A comprehensive reference catalog of human skin DNA virome reveals novel viral diversity and microenvironmental influences.

Human skin serves as a dynamic habitat for a diverse microbiome, including a complex array of viruses whose diversity and roles are not fully understood. A total of 2,760 skin metagenomes from 6 published skin studies were collected. A skin virome catalog was constructed using standard methods in the viromics field. Viral characteristics were identified through cross-cohort meta-analysis and used to characterize viral features across different skin environments. We identified 20,927 viral sequences, which clustered into 2,873 viral operational taxonomic units (vOTUs), uncovering a substantial breadth of viral diversity on human skin. The results also highlight significant differences in viral communities that are associated with varying skin microenvironments. The oily skin is enriched in IMPORTANCE: This study presents a comprehensive reference catalog of the human skin DNA virome, constructed from 2,760 metagenomic datasets collected globally. It identified 20,927 viral sequences, with 90.85% representing previously unknown viruses, greatly expanding our understanding of skin viral diversity. The findings reveal significant differences in viral communities between distinct skin microenvironments (oily, dry, and moist) and highlight close interactions between bacteriophages and their bacterial hosts, suggesting a potential role for the virome in maintaining microbial balance and skin health. This extensive skin viral catalog constitutes a crucial resource for future epidemiological and therapeutic research, potentially facilitating the development of novel phage therapies and diagnostic markers for skin disorders.