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

Jasra Naseeb, Abid Sarwar, Yang Zhennai, Tariq Aziz, Manal F Elkhadragy, Maher S Alwethaynani, Areej A Alhhazmi, Deema Fallatah, Mai M Almsaud, Wafa A Alshehri, Saleh A Alsanie, Nouf Abdullah Alharbi

Journal: Allergologia et immunopathologia 2025;53(6):126-140

PMID: 41229051

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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-terpineol (-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.

Address: Key Laboratory of Geriatric Nutrition and Health of Ministry of Education, Beijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Technology and Business University, Beijing, China.; Key Laboratory of Geriatric Nutrition and Health of Ministry of Education, Beijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Technology and Business University, Beijing, China; [email protected].; Key Laboratory of Geriatric Nutrition and Health of Ministry of Education, Beijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Technology and Business University, Beijing, China; [email protected].; Department of Biology, College of Sciences, Princess Nourah bint Abdulrahman University, P.O. Box 84428, Riyadh 11671, Saudi Arabia.; Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Shaqra University, Alquwayiyah, Riyadh, Saudi Arabia.; Clinical Laboratory Sciences Department, College of Applied Medical Sciences, Taibah University, Medina, Saudi Arabia.; Department of Medical Laboratory Sciences, College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, Al-Kharj, Saudi Arabia.; Department of Biology, College of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh, Saudi Arabia.; Department of Biological Sciences, College of Science, University of Jeddah, Jeddah 23890, Saudi Arabia.; Department of Basic Health Sciences, College of Applied Medical Sciences, Qassim University, Saudi Arabia.; Department of Clinical Nutrition, Medical City, Qassim University, Saudi Arabia.; Department of Basic Health Sciences, College of Applied Medical Sciences, Qassim University, Saudi Arabia.

DOI: 10.15586/aei.v53i6.1497

MeSH Terms: Acne Vulgaris, Humans, Probiotics, Pediococcus acidilactici, Molecular Docking Simulation, Network Pharmacology, Propionibacterium acnes, Fatty Acids, Oleic Acids, Virulence Factors, Bacterial Proteins