Protection of Vaginal Epithelial Cells with Probiotic Lactobacilli and the Effect of Estrogen against Infection by Candida albicans


Some probiotic strains of lactobacilli appear to be protective against vulvovaginal candidiasis. The vaginal epithelial cell line (VK2 E6/E7) was used as a model to assess the protective mechanisms of probiotic lactobacilli for cells chal- lenged with Candida albicans. Co-culture of VK2 cells with Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 prior to C. albicans challenge showed reduced adherence of C. albicans to the VK2 cells and inhibition of C. albicans growth. H2O2 concentrations of 0.3 μg/ml, produced by lactobacilli and estrogen-primed VK2 cells, were inhi-bitory to C. albicans growth. C. albicans growth was also inhibited by 10 μg/ml lactic acid. C. albicans infection was increased by 17β-estradiol through induction of hyphal germination. L. reuteri RC-14, but not L. rhamnosus GR-1, H2O2, or lactic acid inhibited estrogen-stimulated hyphal germination. The results of this study support a role for H2O2 and lactic acid from probiotic bacteria in vaginal epithelial protection from candidiasis and a role for 17β-estradiol in the disease by induction of C. albicans hyphal germination.

Share and Cite:

R. Wagner, S. Johnson and D. Tucker, "Protection of Vaginal Epithelial Cells with Probiotic Lactobacilli and the Effect of Estrogen against Infection by Candida albicans," Open Journal of Medical Microbiology, Vol. 2 No. 3, 2012, pp. 54-64. doi: 10.4236/ojmm.2012.23008.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] M. E. Falagas, G. I. Betsi and S. Athanasiou, “Probiotics for Prevention of Recurrent Vulvovaginal Candidiasis: A Review,” Journal of Antimicrobial Chemotherapy, Vol. 58, No. 2, 2006, pp. 266-272. doi:10.1093/jac/dkl246
[2] J. D. Sobel, “Vulvovaginal Candidosis,” The Lancet, Vol. 369, No. 9577, 2007, pp. 1961-1971. doi:10.1016/S0140-6736(07)60917-9
[3] A. M. Cole, “Innate Host Defense of Human Vaginal and Cervical Mucosae,” Current Topics in Microbiology and Immunology, Vol. 306, 2006, pp. 199-230. doi:10.1007/3-540-29916-5_8
[4] D. A. Eschenbach, S. S. Thwin, D. L. Patton, T. M. Hooton, A. E. Stapleton, K. Agnew, C. Winter, A. Meier and W. E. Stamm, “Influence of the Normal Menstrual Cycle on Vaginal Tissue, Discharge, and Microflora,” Clinical Infectious Diseases, Vol. 30, No. 6, 2000, pp. 901-907. doi:10.1086/313818
[5] J. D. Sobel, “Does Lactobacillus Prevent Post-Antibiotic Vulvovaginal Candidiasis?” Current Infectious Disease Reports, Vol. 7, No. 6, 2005, pp. 443-444. doi:10.1007/s11908-005-0045-6
[6] G. Reid and A. W. Bruce, “Urogenital Infections in Women: Can Probiotics Help?” Postgraduate Medicine Journal, Vol. 79, No. 934, 2003, pp. 428-432. doi:10.1136/pmj.79.934.428
[7] M. A. Strus, A. Kucharska, G. Kukla, M. BrzychczyW?och, K. Maresz and P. B. Heczko, “The In Vitro Activity of Vaginal Lactobacillus with Probiotic Properties Against Candida,” Infectious Diseases in Obstetrics and Gynecology, Vol. 13, No. 2, 2005, pp. 69-75. doi:10.1080/10647440400028136
[8] S. Coudeyras, G. Jugie, M. Vermerie and C. Forestier, “Adhesion of Human Probiotic Lactobacillus rhamnosus to Cervical and Vaginal Cells and Interaction with Vaginosis-Associated Pathogens,” Infectious Diseases in Obstetrics and Gynecology, Vol. 2008, No. 549640, 2008, pp. 1-5. doi:10.1155/2008/549640
[9] A. K. Ildgruben, I. M. Sj?berg and M.-L. K. C. Hammarstr?m, “Influence of Hormonal Contraceptives on the Immune Cells and Thickness of Human Vaginal Epithelium,” Obstetrics & Gynecology, Vol. 102, No. 3, 2003, pp. 571-582. doi:10.1016/S0029-7844(03)00618-5
[10] W. Tarry, W., M. Fisher, S. Shen and M. Mawhinney, “Candida albicans: The Estrogen Target for Vaginal Colonization,” Journal of Surgical Research, Vol. 129, No. 2, 2005, pp. 278-282. doi:10.1016/j.jss.2005.05.019
[11] C. R. Wira, K. S. Grant-Tschudy and M. A. CraneGodreau, “Epithelial Cells in the Female Reproductive Tract: A Central Role as Sentinels of Immune Protection,” American Journal of Reproductive Immunology, Vol. 53, No. 2, 2005, pp. 65-76. doi:10.1111/j.1600-0897.2004.00248.x
