Gut microbial and functional signatures in breast cancer: an integrated metagenomic and machine learning approach to...

Breast cancer is associated with significant restructuring of the gut ecosystem. Gut microbial composition and function may influence cancer development and progression through immune modulation, metabolic regulation, and inflammation-related pathways.

Using shotgun metagenomic sequencing of fecal samples from 38 stage I-III breast cancer patients and 36 age- and body mass index-matched healthy controls. Machine learning models were constructed to evaluate the diagnostic potential of integrated microbial and metabolic features.

Significant alterations were observed in gut microbiota composition, including depletion of beneficial taxa (Limosilactobacillus fermentum, Blautia sp.) and enrichment of Prevotella copri. Pathways involved in short-chain fatty acid and purine metabolism were reduced. The gut phageome exhibited structural changes and altered correlations with bacterial hosts. Predictive analysis revealed depletion of short-chain fatty acids (butyrate, propionate), purine intermediates (hypoxanthine, xanthine), and nicotinate in patients. A machine learning model integrating microbial and predicted metabolic features achieved an area under the curve values of 0.78 in the discovery cohort and 0.73 (recall = 0.74) in an independent validation cohort.

Coordinated gut microbiome, phageome, and metabolome alterations characterize breast cancer, offering potential non-invasive biomarkers and mechanistic insights for disease detection and intervention.