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, a...

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Main Authors: Qi Xu, Aikun Fu, Nan Wang, Zhizhen Zhang
Format: Article
Language:English
Published: MDPI AG 2025-07-01
Series:Microorganisms
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Online Access:https://www.mdpi.com/2076-2607/13/7/1632
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author Qi Xu
Aikun Fu
Nan Wang
Zhizhen Zhang
author_facet Qi Xu
Aikun Fu
Nan Wang
Zhizhen Zhang
author_sort Qi Xu
collection DOAJ
description 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 (<i>p</i> < 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 (<i>Lactobacillus</i>, <i>Desulfovibrio</i>, <i>Helicobacter</i>) colonized both cecal contents and the spleen, with <i>Lactobacillus</i> 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.
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spelling doaj-art-bbfdd1b13df74b9ba6ecf1127168087a2025-08-20T03:35:38ZengMDPI AGMicroorganisms2076-26072025-07-01137163210.3390/microorganisms13071632Temporal and Spatial Dynamics of Tumor–Host Microbiota in Breast Cancer ProgressionQi Xu0Aikun Fu1Nan Wang2Zhizhen Zhang3Ocean College, Zhejiang University, Zhoushan 316021, ChinaSichuan Clinical Research Center for Medical Imaging, Dazhou 635000, ChinaOcean College, Zhejiang University, Zhoushan 316021, ChinaOcean College, Zhejiang University, Zhoushan 316021, ChinaDeciphering 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 (<i>p</i> < 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 (<i>Lactobacillus</i>, <i>Desulfovibrio</i>, <i>Helicobacter</i>) colonized both cecal contents and the spleen, with <i>Lactobacillus</i> 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.https://www.mdpi.com/2076-2607/13/7/1632breast tumorbacteriasplenomegalygut microbiotaspatiotemporal trajectory progression
spellingShingle Qi Xu
Aikun Fu
Nan Wang
Zhizhen Zhang
Temporal and Spatial Dynamics of Tumor–Host Microbiota in Breast Cancer Progression
Microorganisms
breast tumor
bacteria
splenomegaly
gut microbiota
spatiotemporal trajectory progression
title Temporal and Spatial Dynamics of Tumor–Host Microbiota in Breast Cancer Progression
title_full Temporal and Spatial Dynamics of Tumor–Host Microbiota in Breast Cancer Progression
title_fullStr Temporal and Spatial Dynamics of Tumor–Host Microbiota in Breast Cancer Progression
title_full_unstemmed Temporal and Spatial Dynamics of Tumor–Host Microbiota in Breast Cancer Progression
title_short Temporal and Spatial Dynamics of Tumor–Host Microbiota in Breast Cancer Progression
title_sort temporal and spatial dynamics of tumor host microbiota in breast cancer progression
topic breast tumor
bacteria
splenomegaly
gut microbiota
spatiotemporal trajectory progression
url https://www.mdpi.com/2076-2607/13/7/1632
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AT aikunfu temporalandspatialdynamicsoftumorhostmicrobiotainbreastcancerprogression
AT nanwang temporalandspatialdynamicsoftumorhostmicrobiotainbreastcancerprogression
AT zhizhenzhang temporalandspatialdynamicsoftumorhostmicrobiotainbreastcancerprogression