Distinct Bacterial Facial Cutaneous Microbiota Compositions in Adolescents with Acne Vulgaris: A Population-Based Cross-Sectional Observational Study

Background Acne vulgaris (acne) is a prevalent dermatological condition associated with distinct facial cutaneous microbiota compositions. However, existing research has often methodological limitations such as insufficient statistical power and the underrepresentation of diverse adolescents populations, which are highly relevant for understanding acne pathogenesis. Objectives We aimed to compare bacterial facial cutaneous microbiota compositions between acne cases and controls within a large, multiethnic adolescent population, while adjusting for potential confounders. Methods We compared bacterial facial cutaneous microbiota compositions using 16S rRNA sequencing between physician-evaluated acne cases (N=399) and controls (N=527) in adolescents (median age 13) in a population-based study. We additionally evaluated the independent associations of biological sex, puberty stage, perceived skin color, ethnicity, and weight status with facial cutaneous microbiota compositions. Our analytical approaches included assessment of alpha and beta diversity (including Permutational Multivariate Analysis of Variance), relative abundances, univariate coordinate analysis (Analysis of Compositions of Microbiomes with Bias Correction 2), and phylogenetic analyses. Results The overall microbiota composition of acne cases was less rich and diverse than controls (Chao1 β -44.98 (SE 4.36) Shannon β -1.01 (SE 0.07), P<0.01). While acne status was a major contributor to variations in overall microbiota compositions (R2 4.32%, P<0.01), skin color, sex, puberty stage, and weight status also independently contributed to variations (R2 0.44-1.05%, P<0.01). Specifically, acne cases showed higher relative abundances of Cutibacterium and Staphylococcus, and lower abundance of Streptococcus. Following confounder adjustment, bias correction, and phylogenetic analysis, Cutibacterium granulosum (C. granulosum), Cutibacterium acnes (C. acnes), and Staphylococcus epidermidis (S. epidermidis) emerged as the most differentially abundant species in acne cases versus controls (log fold changes: 0.75-2.17, P<0.01). Conclusions Our findings reveal distinct facial microbiota compositions in adolescents with acne, identifying C. granulosum, C. acnes, and S. epidermidis as key microbial signature. This study suggests a significant clinical relevance for C. granulosum in acne pathology and a potential protective role for Streptococcus in acne-free skin. These results underscore the importance of representative study populations in microbiome research and provide important methodological and technical insights for future investigations.