The Evolving Microbial Paradigm in Acne

This review discusses the microbiology of acne vulgaris, a chronic inflammatory condition of the pilosebaceous unit that affects most adolescents and can persist into adulthood. The current standard of care consists largely of antibacterial interventions, based on the traditional view of Cutibacterium acnes as a pathogen. Alternative treatments are suggested by the "comedo switch" hypothesis, which attributes acne to aberrant differentiation of Lrig1+ sebaceous progenitor cells. While there is strong evidence to support this idea, it does not explain the efficacy of antibacterial interventions. We propose a unified mechanism wherein C. acnes phylotype IA1 can act as a trigger for the comedo switch. Unlike commensal strains, phylotype IA1 has high lipase activity, hydrolyzing sebum triglycerides into free fatty acids, specifically palmitic acid. This metabolite stimulates Lrig1+ progenitors, inducing inflammation and initial comedo formation. The review discusses C. acnes phylotypes, emphasizing known virulence factors of IA1, such as enhanced biofilm formation. We evaluate the efficacy and limitations of both old and new antibacterials and in this context present a novel material that disrupts C. acnes biofilms (SmartArrow™). In a trial of 34 subjects with mild-to-moderate acne, this non-antibiotic agent demonstrated a statistically significant reduction in inflammatory lesions and selectively depleted phylotype IA1 by 37%, without compromising microbiome diversity. Our findings support the causal role of C. acnes IA1 in acne inflammation as well as in the comedo switch, and suggest that biofilm disruption represents a promising therapeutic avenue.