CAMBRIDGE, Mass. March 27, 2026 - A new study from the Kwon Lab at the Ragon Institute, published in Cell Host & Microbe, provides the most detailed picture yet of how a promising bacterial therapy works to prevent recurrent bacterial vaginosis (BV) and why it works better for some women than others.
BV is the most common vaginal condition worldwide, affecting more than 25% of reproductive-age women and disproportionately impacting women of lower socioeconomic status and members of racial and ethnic minority groups. It is linked to discharge, pain, and increased risk of preterm birth, cervical cancer, and sexually transmitted infections, including HIV. Standard antibiotic treatment with metronidazole often clears BV initially, but the condition recurs in over half of women within a year.
One reason for recurrence is that after antibiotics, the vaginal microbiome often fails to convert to a bacterial community dominated by the beneficial bacterium Lactobacillus crispatus, which is associated with long-term vaginal health.
LACTIN-V is a live biotherapeutic product containing L. crispatus. In a recent randomized, placebo-controlled trial published in the New England Journal of Medicine, it significantly reduced BV recurrence when given after metronidazole. However, treatment benefits were incomplete, with BV recurring in 30% of women who received LACTIN-V.
To understand how LACTIN-V treatment affected the vaginal microbiome of women in that trial and assess why some benefited while others did not, the Kwon Lab and colleagues analyzed over 1,100 samples from 213 trial participants using microbiome sequencing, L. crispatus strain analysis, immune profiling, and clinical data.
The results showed that 12 weeks after starting treatment, 30% of women who received LACTIN-V had developed a healthy, L. crispatus-dominant vaginal microbiome, compared to just 9% of women receiving placebo — largely explaining the treatment's benefits. L. crispatus colonization was primarily driven by the bacterial strain in LACTIN-V, though in some cases women's own naturally occurring L. crispatus took over.
The study also found that a woman's vaginal microbiome before treatment predicted how well she would respond to LACTIN-V. Women whose microbiomes were predominated by Prevotella or Gardnerella species saw the greatest benefit, while those predominated by Candidatus Lachnocurva vaginae (also known as BVAB1), a bacterium strongly associated with BV, showed little or no improvement. Other factors linked to successful L. crispatus colonization included lower bacterial levels and vaginal pH after metronidazole treatment, as well as certain pre-treatment immune profiles.
"This study's results offer key insights for vaginal health," says Seth Bloom, the paper's co-first author who began the research as a postdoctoral trainee in the Kwon Lab and has since established his own lab. "Our results offer a roadmap to guide development and use of LACTIN-V and similar live biotherapeutic products to improve the health of the millions of women worldwide who experience BV."
The Kwon Lab has also been researching the benefit of vaginal live biotherapeutic products potential across multiple contexts, including a recent Phase 2 trial in South Africa showing the treatment may help reduce HIV risk in young women.
"This study provides the most detailed view to date of how a live biotherapeutic can reshape the vaginal microbiome to promote long-term vaginal health. By identifying the microbial and host factors that determine whether Lactobacillus crispatus successfully colonizes, we can begin to design more precise and effective treatments to improve women's health," says Doug Kwon, the study's senior author.
The study was a collaboration with researchers at University of California San Francisco, UCLouvain in Belgium, Stanford University, and Osel, Inc. with funding provided by the Gates Foundation.
About the Ragon Institute
The Ragon Institute of Mass General Brigham, MIT, and Harvard was established in 2009 with a gift from the Phillip T. and Susan M. Ragon Foundation, with a collaborative scientific mission among these institutions to harness the immune system to combat and cure human disease. Focusing on diseases of global importance, the Ragon Institute draws scientists, clinicians and engineers from diverse backgrounds and areas of expertise to study and understand the immune system with the goal of benefiting patients.
