From Diet to Scar: Novel Mendelian Randomization and Mediation Analyses Linking Dietary Habits, Gut Microbiota, and Hypertrophic Scarring

Hypertrophic scarring (HTS) is a pathological skin condition characterized by excessive collagen deposition during wound healing. Emerging evidence suggests that dietary habits and gut microbiota composition may influence HTS risk via systemic inflammatory and metabolic pathways. However, the causal relationships between these factors remain poorly understood. Mendelian randomization (MR) analysis was conducted to investigate the causal relationships between dietary habits, gut microbiota composition, and HTS risk. Additional analyses included mediation analysis to explore potential intermediary effects of gut microbiota and co-localization analysis to assess shared genetic loci between exposures and HTS. MR analysis identified significant associations between HTS and six dietary preferences, with caffeinated/sweet liking and jam liking increasing HTS risk, while crisps, curry, oranges, and strong flavor liking were protective. For gut microbiota, <i>Eubacterium coprostanoligenes</i>, Collinsella, and Coprococcus1 showed protective effects, whereas Adlercreutzia was positively associated with HTS risk. Mediation analysis did not support gut microbiota as a significant mediator between dietary habits and HTS, and co-localization analysis indicated distinct genetic determinants for these traits. The study highlights the independent roles of dietary habits and gut microbiota in influencing HTS risk, suggesting potential dietary and microbial-targeted interventions for scar prevention. Further research in diverse populations is needed to validate these findings and explore their clinical applications.