Large-scale skin metagenomics reveals extensive prevalence, coordination, and functional adaptation of skin microbiome dermotypes across body sites

The human skin microbiome is increasingly recognized to influence skin health, immune function and disease susceptibility. However, large-scale, multi-site metagenomic studies in the general population remain scarce, limiting our understanding of the full diversity and variability of skin microbial communities across different individuals and body sites. Here, we present the largest- to-date skin microbiome dataset (>3,550 shotgun metagenomes across 18 sampling sites), generated using standardized cohort-wide protocols and rigorous contaminant removal. We define and characterize 17 robust, site-specific dermotypes—distinct microbial configurations—across seven out of nine body sites, whose coordination across disparate skin regions suggests systemic microbiome regulation. We also uncover striking bilateral concordance (median Pearson correlation>0.95 except for axilla) in microbial composition, further suggesting that host-intrinsic factors may contribute more than behavioral influences to shape skin microbiota. We trained near-perfect classifiers for dermotype labels for dermotype identification with as few as five signature species (AUC-ROC>0.98). Dermotype-dependent microbial interactions such as hypoxia-dependent inhibition of S. hominis by S. epidermidis and M. luteus , and metabolic resource utilization (e.g., galactose and histidine metabolism), reveal adaptive specialization within dermotypes, with implications for microbial assembly and host health. Notably, we associate a S. hominis -dominated elbow crease dermotype with skin irritation and itch, suggesting a potential link between microbial shifts and variations in barrier functions. By establishing dermotypes as a key organizing principle of skin microbial ecology, our findings provide a framework for microbiome-based prognostics and personalized therapeutic strategies.