Skin Microbiota and Pathological Scars: A Bidirectional Two-Sample Mendelian Randomization Study

Pathological scars (PSs), resulting from abnormal skin repair, chronic inflammation, and fibrosis, affect millions of people. Previous studies have demonstrated that skin microbiota (SM) plays a role in cutaneous inflammation and healing, but the interplay between PSs and SM remains unclear yet. To investigate the causal associations between SM and two specific PSs: hypertrophic scars (HSs) and keloids. A bidirectional two-sample mendelian randomization (MR) analysis using genetic data for SM, HS, and keloids was conducted. The random-effects inverse variance weighted (IVW) method was used as the primary approach, along with multiple MR methods. False discovery rate (FDR) correction was employed to address multiple testing. In forward analysis, the family Moraxellaceae and order Pseudomonadales exhibited the same significant protective effects on keloids (odds ratio [OR]: 0.849, 95% confidence interval [CI]: 0.770-0.935, q2 = 0.03626). The class Betaproteobacteria (OR: 0.938, 95% CI: 0.894-0.985, q1 = 0.01965) and genus Bacteroides (OR: 0.928, 95% CI: 0.884-0.973, q1 = 0.00889) each demonstrated a suggestive protective effect on HSs and keloids, respectively. Some limited evidence suggested that order Actinomycetales contributes to an increased risk of keloids. In reverse analysis, keloids were found to have negative effects on the class Gammaproteobacteria with limited evidence. There was no detectable evidence of horizontal pleiotropy or heterogeneity. This study provided evidence for the causalities between SM and PSs, which laid foundation for furthering clinical practice and research of microorganism-skin interaction.