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 1 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 Centre for the AIDS Programme 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 2 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 in 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, US, 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.”
Authorship: In addition to Mitchell and Potloane, co-authors include, Laura Symul, Sinaye Ngcapu, Lara Lewis, Michael France, Laura Vermeren, Joseph Elsherbini, Callin Chetty, Nomfuneko A. Mafunda, Asthu Mahabeer Polliah, Andile Mtshali, Asavela Kama, Nzuzo Magini, Nireshni Mitchev, Gugulethu Mzobe, Anam Khan, Briah Cooley Demidkina, Miles Goldenberg, Jiawu Xu, Lindsay Rutt, Breanna Shirtliff, Sarah Cook, Meena Murthy, Fatima Hussain, Jo-Ann S. Passmore, Heather B. Jaspan, Brian Kullin, Anna-Ursula Happel, Lenine Liebenberg, David A. Relman, Susan Holmes, Douglas S. Kwon, and Jacques Ravel.
Disclosures: Mitchell has been a consultant for Freya Biosciences, DIVA Inc and serves on the scientific advisory board of Ancilia Biosciences and Concerto Biosciences. Mitchell has a financial interest in Ancilia Biosciences, a company developing a new class of Live Biotherapeutics and other bacterial products. Mitchell’s interests were reviewed and are managed by MGH and Mass General Brigham in accordance with their conflict-of-interest policies. Ravel is co-founder of LUCA Biologics, a biotechnology company focusing on translating microbiome research into live biotherapeutic drugs for women’s health. Ravel has financial interest in Ancilia Biosciences as a member of its scientific advisory board. Kwon, Ravel, Hussain, Mitchell, France, Passmore, Happel, Ngcapu are all named inventors on patent No. US 2025/0195589 A1 for the LBP tested in the trial.
Funding: This project was funded by the Gates Foundation (INV-019055,INV-037901, and INV-037902.) The findings and conclusions contained within are those of the authors and do not necessarily reflect positions or policies of the Gates Foundation.
Paper cited: Potloane D et al. “VIBRANT: A Phase 1 randomized trial of multi-strain vaginal L. crispatus live biotherapeutic products in people with bacterial vaginosis” Cell Host & Microbe DOI: 10.1016/j.chom.2026.02.016
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“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 2 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 in 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, US, 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.”
Authorship: In addition to Mitchell and Potloane, co-authors include, Laura Symul, Sinaye Ngcapu, Lara Lewis, Michael France, Laura Vermeren, Joseph Elsherbini, Callin Chetty, Nomfuneko A. Mafunda, Asthu Mahabeer Polliah, Andile Mtshali, Asavela Kama, Nzuzo Magini, Nireshni Mitchev, Gugulethu Mzobe, Anam Khan, Briah Cooley Demidkina, Miles Goldenberg, Jiawu Xu, Lindsay Rutt, Breanna Shirtliff, Sarah Cook, Meena Murthy, Fatima Hussain, Jo-Ann S. Passmore, Heather B. Jaspan, Brian Kullin, Anna-Ursula Happel, Lenine Liebenberg, David A. Relman, Susan Holmes, Douglas S. Kwon, and Jacques Ravel.
Disclosures: Mitchell has been a consultant for Freya Biosciences, DIVA Inc and serves on the scientific advisory board of Ancilia Biosciences and Concerto Biosciences. Mitchell has a financial interest in Ancilia Biosciences, a company developing a new class of Live Biotherapeutics and other bacterial products. Mitchell’s interests were reviewed and are managed by MGH and Mass General Brigham in accordance with their conflict-of-interest policies. Ravel is co-founder of LUCA Biologics, a biotechnology company focusing on translating microbiome research into live biotherapeutic drugs for women’s health. Ravel has financial interest in Ancilia Biosciences as a member of its scientific advisory board. Kwon, Ravel, Hussain, Mitchell, France, Passmore, Happel, Ngcapu are all named inventors on patent No. US 2025/0195589 A1 for the LBP tested in the trial.
Funding: This project was funded by the Gates Foundation (INV-019055,INV-037901, and INV-037902.) The findings and conclusions contained within are those of the authors and do not necessarily reflect positions or policies of the Gates Foundation.
Paper cited: Potloane D et al. “VIBRANT: A Phase 1 randomized trial of multi-strain vaginal L. crispatus live biotherapeutic products in people with bacterial vaginosis” Cell Host & Microbe DOI: 10.1016/j.chom.2026.02.016
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