Lacticaseibacillus parahuelsenbergensis THGS-36 alleviates acne-like inflammation and lipogenesis in sebocytes via...

Acne vulgaris is a chronic inflammatory disorder of the pilosebaceous unit and is associated with Cutibacterium acnes overgrowth, excessive sebum production, and persistent inflammatory responses. This study evaluated the anti-acne potential of the cell-free supernatant (CFS) from Lacticaseibacillus parahuelsenbergensis THGS-36 and investigated its host-modulatory effects in sebocytes with a focus on CREB-associated signaling. THGS-36 CFS exhibited dose-dependent antibacterial activity against C. acnes strains KACC 11946 and KACC 19884, with identical minimum inhibitory concentration and minimum bactericidal concentration values of 1.25 mg/mL, and inhibited biofilm formation beginning at a sub-inhibitory concentration. In human sebocytes, 50 μg/mL THGS-36 CFS reduced C. acnes adhesion by 17.2% and significantly suppressed C. acnes CFS-induced secretion of IL-1β, IL-6, IL-8, and TNF-α, concomitant with reduced expression of TLR2 and NFKBIA, as well as decreased phosphorylation of IκBα and p65, indicating attenuation of NF-κB signaling. Under IGF-1 stimulation, THGS-36 CFS decreased lipid accumulation and downregulated lipogenesis-associated transcripts, including SREBF1, FASN, and PPARG. Mechanistically, the anti-inflammatory and anti-lipogenic effects of THGS-36 CFS were associated with stimulus-dependent modulation of CREB phosphorylation. Whole-genome sequencing supported the safety profile of THGS-36 by revealing no detectable virulence- or antibiotic resistance-associated determinants and identifying putative class II bacteriocin gene clusters. Collectively, THGS-36 CFS exerts multi-target anti-acne activity by inhibiting C. acnes growth and biofilm formation while attenuating sebocyte inflammation and lipogenesis, supporting its potential as a safe adjuvant or alternative strategy for acne treatment.