Lacticaseibacillus rhamnosus GG lysate inhibits Staphylococcus aureus biofilm formation in human skin explants.

Staphylococcus aureus is a leading cause of skin and soft tissue infections and a major nosocomial pathogen, with biofilm formation contributing to significantly higher morbidity and mortality. In atopic dermatitis (AD), where skin barrier dysfunction and microbial dysbiosis are common features, S. aureus abundance and biofilm formation are associated with disease severity and flare recurrence. We previously demonstrated that a lysate of Lacticaseibacillus rhamnosus GG (LGG)- a common human commensal and widely used probiotic strain- can inhibit S. aureus attachment to human keratinocytes by mechanisms including displacement and competitive exclusion. In this study, we extended these findings utilizing organ-cultured human skin to evaluate the protective effects of LGG lysate against S. aureus challenge in a physiologically relevant model. LGG lysate preserved skin integrity by preventing S. aureus penetration, proliferation, eDNA release and biofilm maturation. These effects were dose-dependent and effective when the lysate was applied from 24 hours pre-S. aureus inoculation to up to 3 hours post inoculation. Together, these data provide mechanistic insight into microbiome- pathogen interactions at the skin surface which could be exploited for therapeutic potential, particularly in the prevention of nosocomial S. aureus skin infections and mitigating S. aureus-driven flares in AD.