Breast cancer in postmenopausal women is associated with an altered gut metagenome Original paper

What was studied?

This original research article investigated the altered gut metagenome in postmenopausal women with breast cancer, a focus central to the breast cancer gut metagenome keyphrase. Using shotgun metagenomic sequencing, the authors examined how microbial composition and functional gene profiles differ between breast cancer patients and healthy controls. The study sought to clarify whether distinct microbial signatures, metabolic functions, or virulence-associated genes define the gut microbiota of breast cancer patients, particularly in the postmenopausal state. Their working hypothesis was that cancer-associated dysbiosis might influence systemic immunity, estrogen metabolism, and inflammation—pathways increasingly implicated in breast carcinogenesis.

Who was studied?

The cohort included 133 women divided by menopausal status and disease condition: 18 premenopausal patients, 25 premenopausal controls, 44 postmenopausal patients, and 46 postmenopausal controls. All participants were treatment-naïve at the time of fecal collection, and none had used antibiotics, steroids, probiotics, or herbal medicines for at least three months prior. The population primarily included Han and Zhuang ethnic groups in China. Clinical exclusion criteria removed confounders such as diabetes, inflammatory bowel disease, and infectious conditions, ensuring that detected microbiome alterations reflected disease-associated, not treatment- or comorbidity-driven, differences.

Most important findings

The most striking discovery was that microbial dysbiosis appeared almost exclusively in postmenopausal breast cancer patients, not in premenopausal women. Species richness and beta diversity were significantly increased in postmenopausal patients, and 45 species differed between postmenopausal patients and controls. Pathogenic or opportunistic organisms such as Escherichia coli, Klebsiella sp., Enterococcus gallinarum, Shewanella putrefaciens, and Erwinia amylovora were enriched. Beneficial taxa, including Eubacterium eligens and Lactobacillus vaginalis were depleted—species typically associated with butyrate production and mucosal integrity. Furthermore, functional metagenomic analysis revealed enrichment of genes involved in lipopolysaccharide biosynthesis, iron transport, secretion systems, and phosphotransferase systems in postmenopausal patients. These functions align with pathways known to potentiate inflammation, metabolic imbalance, and carcinogenic processes. Butyrate-synthesis pathways were notably reduced, consistent with depleted Roseburia inulinivorans and related beneficial taxa. Correlations with clinical indices showed weak but reproducible links between enriched bacteria and inflammatory markers such as high-sensitivity C-reactive protein and estradiol levels.

Key implications

This study demonstrates that postmenopausal breast cancer is associated with a distinctive gut metagenomic signature, suggesting potential microbial contributions to cancer risk via estrogen metabolism, chronic inflammation, and immune modulation. While causality cannot be inferred, the magnitude and consistency of dysbiosis underscore the potential for microbial biomarkers in early detection or risk stratification. Reduced butyrate production and increased LPS-associated pathways identify mechanistic targets aligned with known cancer-promoting processes. These insights support the utility of microbiome profiling in precision oncology and highlight the need for longitudinal studies to clarify temporal and causal relationships.

Citation

Zhu J, Liao M, Yao Z, et al. Breast cancer in postmenopausal women is associated with an altered gut metagenome.Microbiome. 2018;6:136. doi:10.1186/s40168-018-0515-3