Temporal and Spatial Dynamics of Tumor-Host Microbiota in Breast Cancer Progression

Deciphering the spatiotemporal distribution of bacteria during breast cancer progression may provide critical insights for developing bacterial-based therapeutic strategies. Using a murine breast cancer model, we longitudinally profiled the microbiota in breast tumor tissue, mammary gland, spleen, and cecal contents at 3-, 5-, and 7- weeks post-tumor implantation through 16S rRNA gene sequencing. Breast tumor progression was associated with lung metastasis and splenomegaly, accompanied by distinct tissue-specific microbial dynamics. While alpha diversity remained stable in tumors, mammary tissue, and cecal contents, it significantly increased in the spleen (p < 0.05). Longitudinal analysis revealed a progressive rise in Firmicutes and a decline in Proteobacteria abundance within tumors, mammary tissue, and cecum, whereas the spleen microbiota displayed unique phylum-level compositional shifts. Tissue- and time-dependent microbial signatures were identified at phylum, genus, and species levels during breast tumor progression. Strikingly, the spleen microbiota integrated nearly all genera enriched in other sites, suggesting its potential role as a microbial reservoir. Gut-associated genera (Lactobacillus, Desulfovibrio, Helicobacter) colonized both cecal contents and the spleen, with Lactobacillus consistently detected across all tissues, suggesting microbial translocation. The spleen exhibited uniquely elevated diversity and compositional shifts, potentially driving splenomegaly. These results delineated the trajectory of microbiota translocation and colonization, and demonstrated tissue-specific microbial redistribution during breast tumorigenesis, offering valuable implications for advancing microbiome-targeted cancer therapies.