Abstract:
Breast cancer remains the leading cause of cancer-related deaths among women, despite
advancements in diagnostic and treatment modalities. Recent progress in metagenomic
analysis has highlighted the potential influence of the gut microbiome on human health and
disease outcomes, including breast cancer. Additionally, metabolites produced by gut
microbial communities have shown health benefits and potential anticancer activity.
However, the specific mechanisms by which these secondary metabolites affect breast
cancer are not well understood. This study aimed to investigate the gut microbiome's taxa
and secondary metabolites in breast cancer patients. It used machine learning approaches
to associate these factors with clinical metadata, elucidating their role in breast cancer.
Utilizing metagenomic analysis, this research explored the gut taxonomic landscape of BC
patients, while antiSMASH analysis was employed to identify metabolite biosynthetic
gene clusters. Machine Learning models were applied to associate these taxa and
metabolite BGCs with clinical metadata. This study identified 471 species and 40
metabolites in the metagenomic samples of breast cancer patients. The statistical analysis
further revealed a significant association (p<0.05) between the species E. coli and the
metabolites siderophore and thiopeptide with breast cancer groups. The random forest
model outperformed with a combined area under the curve of 78% in classifying samples
into breast cancer groups and healthy controls. This research proposes a hypothesis of the
underlying mechanism, supported by literature and statistical evidence (p<0.05), that under
iron-limiting conditions, E. coli produces siderophores to scavenge iron from the host,
resulting in increased angiogenesis and breast cancer progression due to the iron scarcity
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of the host. While this hypothesis requires further functional analysis, it opens new avenues
for breast cancer therapy development. This study provides a novel perspective on the gut
microbiome's role in breast cancer, suggesting potential therapeutic targets and strategies
for future research
