Open Journal of Medical Microbiology
Vol.2 No.3(2012), Article ID:22814,11 pages DOI:10.4236/ojmm.2012.23008

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

R. Doug Wagner, Shemedia J. Johnson, Danielle R. Tucker

Microbiology Division, National Center for Toxicological Research, Jefferson, USA


Received April 9, 2012; revised May 11, 2012; accepted May 19, 2012

Keywords: Probiotic; Epithelial Cells; Candidiasis; Estrogen; 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 challenged 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 inhibitory 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.

1. Introduction

The vaginal microbiota is one of the first lines of defense against vulvovaginal candidiasis (VVC). The cultivable normal vaginal microbiota is predominantly populated by Lactobacillus iners, Lactobacillus jensenii, and Lactobacillus crispatus [1], which tend to suppress growth of other bacterial species by production of lactic acid and antimicrobial products [2]. The low pH is considered a result of microbial metabolic products (mostly lactic acid) of glycogen, which is produced by vaginal epithelial cells [3]. During menses, the composition of the vaginal microbiota is destabilized [4] and it is at that time that probiotic lactobacilli may have a role to play in maintenance of the barrier to C. albicans infection. Although numerous strains of lactobacilli have been tested as probiotics as replacements for commensal bacterial resistance to VVC, many are not effective [5]. Some in vivo experiments have shown that L. rhamnosus GR-1 and L. reuteri RC-14 may be effective treatments for VVC [6]. If they are effective, their value may be in the production of H2O2, which is only produced by some strains of Lactobacillus spp. [7]. Adherence to the VK2 cells may also be a protective factor of these putative effective strains. For example, in one study, the probiotic effects of one Lactobacillus sp. strain that inhibited C. albicans growth was associated with being strongly adherent to VK2 (E6/E7) vaginal epithelial cells [8].

Estrogens appear to affect both the infectivity of C. albicans and the recruitment of host defenses. Although C. albicans colonizes the vaginal tract as a commensal organism most of the time, conventional wisdom says that it can change to a virulent, invasive state by a mechanism that is still not clearly understood [2]. This process appears to be enhanced during the luteal phase of the menstrual cycle when there is a localized high estrogen concentration, which can also occur during high estrogen contraceptive use [2]. Some hormonal contraceptives induce epithelial hyperplasia in the vaginal tissues, even greater than normally occurs during the luteal phase of the menstrual cycle [9]. The presence of estrogen binding proteins expressed by C. albicans appears to be specific for estrogen and induces vaginal colonization in a rat model [10]. In vitro cell culture experiments show that estrogen causes a reduction in the transepithelial electrical resistance (TEER) of differentiated vaginal epithelial cell monolayers, which indicates a reduction in tight junctions between cells [11]. The loss of tight junctions under the control of estrogen could provide an increased opportunity for Candida sp. to invade vaginal tissue. Additional evidence for the role of estrogen in VVC has been shown in animal experiments, where it may have promoted germination of C. albicans and increased infection of the cornified vaginal epithelial tissues [12]. Thus, estrogen is an fectious Disease, Vol. 181, No. 4, 2000, pp. 1441-1446. doi:10.1086/315406