Integrated microbiome–metabolome analysis identifies a Staphylococcus aureus-associated decanoic acid inflammatory pathway in seborrheic dermatitis

Seborrheic dermatitis (SD) is a common inflammatory dermatosis whose pathogenic drivers remain incompletely understood. We integrated bacterial 16S rRNA gene and fungal ITS1 amplicon profiling with scalp metabolomics in patients with SD and healthy controls. Lesional skin showed Staphylococcus enrichment and Cutibacterium depletion, without a corresponding increase in Malassezia . Decanoic acid (DA) was elevated in SD scalp and showed positive nominal associations with Staphylococcus abundance and qPCR-measured S. aureus . In a tape-stripped mouse model, S. aureus exposure was accompanied by increased cutaneous DA and remodeling of the fatty-acid profile. Topical DA phenocopied several features observed after S. aureus exposure, including epidermal thickening, inflammatory-cell recruitment, and increased IL-1β staining. RNA sequencing identified 1,134 differentially expressed genes shared by DA- and S. aureus -treated skin, involving inflammatory, chemotactic, and epidermal-differentiation programs. Together, these data identify an S. aureus -associated DA response and provide functional evidence that DA can contribute to cutaneous inflammation and perturbed epidermal differentiation in SD.