbiosis

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review