Microbiota effects and predictors of Lactobacillus crispatu s colonization after treatment with a vaginal live biotherapeutic: results from a randomized, double-blinded, placebo-controlled trial

Bacterial vaginosis (BV) affects >25% of women worldwide and often recurs following treatment with the standard-of-care antibiotic metronidazole (MTZ). Treatment with LACTIN-V, a live biotherapeutic product (LBP) containing the Lactobacillus crispatus strain CTV-05, reduced recurrent BV (rBV) in a Phase 2b clinical trial, but efficacy was incomplete. We analyzed trial samples to characterize microbiota and immune effects and identify correlates of treatment success. By week 12, an L. crispatus -dominant microbiota was achieved in 30% of LBP recipients compared to 9% of those in the placebo group (benefit ratio: 3.31; p < 0.005). Most of this effect was due to CTV-05 colonization, although native L. crispatus strains were also present and increased over time. Inflammatory cytokines decreased in both arms after MTZ, but returned to baseline in the placebo group. Successful L. crispatus colonization was associated with pre-MTZ microbiota composition, baseline inflammatory cytokine profiles, post-MTZ total bacterial load, and selected clinical and behavioral variables. These findings elucidate LBP effects on vaginal microbiota and identify predictors of treatment success, informing strategies to develop more effective interventions to improve womens health.