Integrated Microbiome and metabolome analysis reveals Microbial-Metabolic interactions in psoriasis pathogenesis

Psoriasis is a chronic inflammatory skin disorder with unclear etiology. The roles of skin microbiome and metabolic dysregulation in psoriasis pathogenesis are not yet fully understood.

We conducted an integrated microbiome and untargeted metabolomic analyses on skin samples from 29 patients with psoriasis and 31 healthy controls. The skin microbiota was characterized using 16 S rRNA gene sequencing, and untargeted metabolomic profiling was performed using LC-MS/MS. Multivariate statistical analyses were used to identify differential microbes and metabolites, followed by correlation analyses to explore microbe-metabolite interactions.

Psoriatic lesions exhibited significantly higher skin microbial alpha diversity compared to healthy controls. Principal component analysis revealed distinct microbial community structures between the two groups. At the genus level, Corynebacterium and Staphylococcus were significantly enriched in psoriatic lesions, while Cutibacterium was notably reduced. Metabolomic analysis identified 63 differential metabolites, with 39 upregulated and 24 downregulated in psoriatic lesions. These metabolites were primarily involved in lipid metabolism (particularly phospholipids and sphingolipids), amino acid metabolism, and inflammatory mediator pathways. Correlation analysis revealed significant associations between microbial alterations and metabolic dysregulation. Cutibacterium abundance was negatively correlated with inflammatory lipids and positively correlated with antioxidant metabolites, whereas Staphylococcus and Corynebacterium exhibited the opposite pattern. Notably, the abundance of Propionibacteriaceae strongly correlated with glutathione levels (r = 0.821, P < 0.001), indicating a potential role of microbiome-mediated oxidative stress in psoriasis.

This study highlights significant alterations in both the skin microbiome and metabolome in patients with psoriasis, revealing complex microbe-metabolite interaction networks. The findings suggest that microbial dysbiosis, particularly the decreased abundance of Cutibacterium and the increased abundance of Staphylococcus/Corynebacterium, may contribute to psoriasis pathogenesis by modulating lipid metabolism, inflammatory pathways, and oxidative stress responses.