[12] O. S. Kinsman and A. E. Collard, “Hormonal Factors in Vaginal Candidiasis in Rats,” Infection and Immunity, Vol. 53, No. 3, 1986, pp. 498-504.
[13] A. Cassone, F. De Bernardis and G. Santoni, “Anticandidal Immunity and Vaginitis: Novel Opportunities for Immune Intervention,” Infection and Immunity, Vol. 75, No. 10, 2007, pp. 4675-4686. doi:10.1128/IAI.00083-07
[14] M. L. Peterson, K. Ault, M. J. Kremer, A. J. Klingelhutz, C. C. Davis, C. A. Squier and P. M. Schlievert, “The Innate Immune System is Activated by Stimulation of Vaginal Epithelial Cells with Sataphylococcus aureus and Toxic Shock Syndrome Toxin 1,” Infection and Immunity, Vol. 73, No. 4, 2005, pp. 2164-2174 doi:10.1128/IAI.73.4.2164-2174.2005
[15] M. Schaller, K. Zakikhany, J. R. Naglik, G. Weindl and B. Hube, “Models of Oral and Vaginal Candidiasis Based on In Vitro Reconstituted Human Epithelia,” Nature Protocols, Vol. 1, No. 6, 2006, pp. 2767-2773. doi:10.1038/nprot.2006.474
[16] C. Hollmer, M. Essmann, K. Ault and B. Larsen, “Aherence and Blocking of Candida albicans to Cultured Vaginal Epithelial Cells: Treatments to Decrease Adherence,” Infectious Diseases in Obstetrics and Gynecology, Vol. 2006, No. 98218, 2006, pp. 1-6. doi:10.1155/IDOG/2006/98218
[17] A. M. Geshnizgani and A. B. Onderedonk, “Defined Medium Simulating Genital Tract Secretions for Growth of Vaginal Microflora,” Journal of Clinical Microbiology, Vol. 30, No. 5, 1992, pp. 1323-1326.
[18] S. Al-Mushrif and B. M. Jones, “A Study of the Prevalence of Hydrogen Peroxide Generating Lactobacilli in Bacterial Vaginosis: The Determination of H2O2 Concentrations Generated In Vitro, by Isolated Strains and the Levels Found in Vaginal Secretions of Women with and without Infection,” Journal of Obstetrics and Gynaecology, Vol. 18, No. 1, 1998, pp. 63-67. doi:10.1080/01443619868325
[19] H. Motulsky, “Intuitive Biostatistics,” Oxford University Press, New York, 1995.
[20] R. A. Gaffney, M. F. Venegas, C. Kanerva, E. L. Navas, B. E. Anderson, J. L. Duncan and A. J. Schaeffer, “Effect of Vaginal Fluid on Adherence of Type 1 Piliated Escherichia coli to Epithelial Cells,” The Journal of Infectious Diseases, Vol. 172, No. 6, 1995, pp. 1528-1535. doi:10.1093/infdis/172.6.1528
[21] R. Gossrau, W. M. Frederiks and C. J. F. van Noorden, “Histochemistry of Reactive Oxygen-Species (ROS)Generating Oxidases in Cutaneous and Mucous Epithelia of Laboratory Rodents with Special Reference to Xanthine Oxidase,” Histochemistry and Cell Biology, Vol. 94, No. 5, 1990, pp. 539-544. doi:10.1007/BF00272619
[22] G. I. Gorodeski, U. Hopfer, C. C. Liu and E. Margles, “Estrogen Acidifies Vaginal pH by Up-Regulation of Proton Secretion via the Apical Membrane of Vaginal-Ectocervical Epithelial Cells,” Endocrinology, Vol. 146, No. 2, 2005, pp. 816-824. doi:10.1210/en.2004-1153
[23] R. C. R. Martinez, et al., “Effect of Lactobacillus rhamnosus GR-1 and Lactobacillus reuteri RC-14 on the Ability of Candida albicans to Infect Cells and Induce Inflammation,” Microbiology and Immunology, Vol. 53, No. 9, 2009, pp. 487-495. doi:10.1111/j.1348-0421.2009.00154.x
[24] J. Kaewsrichen, K. Peeyananjarassri and J. Kongprasertkit, “Selection and Identification of Anaerobic Lactobacilli Producing Inhibitory Compounds Against Vaginal Pathogens,” FEMS Immunology and Medical Microbiology, Vol. 48, No. 1, 2006, pp. 75-83. doi:10.1111/j.1574-695X.2006.00124.x
[25] P. Cadieux, et al., “Evaluation of Reuterin Production in Urogenital Probiotic Lactobacillus reuteri RC-14,” Applied and Environmental Microbiology, Vol. 74, No. 15, 2008, pp. 4645-4649. doi:10.1128/AEM.00139-08
[26] X. Li, L. Y. Zhou and G. I. Gorodeski, “Estrogen Regulates Epithelial Cell Deformability by Modulation of Cortical Actomyosin through Phosphorylation of Nonmuscle Myosin Heavy-Chain II-B Filaments,” Endocrinology, Vol. 147, No. 11, 2006, pp. 5236-5248. doi:10.1210/en.2006-0779
[27] X. Zhang, M. Essmann, E. T. Burt and B. Larsen, “Estrogen Effects on Candida albicans: A Potential Virulence-Regulating Mechanism,” Journal of Infectious Disease, Vol. 181, No. 4, 2000, pp. 1441-1446. doi:10.1086/315406

Copyright © 2024 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.