Skin Microbiome Shifts in Basal Cell Carcinoma:A Pilot Whole-Genome Sequencing Study

Document Type

Conference Proceeding

Publication Date

7-1-2026

Publication Title

J Am Acad Dermatol

Keywords

Dermatology

Abstract

The skin microbiome plays a complex role in regulating inflammatory signaling pathways, and its disruption has been linked to inflammatory dermatoses; however, its contribution to skin cancer remains poorly defined. In this case series, we compared the cutaneous microbiome of basal cell carcinoma (BCC) to matched perilesional and non-lesional skin using whole-genome shotgun sequencing (WGS). Four patients with biopsy-confirmed nodular BCC were enrolled and swabbed prior to Mohs surgery. Sampling included two BCC sites, two perilesional sites, two non-lesional sun-exposed sites, and two non-lesional non–sun-exposed sites, for a total of 32 specimens. Non-lesional samples served as controls. Statistical analysis included univariate (Wilcoxon, Kruskal–Wallis), multivariate (PERMANOVA), and differential abundance methods (MaAsLin2) to compare microbial composition and feature abundance across samples, with linear models adjusted for age. Compared to control skin, BCC demonstrated significantly reduced microbial species richness and diversity, with distinct compositional differences. Notably, Cutibacterium acnes was significantly decreased at BCC sites relative to matched controls. Predicted functional pathway analyses further revealed downregulation of L-cysteine biosynthesis and NAD de novo synthesis, alongside upregulation of all-trans farnesol and polyisoprenol biosynthesis pathways in BCC compared to non-lesional skin. The skin microbiome in BCC differs markedly from matched non-lesional skin, suggesting a role in tumorigenesis. This relationship may be bidirectional, with microbiome changes contributing to cancer development while BCC growth itself alters the local microbial community. Further research is warranted to disentangle these interactions and clarify how tumor–microbiome dynamics influence skin cancer development.

Volume

95

Issue

1

First Page

AB406

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