Roles of skin microbiota in hidradenitis suppurativa: insights from a two-sample mendelian randomization analysis

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease associated with unique lesional dysbiotic features. However, the role of the microbiology in the pathogenesis of HS remains in dispute. We aimed to conduct a two-sample Mendelian randomization study to investigate the relationship between skin microbiota and HS. A two-sample Mendelian randomization study was performed using the summary statistics of skin microbiota from summary GWAS data of the European descent from two cross-sectional, population-based German cohorts, KORA FF4 (n = 324) and PopGen (n = 273). The summary statistics of hidradenitis suppurativa were obtained from the FinnGen DF10 (1,070 cases and 394,105 controls). Inverse variance weighted (IVW), MR-Egger regression, weighted median, simple mode, weighted mode, and MRPRESSO were used to examine the causal association between skin microbiota and hidradenitis suppurativa. Cochran's Q statistics were used to quantify the heterogeneity of instrumental variables. Our study suggested that genus Corynebacterium in dry skin is significantly associated with HS after false discovery rate (FDR) correction (odds ratio (OR) = 1.04, 95% confidence interval (CI): 1.02-1.06, P = 0.0002, FDR adjusted P = 0.035). Additionally, we found genus Micrococcus in moist skin (OR = 1.10, 95% CI: 1.03-1.18, P = 0.0060, FDR adjusted P = 0.360), species Streptococcus salivarius in dry skin (OR = 1.03, 95% CI: 1.01-1.05, P = 0.0070, FDR adjusted P = 0.360), and species Propionibacterium granulosum (OR = 1.02, 95% CI: 1.00-1.04, P = 0.0460, FDR adjusted P = 0.970) are potentially associated with HS before FDR adjustment. No evidence of the effect in the reverse direction for HS on skin microbial features. This two-sample Mendelian randomization study found that genus Corynebacterium was causally associated with HS. Further studies are needed to clarify the protective effect of prebiotics, probiotics or microbiome transplants on HS.