The study of host-bacterial relationships and immune function in different vaginal environments (THRIVE Study)

Abstract

<h3>Objectives</h3> Bacterial vaginosis (BV) is a common gynecologic complaint, prone to recurrence, with limited therapeutic options. The purpose of this study is to identify bacterial or host drivers of BV recurrences. <h3>Methods</h3> A prospective study of women with BV is ongoing, utilizing a multi-‘omic approach to characterize the vaginal mucosal system. BV is diagnosed based on Amsel criteria and Nugent scoring at recruitment, with BV+ participants receiving treatment. Extensive sampling, including cervical biopsies, is clinically performed at 0, 1, and 6 months, and participants self-collect vaginal swabs (daily) and rectal swabs (monthly) for 6 months. Collected specimens are analyzed using multiparameter flow cytometry, microbiologic culture, 16S rRNA sequencing, metaproteomics, metagenomics and metabolomics. Monthly questionnaires are collected detailing diet, vaginal hygiene and sexual practices. <h3>Results</h3> We have currently enrolled 37 participants (9 completed: 3 BV+, 6 BV-). Preliminary analysis demonstrates 83% of BV- participants had a Lactobacillus dominant profile (n=6). Two BV+ participants had polymicrobial profiles and one was Gardnerella dominant (n=3). Flow cytometry analysis identified significant decreases in T cell subsets (<i>p</i>=0.008) including CD8+ (<i>p</i>=0.03) and CD4-CD8- (p=0.021) T cells in the genital tract of BV+ participants. We have 84% participant retention and 83% average daily swabs collected per month, with no serious adverse effects and few women declining biopsies. <h3>Conclusions</h3> We have established a prospective cohort to characterize the daily temporal dynamics of the vaginal microbiome in BV recurrence with high resolution. This study will be used to identify drivers of recurrent BV which are putative targets for novel, long-lasting therapeutic interventions.