Gut microbiota-derived metabolites in keloid and hypertrophic scarring

Keloids and hypertrophic scars are fibro-proliferative skin disorders that arise from aberrant wound healing and are characterized by excessive collagen deposition and chronic inflammation. Although traditionally viewed as strictly local cutaneous phenomena, growing evidence suggests that systemic influences-particularly the gut microbiota and its metabolites-may influence scar pathogenesis. The gut microbiota produces a wide range of bioactive compounds, including short-chain fatty acids (SCFAs), bile acids, and tryptophan derivatives, which are hypothesized to modulate immune responses and pro-fibrotic signaling pathways such as TGF-β and Wnt/β-catenin. Observations from systemic fibrotic disorders-for example, liver and pulmonary fibrosis-link microbial dysbiosis to aberrant extracellular-matrix remodeling. Although direct evidence in skin fibrosis is still limited, recent multi-omics analyses and microbiota-transplantation studies imply that gut-derived factors may influence dermal fibroblast behavior. This review therefore synthesizes the emerging conceptual and mechanistic connections between gut microbial metabolites and pathological scar formation, proposes a possible skin-gut-fibrosis axis, and outlines potential avenues for therapeutic intervention in keloids and hypertrophic scars.