Decoding the anti-aging effect of retinol in reshaping the human skin microbiome niches

Abstract Retinol has been widely added to skincare products due to its ability to promote the proliferation of skin keratinocytes and regulate skin cell collagen expression. While it is known the skin harbors a myriad of commensal bacteria, the impact of retinol on the skin microbiome, as well as the role of the skin microbiome in mediating the anti-aging properties of retinol, remains poorly understood. In this study, we incorporated phenomics, metagenomics and metabolomics to explore the human skin alterations during the anti-aging process mediated by retinol, and potential interactions between retinol, skin microbiome and metabolites. Topical retinol significantly improved skin conditions, including enhancing skin hydration, acidifying the epidermis, strengthening the skin barrier, and reducing the number and volume of wrinkles. Furthermore, retinol also reshaped the skin microecology by altering the structure and function of the skin microbiome as well as the host and microbial metabolites. Through GEM construction, we identified 2 skin microorganism, Sericytochromatia sp. and Corynebacterium kefirresidentii capable of oxidizing retinol to retinal. Over 10 skin microbes can utilize UDP-glucose as a carbon source, potentially accelerating RAG hydrolysis and increasing glucuronic acid consumption. The retinoic acid and retinol generated by RAG hydrolysis are reused by skin cells and microbes, enhancing retinol metabolism and its effective duration. This combined effect between the skin microbiome and retinol improves skin condition and anti-aging efficacy.