O-280 Vaginal microbiota transplant (VMT) without antibiotic pretreatment reveals changes in vaginal microbiota and immune profile in women with asymptomatic dysbiosis – a randomized, placebo-controlled trial
Authors: Van Hylckama Vlieg J  E T , Mortensen B , Bosma E , DeLong K , Baek Juel H , Rich R , Axelsen A  M , Acosta C , Bloch Thomsen A , Svarre Nielsen H , Wrønding T , Patel S , Dinan T , McCarthy F  P , Ensign L  M 
Published: July 2024

Abstract

Study question
Investigate the safety of VMT and explore its effects on the vaginal microbiomes and local inflammation in healthy, asymptomatic volunteer women screened for vaginal dysbiosis

Summary answer
We demonstrate safety and engraftment of donor bacteria in 50% of recipients, and a distinct shift in local inflammatory markers following resolution of vaginal dysbiosis

What is known already
Dominance by a subset of vaginal Lactobacillus species is considered healthy. Dysbiosis characterized by high abundance of anaerobic species is observed in around one third of women, and affects fertility, pregnancy outcomes, risk of STIs and UTIs, and potentially cancer treatment. Current use of antibiotics is often insufficient with high recurrence rates and potentially antibiotic resistance. There is a clear need for alternatives and recently it was shown that VMT following antibiotic treatment resulted in long-lasting improvements in symptoms of bacterial vaginosis in four out of five patients, but RCTs without the use of antibiotics remain to be reported.

Study design, size, duration
We performed a randomized, placebo-controlled double-blinded trial in 34 recipients randomized in an active:placebo 3:1 ratio. Subjects in the active arm received VMTs from donor cervicovaginal secretions (CVS) while placebo participants received saline. All recipients were dosed on 3 consecutive days with active arm recipients receiving all 3 VMTs originating from the same donor. All recipients were followed for safety and efficacy assessments for 6 menstrual cycles after dosing.

Participants/materials, setting, methods
Donors: CVS was obtained from healthy subjects screened to be negative for a broad panel of infections and having lactobacilli-dominant vaginal microbiomes.
RCT: Healthy, asymptomatic women aged 18 to 45 whose vaginal microbiome had combined lactobacilli relative abundance &lt;10% and combined relative abundance of dysbiosis-associated bacteria &gt;20% were included. VMTs were applied vaginally on three consecutive days. Follow-up visits were performed 1 week after the last VMT and then once every cycle for 6 cycles.

Main results and the role of chance
Here, we report the successful implementation of a donor program to obtain screened, frozen, and banked donor CVS to be used in the first VMT intervention RCT. In the ITT population, the primary efficacy analysis showed statistically significant increase from baseline in relative abundance of vaginal lactobacilli to follow-up timepoints 1 week and 3 cycles post intervention in the active arm, while no statistical significant change was observed in the placebo arm at any follow-up timepoint.
Also, time-resolved metagenomic analysis showed that 50% of women treated with VMT displayed a shift of the vaginal microbiome toward the Lactobacillus-dominated donor CVS sample, confirmed with strain-level engraftment analysis. We observed no serious treatment-associated adverse events and the intervention was well tolerated. Further, the successful “twinning” of the recipient to match the donor microbiome post-VMT also led to a dramatic shift toward an anti-inflammatory environment based on transcriptomic analysis of CVS.

Limitations, reasons for caution
Recipients were asymptomatic and mainly Caucasian, which limits generalizability to other ethnicities and the symptomatic spectrum of vaginal dysbiosis. Due to COVID-19-related recruitment issues, the cohort size ended below the targeted number of n = 40. Future studies will aim to identify factors driving engraftment and its impact on clinical outcomes.

Wider implications of the findings
Vaginal microbial interventions including VMT have great potential as the first therapeutic intervention that provides effective and long-term vaginal microbiota restoration, positively impacting a wide variety of diseases and conditions affecting the female reproductive tract.

Trial registration number
NCT05114031