Skin Microbiome Patterns Associated with Basal Cell Carcinoma: A Case Series

Basal cell carcinoma (BCC) is the most common malignancy worldwide, yet the role of the skin microbiome in BCC remains poorly defined. In this cross-sectional observational case series, we compared the cutaneous microbiome of BCC lesions with matched perilesional and control skin using whole-genome shotgun sequencing in an intra-patient, multi-site sampling design. BCC samples demonstrated reduced microbial richness and significant shifts in community composition compared with matched control skin. Specifically, BCC lesions exhibited significantly lower Chao1 diversity (β = -484.6, 95% CI: -772.1 to -197.2, p = 0.003). Differences in overall microbial composition were confirmed by PERMANOVA analysis based on Bray-Curtis and Jaccard distance metrics (R² = 12.6% and 9.7%, respectively; both p = 0.01). At the species level, Cutibacterium acnes was significantly reduced in BCC samples compared with controls (β = -0.31, 95% CI: -0.45 to -0.16, p = 0.0004), corresponding to an approximately 27% lower geometric mean relative abundance. Functional profiling suggested shifts in microbial metabolic potential, with pathways related to redox balance and lipid-associated processes differentially represented in BCC samples relative to controls. Together, these findings demonstrate that BCC lesions are associated with localized alterations in microbial diversity, community composition, and inferred functional potential. These results support the presence of a tumor-associated microbiome signature in BCC; however, further studies in larger and more diverse cohorts are needed to determine whether these changes contribute to tumor development or reflect adaptation to the tumor microenvironment.