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

What was studied?

This study examined the composition and functional potential of the human mammary microbiota prior to breast cancer diagnosis, with the focus phrase mammary microbiota prior to breast tumor diagnosis guiding the analysis. The authors compared microbiota profiles from four tissue types—healthy, prediagnostic, adjacent normal, and tumor to determine whether microbial changes precede clinically detectable breast cancer. Using 16S rRNA gene sequencing of the V3–V4 region and functional inference via PICRUSt2, the researchers assessed how bacterial communities and their predicted metabolic capabilities shift from health to malignancy. The overarching aim was to identify early microbial alterations that could signal cancer susceptibility or reflect tumor-related microenvironment changes.

Who was studied?

Breast tissue samples were obtained from 137 women, contributing 159 samples. Healthy tissue (H, n=49) and prediagnostic samples (PD, n=15) came from donors in the Susan G. Komen Tissue Bank—unique because these tissues are histologically normal and collected from women without breast disease at the time of donation. Women whose healthy samples were later associated with cancer diagnosis formed the PD group, providing rare insight into earliest-stage alterations. Cancer-associated tissues included adjacent normal (AN, n=49) and tumor samples (T, n=46). Donors ranged widely in age and demographic characteristics. Tissue types were sequenced deeply enough to allow robust taxonomic and functional profiling.

Most important findings

Across pages 4–7, ordination analyses showed that microbiota composition in PD tissue resembled healthy tissue but exhibited an emerging divergence, forming an intermediate signature between H and cancer-associated tissues. Family-level shifts were evident, including increased Bacillaceae and Burkholderiaceae and decreased Xanthobacteraceae in PD, AN, and T tissues relative to healthy samples. Specific taxa enriched in PD tissue included Streptococcus spp. (ASVs 7, 415), Corynebacterium, Bradyrhizobium, and Sphingomonas. Differential abundance analyses showed that many taxa decreased rather than increased in PD, AN, and T tissues, suggesting loss of community functionality. Functional predictions (pages 8–9) highlighted significant reductions in metabolic pathways, particularly those involved in xenobiotic degradation, nutrient transport, glutathione metabolism, and lipid metabolism—the latter notable given host transcriptomic evidence of lipid pathway upregulation prior to cancer development. The functional loss was consistent across PD, AN, and T tissues, implying early and progressive metabolic disruption of the mammary microbiota. Correlation analyses revealed altered host–microbiota interactions in PD tissue, including a reversed direction of association between microbial functions and expression of CYP24A1, a gene involved in xenobiotic and steroid metabolism, suggesting early microenvironmental disturbances connected to carcinogenesis.

Key implications

The study provides robust evidence that microbial dysbiosis and functional impairment arise prior to breast cancer diagnosis, indicating a potential early biomarker signature. The intermediate PD microbiota profile suggests that subtle shifts—particularly enrichment of Streptococcus spp. and loss of metabolic functions—may mark susceptibility or early tumor-microenvironment interaction. Reduced xenobiotic and glutathione-related pathways imply weakened microbial contributions to carcinogen detoxification, possibly facilitating tumor initiation. The altered correlations between microbial pathways and host gene expression further support a model in which microbe–host crosstalk deteriorates before tumors form. These findings encourage the development of microbiome-based early detection tools and the exploration of microbial-targeted prevention strategies.

Citation

Hoskinson C, Zheng K, Gabel J, et al. Composition and functional potential of the human mammary microbiota prior to and following breast tumor diagnosis.mSystems. 2022;7(3):e01489-21. doi:10.1128/msystems.01489-21