Martin P. Pagac, Bala Davient, Luca Antonio Plado, Hilbert Yuen In Lam, Shi Mun Lee, Aarthi Ravikrishnan, Wee Ling Esther Chua, Sneha Muralidharan, Aishwarya Sridharan, Antony S. Irudayaswamy, Ramasamy Srinivas, Stephen Wearne, Ahmad Nazri Mohamed Naim, Eliza Xin Pei Ho, H. Q. Amanda Ng, Junmei Samantha Kwah, Eileen Png, Anne K. Bendt, Markus R. Wenk, Federico Torta, Niranjan Nagarajan, John Common, Yap Seng Chong, Elizabeth Huiwen Tham, Lynette Pei-Chi Shek, Evelyn Xiu Ling Loo, John Chambers, Yik Weng Yew, Marie Loh & Thomas L. Dawson Jr
13 January 2025

Sebaceous free fatty acids are metabolized by multiple skin microbes into bioactive lipid mediators termed oxylipins. This study investigated correlations between skin oxylipins and microbes on the superficial skin of pre-pubescent children (N = 36) and adults (N = 100), including pre- (N = 25) and post-menopausal females (N = 25). Lipidomics and metagenomics revealed that Malassezia restricta positively correlated with the oxylipin 9,10-DiHOME on adult skin and negatively correlated with its precursor, 9,10-EpOME, on pre-pubescent skin. Co-culturing Malassezia with keratinocytes demonstrated a link between 9,10-DiHOME and pro-inflammatory cytokines IL-1β and IL-6 production. We also observed strong correlations between other skin oxylipins and microbial taxa, highlighting life stage differences in sebum production and microbial community composition. Our findings imply a complex host-microbe communication system mediated by lipid metabolism occurring on human skin, warranting further research into its role in skin health and disease and paving the way towards novel therapeutic targets and treatments.

The skin is the body’s largest organ and serves critical structural, sensing, protective, and thermoregulatory functions. Embedded within the skin are multiple diversly functional appendages, including the sebaceous gland, that define regional environs and allow the skin to maintain its physiological function¹. Sebaceous secretions (sebum) are deposited onto the skin’s outermost layer (the stratum corneum), moisturizing skin and influencing the skin’s microbial population^2,3. Sebum is composed largely of triglycerides of saturated and unsaturated C16 and C18 fatty acids, wax esters, squalene, free fatty acids (FAs), cholesterol, and cholesterol esters^4,5. Skin microbes secrete lipases that digest triglycerides, releasing free FAs^6,7,8.

Read more.