From Acidification to DNA Intercalation: Dual Impact of Hydroxy Acids on the Epidermal Barrier and Skin Microbiota

The physiological acidity of the skin microenvironment constitutes a paramount component of passive innate defense against pathogenic colonization and subsequent dysbiosis. The objective of this review is to critically evaluate the sequelae of chronic epidermal barrier exposure to chemical exfoliants and to elucidate the impact of hydroxy acids on microbiota stability. An analysis of recent literature delineates fundamental discrepancies in their antimicrobial mechanisms, inflammatory modulation, and induction of stratum corneum desquamation. Conventional exfoliants, notably glycolic and salicylic acids, exhibit the capacity for passive diffusion into bacterial cells, where they undergo dissociation, precipitating destructive cytoplasmic acidification; furthermore, salicylic acid specifically downregulates crucial transcription factors. While these mechanisms facilitate the efficacious eradication of pathogenic organisms, they concurrently jeopardize commensal populations, which may paradoxically pave the way for secondary dysbiosis and opportunistic colonization. Next-generation acids, such as lactobionic acid, emerge as a highly promising, albeit insufficiently investigated, alternative. They exhibit the capacity to compromise bacterial cell walls and intercalate with microbial DNA. Future paradigms regarding the utilization of hydroxy acids in clinical dermatology must extend beyond traditional macroscopic endpoints to encompass the preservation of microbiome diversity and stability, thereby precluding chronic impairment of the associated protective barrier.