Objective:

To systematically characterize the dynamic changes in the gut microbiota and serum metabolome from benign breast disease to breast cancer and postchemotherapy, and evaluate its potential in diagnosis and disease monitoring, particularly focusing on specific microbial and metabolic alterations.

Key Findings:

• Significant separation of microbial community structure among BBD, BC, and PCBC groups, indicating distinct microbial profiles.
• BBD group enriched with beneficial bacteria; BC group showed enrichment of inflammation-associated genera; PCBC group accumulated opportunistic pathogens, highlighting the shift in microbial dynamics.
• Metabolomic profiles indicated disruption in energy, amino acid, and lipid metabolism in BC, with adaptive pathways activated in PCBC, suggesting metabolic reprogramming.
• Differentially abundant metabolites showed potential as biomarkers with AUC values greater than 0.75, indicating their diagnostic relevance.

Interpretation:

The study reveals a transition in the gut microbiota and serum metabolome from a protective state in benign conditions to an inflammatory state in cancer, with significant implications for diagnosis and monitoring of breast cancer progression.

Limitations:

• The study is limited to female participants, which may affect generalizability to other populations.
• Cross-sectional design may not capture all dynamic changes over time, limiting causal interpretations.

Conclusion:

The integrated multiomics model characterizes biological differences across breast disease stages and identifies potential biomarkers for clinical assessment, providing insights into microbiome-related mechanisms in breast cancer.