VIRGO2 Expands Our Ability to Perform Functional Analyses of Vaginal Microbiomes
In a new study published in Nature Communications, we present VIRGO2, a substantially expanded and remastered non-redundant gene catalog designed specifically for the vaginal microbiome. VIRGO2 builds on our original VIRGO resource and reflects more than a decade of work aimed at moving beyond taxonomic descriptions toward a deeper, functional, and ecological understanding of vaginal microbial communities.
VIRGO2 comprises over 1.7 million well-annotated genes, generated from more than 2,500 metagenomes and 4,000 microbial genomes collected across multiple continents. Compared to its predecessor, VIRGO2 greatly improves geographic representation, captures substantially more microbial diversity, and includes robust annotation of bacteria, fungi, and bacteriophages—components of the vaginal ecosystem that have historically been undercharacterized.
Using VIRGO2, we uncover new insights into the functional complexity of the vaginal microbiome. These include improved resolution of closely related bacterial species, identification of previously uncharacterized vaginal microbes, and the ability to distinguish functional activity that is not apparent from microbial abundance alone. By integrating metagenomic and metatranscriptomic data, VIRGO2 enables the study of what microbes are doing in vivo, not just which microbes are present.
Importantly, VIRGO2 allowed us to examine how microbial communities diLer in their metabolic strategies, including how they access host-derived nutrients such as glycogen and mucins, and how bacterial, fungal, and viral populations interact within the vaginal niche. These insights are critical for understanding why some vaginal microbiomes are associated with health while others are linked to conditions such as bacterial vaginosis, increased susceptibility to infection, and adverse reproductive outcomes.
VIRGO2 is released as an open, community resource, along with validated software tools to support reproducible analysis of vaginal microbiome multi-omic data. We anticipate that this resource will accelerate discovery, enable cross-study comparability, and support the rational design of diagnostics, therapeutics, and live biotherapeutic products aimed at improving vaginal health.
Reference
VIRGO2: an enhanced gene catalog of the vaginal microbiome provides insights into its functional and ecology complexity.
France MT, Chaudry I, Rutt L, Quain M, Shirtliff B, McComb E, Maros A, Alizadeh M, Hussain FA, Elovitz MA, Relman DA, Rahman A, Brotman RM, Price JT, Kassaro MP, Holm JB, Ma B, Ravel J.
Nat Commun. 2025 Dec 6. doi: 10.1038/s41467-025-67136-2.