Comprehensive profiles and diagnostic value of menopausal-specific gut microbiota in premenopausal breast cancer Original paper

What was studied

This original research article investigated menopausal-specific gut microbiota patterns in premenopausal breast cancer, a focus that remains underexplored despite rising disease incidence in younger Asian women. Comprehensive profiles of the gut microbiome were generated using 16S rRNA sequencing, and the work emphasized how menopausal status shapes distinct microbial signatures. The study also assessed whether these signatures could serve as diagnostic biomarkers capable of distinguishing breast cancer patients from age-matched controls.

Who was studied

The study enrolled 267 Taiwanese women: 100 premenopausal breast cancer patients, 100 postmenopausal breast cancer patients, and 67 healthy controls matched by age and menopausal status. All patients had newly diagnosed stage I–II disease and provided stool samples before receiving any treatment. Clinical data—including age, BMI, tumor grade, stage, receptor status, and tumor size—were collected to evaluate relationships between microbiota and disease characteristics. This cohort structure allowed precise comparison of microbiota alterations specific to menopausal physiology.

Most important findings

Diversity analysis revealed that α-diversity was significantly reduced only in premenopausal breast cancer, indicating a distinct dysbiosis not seen in postmenopausal disease. Microbial composition (β-diversity) differed across all groups, underscoring broad community shifts associated with cancer. Fourteen discriminatory taxa emerged across menopausal strata. In premenopausal breast cancer, Bifidobacterium longum, B. bifidum, and B. adolescentis were markedly depleted, while Anaerostipes and Bacteroides fragilis were enriched. This pattern suggests loss of protective SCFA-producing and antitumor bacteria alongside expansion of taxa linked to inflammation and estrogen-related pathways. Conversely, postmenopausal breast cancer showed elevated Proteobacteria and Klebsiella pneumoniae—both dysbiosis markers—and reduced Akkermansia muciniphila and Phascolarctobacterium, taxa generally associated with metabolic health. Universal breast cancer signatures included loss of Faecalibacterium prausnitzii and Ruminococcus gnavus and increased Sutterella and Haemophilus parainfluenzae, reflecting shared microbial disruptions regardless of menopausal status. Diagnostic modeling achieved strong performance, with AUC values of 0.826 for premenopausal and 0.887 for postmenopausal states, demonstrating that these microbiome shifts have measurable predictive value.

Key implications

The study identifies actionable links between menopausal physiology, microbial ecology, and breast cancer biology. Premenopausal disease appears driven by loss of beneficial taxa and gain of procarcinogenic microbes such as Bacteroides fragilis, potentially influencing estrogen metabolism, inflammation, and oncogenic signaling. Postmenopausal disease reflects a shift toward pathogen-associated dysbiosis. These findings highlight the relevance of incorporating menopausal status into microbiome-based diagnostics and support the development of preventive or restorative interventions aimed at “rebiosis.” The distinctiveness of premenopausal microbiome alterations positions these microbial signatures as promising tools for early detection in younger populations.

Citation

Hou MF, Ou-Yang F, Li CL, et al. Comprehensive profiles and diagnostic value of menopausal-specific gut microbiota in premenopausal breast cancer. Experimental & Molecular Medicine. 2021;53:1636-1646. doi:10.1038/s12276-021-00686-9