Although bacterial vaginosis (BV) affects 30% of women worldwide and is associated with adverse health outcomes, current standard-of-care antibiotics fail in over half of cases and treatments have not improved in over 40 years. Probiotics have been proposed as alternative treatments, but fail to restore an optimal lactobacilli-dominated microbiome in the vast majority of patients. Here, we present findings from a pilot clinical trial demonstrating the successful engraftment of vaginal microbiota transplantations (VMTs) after antibiotic treatment in individuals with recurrent BV. Following an investigational donation protocol under an FDA IND, we treated eight recipients with material from a single donor. Using 16S rRNA gene amplicon sequencing we show that VMT results in a shift toward an optimal, Lactobacillus crispatus-dominated microbial community in three out of four VMT recipients at one month post-transplant. In two successful transplantations, this shift lasted at least six months post-VMT. In contrast, no placebo recipients exhibited L. crispatus dominance. Bacterial culturing and whole genome sequencing combined with metagenomic sequencing from donations and recipient longitudinal samples revealed colonization by donor-derived strains of L. crispatus in VMT recipients. Additionally, we observed no increase in genital inflammatory markers or changes in endocervical immune cell proportions when comparing treatment to placebo, indicating transplant safety. Together, these findings support the hypothesis that transferring the entire vaginal microbiota can lead to a more complete restoration of the vaginal ecosystem compared to single strain probiotics and lay the foundation for designing novel microbial therapies for BV.

Vaginal microbiota transplantations lead to stable L. crispatus engraftment in the microbiomes of certain patients with recurrent bacterial vaginosis.

CM has been a consultant for Freya Biosciences and serves on the scientific advisory board of Ancilia Biosciences and Concerto Biosciences. CM has a financial interest in Ancilia Biosciences, a company developing a new class of Live Biotherapeutics and other bacterial products. Dr. Mitchells interests were reviewed and are managed by MGH and Mass General Brigham in accordance with their conflict of interest policies. DK is the CSO of Day Zero Diagnostics.

NCT04046900

This study was funded by the National Institutes of Health grant 5R01AI158836-04 (CM, DK). FH received support from the Schmidt Science Fellowship.

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