Composition and Functional Potential of the Human Mammary Microbiota Prior to and Following Breast Tumor Diagnosis

Abstract

Microbiota studies have reported changes in the microbial composition of the breast upon cancer development. However, results are inconsistent and limited to the later phases of cancer development (after diagnosis). We analyzed and compared the resident bacterial taxa of histologically normal breast tissue (healthy, H, n = 49) with those of tissues donated prior to (prediagnostic, PD, n = 15) and after (adjacent normal, AN, n = 49, and tumor, T, n = 46) breast cancer diagnosis (n total = 159). DNA was isolated from tissue samples and submitted for Illumina MiSeq paired-end sequencing of the V3-V4 region of the 16S gene. To infer bacterial function in breast cancer, we predicted the functional bacteriome from the 16S sequencing data using PICRUSt2. Bacterial compositional analysis revealed an intermediary taxonomic signature in the PD tissue relative to that of the H tissue, represented by shifts in Bacillaceae, Burkholderiaceae, Corynebacteriaceae, Streptococcaceae, and Staphylococcaceae. This compositional signature was enhanced in the AN and T tissues. We also identified significant metabolic reprogramming of the microbiota of the PD, AN, and T tissue compared with the H tissue. Further, preliminary correlation analysis between host transcriptome profiling and microbial taxa and genes in H and PD tissues identified altered associations between the human host and mammary microbiota in PD tissue compared with H tissue. These findings suggest that compositional shifts in bacterial abundance and metabolic reprogramming of the breast tissue microbiota are early events in breast cancer development that are potentially linked with cancer susceptibility. IMPORTANCE: The goal of this study was to determine the role of resident breast tissue bacteria in breast cancer development. We analyzed breast tissue bacteria in healthy breast tissue and breast tissue donated prior to (precancerous) and after (postcancerous) breast cancer diagnosis. Compared to healthy tissue, the precancerous and postcancerous breast tissues demonstrated differences in the amounts of breast tissue bacteria. In addition, breast tissue bacteria exhibit different functions in pre-cancerous and post-cancerous breast tissues relative to healthy tissue. These differences in function are further emphasized by altered associations of the breast tissue bacteria with gene expression in the human host prior to cancer development. Collectively, these analyses identified shifts in bacterial abundance and metabolic function (dysbiosis) prior to breast tumor diagnosis. This dysbiosis may serve as a therapeutic target in breast cancer prevention.