Genomic landscape of the human vaginal microbiome is linked to host genetics and population of origin

Key Points:

• The Peacock Project collected and analyzed 10,665 cervicovaginal samples from diverse Chinese populations, integrating microbiome, phenotypic, and genomic data to systematically characterize the vaginal microbiome, including healthy and disease states such as bacterial vaginosis (BV) and HPV infection.
• A comprehensive Global Vaginal Microbiome Genome (GVMG) catalog was constructed by combining the Peacock cohort metagenomes with 2,967 publicly available vaginal metagenomes, resulting in 65,055 genomes (36,059 prokaryotic, 28,953 viral, and 43 eukaryotic), representing the most extensive vaginal microbiome genomic repository to date with significant expansion over previous catalogs.
• The study identified 890 species-level genome bins (SGBs) of vaginal prokaryotes, including 116 previously unknown species, and revealed substantial geographic genetic variation within species, especially in non-Lactobacillus taxa, highlighting population-specific microbial strain diversification.
• Host genome-wide association studies (M-GWAS) in over 3,000 Chinese women uncovered 18 genetic loci significantly associated with vaginal microbial species abundance, notably linking OPRK1 with Ureaplasma urealyticum and ADAP1 with Lactobacillus mulieris, suggesting strong host genetic influence on vaginal microbiome composition.
• Functional analyses of microbial genomes revealed diverse metabolic and pathogenic potentials, including enzymes linked to BV pathology and population-specific biosynthetic gene clusters, while viral analyses expanded known vaginal virome diversity and showed phage-host interactions correlated with health and disease states.