Xu Qi, Fu Aikun, Wang Nan, Zhang Zhizhen
Ocean College, Zhejiang University, Zhoushan 316021, China.
Sichuan Clinical Research Center for Medical Imaging, Dazhou 635000, China.
Microorganisms. 2025 Jul 10;13(7):1632. doi: 10.3390/microorganisms13071632.
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 ( < 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 (, , ) colonized both cecal contents and the spleen, with 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.
破译乳腺癌进展过程中细菌的时空分布，可能为制定基于细菌的治疗策略提供关键见解。利用小鼠乳腺癌模型，我们通过16S rRNA基因测序，在肿瘤植入后3周、5周和7周，对乳腺肿瘤组织、乳腺、脾脏和盲肠内容物中的微生物群进行了纵向分析。乳腺肿瘤进展与肺转移和脾肿大相关，伴有明显的组织特异性微生物动态变化。虽然肿瘤、乳腺组织和盲肠内容物中的α多样性保持稳定，但脾脏中的α多样性显著增加（<0.05）。纵向分析显示，肿瘤、乳腺组织和盲肠内厚壁菌门丰度逐渐上升，变形菌门丰度下降，而脾脏微生物群显示出独特的门水平组成变化。在乳腺肿瘤进展过程中，在门、属和种水平上鉴定出了组织和时间依赖性的微生物特征。引人注目的是，脾脏微生物群整合了几乎所有在其他部位富集的属，表明其作为微生物库的潜在作用。与肠道相关的属（如、、）在盲肠内容物和脾脏中均有定殖，在所有组织中均持续检测到，提示微生物易位。脾脏表现出独特的多样性升高和组成变化，可能导致脾肿大。这些结果描绘了微生物群易位和定殖的轨迹，并证明了乳腺肿瘤发生过程中组织特异性的微生物重新分布，为推进针对微生物组的癌症治疗提供了有价值的启示。
