Integrated analysis of age-related microbiome and metabolites reveals youth-associated metabolites in young Korean women’s skin

Alterations in the composition and functional potential of the skin microbiome are closely associated with aging. Nevertheless, integrative analyses that concurrently examine microbial composition, functional gene profiles, and skin surface metabolomics remain limited, particularly among Asian populations. In this study, we performed a comprehensive multi-omics analysis integrating skin microbiome and surface metabolomic data from Korean women to explore metabolites associated with youthful skin state. Twenty-three healthy female participants in their 20s and 60s were recruited. Skin physiological parameters were assessed, and microbiome and metabolite samples were collected from the cheek area. Unsupervised clustering of microbiome functional profiles revealed three microbial community patterns that were not strictly aligned with chronological age. Based on these patterns, samples were grouped into three functional groups. The cluster enriched in participants in their 20s showed higher relative abundance of Cutibacterium and enrichment of microbial pathways related to carbohydrate and energy metabolism. Metabolomic profiling showed that phenyllactic acid (PLA) and hydroxyphenyllactic acid were more abundant in participants in their 20s and in the functionally young cluster. These metabolite patterns were accompanied by higher abundance of genes associated with phenylalanine metabolism. In vitro experiments further showed that PLA increased procollagen production and reduced the secretion of collagen-degrading enzymes in human dermal fibroblasts under inflammatory conditions. Together, these findings suggest links between microbiome functional profiles, phenylalanine-related metabolites, and skin physiology. This study provides an integrated view of microbiome–metabolite relationships in Korean skin and identifies PLA as a candidate metabolite associated with youthful skin environments.