Malassezia and the Asian menopausal skin

Menopause is accompanied by skin changes, including complaints of itch, redness, and dry skin, linked to epidermal thinning and reduced sebaceous gland activity. These changes can cause microbiome dysbiosis, leading to dermatoses. Malassezia , a ubiquitous, lipid-dependent, and dominant skin fungus, is associated with multiple skin and systemic diseases. However, the mechanism for its pathogenicity in the context of host physiological changes, such as menopause, remains unexplored. We investigated the skin metagenomes of 345 Asian women spanning pre-, peri-, and post-menopause, revealing menopausal stage-specific differences in prevalence and abundance of Malassezia species. In keratinocyte co-culture, Malassezia elicited cytotoxicity beyond a critical fungal threshold, invaded keratinocytes, and induced inflammation. Transcriptomic profiling of keratinocytes exposed to toxic fungal loads revealed a gene expression profile characteristic of the hyperproliferative and undifferentiated phenotype present in many inflammatory dermatological diseases. Our findings reveal a mechanistic link between menopause-driven changes in skin physiology and Malassezia -mediated keratinocyte dysfunction.