Lacticaseibacillus paracasei-Derived Cell-Free Supernatant-10 as a Novel Therapeutic for Acne Vulgaris: Efficacy and Mechanisms in a Murine Model

Previous research has shown that the cell-free supernatant (CFS) from Lacticaseibacillus paracasei has potent antimicrobial properties, but the mechanisms underlying its therapeutic effects on acne vulgaris remain unclear. We investigated the effects of L. paracasei LPH01 cell-free supernatant (CFS-10) using a Propionibacterium acnes -induced acne-like mouse model. Our results demonstrated that topical CFS-10 treatment significantly alleviated skin lesions, reduced inflammatory cell infiltration, and suppressed pro-inflammatory cytokine expression in acne-induced mice. Furthermore, CFS-10 substantially inhibited skin lipid synthesis, and reduced sebum secretion by downregulating the expression of key genes and proteins involved in the PPAR-γ/SREBP-1 signaling pathway. Transcriptome analysis revealed that CFS-10 mitigated inflammation by inhibiting the TLR4/NF-κB signaling pathway and reducing inflammation-related gene expression. Additionally, CFS-10 strengthened the skin barrier, restored skin microbiota homeostasis, increased beneficial Lactobacillus species, and decreased pathogenic Staphylococcus . Our results provide thereby establishing a robust theoretical foundation for its therapeutic application in acne management.