Intratumoural microbial metabolites in breast cancer: A longitudinal study on association with metastatic progression

Delayed diagnosis and metastasis remain major challenges in breast cancer. While the gut microbiome's influence on tumour progression is established, the presence and role of intratumoural microbial metabolites in breast cancer and their association with metastasis remain unexplored. Paired tumour and adjacent tissues were collected from 50 breast cancer patients at baseline. Patients were followed for five years; 10 who developed distant metastasis were classified as pre-metastatic, and 10 who remained disease-free formed the non-metastatic group. Untargeted LC–MS/MS-based metabolomics was performed to profile host and microbial metabolites. Multivariate analysis and pathway enrichment were used to identify discriminatory signatures. Elevated levels of carnitine, indole, tryptophan-derived metabolites, ceramides and polyamines were observed in tumour tissues on comparison with adjacent tissues. Interestingly, these metabolites were downregulated in tumour tissues of patients who progressed for metastasis (pre-metastatic) with increase in N-methylhistamine and taurolithocholic acid sulfate, suggesting metabolic reprogramming during metastatic priming. Baseline host–microbial metabolic disruptions in breast tumours are linked to future metastasis, with metabolites like indoles, bile acids, and polyamines showing promise as early biomarkers and therapeutic targets in precision oncology.