A unique microbiota for normal breast tissue

Abstract

Background Microbial dysbiosis has emerged as a factor in most cancers, including breast cancer. However, whether changes in microbial composition of the breast are a cause, or a consequence, of tumor development remains unclear. Here, we analyzed the microbiota of normal breast tissue (N = 403) by sequencing the nine hypervariable regions of the 16S rRNA gene (V1V2, V2V3, V4V5, V5V7, and V7V9). Results We defined the V1V2 amplicon as optimal for our analysis and identified Lactobacillaceae (Firmicutes phylum), Acetobacterraceae, and Xanthomonadaceae (both Proteobacteria phylum) as the most abundant families in the normal breast. However, Ralstonia (Proteobacteria phylum) was more abundant in breast tumors and histologically normal tissues adjacent to malignant tumors (N = 31 and N = 61, respectively). We also conducted a correlation analysis between the microbiome and known breast cancer risk factors. Abundances of the bacterial taxa Acetotobacter aceti, Lactobacillus vini, Lactobacillus paracasei, and Xanthonomas sp. were associated with age (p < 0.0001), racial background (p < 0.0001), and parity (p < 0.0001). Finally, transcriptome analysis of normal breast tissues showed an enrichment in metabolism- and immune-related genes in the tissues with abundant Acetotobacter aceti, Lactobacillus vini, Lactobacillus paracasei, and Xanthonomas sp., whereas the presence of Ralstonia in the normal tissue was linked to genes involved in the carbohydrate metabolic pathway. Conclusions This study defines the microbial features of normal breast tissue, thus providing a basis to understand cancer-related dysbiosis. Moreover, the findings reveal that lifestyle factors can significantly affect the breast microbial composition.