The change in the skin microbiome as individuals age is only partially known. To provide a better understanding of the impact of aging, whole-genome sequencing analysis was performed on facial skin swabs of 100 healthy female Caucasian volunteers grouped by age and wrinkle grade. Volunteers’ metadata were collected through questionnaires and non-invasive biophysical measurements. A simple model and a biological statistical model were used to show the difference in skin microbiota composition between the two age groups. Taxonomic and non-metric multidimensional scaling analysis showed that the skin microbiome was more diverse in the older group (≥55 yo). There was also a significant decrease in Actinobacteria, namely in Cutibacterium acnes, and an increase in Corynebacterium kroppenstedtii. Some Streptococcus and Staphylococcus species belonging to the Firmicutes phylum and species belonging to the Proteobacteria phylum increased. In the 18–35 yo younger group, the microbiome was characterized by a significantly higher proportion of Cutibacterium acnes and Lactobacillus, most strikingly, Lactobacillus crispatus. The functional analysis using GO terms revealed that the young group has a higher significant expression of genes involved in biological and metabolic processes and in innate skin microbiome protection. The better comprehension of age-related impacts observed will later support the investigation of skin microbiome implications in antiaging protection.

Systems biology research on host-associated microbiota focuses on two fundamental questions: which microbes are present and how do they interact with each other, their host, and the broader host environment? Metagenomics provides us with a direct answer to the first part of the question: it unveils the microbial inhabitants, e.g., on our skin, and can provide insight into their functional potential. Yet, it falls short in revealing their active role. Metabolomics shows us the chemical composition of the environment in which microbes thrive and the transformation products they produce. In particular, untargeted metabolomics has the potential to observe a diverse set of metabolites and is thus an ideal complement to metagenomics. However, this potential often remains underexplored due to the low annotation rates in MS-based metabolomics and the necessity for multiple experimental chromatographic and mass spectrometric conditions. Beyond detection, prospecting metabolites’ functional role in the host/microbiome metabolome requires identifying the biological processes and entities involved in their production and biotransformations. In the present study of the human scalp, we developed a strategy to achieve comprehensive structural and functional annotation of the metabolites in the human scalp environment, thus diving one step deeper into the interpretation of “omics” data. Leveraging a collection of openly accessible software tools and integrating microbiome data as a source of functional metabolite annotations, we finally identified the specific metabolic niche of Staphylococcus epidermidis , one of the key players of the human skin microbiome.

Although metabolomics data acquisition and analysis technologies have become increasingly sophisticated over the past 5–10 years, deciphering a metabolite’s function from a description of its structure and its abundance in a given experimental setting is still a major scientific and intellectual challenge. To point out ways to address this ‘data to knowledge’ challenge, we developed a functional metabolomics strategy that combines state-of-the-art data analysis tools and applied it to a human scalp metabolomics dataset: Skin swabs from healthy volunteers with normal or oily scalp (Sebumeter score 60–120, n = 33; Sebumeter score > 120, n = 41) were analyzed by LC-MS/MS, yielding four metabolomics datasets for RP18 or HILIC separation in ESI+ or ESI− ionization mode. Following our data analysis strategy, we were able to obtain increasingly comprehensive structural and functional annotations, by applying the GNPS (Wang et al ., Nat. Biotechnol. 2016), SIRIUS (Dührkop et al . Nat. Methods 2019), and MicrobeMASST (Zuffa et al ., bioRxiv 2023) tools. We finally combined the metabolomics data with a corresponding metagenomic sequencing dataset using MMvec (Morton et al., Nat. Methods 2019), gaining insights into the metabolic niche of one of the most prominent microbes on the human skin, Staphylococcus epidermidis . IMPORTANCE: Systems biology research on host-associated microbiota focuses on two fundamental questions: Which microbes are present and how do they interact with each other, their host, and the broader host environment? Metagenomics provides us with a direct answer to the first part of the question: it unveils the microbial inhabitants, e.g., on our skin, and can provide insight into their functional potential. Yet, it falls short in revealing their active role. Metabolomics shows us the chemical composition of the environment in which microbes thrive and the transformation products they produce. In particular, untargeted metabolomics has the potential to observe a diverse set of metabolites and is thus an ideal complement to metagenomics. However, this potential often remains underexplored due to the low annotation rates in MS-based metabolomics and the necessity for multiple experimental chromatographic and mass spectrometric conditions. Beyond detection, prospecting metabolites’ functional role in the host/microbiome metabolome requires identifying the biological processes and entities involved in their production and biotransformations. In the present study of the human scalp, we developed a strategy to achieve comprehensive structural and functional annotation of the metabolites in the human scalp environment, thus diving one step deeper into the interpretation of ‘omics’ data. Leveraging a collection of openly accessible software tools and integrating microbiome data as a source of functional metabolite annotations, we finally identified the specific metabolic niche of Staphylococcus epidermidis , one of the key players of the human skin microbiome.