Breast cancer but not the menopausal status is associated with small changes of the gut microbiota Original paper

What was studied?

This original research study investigated the focus keyphrase: gut microbiota in breast cancer, specifically examining whether menopausal status influenced gut microbial composition in women with newly diagnosed breast cancer. Using deep shotgun metagenomic sequencing of fecal samples, the researchers compared microbial diversity, taxonomic composition, enterotypes, and microbial metabolic pathways across premenopausal and postmenopausal breast cancer patients and matched cancer-free controls. They aimed to clarify whether breast cancer-associated dysbiosis reflects underlying hormonal differences or disease-specific microbial signatures.

Who was studied?

The study enrolled 174 Polish women: 88 newly diagnosed breast cancer patients and 86 cancer-free controls. Participants were subgrouped by menopausal status using STRAW criteria: 47 pre/perimenopausal cases and 51 controls, and 41 postmenopausal cases and 35 controls. Tumor histology was predominantly ductal, with broad representation of luminal A, luminal B, HER2-enriched, and triple-negative subtypes. Women with recent antibiotic use or gastrointestinal disease were excluded. Fecal samples were collected before treatment initiation.

Most important findings

Across 460 identified species, the overall gut microbiota structure did not differ meaningfully between pre- and postmenopausal women, regardless of cancer status. Instead, the dominant signature was a breast cancer–associated dysbiosis present in both menopausal groups. The Shannon diversity index remained largely unchanged, but beta-diversity clearly distinguished breast cancer patients from matched controls at both genus and species levels. Controls were enriched in Bacteroides-dominant enterotypes, whereas breast cancer patients showed more Prevotella and Alistipes enterotypes. Taxa differing between premenopausal cases and controls included reduced Gemmiger, Ruthenibacterium, Bifidobacterium, and multiple Actinobacteria-related families. In postmenopausal women, cancer cases showed decreased Bacteroides thetaiotaomicron, Parabacteroides distasonis, Blautia obeum, and Dorea, alongside increased Agathobaculum and Enterorhabdus. Machine-learning models consistently identified Faecalibacterium prausnitzii, Alistipes finegoldii, Parabacteroides distasonis, and Enterorhabdus caecimuris as key discriminatory species. Metabolic pathway analysis revealed minimal functional disruption: premenopausal cancer patients showed downregulated NAD salvage pathways and upregulated hexitol fermentation pathways, while postmenopausal cases exhibited increased glutaryl-CoA degradation.

Key implications

These findings show that breast cancer—not menopausal status—drives subtle but consistent gut microbiome alterations. The microbial signatures point toward reduced short-chain-fatty-acid–producing taxa, disrupted estrogen-modulating bacteria, and shifts in enterotypes associated with systemic inflammation. Importantly, machine-learning outputs suggest that microbial profiles may hold diagnostic value regardless of menopausal status. The study strengthens the evidence that gut microbiota participates in breast cancer pathophysiology, but also highlights high inter-individual variability and the need for geographically diverse cohorts.

Citation

Zeber-Lubecka N, Kulecka M, Jagiełło-Gruszfeld A, Dąbrowska M, Kluska A, Piątkowska M, et al. Breast cancer but not the menopausal status is associated with small changes of the gut microbiota. Frontiers in Oncology. 2024;14:1279132. doi:10.3389/fonc.2024.1279132