Multi-strain probiotic therapy shows promise in preventing bacterial vaginosis recurrence

A global team of experts has identified a promising new approach to prevent recurrence of bacterial vaginosis (BV), a condition that affects millions of women worldwide. In a Phase I randomized clinical trial of women in the U.S. and South Africa, researchers found that a short course of a multi-strain probiotic restored protective bacteria to the vagina, significantly reducing disease recurrence.

Results from the study, a collaboration between investigators from Mass General Brigham, the Center for the AIDS Program of Research in South Africa (CAPRISA), and collaborators from the Vaginal Microbiome Research Consortium, are published in Cell Host & Microbe.

“Bacterial vaginosis is associated with not only bothersome and disruptive symptoms, but also poor reproductive health outcomes,” said corresponding author Caroline Mitchell, MD, MPH, director of the Vulvovaginal Disorders Program at Massachusetts General Hospital and an obstetrician/gynecologist in the Mass General Brigham Department of Obstetrics and Gynecology.

“For decades, we’ve relied on medications that clear the infection but do not restore beneficial bacteria, leaving the vaginal environment vulnerable. We wanted to see if we could ‘re-seed’ that environment with protective bacteria and help the body stay healthy on its own.”

Globally, BV affects approximately 30% of women, causing discharge, odor, and irritation, and is associated with increased risk for preterm birth, HIV acquisition and abnormal cell growth on the cervix. BV is a disruption of the vaginal microbiome, the environment of microorganisms that live in the vagina.

Although antibiotics provide short-term symptom relief, up to 60% of women have BV again within six months. After antibiotic treatment, very few women have an optimal vaginal bacterial community, which is one composed primarily of Lactobacillus crispatus.

Earlier Phase II clinical trials of a single-strain live biotherapeutic reduced BV recurrence after 12 weeks of dosing, but the beneficial bacteria failed to remain in more than half of participants. To make a better probiotic treatment, the researchers created a live biotherapeutic product containing multiple strains of L. crispatus.

Their trial, called VIBRANT (Vaginal lIve Biotherapeutic RANdomized Trial), was a multi-institutional collaboration led by the Vaginal Microbiome Research Consortium. Mitchell is the regulatory sponsor, overseeing the manufacturing and FDA-approval process. The CAPRISA team in Vulindlela, South Africa, led participant enrollment and sample analysis in collaboration with U.S. researchers.

Disebo Potloane, MB, ChB, who led the trial at CAPRISA’s rural South African research clinic said, “HIV remains a major challenge for young women in Africa and reducing their risk of infection has been an elusive goal. The encouraging results of the VIBRANT trial bode well for development of strategies aimed at removing a fundamental cause of their HIV risk.”

Potloane acknowledged her collaborators in this initiative, saying that these results lay a good foundation for the pathway to potential new HIV prevention strategies for women.

Ninety participants from Vulindlela, South Africa and Boston, U.S., enrolled in the trial. Each received antibiotics and one of three treatments—placebo tablets, 6-strain tablets or 15-strain tablets—for seven days. Zero, three, or seven tablets contained probiotic bacteria, with any remaining days containing placebos.

Researchers used genetic sequencing to test for beneficial bacteria weekly for five weeks. They found that the vaginal microbiomes of two-thirds of participants (66%) had protective L. crispatus bacteria within the first five weeks.

Nearly half of that group still had the bacteria in the prolonged follow-up at 12 weeks, even though some only received three days of active treatment. Participants with protective bacteria at five weeks were significantly less likely to get BV again during the study timeframe.

The research team is planning a follow-up trial to optimize the treatment before initiating larger-scale clinical trials aimed at securing FDA approval of vaginal live biotherapeutics for BV. Beyond the clinical implications, the VIBRANT trial provides a rare window into the biological mechanisms of the vaginal microbiome.

“We are woefully ignorant about the basic biology of the vaginal environment,” said Mitchell. “This study is about more than just testing a new product; it’s one of the only ways we have to actually study these beneficial bacteria and identify what leads to colonization.”