A New Insight into Acne Pathogenesis: Multi-Omics Links a Metabolite to C. acnes Expansion and Lipid Accumulation

Background: Gut microbiota dysbiosis is implicated in dermatoses, including acne vulgaris. However, gut microbial and metabolomic profiles in acne remain uncharacterized. Methods: We performed metagenomic and metabolomic analyses on fecal samples from 29 acne patients and 20 healthy controls. Functional annotations utilized multiple databases. Integrated metagenomic-metabolomic analysis was conducted to identify metabolites, and their effects were subsequently validated in a mouse acne model. Finally, a five-fold cross-validated random forest model evaluated discriminatory capacity of microbial, metabolic, and multi-omics signatures for acne and its subtypes. Results: Acne patients exhibited reduced gut microbial diversity and decreased abundance of beneficial genera (eg, Blautia, Faecalibacterium ) and species (eg, Anaerotardibacter muris, Firmicutes bacterium CAG:321, Clostridium sp. CAG:245, Ruminococcus sp. OM06-36AC ). Differentially enriched microbial pathways involved amino acid metabolism. Integrated analysis revealed positive correlations between the key microbes driving the selected pathways and the associated metabolites which promoted the growth of C. acnes . The integrated multi-omics model yielded high diagnostic accuracy (validation AUC=0.921, test AUC=0.915), outperforming single-omic models, showed optimal gender discrimination (test AUC=1.00) and subtype-specific predictive efficacy, with key microbial and metabolite biomarkers identified for acne subtype classification and disease progression regulation. Conclusion: Acne vulgaris demonstrates distinct gut microbiota and metabolite signatures. Our integrated data suggest that gut microbiota may influence acne development via metabolic changes, and some of these metabolites might possess acne‑promoting properties.