A reconstructed human epidermal model (RHE) colonized with human microbiota and sebum was developed to reproduce the complexity of the skin ecosystem in vitro. The RHE model was exposed to simulated solar radiation (SSR) with or without SPF50+ sunscreen (with UVB, UVA, long-UVA, and visible light protection). Structural identification of discriminant metabolites was acquired by nuclear magnetic resonance and metabolomic fingerprints were identified using reverse phase-ultra high-performance liquid chromatography-high resolution mass spectrometry, followed by pathway enrichment analysis. Over 50 metabolites were significantly altered by SSR (p < 0.05, log2 values), showing high skin oxidative stress (glutathione and purine pathways, urea cycle) and altered skin microbiota (branched-chain amino acid cycle and tryptophan pathway). 16S and internal transcribed spacer rRNA sequencing showed the relative abundance of various bacteria and fungi altered by SSR. This study identified highly accurate metabolomic fingerprints and metagenomic modifications of sun-exposed skin to help elucidate the interactions between the skin and its microbiota. Application of SPF50+ sunscreen protected the skin ecosystem model from the deleterious effects of SSR and preserved the physiological interactions within the skin ecosystem. These innovative technologies could thus be used to evaluate the effectiveness of sunscreen.
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