Background

The vaginal microbiome is closely linked to women's reproductive health, including bacterial vaginosis, Human Papillomavirus (HPV) infection, and preterm birth. However, the 16S rRNA analysis commonly used in existing studies struggles to distinguish bacteria at the species/strain level and fails to capture viruses and fungi. Furthermore, sample compositions centered on Western populations and pregnant women have limited the ability to explain microbial diversity in the global population.

The sample contains over 90% human DNA, making microbial genome recovery difficult. Paradoxically, leveraging this human DNA allows for the simultaneous analysis of host genetic variants and microbial composition from the same sample. The research team integrated 2,967 public datasets and 1,433 bacterial isolates centered on the metagenome of 10,005 Chinese individuals to trace the connections between hosts and microbes. The study was published in Nature Genetics in June 2026, and a September correction notice only rectified the author names and the position of Figure 5b. The research findings and conclusions remained unchanged.

Key Findings

The Global Viral Metagenome Assembled Genomes (GVMG) constructed by the research team consists of a total of 65,055 genomes. This includes 36,059 genomes from 890 prokaryotic species, 43 genomes from 11 fungal species, and 28,953 genomes from 6,577 viral taxonomic units. The number of genomes is 1.9 times greater than that of the existing VMGC, and lineages comprising 13.0% of prokaryotic species and 79.0% of viral taxonomic units were not present in existing public repositories. Among the prokaryotic genomes, the proportion of high-quality or near-complete genomes was 68.1%, surpassing the 48.2% observed in VMGC.

Differences between populations were distinct. The community type dominated by BVAB1, a bacterium related to bacterial vaginosis, was 0.46% in the Chinese cohort but 12.38% in the US cohort. Among viruses, 56.5% could not be found in other major vaginal, intestinal, or oral virome databases, and phage-host associations corresponding to the dominant lactobacilli, Lactobacillus iners and L. crispatus, were also identified.

The researchers analyzed the relationship between 5.46 million human genetic variants and 54 species of gut microbiota using data from a discovery cohort of 3,137 individuals and a validation cohort of 3,227 plus 506 individuals. As a result, they identified seven host gene loci that met the study-wide significance level and were replicated in an independent cohort. The strongest signal was the association between an OPRK1-adjacent variant on chromosome 8 and the potential pathogen Ureaplasma urealyticum. The effect size β was 1.24, with a P-value of 1.50×10⁻⁵⁵. Associations involving ADAP1-Lactobacillus mulieris and an PRAMEF1-adjacent variant-Bifidobacterium piotii were also replicated in the same direction across both validation cohorts.

Significance and Outlook

This study expands the view of the vaginal microbiome from simple bacterial proportions to an ecosystem encompassing viruses, fungi, and intra-strain genetic variations. It revealed that the same microbial species can differ in genetic and functional composition depending on the population of origin, suggesting that diagnostic criteria or probiotics developed in specific regions may not be directly applicable to other populations.

However, association does not imply causation. Whether OPRK1 variants directly regulate the colonization of *U. Whether urealyticum directly regulates colonization, or whether hormones, immunity, and environmental factors intervene, must be confirmed through cellular and animal experiments. A limitation remains that the large-scale new data is centered on Chinese populations. Longitudinal studies encompassing diverse ancestral groups, followed by functional validation, are necessary to enable genotype-based infection risk prediction or personalized microbial therapies.