Exploring potential of vaginal Lactobacillus isolates from South African women for enhancing treatment for bacterial vaginosis

Abstract

Antibiotics continue to be the standard-of-care for bacterial vaginosis (BV), although recurrence rates are high. Vaginal probiotics may improve durability of BV treatment, although few probiotics for vaginal health contain Lactobacillus spp. that commonly colonize the lower female genital tract. Characteristics of vaginal Lactobacillus strains from South African women were evaluated for their probiotic potential in vitro compared to strains from commercial vaginal products, including growth at varying pHs, ability to lower pH, produce D-/L-lactate and H 2 O 2 , influence growth of BV-associated Gardnerella vaginalis and Prevotella bivia, adherence to cervical cells and susceptibility to antibiotics. Fifty-seven Lactobacillus strains were purified from cervico-vaginal fluid, including L. crispatus, L. jensenii, L. gasseri, L. mucosae, and L. vaginalis. L crispatus strains grew better at pHs below 4.5 and lowered pH more effectively than other strains. Production of D-/L-lactate and H 2 O 2 varied between Lactobacillus species and strains. Lactobacillus strains generally inhibited P. bivia more uniformly than G. vaginalis isolates. All vaginal Lactobacillus isolates were resistant to metronidazole while susceptibility to clindamycin varied. Furthermore, vaginal Lactobacillus strains tended to be broadly susceptible to penicillin, amoxicillin, rifampicin and rifabutin. Whole-genome-sequencing of five of the best-performing vaginal Lactobacillus strains confirmed their likely safety, due to antimicrobial resistance elements being largely absent, while putative intact prophages were present in the genomes of two of the five strains. Overall, vaginal Lactobacillus strains largely performed better in these in vitro assays than probiotic strains currently used in probiotics for vaginal health. Including the best-performing vaginal Lactobacillus isolates in a regionspecific probiotic for vaginal health may result in improved BV treatment options.

Testing the regulatory framework in South Africa – a single-blind randomized pilot trial of commercial probiotic supplementation to standard therapy in women with bacterial vaginosis

“…The selected OTC oral/vaginal probiotic, like all those available in South Africa, does not contain Lactobacillus spp. that are commonly present in the FGT and associated with vaginal health, internationally and in South African women, such as L. crispatus, L. gasseri or L. jensenii [19,43]. Others have shown that vaginal Lactobacillus spp.…”

“…are highly adapted to this ecological niche [44], and since the product did not contain those highly adapted Lactobacillus spp., they might have failed to colonize, which is in agreement with our microbiological results. For a successful colonization and subsequent ability to confer a health benefit to the host, the bacteria need to fulfil a broad range of other criteria including adherence to vaginal epithelial cells, production of lactic acid, decrease of vaginal pH, decrease of inflammatory cytokines, and inhibition of BV-associated bacteria, such as G. vaginalis or P. bivia [43]. We have isolated and characterised the Lactobacillus strains contained in this OTC phenotypically and compared their characteristics to vaginal Lactobacillus strains from healthy South African women [43].…”

“…For a successful colonization and subsequent ability to confer a health benefit to the host, the bacteria need to fulfil a broad range of other criteria including adherence to vaginal epithelial cells, production of lactic acid, decrease of vaginal pH, decrease of inflammatory cytokines, and inhibition of BV-associated bacteria, such as G. vaginalis or P. bivia [43]. We have isolated and characterised the Lactobacillus strains contained in this OTC phenotypically and compared their characteristics to vaginal Lactobacillus strains from healthy South African women [43]. We did in fact find that vaginal Lactobacillus strains largely performed better in these in vitro assays than the strains currently used in probiotics for vaginal health, suggesting that it might not be ideal to include these strains in commercial probiotics for vaginal health.…”

Presence and Persistence of Putative Lytic and Temperate Bacteriophages in Vaginal Metagenomes from South African Adolescents

“…Prophage sequences have been identified in genomes of various vaginal Lactobacillus spp. using in vitro and whole genome sequencing approaches [13,[44][45][46][47]. Recent metagenomic surveys of the women from high-income countries have revealed the presence of known Lactobacillus bacteriophages in the vagina [48,49], suggesting that they can be induced and actively transmitted in the FGT.…”

Probiogenomics Analysis of 97 Lactobacillus crispatus Strains as a Tool for the Identification of Promising Next-Generation Probiotics

“…The host-associated microbiota is considered a primary contributor to the healthy status of many human compartments, such as the gastrointestinal tract (GIT) and the urogenital tract [ 1 ]. Regarding the latter, recent literature revealed that the vaginal microbiota is fundamental in both biological and chemical homeostasis [ 2 ]. In this context, it is well-known that bacteria harbored by the vaginal environment participate in maintaining a low pH, which on average should range between 3.8 and 4.5 in a healthy condition [ 3 ].…”