Gardnerella vaginalis and Prevotella bivia Trigger Distinct and Overlapping Phenotypes in a Mouse Model of Bacterial Vaginosis

Abstract

Background Bacterial vaginosis (BV) is a common imbalance of the vaginal microbiota characterized by overgrowth of diverse Actinobacteria, Firmicutes, and Gram-negative anaerobes. Women with BV are at increased risk of secondary reproductive tract infections and adverse pregnancy outcomes. However, which specific bacteria cause clinical features of BV is unclear. Methods We previously demonstrated that Gardnerella vaginalis could elicit many BV features in mice. In this study, we established a BV model in which we coinfected mice with G. vaginalis and another species commonly found in women with BV: Prevotella bivia. Results This coinfection model recapitulates several aspects of human BV, including vaginal sialidase activity (a diagnostic BV feature independently associated with adverse outcomes), epithelial exfoliation, and ascending infection. It is notable that G. vaginalis facilitated uterine infection by P. bivia. Conclusions Taken together, our model provides a framework for advancing our understanding of the role of individual or combinations of BV-associated bacteria in BV pathogenesis.

Gardnerella vaginalis as a Cause of Bacterial Vaginosis: Appraisal of the Evidence From in vivo Models

“…In this model, G. vaginalis titers in the vagina and uterine horns were not significantly different between mono and co-infected groups. Consistent with the G. vaginalis inoculation model reported in 2013, no clinical signs of inflammation were observed in the vaginas or uterine horns of mono or co-infected animals (Gilbert et al, 2013(Gilbert et al, , 2019.…”

“…In addition to findings that certain strains of Gardnerella can reproduce features of BV in experimental models, there is also evidence to support the conclusion that Gardnerella can influence whether other organisms cause pathophysiology. Specifically, vaginal colonization by the JCP8151B strain caused mice to experience higher titer ascending uterine infections by Prevotella bivia compared to animals that received only P. bivia (Gilbert et al, 2019). The JCP8151B strain was also able to trigger recurrent UTI caused by uropathogenic E. coli that re-emerged from long lasting reservoirs inside epithelial cells in response to bladder exposure to Gardnerella, but not Lactobacillus crispatus (Gilbert et al, 2017).…”

“…In 2019, Gilbert et al described an estradiol-treated mouse coinfection model with G. vaginalis and Prevotella bivia (Gilbert et al, 2019). Prevotella species are prevalent in the vaginal microbiome of women with BV (Srinivasan et al, 2012).…”

“…Differences in the mouse strain, housing conditions, and/or vaginal microbiome could strongly impact susceptibility and response to G. vaginalis infection. For example, Teixeira et al (2012) observed "inflammatory lesions" upon G. vaginalis infection in their germ-free mice, while Gilbert et al (2013Gilbert et al ( , 2019 have specifically noted a lack of inflammatory response in their model using C57Bl/6 mice raised under conventional conditions (Teixeira et al, 2012;Gilbert et al, 2013Gilbert et al, , 2019. Additionally, many of the mouse models require β-estradiol administration to bring mice into pro-estrus for the duration of the experiment and avoid the PMN-rich post-ovulation period of the estrus cycle (Gilbert et al, 2013).…”

Vaginal microbiota and the potential of Lactobacillus derivatives in maintaining vaginal health

“…However, Lactobacillus -dominated vaginal microbiota is displaced by the overgrowth of Gardnerella species and other BVAB when vaginal dysbiosis happens [ 100 ]. Recent studies have demonstrated that the synergistic interactions between BVAB such as G. vaginalis and A. vaginae significantly enhanced the severity of BV by increasing bacterial burden [ 101 , 102 ]. Another important feature of BV is polymicrobial biofilm formation mainly by G. vaginalis , while the presence of other co-colonised BVAB was shown to enhance the biofilm thickness of G. vaginalis growth [ 85 , 103 – 105 ].…”