Epidermal barrier dysregulation in atopic skin predisposes for excessive growth of the allergy-associated yeastMalassezia

ABSTRACT The skin barrier is vital for protection against environmental threats including insults caused by skin-resident microbes. Dysregulation of the barrier is a hallmark of atopic dermatitis (AD) and ichthyosis, with variable consequences for host immune control of colonizing commensals and opportunistic pathogens. While sensitisation to Malassezia , the most abundant commensal fungus of the skin, is common in AD, its relevance for pathogenesis remains unclear. Here we show that in barrier-disrupted skin, Malassezia acquires enhanced fitness. This is not a consequence of the dysregulated allergic immune status characteristic for AD but is rather explained by structural and metabolic changes in the cutaneous niche that provide increased accessibility and a favourable lipid profile, to which the lipid-dependent yeast adapts for enhanced nutrient assimilation. These findings reveal fundamental insights into the role of the mycobiota in the pathogenesis of common skin barrier disorders.