Biogeography and individuality shape function in the human skin metagenome

The varied topography of human skin offers a unique opportunity to study how the body’s microenvironments influence the functional and taxonomic composition of microbial communities. Phylogenetic marker gene-based studies have identified many bacteria and fungi that colonize distinct skin niches. Here, metagenomic analyses of diverse body sites in healthy humans demonstrate that local biogeography and strong individuality define the skin microbiome. We developed a relational analysis of bacterial, fungal, and viral communities, which showed not only site-specificity but also individual signatures. We further identified strain-level variation of dominant species as heterogeneous and multiphyletic. Reference-free analyses captured the uncharacterized metagenome through the development of a multi-kingdom gene catalog, which was used to uncover genetic signatures of species lacking reference genomes. This work is foundational for human disease studies investigating inter-kingdom interactions, metabolic changes, and strain tracking and defines the dual influence of biogeography and individuality on microbial composition and function.