A NEW randomised, placebo-controlled clinical trial has shown that a slow-release, multi-strain synbiotic vaginal tablet containing Lactobacillus crispatus can effectively restore an optimal vaginal microbiome, potentially reducing risks linked to vaginal dysbiosis.
Vaginal dysbiosis, characterised by reduced L. crispatus dominance and increased anaerobic microbes, is associated with infections, inflammation, and pregnancy complications. While probiotic interventions have shown some benefits, efficacy has been inconsistent due to factors such as non-native strains, oral administration, and lack of growth-supporting ingredients.
Researchers developed a novel vaginal synbiotic (VS-01) comprising three L. crispatus strains isolated from women with stable, optimal microbiomes. Together, these strains covered over 70% of the L. crispatus pangenome and inhibited Gardnerella and Candida in preclinical testing. The formulation also included substrates such as maltose and glutamine, and environmental optimisers like calcium L-lactate, to promote colonisation.
The trial (n = 70) compared VS-01 to placebo, a fast-release vaginal capsule with the same strains, an oral capsule, and an over-the-counter oral probiotic. Among women with baseline dysbiosis, VS-01 achieved a 90% conversion to the optimal Community State Type I microbiome at day 21, versus 11% for placebo (p < 0.002). Colonisation persisted in over half of participants up to 30 days post-dosing.
VS-01 also significantly reduced Candida (236-fold), Gardnerella vaginalis, mucin-degrading sialidase genes, and pro-inflammatory cytokine IL-1α, indicating improvements in microbial balance, mucus barrier integrity, and inflammation. The slow-release tablet outperformed the fast-release capsule and both oral formulations, suggesting that mucoadhesive properties and extended dissolution enhance colonisation.
No serious adverse events were reported, and all formulations were well tolerated. The study’s strengths include direct comparison of delivery methods, deep metagenomic sequencing, and novel bioinformatics analysis. Limitations include the healthy, asymptomatic study population and biomarker-based rather than clinical endpoints.
This is the first randomised trial to demonstrate that a vaginally applied multi-strain L. crispatus synbiotic can achieve and sustain an optimal microbiome without antibiotic pretreatment. The findings support further trials to confirm clinical benefits in preventing microbiome-mediated conditions such as bacterial vaginosis and recurrent urinary tract infections.
Reference
Ravel J et al. Impact of a multi-strain L. crispatus-based vaginal synbiotic on the vaginal microbiome: a randomized placebo-controlled trial. NPJ Biofilms Microbiomes. 2025;11(1):158.
