Metagenomic analysis reveals the diversity of the vaginal virome and its association with vaginitis

Xiang Lu ¹ Qiang Lu ² Rong Zhu ² Mingzhong Sun ² Hongmei Chen ² Zhihu Ge ² Yuchen Jiang ² Zhipeng Wang ² Lingzhi Zhang ² Wen Zhang ¹ Ziyuan Dai ^2*

• ¹ Jiangsu University, Zhenjiang, Jiangsu Province, China
• ² Yancheng Third People's Hospital, Yancheng, China

The human vaginal virome is a critical component of the vaginal microbiome, yet its diversity and potential role in health and disease remain poorly understood. In this study, we performed metagenomic sequencing on 24 vaginal swab libraries from 267 women, including both healthy individuals and those diagnosed with vaginitis. Our analysis revealed that DNA viruses predominated in the vaginal virome, with Anelloviridae and Papillomaviridae being the most prevalent eukaryotic viruses, while Siphoviridae and Microviridae were the dominant bacteriophages. Compared to the healthy control group, the vaginitis group exhibited significantly lower alpha diversity (Shannon, Richness, and Pielou indices) and greater beta diversity dispersion, indicating distinct viral community compositions. Anelloviruses, detected in both groups, showed extensive lineage diversity, frequent recombination events, and substantial phylogenetic divergence, suggesting a complex evolutionary history and potential immunological interactions. HPV diversity and richness were significantly higher in the vaginitis group, with a more unbalanced viral lineage distribution. Furthermore, our findings highlighted novel phage-bacterial associations, suggesting a potential role of bacteriophages in modulating the vaginal microbiome.These results provide valuable insights into the composition of the vaginal virome, its relationship with vaginal dysbiosis, and potential implications for reproductive health. Future studies should incorporate individual-level sequencing and metatranscriptomic approaches to explore intra-host viral variability, assess viral activity, and further elucidate the functional roles of the vaginal virome in host-microbiome interactions.