Breast cancer patients from the Midwest region of the United States have reduced levels of short-chain fatty acid-producing gut bacteria Original paper

What was studied?

This original research article examined gut microbiome composition in breast cancer patients from the Midwestern United States to characterize potential disease-related microbial signatures, with emphasis on short-chain fatty acid (SCFA)–producing bacteria. The focus keyphrase SCFA-producing gut bacteria in breast cancer is central to the study’s aim, which was to determine whether breast cancer is associated with a loss of health-promoting anaerobes known for generating butyrate, propionate, and acetate. Using 16S rRNA sequencing of fecal samples and predictive functional profiling (PICRUSt2), the researchers assessed taxonomic differences, bacterial diversity, and metabolic pathway shifts. The investigation addressed regional variability in microbiome structure, adding insight to how microbial dysbiosis may contribute to breast cancer biology, especially regarding SCFA-linked immune, metabolic, and epithelial regulatory pathways.

Who was studied?

The study analyzed stool samples from 22 breast cancer patients and 19 healthy controls, matched for sex, race, and body mass index. Participants were predominantly white Midwestern adults recruited from the University of Iowa. BC patients were older on average and represented a range of clinical stages and treatment histories, though chemotherapy had concluded ≥145 days before sample collection; radiation therapies were completed ≥31 days prior. Most BC patients were receiving hormonal therapy. Healthy controls were female adults recruited separately and screened for recent antibiotic or laxative exposure. These demographics allowed controlled comparison of gut microbial structure while acknowledging age as a potential confounder.

Most important findings

The study found clear gut microbial dysbiosis in breast cancer, characterized by significant reductions in several beneficial SCFA-producing taxa. Beta-diversity analyses showed distinct clustering of BC vs. controls, despite no differences in alpha diversity. Of 519 species identified, 16 differed significantly between groups. Notably reduced in BC were Faecalibacterium prausnitzii, Parabacteroides merdae, Lachnospira pectinoschiza, Lachnoclostridium edouardi, Alistipes spp., and Oscillibacter spp.—all recognized SCFA producers involved in butyrate, propionate, acetate, or valerate formation. These species play key roles in anti-inflammatory signaling, epithelial barrier maintenance, serotonin regulation, and metabolic homeostasis. Machine-learning analysis (Random Forest) confirmed the relevance of many depleted SCFA-producing species. In contrast, BC patients exhibited increased levels of Intestinibacter bartlettii, Faecalitalea spp., Eggerthella lenta, Actinomyces spp., Blautia spp., and Oscillospiraceae species. Some enriched taxa can generate SCFAs but are also associated with inflammatory states. Functional pathway inference revealed decreased pyruvate-to-propionate fermentation and increased acetate-to-methane conversion, collectively suggesting reduced SCFA availability and heightened methane production, a pattern associated with slower intestinal transit, obesity, and systemic inflammation.

Key implications

The findings indicate that Midwest breast cancer patients possess a distinct dysbiosis marked by loss of SCFA-producing gut bacteria and reduced microbial metabolic capacity for SCFA synthesis. This shift may contribute to cancer-related inflammation, metabolic dysfunction, and impaired mucosal immunity, offering a mechanistic connection between gut ecology and breast cancer pathobiology. Reduced SCFA-associated signaling could influence tumor environments through immune modulation and epithelial integrity pathways. The study supports the inclusion of SCFA-producing taxa in microbiome signature databases for breast cancer risk, prognosis, and therapeutic development, underscoring the value of region-specific microbial profiling.

Citation

Shrode RL, Knobbe JE, Cady N, et al. Breast cancer patients from the Midwest region of the United States have reduced levels of short-chain fatty acid-producing gut bacteria.Scientific Reports. 2023;13:526. doi:10.1038/s41598-023-27436-3