From acidification to multi-targeted cellular modulation: dual impact of hydroxy acids on the skin microbiota and the epidermal barrier

Maintaining proper skin surface acidity is essential for both epidermal barrier integrity and microbial homeostasis. This review examines the dual impact of hydroxy acids on the host-microbiota interface, focusing on their antimicrobial mechanisms, inflammatory modulation, and barrier remodeling. Traditional agents, such as glycolic and salicylic acids, induce exfoliation through desmosomal disruption and exert bactericidal effects via intracellular acidification. Salicylic acid specifically penetrates pilosebaceous units to suppress sebocyte lipogenesis, attenuate pro-inflammatory cascades, and downregulate bacterial virulence factors. However, aggressive exfoliation can compromise the epidermal barrier, which increases the risk of secondary dysbiosis. In contrast, next-generation polyhydroxy acids (such as lactobionic acid) reinforce structural cohesion and inhibit matrix metalloproteinases. These newer agents also, as demonstrated by in vitro models, can disrupt the bacterial cell envelope, destabilize biofilms, and are hypothesized to potentially interact with microbial DNA without causing severe irritation. Future therapeutic approaches need to balance clinical macroscopic endpoints with the preservation of microbiome diversity to avoid chronic microenvironment impairment. Our findings demonstrate how acid-induced pH reduction directly modulates bacterial virulence factors and suggests a potential to modulate microbial environments.