Optimizing Skin Surface Metabolomics: A Comprehensive Evaluation of Sampling Methods, Extraction Solvents, and Analytical Techniques

Characterizing the metabolite fingerprint from the skin surface provides invaluable insights into skin biology and microbe-host interactions. To ensure data accuracy and reproducibility, it is essential to develop standard operating procedures (SOPs) for skin surface metabolomics. However, there is a notable lack of studies in this area. Here, we thoroughly evaluated different sampling materials, extraction solvents, taping methods (frequency and number of tapes) and analytical techniques to optimize skin surface metabolomics. Our results showed that the combination of D-Squame® D100 tape with a methyl tert-butyl ether/methanol extractant is optimal for skin surface lipidomics. Performing the skin taping procedure five times with one tape yields sufficient biomass for lipid analysis, while the optimal taping procedure varies for water-soluble compounds. In addition, our study identified associations among the skin surface metabolites, some of which potentially underlie the formation of microbial cutotypes and offer insights into host-microbe interactions.