Investigating the causal relationship between skin microbiota and hypertrophic scar using bidirectional mendelian randomization.

Abstract

Hypertrophic scar (HS) is acknowledged as a pathological fibro-proliferative disease of the dermis, resulting from excessive connective tissue growth. HS significantly impacts patient quality of life due to both social and functional issues. Despite various treatments, therapeutic effectiveness remains limited, necessitating further exploration of underlying factors and mechanisms. The current study was designed to determine the causal relationship between skin microbiota and HS employing a bidirectional Mendelian randomization (MR) approach. We utilized genome-wide association study (GWAS) data from the PopGen cohort and the FinnGen database. Independent single nucleotide polymorphisms (SNPs) linked to the skin microbiota were identified as instrumental variables (IVs) chosen for the two-sample MR analysis. Key analytical approaches included inverse variance weighting (IVW), MR-Egger, simple median, simple mode, and weighted mode, with MR-Egger intercept test and Cochrane's Q test used to detect potential horizontal pleiotropy and heterogeneity. The two-sample MR analysis identified significant causal relationships between specific skin microbiota features and HS. Notably, Enhydrobacter, Micrococcus, and Acinetobacter on moist skin exhibited protective effects against HS, whereas Finegoldia and Lactobacillales on dry skin were linked to an increased risk of HS. Sensitivity analyses verified the strength of these results, revealing no notable horizontal pleiotropy or heterogeneity. Our research reveals a unidirectional causal relationship between certain skin microbiota and HS, suggesting that modulation of skin microbiota could be a novel therapeutic approach for HS management. These results emphasize the significance of considering skin microbiota in the pathogenesis and treatment of HS.