Characterization of Vaginal Microbial Community Dynamics in the Pathogenesis of Incident Bacterial Vaginosis, a Pilot Study

Abstract

Background Despite more than 60 years of research, the etiology of bacterial vaginosis (BV) remains controversial. In this pilot study, we used shotgun metagenomic sequencing to characterize vaginal microbial community changes before the development of incident BV (iBV). Methods A cohort of African American women with a baseline healthy vaginal microbiome (no Amsel criteria, Nugent score 0–3 with no Gardnerella vaginalis morphotypes) were followed for 90 days with daily self-collected vaginal specimens for iBV (≥2 consecutive days of a Nugent score of 7–10). Shotgun metagenomic sequencing was performed on select vaginal specimens from 4 women, every other day for 12 days before iBV diagnosis. Sequencing data were analyzed through Kraken2 and bioBakery 3 workflows, and specimens were classified into community state types. Quantitative polymerase chain reaction was performed to compare the correlation of read counts with bacterial abundance. Results Common BV-associated bacteria such as G. vaginalis, Prevotella bivia, and Fannyhessea vaginae were increasingly identified in the participants before iBV. Linear modeling indicated significant increases in G. vaginalis and F. vaginae relative abundance before iBV, whereas the relative abundance of Lactobacillus species declined over time. The Lactobacillus species decline correlated with the presence of Lactobacillus phages. We observed enrichment in bacterial adhesion factor genes on days before iBV. There were also significant correlations between bacterial read counts and abundances measured by quantitative polymerase chain reaction. Conclusions This pilot study characterizes vaginal community dynamics before iBV and identifies key bacterial taxa and mechanisms potentially involved in the pathogenesis of iBV.

Phase variable colony variants are conserved across Gardnerella spp. and exhibit different virulence-associated phenotypes

“…Nearly all women are colonized with Gardnerella spp., but approximately one-third of women of reproductive age develop BV ( 26 ). In the days preceding symptomatic BV, the number of Gardnerella cells greatly increases and the number of Lactobacillus cells plummets ( 10 ). Vaginal pH increases due to the loss of lactic acid production.…”

“…Patients with BV are predisposed to adverse pregnancy outcomes including amnionitis, postpartum endometritis, and premature delivery, the leading cause of neonatal mortality ( 8 , 9 ). It is hypothesized that Gardnerella serve as primary colonizers of the vaginal mucosa, and they increase in relative abundance 3–4 days prior to the onset of symptomatic BV ( 7 , 10 ). It is also thought that Gardnerella dampen the host immune response and establish the BV biofilm prerequisite to the arrival of secondary colonizers, such as Fannyhessea vaginae and Sneathia spp.…”

Association of Chlamydia trachomatis burden with the vaginal microbiota, bacterial vaginosis, and metronidazole treatment

“…In this study, while the use of relative abundances was sufficient to detect significant reductions of many BVAB and increases in Lactobacillus following successful MTZ treatment, the magnitude of the effects that these bacteria have on the genital environment are directly linked to their absolute abundances or burden, the quantification of which may be required to understand the relationship between the vaginal microbiota, genital environment, and chlamydial clearance. Future studies would benefit from the quantification of absolute abundances of dominant vaginal bacterial taxa or by inferring absolute abundances from total bacterial burden in combination with compositional data ( Tettamanti Boshier et al., 2020 ; Elnaggar et al., 2023a ; Elnaggar et al., 2023b ).…”

The Role of Prevotella Species in Female Genital Tract Infections

“…Notably, it is unknown whether anaerobic bacteria cause the loss or displacement of Lactobacillus spp. but it is a proposed step in some FGTI etiologies such as BV [25]; other studies have found that Lactobacillus phages could also play a role [26,27]. Regardless, the loss or displacement of the protective lactic acid-producing lactobacilli encourages FGTI-associated bacteria, such as Prevotella spp., to colonize the vaginal epithelium [28,29].…”