Therapeutic potential of vaginal lactobacilli for women’s health: Interaction with pathogens and epithelium cells.

The vaginal microbiota of healthy reproductive-age women is dominated by Lactobacillus spp., which protect against numerous uropathogens. This study aims to identify lactobacilli with antagonist activity toward Candida, Chlamydia, and HIV that mostly affect women’s health. From vaginas of healthy women, we isolated seventeen Lactobacillus strains, highly represented in the vaginal microbiota: L. crispatus (BC1-BC8), L. gasseri (BC9-BC14), and L. vaginalis (BC15-BC17). The broadest anti-Candida activity was observed for L. crispatus (BC1, BC4, BC5) and L. vaginalis BC15. Most of lactobacilli reduced Candida adhesion to HeLa cells by multiple mechanism including exclusion, competition, and displacement. Histone deacetylases inhibition was hypothesized to support the antifungal activity of Lactobacillus. Next, mainly L. crispatus strains inhibited Chlamydia by secreting metabolites in a concentration/pH dependent mode at short contact times. Lactate production, vaginal acidification, and glucose consumption seemed to be crucial for the anti-Chlamydia activity. The metabolic profiles of Lactobacillus-conditioned medium (CM) also correlated with the anti-Chlamydia/Candida activity. Finally, lactobacilli inhibited HIV-1 replication in human tissues ex vivo by multiple mechanisms: Acidification. The pH of Lactobacillus-CM was ≤ 4.6. Tissue culture acidification with HCl to this pH abrogated HIV-1 replication. However, Lactobacillus-CM, diluted 5-fold (neutral pH), also suppressed HIV-1 infection, as opposed to HCl-treated medium at the same pH, suggesting the existence of other anti-HIV factors. Lactate. Addition of lactate isomers D and L to tissue culture, at the average titers found in all Lactobacillus-CM, inhibited HIV-1 replication. Isomer L was produced in higher quantities and was mostly responsible for HIV-1 inhibition. Virucidal effect. Incubation of HIV-1 in Lactobacillus-CM suppressed virus infectivity. Lactobacilli cells adsorbed HIV-1, decreasing the number of virions. This results support role of lactobacilli in protecting the female genital tract from uropathogens, and are prerequisites for the development of new probiotic agents as an effective strategy to enhance vaginal health.