Abstract
BACKGROUND: The skin microbiome plays a critical role in regulating epidermal differentiation and immune responses. Understanding of how individual microbial species influence the expression of barrier proteins and lipid synthesis pathways is essential for elucidating their contributions to skin barrier function. OBJECTIVE: This study aimed to investigate the distinct effects of Staphylococcus aureus (S. aureus), Staphylococcus hominis (S. hominis), and Cutibacterium acnes (C. acnes) on the skin barrier protein expression and lipid synthesis, thereby clarifying their roles in maintaining skin barrier integrity and homeostasis. METHODS: Keratinocyte 2-dimensional monolayer cultures and self-assembled 3-dimensional skin models were treated with S. aureus, S. hominis, or C. acnes. Alterations in skin barrier proteins and lipid synthesis were assessed using quantitative real-time polymerase chain reaction, immunofluorescence staining, and Oil Red O staining. RESULTS: S. aureus significantly downregulated the messenger ribonucleic acid expression of skin barrier proteins and lipid synthesis enzymes, resulting in reduced lipid accumulation. In contrast, S. hominis upregulated barrier protein expression and enhanced lipid accumulation. Similarly, C. acnes increased the expression of both skin barrier proteins and lipid synthesis enzymes, leading to a marked increase in lipid accumulation. CONCLUSION: Collectively, these findings suggest that S. aureus compromises the skin barrier function by downregulating the expression of barrier-associated proteins and lipid synthesis enzymes, whereas S. hominis and C. acnes enhance barrier integrity by upregulating these components. These differential microbial effects elucidate potential mechanisms by which the skin microbiome contributes to barrier homeostasis.