A Description of the THRIVE (The Study of Host-Bacterial Relationships and Immune Function in Different Vaginal Environments) Bacterial Vaginosis Observational Study

Abstract

Objectives: Bacterial vaginosis (BV) contributes to poor reproductive health and is characterized by a displacement of Lactobacillus in the vaginal microbiome. However, treatment for BV is limited to antibiotics and half of the women treated experience recurrence within a year. THRIVE (The Study of Host-Bacterial Relationships and Immune Function in Different Vaginal Environments) is a prospective study in Winnipeg, Manitoba, Canada, which is designed to capture the daily variation of the microbiome and host mucosal immunity during treatment. The objective of this study is to identify host and bacterial factors that associate with vaginal microbiome stability to better inform therapeutic interventions.

Methods: Women treated for BV, and controls, are followed for 6 months collecting daily vaginal swabs and monthly questionnaires. Comprehensive mucosal sampling, including swabs, cytobrushes, biopsies, and blood are collected at baseline, months 1 and 6 post-enrolment.

Results: We performed analysis on the first 52 participants, (19 BV+, 33 BV-). Molecular profiling by 16s RNA sequencing showed 20 women with non-Lactobacillus-dominant microbiomes and 32 with Lactobacillus-dominant microbiomes, with increased microbial diversity in non-Lactobacillus-dominant microbiomes (P = 3.1E-05). A pilot analysis in 2 participants demonstrates that multi-omics profiling of self-collected daily swabs provides high-quality data identifying 73 bacterial species, 1773 mucosal proteins and 117 metabolites. Initial flow cytometry analysis showed an increased cluster of differentiation (CD)4+ T cells and neutrophil activation (CD11b+CD62L^neg/dim) in the positive participant at baseline, while after treatment these shifted and resembled the control participant.

Conclusions: This study provides a framework to comprehensively investigate the kinetics of vaginal mucosal microbiome alterations, providing further insight into host and molecular features predicting BV recurrence.

Keywords: bacterial vaginosis; cohort studies; microbiome; mucosal immunity; reproductive health.