Effects of the Intestinal Microbiome and Metabolites on Neoadjuvant Chemotherapy Efficacy in Breast Cancer

Abstract

Background: Imbalances in the intestinal microbiome are closely associated with the occurrence and development of cancer, and can affect tumorigenesis by influencing the inflammatory response, regulating the immune system, producing specific metabolites, and participating in tumor signaling pathways. Methods: This study investigated the relationships among intestinal microbial dynamics, metabolite profiles, and neoadjuvant chemotherapy (NAC) outcomes in patients with breast cancer. Patients were stratified by Miller-Payne (MP) grade into good (MP 4–5) or poor (MP 1–3) responders. Fecal samples from patients (pre- and post-NAC) were analyzed via 16S rRNA sequencing and untargeted metabolic analysis. Results: After neoadjuvant chemotherapy, the species diversity and abundance of the intestinal microbiome significantly decreased, and these trends were not correlated with neoadjuvant chemotherapy efficacy. Fusobacterium abundance remained significantly higher in poor responders than good responders post-NAC, thus suggesting its association with chemoresistance. The Firmicutes/Bacteroidetes ratio was lower in patients with breast cancer than healthy controls, and was correlated with the therapeutic response: this ratio rose post-NAC but remained suboptimal in poor responders. Untargeted metabolomics identified upregulated amino acids (Thr-Thr and histidine) in poor responders and elevated lipids (C17-sphinganine) in good responders. ROC (receiver operating characteristic curve) analysis validated these metabolites (AUC >0.7) as predictive biomarkers. KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis highlighted enrichment in mTOR signaling, endocrine resistance, and estrogen signaling pathways. Conclusions: These findings underscore the intestinal microbiome’s potential as a predictor of NAC efficacy and a therapeutic target. Modulating Fusobacterium or metabolite pathways may enhance chemotherapy response.

Keywords

Breast cancer / intestinal microbiome / metabolites / neoadjuvant chemotherapy

References

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