The Vaginal Microbiome Research Consortium (VMRC)

Problem Statement

Microbial communities in the human vagina exhibit symbiotic relationships with the host and play critical roles in maintaining health and preventing disease. These roles include protection against colonization and disease by pathogens and regulation of local immune responses. Several different kinds of vaginal communities occur in reproductive age women and are associated with health; the majority of these community types are dominated by one of several Lactobacillus species (L. iners, L. crispatus, L. gasseri, and L. jensenii), each of which is believed to provide key ecosystem services. Lactic acid production is a particularly important trait of these species, one consequence of which is acidification of the vaginal habitat. Lactobacillus species and strains vary in their production of lactic acid, as well as in their associations with vaginal health- and disease-associated states. Other members of these Lactobacillus-dominated communities presumably play supporting and/or modulating roles in community-associated beneficial services. In contrast, a distinct set of vaginal communities is characterized by low-Lactobacillus abundance and high species diversity, including the presence of Gardnerella vaginalis and other strict and facultative anaerobic bacteria; these low-Lactobacillus, high diversity communities are sometimes associated with adverse health states, such as bacterial vaginosis, and increased risks of HIV acquisition, sexually-transmitted infections, vaginal candidiasis, and premature birth. These adverse states are believed to be associated with either overt or subclinical local inflammation, suggesting a potentially important role for host responses in these outcomes.

Vaginal community composition is temporally dynamic as the community composition shifts from one type to another (e.g., Lactobacillus-dominant versus Lactobacillus-impoverished), but this dynamic behavior differs among individual women. Importantly, the relationships between community composition and function (ecosystem services), potential functional changes during these periods of shift, and the drivers responsible for these shifts are all poorly understood. Some have hypothesized that the frequency and the duration of shifts to a low-Lactobacillus state correlate with risk of adverse health and that combinations of microbial species and strains (bacterial, viral and fungal), genes and/or gene expression, metabolites and host immune factors in the vagina may explain the frequency of changes and duration of the alternative community states. As in any robust ecosystem, the interactions among these features and factors are likely to play fundamental roles in determining stability and function. Given variation in composition, communities presumably will also differ in the number and kinds of interactions among community members and the host. Work on this critical ecosystem so far has focused on individual features and failed to take a holistic, ‘systems’ approach with measurements of many features, both microbial and host-based, and an integrative strategy. As a result, we have an insufficient understanding about the relationships among community species and strain composition, ecological functions, stability of the vaginal microbiota, and risk for disease or adverse gestational outcome. We aim to leverage improved understanding of vaginal microecology to develop a novel Live Biotherapeutics Product (LBP) to modulate the composition and function of the vaginal microbiome.

Goal: The overarching goal of the VMRC is to identify correlates of stability and resilience in the vaginal microbiota and leverage these features to devise a framework for an intervention to maintain/restore vaginal health, such as innovative Live Biotherapeutic Products.

References:

Potloane et al. VIBRANT: Vaginal lIve Biotherapeutic RANdomized Trial: A Phase 1 randomized trial of multi-strain vaginal L. crispatus live biotherapeutic products in people with bacterial vaginosis. medRxiv 2025.09.18.25336053; doi: 10.1101/2025.09.18.25336053

Chetty et al. Randomized trial of multi-strain Lactobacillus crispatus vaginal live biotherapeutic products after antibiotic therapy for bacterial vaginosis: study protocol for VIBRANT (vaginal lIve biotherapeutic RANdomized trial). ContempClin Trials Commun. 2025 Sep 16;48:101554. doi: 10.1016/j.conctc.2025.101554. PMID: 41050878

France, M. T. et al. VIRGO2: an enhanced gene catalog of the vaginal microbiome provides insights into its functional and ecology complexity. Nat. Commun. (2025) doi:10.1038/s41467-025-67136-2.

Erchick, D. J. et al. Associations between Nugent‐bacterial vaginosis and preterm birth and other adverse pregnancy outcomes in rural northwestern Bangladesh. Int. J. Gynecol. Obstet. (2025) doi:10.1002/ijgo.70691.

Kan, L. et al. Factors associated with Nugent-bacterial vaginosis in pregnancy and postpartum among women in rural northwestern Bangladesh. PLOS Glob. Public Heal. 5, e0004768 (2025).

Pelayo, P. et al. Prevotella are major contributors of sialidases in the human vaginal microbiome. Proc. Natl. Acad. Sci.121, e2400341121 (2024).

Symul, L. et al. Sub-communities of the vaginal microbiota in pregnant and non-pregnant women. Proc. R. Soc. B 290, 20231461 (2023).

Jenkins, D. J. et al. Bacterial amylases enable glycogen degradation by the vaginal microbiome. Nat. Microbiol. 8, 1641–1652 (2023).

Mahajan, G. et al. Vaginal microbiome-host interactions modeled in a human vagina-on-a-chip. Microbiome 10, 201 (2022).

France, M. T., Clifford, J., Narina, S., Rutt, L. & Ravel, J. Complete Genome Sequences of Ezakiella coagulans C0061C1 and Fenollaria massiliensis C0061C2. Microbiol Resour Announc e00444-22 (2022) doi:10.1128/mra.00444 22.

Price, J. T. et al. HIV-associated vaginal microbiome and inflammation predict spontaneous preterm birth in Zambia. Sci Rep-uk 12, 8573 (2022).

France, M., Alizadeh, M., Brown, S., Ma, B. & Ravel, J. Towards a deeper understanding of the vaginal microbiota. Nat Microbiol 7, 367–378 (2022).

France, M. T. et al. Insight into the ecology of vaginal bacteria through integrative analyses of metagenomic and metatranscriptomic data. Genome Biol 23, 66 (2022).

France, M. T. et al. Complete Genome Sequences of Six Lactobacillus iners Strains Isolated from the Human Vagina. Microbiol Resour Announc 9, 826–3 (2020).