The skin commensal yeast Malassezia promotes tissue homeostasis via the aryl hydrocarbon receptor.

Ibanez, E. G.; Stockmaier, M.; Barone, G.; Staropoli, A.; Karakaya, T.; Beer, H.-D.; Vinale, F.; Ianiri, G.; LeibundGut-Landmann, S.

doi:10.1101/2025.03.26.645515

bioRxiv · 10.1101/2025.03.26.645515

The skin commensal yeast Malassezia promotes tissue homeostasis via the aryl hydrocarbon receptor.

Ibanez, E. G.·Stockmaier, M.·Barone, G.·Staropoli, A.·Karakaya, T.·Beer, H.-D.·Vinale, F.·Ianiri, G.·LeibundGut-Landmann, S.

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Abstract

As an abundant fungal colonizer of human skin, Malassezia has long been associated with pathological skin conditions, yet its role in skin homeostasis remain poorly understood. Here, we demonstrate that Malassezia furfur plays an active role in maintaining epidermal integrity by producing tryptophan-derived metabolites that activate the aryl hydrocarbon receptor (AhR), a key regulator of keratinocyte differentiation and inflammation. Using a fungal mutant defective in indole production, we show that M. furfur-derived AhR activation is required to restore barrier function and control inflammation in diseased skin. AhR-deficient mice fail to benefit from M. furfur-mediated barrier protection, underscoring the importance of microbial-derived AhR agonists in skin physiology. These findings establish a previously unrecognized mutualistic role for Malassezia in epidermal homeostasis, challenging its perception as solely a pathogenic fungus and expanding our understanding of the skin microbiotas influence on barrier function and immune regulation. KEY FINDINGSO_LIMalassezia-derived indoles reprogram epidermal gene expression to enhance keratinocyte function. C_LIO_LIAhR activation by Malassezia restores skin barrier integrity and reduces inflammation. C_LIO_LIMalassezia Sul1-dependent tryptophan metabolism is essential for the production of AhR agonists. C_LIO_LIThe barrier protective effects of Malassezia are mediated specifically through keratinocyte intrinsic AhR signaling. C_LI

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Ibanez, E. G., Stockmaier, M., Barone, G., Staropoli, A., Karakaya, T., Beer, H.-D., Vinale, F., Ianiri, G., LeibundGut-Landmann, S.. 2025-03-26. The skin commensal yeast Malassezia promotes tissue homeostasis via the aryl hydrocarbon receptor.. https://doi.org/10.1101/2025.03.26.645515

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