Network pharmacology-guided probiotic metabolite therapy for acne vulgaris to target Cutibacterium acnes CAMP factors through Pediococcus acidilactici BCBH1 fatty acids

Abstract

Acne vulgaris is a chronic inflammatory skin disorder predominantly caused by Cutibacterium acnes and its virulence-associated CAMP (Christie–Atkins–Munch-Petersen) factors, particularly CAMP1 and CAMP2, which contribute to inflammation and bacterial survival. With increasing antibiotic resistance and concerns over microbiome disruption from conventional treatments, probiotic-derived postbiotics present a promising alternative. This study aimed to investigate the anti-acne potential of fatty acids produced by Pediococcus acidilactici BCBH1, targeting CAMP1 and CAMP2 proteins of C. acnes using a network pharmacology-guided approach. Metabolite profiling via GC-MS identified vaccenic acid as a major fatty acid metabolite (4.88 mg/L at 48 h under 10% linoleic acid stress). Virulence prediction confirmed high pathogenicity of CAMP1 (score 0.9055) and CAMP2 (score 0.9927). Molecular docking revealed strong binding affinities of vaccenic acid to CAMP1 and CAMP2 with binding energies of –9.6 kJ/mol and –9.3 kJ/mol, respectively, outperforming traditional anti-acne compound 4-terpin-eol (–9.0 kJ/mol and –8.7 kJ/mol). Molecular dynamics simulations further validated the stable interaction of vaccenic acid with CAMP proteins over 100 ns. Pharmacokinetic analyses indicated vaccenic acid’s favorable absorption and safety profiles with no blood–brain barrier permeability. These findings highlight vaccenic acid as a potent, microbiome-friendly therapeutic candidate for acne management. Future work should focus on experimental validation, formulation development, and combinatorial strategies to enhance clinical efficacy and safety. © 2025 Codon Publications. Published by Codon Publications.