Multi-omics Analysis Reveals an Altered Skin Surface Lipid Profile in Moderate-to-Severe Acne Patients with Correlated Changes in the Skin Microbiome: A Cross-Sectional Study

Objective: Acne is a prevalent inflammatory skin condition that has a multifactorial pathogenesis, including sebum overproduction and dysbiosis. Despite the recognized influence of skin surface lipids (SSLs) on acne pathogenesis, the interplay between SSLs and the skin microbiome remains underexplored. We aimed to determine the roles of SSLs and the skin microbiome in the pathogenesis of acne and to clarify their relationship. Methods: Skin microbial samples and SSL samples were collected from 21 patients with moderate-to-severe acne and 20 healthy controls from September 2024 to October 2024 at the Hospital for Skin Diseases (Institute of Dermatology), Chinese Academy of Medical Sciences & Peking Union Medical College. The differences in the SSL profiles between the acne patients and healthy controls were compared by absolute quantitative lipidomics using ultra-performance liquid chromatography-tandem mass spectrometry with orthogonal partial least squares analysis. The compositions of the skin microbiomes were analyzed by 16S rRNA gene sequencing. Results: The analyses revealed marked differences in the lipid compositions, with significant increases in ceramides (Cer; P =0.046), diacylglycerol (DG; P =0.035), phosphatidylethanolamine (PE; P =0.017), and triglycerides (TG; P =0.002) in the acne patients compared with the findings in the healthy controls. Cer, DG, and PE were significantly elevated in female acne patients only ( P =0.009, P =0.004, and P =0.014, respectively), while TG was significantly elevated in male acne patients only ( P =0.005). Correlation analyses between the SSL alterations and the microbiome revealed that Bacteroides and Ruminococcus had positive correlations with Cer (d18:2/16:0(2OH)) ( r =0.48, P =0.026 and r =0.61, P =0.003, respectively) and Cer (t18:0/24:1(2OH)) ( r =0.48, P =0.027 and r =0.47, P =0.034, respectively) in the acne patients, and negative correlations with Cer (t18:0/24:1(2OH)) ( r =−0.51, P =0.023 and r =−0.47, P =0.035, respectively) in the healthy controls. Staphylococcus exhibited significant correlations with several lipids in the healthy controls ( P <0.05), but not in the acne patients. Conclusions: The present study found significant differences in the SSL composition and skin microbiome in acne patients and revealed their correlations, suggesting that SSLs and the skin microbiome play significant roles in the pathogenesis of acne.