Gut Microbiome Predicts Breast Cancer Chemo Response

The gut microbiome’s composition appears to play a crucial role in predicting the effectiveness of neoadjuvant chemotherapy (NAC) for breast cancer patients, potentially offering a new therapeutic avenue.

Microbiome Shift Post-Chemo

Research published in BIO Integration suggests that after neoadjuvant chemotherapy, the diversity and abundance of intestinal species significantly decreased; however, these shifts didn’t correlate with chemo efficacy. According to the study, Fusobacterium abundance remained significantly higher in poor responders compared to good responders after NAC, indicating a potential link with chemoresistance.

Ratio Imbalance

The Firmicutes/Bacteroidetes ratio was lower in breast cancer patients compared to healthy individuals and correlated with therapeutic response. While this ratio increased after NAC, it remained suboptimal in poor responders.

Metabolic Markers Identified

Untargeted metabolomics pinpointed upregulated amino acids, specifically threonine-threonine (Thr-Thr) and histidine, in patients who responded poorly to chemotherapy. Conversely, elevated levels of lipids, specifically C17-sphinganine, were found in patients who responded well. According to a recent study by the National Cancer Institute, metabolic profiling is becoming increasingly important to predict drug efficacy, which may improve cancer treatment outcomes (NCI, 2024). These metabolites demonstrated potential as predictive biomarkers, confirmed by ROC analysis with an AUC greater than 0.7.

Pathway Analysis

Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis highlighted enrichment in mTOR signaling, endocrine resistance, and estrogen signaling pathways, offering potential targets for improving treatment outcomes.

Potential Therapeutic Target

The study, led by J. Fu, suggests the gut microbiome’s potential as both a predictor of NAC efficacy and a therapeutic target. Modulating Fusobacterium or specific metabolite pathways might improve how patients respond to chemotherapy.

According to the study “Effects of the Intestinal Microbiome and Metabolites on Neoadjuvant Chemotherapy Efficacy in Breast Cancer,” these imbalances in the intestinal microbiome are closely associated with the occurrence and development of cancer, and can affect tumorigenesis.

Study Details

The research stratified patients based on Miller-Payne (MP) grade, categorizing them as good (MP 4-5) or poor (MP 1-3) responders. Fecal samples, collected both before and after NAC, underwent analysis using 16S rRNA sequencing and untargeted metabolic analysis.