Abstract

Despite over 60 years of research, the etiology of bacterial vaginosis (BV) remains controversial. In this pilot study, we utilized shotgun metagenomic sequencing to characterize vaginal microbial community changes prior to the development of incident BV (iBV). 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 prior to iBV diagnosis. Sequencing data were analyzed through Kraken2 and bioBakery 3 workflows, and specimens were classified into community state types (CSTs). Quantitative PCR (qPCR) was performed to compare the correlation of read counts to bacterial abundance. Common BV-associated bacteria such as G. vaginalis, Prevotella bivia, and Fannyhessea vaginae were increasingly identified in the participants prior to iBV. Linear modeling indicated significant increases in G. vaginalis and F. vaginae relative abundance prior to iBV, while the relative abundance of Lactobacillus spp. declined over time. The Lactobacillus spp. decline correlated with the presence of Lactobacillus phages. We observed enrichment in bacterial adhesion factor genes on days prior to iBV. There were also significant correlations between bacterial read counts and abundances measured by qPCR. This pilot study characterizes vaginal community dynamics prior to iBV and identifies key bacterial taxa and mechanisms potentially involved in the pathogenesis of iBV.

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