Metabolomic profiling of sebum in acne to identify targeted treatment options beyond isotretinoin
Dr. Vishnu M Moodalgiri
MBBS, MD (Dermatology , Venereology & Leprology), FRGUHS (Cosmetology), Consultant – Dermatology & Aesthetics
Apollo Health and Lifestyle limited
Hyderabad
The pathogenesis of acne vulgaris involves excess sebum production, altered keratinization, Cutibacterium acnes involvement, and Th17-driven inflammation. Isotretinoin, the most effective anti-acne therapy, acts by upregulating transcription factors (p53, FoxO1, FoxO3), reducing sebaceous activity and inflammation. However, it carries notable side effects.
Metabolomic profiling offers a personalized approach to acne management. By analyzing metabolites in sweat or sebum, it can identify biomarkers, assess treatment response, and optimize therapy. Lipidomic studies show that changes in sebaceous lipids and ceramide ratios disrupt the skin barrier, contribute to hyperkeratinization, and increase inflammation. While isotretinoin reduces sebaceous activity, targeting specific lipid alterations and associated inflammation may offer complementary treatment strategies.
Cutibacterium acnes thrives in sebum-rich environments and stimulates cytokines like IL-1, which promotes hyperkeratinization and inflammation. Variations in sebum composition across facial regions (e.g., T-zone) contribute to the diversity of acne lesions.
Systemic metabolic changes also influence acne development. Diets high in refined carbohydrates and dairy increase insulin and IGF-1 levels, activating mTORC1—a key player in androgen synthesis and proinflammatory pathways. This metabolic dysregulation offers new treatment opportunities. For instance, metformin, by activating AMPK and inhibiting mTORC1, may benefit patients with acne and metabolic syndrome. Dietary counseling may also aid in improving acne through metabolic regulation.
Recent metabolomic studies highlight lipid alterations in acne patients, such as omega-3 fatty acid deficiency and increased proinflammatory lipids. This supports the use of ceramide-rich topicals, lipid-modulating agents, and dietary interventions as alternatives to systemic retinoids.
Microbiome-based therapies, including probiotics and prebiotics, are emerging as non-antibiotic options with fewer side effects.
Despite challenges in standardizing metabolomic data due to individual variability, ongoing research and improved protocols may enable more personalized, effective acne treatments in clinical practice.
Reference: Aust N, Stein M, Saeed Z, et al. Metabolomic profiling of sebum in acne patients to identify precision treatment targets beyond isotretinoin. Dermis. 2025; 5(3):40.
