Targeting polymicrobial skin infections in atopic dermatitis: role of Pichia kudriavzevii postbiotics as innovative tools for human health.

Atopic dermatitis (AD) is a chronic inflammatory skin disorder associated with microbial dysbiosis and persistent biofilm-forming infections, particularly involving Candida parapsilosis and Staphylococcus aureus. Postbiotics have recently emerged as promising alternatives to live probiotics due to their stability, safety, and antimicrobial properties. In this study, we evaluated the in vitro biological activity of two postbiotic preparations derived from the probiotic yeast Pichia kudriavzevii isolated from a homemade kefir: cell-free supernatant (CFS) and extracellular vesicles (EVs) against two clinical isolates of S. aureus and C. parapsilosis. While S. aureus demonstrated high vulnerability to postbiotic treatments, C. parapsilosis and the dual-species biofilm exhibited significantly higher tolerance. Results indicate a susceptibility gradient to postbiotic treatments, with S. aureus being the most vulnerable and C. parapsilosis more tolerant probably due to its structural and morphological characteristics. Treatment with CFS and EVs also reduced microbial adhesion and invasion of HaCaT keratinocytes, lowering microbial loads to 3.7-6.6 and 3.6-6.1 log10 CFU/mL, respectively. Furthermore, both postbiotics attenuated the inflammatory response by decreasing IL-6 and IL-8 production in pathogen-infected keratinocytes . Notably, EVs exhibited superior wound-healing activity by promoting keratinocyte migration and accelerating wound closure ( > 90% after 24 h). These findings highlight the potential of P. kudriavzevii-derived postbiotics as multifunctional agents capable of controlling biofilm-associated infections, modulating inflammation, and supporting tissue repair. Their application may represent a novel therapeutic approach for the management of chronic skin lesions associated with AD.