Microbial functions in skin inflammation: a Mendelian randomization study.

Inflammatory skin diseases (ISDs) represent a significant global health burden, yet the role of the human microbiome in their pathogenesis remains unclear. This study employed a comprehensive two-sample Mendelian randomization (MR) framework to investigate potential causal associations between multi-site microbiota (3117 oral, 412 gut, and 150 skin microbial features) and five major ISDs: psoriasis, atopic dermatitis, acne, seborrheic dermatitis, and urticaria. Genetic instruments were selected from large-scale genome-wide association studies (GWAS) of microbiota composition and ISD outcomes. The inverse variance weighted (IVW) method served as the primary analytical approach, supplemented by MR-Egger regression, weighted median, and MR-PRESSO for sensitivity analyses. Multiple testing was controlled using the false discovery rate (FDR) method. Our analyses identified numerous suggestive associations between specific microbial taxa, metabolic pathways, and ISD risk. Notably, shared microbial signatures were observed across multiple ISDs, suggesting potentially shared microbiome-associated pathogenic pathways. These results provide genetic evidence supporting a role for the microbiome in ISD susceptibility and highlight potential microbial targets for future therapeutic development.