CAMRI Study Reveals Functional Diversity in Vaginal Microbiomes, Challenging One-Size-Fits-All Views of Dysbiosis

A new study led by investigators at the Center for Advanced Microbiome Research and Innovation (CAMRI) is reshaping how scientists and clinicians understand the vaginal microbiome. Published in mBio, the researchdemonstrates that vaginal microbial communities that appear similar at the species level can behave very differently, both functionally and in how they interact with the host immune system 

Led by Dr. Johanna B. Holm, Assistant Professor at the University of Maryland School of Medicine and a CAMRI investigator, the study moves beyond traditional microbiome classifications to reveal previously hidden ecological and immunological diversity. The findings have important implications for diagnosing and treating conditions such as bacterial vaginosis (BV), which affects millions of women worldwide and is often difficult to manage with current therapies.

Looking beyond “who is there” to “what they are doing”

For years, vaginal microbiomes have been categorized into community state types (CSTs) largely based on which bacterial species predominate. Microbiomes dominated by Lactobacillus species are typically considered optimal, while those dominated by Gardnerella and other anaerobes are often labeled dysbiotic.

“But taxonomy alone doesn’t tell the whole story,” said Dr. Holm. “Two microbiomes dominated by the same species can behave very differently in terms of metabolism, gene expression, and immune activation.”

To capture this hidden complexity, the CAMRI team used the expanded VIRGO2, a non-redundant vaginal microbial gene catalog, and developed a new computational framework called VISTA (Vaginal Inference of Subspecies and Typing Algorithm). This approach classifies vaginal microbiomes based on shared functional genes, rather than species names alone, allowing researchers to identify 25 distinct metagenomic community state types (mgCSTs).

Redefining Gardnerella-dominated communities

One of the most striking findings concerns Gardnerella, a genus long associated with BV. Using VISTA, Dr. Amanda Williams, a postdoctoral fellow in Dr. Holm’s laboratory, showed that Gardnerella-dominated microbiomes are not a single pathological state but instead span multiple functional profiles.

Some Gardnerella-predominated microbiomes exhibited high functional diversity and strong inflammatory immune signatures, while others showed immune profiles similar to healthy, Lactobacillus-dominated states. In particular, one newly defined community type displayed low inflammation and active lactate metabolism despite being dominated by Gardnerella.

“These results challenge the assumption that Gardnerella dominance automatically means disease,” said Dr. Holm. “Functional context matters, and in some cases, it may matter more than species composition alone.”

Linking microbes, genes, and immunity

By integrating metagenomic, metatranscriptomic, and immune marker data, the study demonstrates that different vaginal microbiome types are associated with distinct immune landscapes. Certain functional community types were associated with elevated inflammatory cytokines linked to adverse reproductive outcomes, whereas others exhibited immune quiescence.

This integrative approach underscores CAMRI’s commitment to mechanistic microbiome science, connecting microbial genes and activities to host biology rather than relying on descriptive surveys alone.

Toward precision women’s health

The implications of this work extend well beyond classification. By providing a scalable, open-access framework for functional microbiome typing, VISTA enables precision diagnostics, improved clinical stratification, and more targeted therapeutic strategies.

“Ultimately, our goal is to move toward interventions that are tailored to how a microbiome functions, not just which bacteria are present,” said Holm. “This study provides a foundation for that shift.”

The work has already drawn broad attention from scientific and medical media, highlighting growing recognition that vaginal microbiome research is entering a new, more nuanced phase, one with direct relevance for women’s reproductive and gynecologic health.