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

What was studied?

This study investigated the composition and functional potential of the human mammary microbiota in healthy breast tissues and those associated with breast cancer development. The researchers focused on tissue samples collected before cancer diagnosis (prediagnostic or PD), as well as adjacent normal (AN) and tumor (T) tissues from breast cancer patients. Using 16S rRNA sequencing and functional metagenomic predictions, they aimed to identify bacterial dysbiosis and metabolic changes associated with breast cancer progression.

Who was studied?

A total of 141 women were included in the study, contributing 159 breast tissue samples. These included 49 samples from healthy individuals (H), 15 from prediagnostic cases (PD), 49 from adjacent normal tissues (AN), and 46 from tumor tissues (T). The prediagnostic samples were obtained from women who later developed breast cancer, allowing researchers to explore early microbial changes.

What were the most important findings?

The study revealed significant bacterial dysbiosis and metabolic reprogramming in PD, AN, and T tissues compared to healthy tissues. Prediagnostic tissues exhibited an intermediary bacterial composition between healthy and cancerous tissues. Shifts in specific bacterial families such as Bacillaceae, Streptococcaceae, and Corynebacteriaceae were detected in PD tissues and were more pronounced in AN and T tissues. Functional analysis revealed reduced bacterial metabolic activities, particularly pathways related to xenobiotics degradation, which could otherwise protect against carcinogenesis. Additionally, altered correlations between host gene expression and microbial functions were observed, highlighting potential early microbial responses to tumor microenvironments.

What are the greatest implications of this study?

This research highlights the mammary microbiota’s potential as a critical biomarker for early breast cancer detection and risk stratification by revealing bacterial dysbiosis and metabolic reprogramming in prediagnostic tissues, suggesting microbial changes may precede clinical symptoms or histological abnormalities. The identification of an intermediary microbiota composition in prediagnostic tissues supports the microbiome’s role in early cancer development, indicating microbial shifts as potential early drivers or responders to tumorigenesis. A significant reduction in metabolic functions, such as xenobiotic degradation, in cancer-associated tissues implies a diminished microbial ability to detoxify carcinogens, increasing susceptibility to tumor formation. Altered correlations between microbial taxa and host gene expression further suggest dynamic interactions influencing immune responses, inflammation, and cellular proliferation, with positive associations between microbial functions and tumor-related genes pointing to potential mechanistic links to cancer progression.

These findings not only enhance understanding of the microbiota’s role in breast cancer but also offer clinical translation opportunities, including the development of non-invasive diagnostic tools based on prediagnostic microbial signatures, microbiome-modulating therapies to target dysbiosis, and therapeutic interventions aimed at restoring protective bacterial functions and reducing cancer risk.