Monitoring radiation exposure through skin swab multi-omic profiling.

Exposure to ionizing radiation poses major health risks across medical, occupational, and spaceflight settings, driving the need for rapid, non-invasive biodosimetry tools. As the body's most accessible organ and the most frequent site of radiation injury, the skin represents a promising interface for monitoring exposure. Using colonized human skin equivalents (coHSE; 0 Gy n = 8, 1 Gy n = 6, 4 Gy n = 6) and mice (n = 6/group) models, we performed multi-omic profiling, integrating metabolomics, lipidomics, and metagenomics, on skin swab samples collected after exposure to 0, 1, or 4 Gy of x-rays. We identified two distinct metabolite panels: one discriminating irradiated from non-irradiated skin, and another distinguishing dose-specific response. These panels included conserved radiation-responsive metabolites (e.g., uric acid, xanthine, taurine) and skin-specific markers associated with barrier integrity (e.g., proline, arginine). Diacylglycerol network enrichment and shifts in radioprotective microbial taxa, including Lachnospiraceae and Lactobacillales, further supported a repair-driven molecular response. These data support the feasibility of skin swab signatures for non-invasive exposure classification, providing a molecular and microbial framework for skin based monitoring measure development and motivating validation in human cohorts for real-world biodosimetry.