O10 Skin-resident fungi metabolize skin sebum lipids into host modulatory oxylipins

Introduction and aims Cancer-associated fibroblasts (CAFs) play an important role in the oxylipins (oxygenated derivatives of polyunsaturated fatty acids), are detected on the skin surface and influence skin immunology and host–microbe signalling, yet their biological origin remains unclear. Malassezia are lipid-dependent yeasts that dominate the human scalp mycobiome and are implicated in dandruff and seborrhoeic dermatitis, in addition to scalp homeostasis. We hypothesized that Malassezia actively contributes to the oxylipin pool present on the human scalp. Methods A three-visit clinical intervention study was conducted in 68 healthy adults (aged 21–65 years). Scalp samples were collected at baseline before changes in scalp hygiene, after 5 days of control shampoo use, and after a further 5 days of antifungal shampoo use (containing 1% selenium sulfide). Scalp oxylipins were collected using ethanolic cup washes, and genomic DNA was obtained by scalp swabbing. Oxylipins were quantified by targeted ultra-performance liquid chromatography-tandem mass spectrometry using deuterated and authentic standards, and microbial abundance was measured by quantitative polymerase chain reaction. In vitro stable isotope tracing experiments used Malassezia globosa strain CBS7966 grown in biological triplicate. Results In vitro, Malassezia secrete the octadecanoids 9,10-dihydroxyoctadecenoic acid (9,10-DiHOME) and 9,10-dihydroxyoctadecanoic acid (9,10-DiHODA), with stable isotope tracing confirming metabolism of linoleic and oleic acids into these products, respectively. In vivo, antifungal treatment significantly reduced scalp Malassezia abundance but not the main scalp microbiome prokaryotic species Staphylococcus epidermidis and Cutibacterium acnes. The levels of multiple scalp-surface oxylipins, including 9,10-DiHOME, were significantly reduced following antifungal treatment (paired Wilcoxon test), closely mirroring reductions in Malassezia abundance, while no consistent associations were observed with bacterial species. Conclusions These data provide in vivo evidence that Malassezia contributes to the scalp oxylipin pool, supporting a link between fungal lipid metabolism, scalp oxylipin signalling, and potentially inflammatory conditions such as dandruff and seborrhoeic dermatitis.