Multi-omics characterization of the skin microbiota reveals the anti-aging roles of Stenotrophomonas maltophilia

BACKGROUND: Shifts in the skin microbiome have shown a close link to chronological age. However, the contribution of the skin microbiome in skin-aging phenotypes remains unclear. RESULTS: To explore this, we performed phenotypic, metabolomic, metagenomic, and functional analyses on a cohort with divergent skin-aging phenotypes. Genome-scale metabolic models (GEMs) integrated with metabolomic analysis revealed that Stenotrophomonas maltophilia, enriched in the younger group (categorized by AI-predicted age and skin elasticity), utilizes the glutathione cycle to maintain redox homeostasis. Cellular experiments showed its metabolites enhanced GSH synthesis and alleviated oxidative-stress-induced phenotypic skin-aging by upregulating key genes in fibroblasts, including GCLM, PGD, SOD2, and NQO1. In addition, GEMs highlighted its potential in maintaining youthful skin phenotypes through the regulation of host metabolic pathways involving betaine, lysolecithin, and porphyrin. In parallel, Acinetobacter guillouiae was found to influence host melanin metabolism by degrading dopamine (DA) and 3-methoxytyramine (3-MT), offering potential therapeutic strategies for mitigating pigmentation. CONCLUSIONS: Our findings highlight the dynamic interplay between skin microbiota and the host in phenotypic skin-aging, offering new insights for designing interventions to maintain youthful skin. Video Abstract.