Integrated Metagenomic and Lipidomic Profiling Reveals Dysregulation of Facial Skin Microbiome in Moderate Acne Vulgaris

Acne vulgaris is a prevalent chronic inflammatory dermatosis primarily affecting the pilosebaceous units. Current therapeutic approaches often exhibit limited efficacy and high recurrence rates. To investigate the microbiome-related mechanisms of acne vulgaris, facial skin samples from 19 patients with moderate acne and 20 healthy individuals were analyzed using an integrated metagenomic and lipidomic profiling strategy. Metagenomic analysis revealed a significant reduction in microbial diversity (Chao index) in acne-affected skin compared to healthy controls (<i>p</i> < 0.001). The relative abundance of <i>Staphylococcus</i>, particularly <i>Staphylococcus epidermidis</i>, was significantly elevated in acne group (<i>p</i> < 0.05), while <i>Cutibacterium acnes</i> levels remained unchanged. Carbon metabolism pathways were enriched in the acne group (<i>p</i> < 0.05), predominantly driven by <i>Cutibacterium</i>, whereas other enriched metabolic pathways, such as ABC transporters and glycine, serine, and threonine metabolism (<i>p</i> < 0.05), showed a greater contribution from <i>Staphylococcus</i>. Virulence factors enriched in acne samples were primarily offensive in nature and largely attributed to <i>Staphylococcus</i>. Moreover, acne-associated microbiome exhibited a significantly higher prevalence of resistance genes against fluoroquinolones, fosfomycin, and triclosan (<i>p</i> < 0.05). Untargeted lipidomic analysis demonstrated significantly elevated total serum and triglyceride levels, along with a reduction in fatty acid chain length and a higher degree of saturation compared to the healthy group (<i>p</i> < 0.01). Specific triglycerides significantly enriched in the acne group, such as TG (15:0_14:0_16:0) + NH₄, exhibited a significant positive correlation with <i>Staphylococcus</i>. This correlation is associated with elevated clinical erythema and melanin indices, suggesting that <i>Staphylococcus</i> is implicated in the development of acne-related inflammation. Additionally, <i>Thermus</i> exhibits negative correlations with acne-associated lipids and inflammatory parameters, potentially exerting a protective role. These findings suggest that <i>Cutibacterium</i> and <i>Staphylococcus</i> play differential yet synergistic roles in acne pathogenesis. The observed skin microbiome dysbiosis and lipid metabolic alterations provide novel insights into the pathophysiology of acne vulgaris, which may inform the development of targeted therapeutic strategies.