AUTHOR=Lu Xiang , Lu Qiang , Zhu Rong , Sun Mingzhong , Chen Hongmei , Ge Zhihu , Jiang Yuchen , Wang Zhipeng , Zhang Lingzhi , Zhang Wen , Dai Ziyuan TITLE=Metagenomic analysis reveals the diversity of the vaginal virome and its association with vaginitis JOURNAL=Frontiers in Cellular and Infection Microbiology VOLUME=Volume 15 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2025.1582553 DOI=10.3389/fcimb.2025.1582553 ISSN=2235-2988 ABSTRACT=IntroductionThe human vaginal virome is an essential yet understudied component of the vaginal microbiome. Its diversity and potential contributions to health and disease, particularly vaginitis, remain poorly understood.MethodsWe conducted metagenomic sequencing on 24 pooled vaginal swab libraries collected from 267 women, including both healthy individuals and those diagnosed with vaginitis. Viral community composition, diversity indices (Shannon, Richness, and Pielou), and phylogenetic characteristics were analyzed. Virus–host associations were also investigated.ResultsDNA viruses dominated the vaginal virome. Anelloviridae and Papillomaviridae were the most prevalent eukaryotic viruses, while Siphoviridae and Microviridae were the leading bacteriophages. Compared to healthy controls, the vaginitis group exhibited significantly reduced alpha diversity and greater beta diversity dispersion, indicating altered viral community structure. Anelloviruses, detected in both groups, showed extensive lineage diversity, frequent recombination, and pronounced phylogenetic divergence. HPV diversity and richness were significantly elevated in the vaginitis group, alongside an unbalanced distribution of viral lineages. Novel phage–bacterial associations were also identified, suggesting a potential role for bacteriophages in shaping the vaginal microbiome.DiscussionThese findings provide new insights into the composition and structure of the vaginal virome and its potential association with vaginal dysbiosis. The distinct virome characteristics observed in women with vaginitis highlight the relevance of viral communities in reproductive health. Future studies incorporating individual-level sequencing and metatranscriptomics are warranted to explore intra-host viral dynamics, assess viral activity, and clarify the functional roles of vaginal viruses in host–microbiome interactions.