{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T14:47:34Z","timestamp":1783608454398,"version":"3.55.0"},"reference-count":42,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T00:00:00Z","timestamp":1752105600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"2025 Open Research Grants\u2014Sichuan Clinical Research Center for Medical Imaging (Dazhou)","award":["YXYX2504"],"award-info":[{"award-number":["YXYX2504"]}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Microorganisms"],"abstract":"<jats:p>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 &lt; 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.<\/jats:p>","DOI":"10.3390\/microorganisms13071632","type":"journal-article","created":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T15:36:58Z","timestamp":1752161818000},"page":"1632","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Temporal and Spatial Dynamics of Tumor\u2013Host Microbiota in Breast Cancer Progression"],"prefix":"10.3390","volume":"13","author":[{"given":"Qi","family":"Xu","sequence":"first","affiliation":[{"name":"Ocean College, Zhejiang University, Zhoushan 316021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aikun","family":"Fu","sequence":"additional","affiliation":[{"name":"Sichuan Clinical Research Center for Medical Imaging, Dazhou 635000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Wang","sequence":"additional","affiliation":[{"name":"Ocean College, Zhejiang University, Zhoushan 316021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhizhen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Ocean College, Zhejiang University, Zhoushan 316021, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,10]]},"reference":[{"key":"ref_1","first-page":"11450","article-title":"Impact of COVID-19 on the relapse and reawakening of dormant tumor cells in breast cancer","volume":"8","author":"Rastogi","year":"2020","journal-title":"Nveonat. Volatiles Essent Oils J. Nveo."},{"key":"ref_2","first-page":"209","article-title":"Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"71","author":"Sung","year":"2021","journal-title":"CA Cancer J. Clin."},{"key":"ref_3","first-page":"524","article-title":"Breast Cancer Statistics","volume":"72","author":"Giaquinto","year":"2022","journal-title":"CA Cancer J. Clin."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Di Modica, M., Arlotta, V., Sfondrini, L., Tagliabue, E., and Triulzi, T. (2022). The Link Between the Microbiota and HER2+ Breast Cancer: The New Challenge of Precision Medicine. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.947188"},{"key":"ref_5","first-page":"177","article-title":"Gut and Breast Microbiota as Endocrine Regulators of Hormone Receptor-positive Breast Cancer Risk and Therapy Response","volume":"164","author":"Alana","year":"2023","journal-title":"Endocrinology"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Hieken, T.J., Chen, J., Hoskin, T.L., Walther-Antonio, M., Johnson, S., Ramaker, S., Xiao, J., Radisky, D.C., Knutson, K.L., and Kalari, K.R. (2016). The Microbiome of Aseptically Collected Human Breast Tissue in Benign and Malignant Disease. Sci. Rep., 6.","DOI":"10.1038\/srep30751"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Hadzega, D., Minarik, G., Karaba, M., Kalavska, K., Benca, J., Ciernikova, S., Sedlackova, T., Nemcova, P., Bohac, M., and Pindak, D. (2021). Uncovering microbial composition in human breast cancer primary tumor tissue using transcriptomic rna-seq. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22169058"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"3007","DOI":"10.1128\/AEM.00242-14","article-title":"Microbiota of Human Breast Tissue","volume":"80","author":"Urbaniak","year":"2014","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_9","first-page":"1027","article-title":"Microbiota composition in bilateral healthy breast tissue and breast tumors","volume":"31","author":"Klann","year":"2020","journal-title":"Cancer Causes Control."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Furuta, S. (2024). Microbiome-Stealth Regulator of Breast Homeostasis and Cancer Metastasis. Cancers, 16.","DOI":"10.20944\/preprints202408.1643.v1"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1186\/s13058-023-01677-6","article-title":"Exploring breast tissue microbial composition and the association with breast cancer risk factors","volume":"25","author":"German","year":"2023","journal-title":"Breast Cancer Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1186\/s42269-020-00447-0","article-title":"Sphingomonadaceae: Protective against breast cancer?","volume":"44","author":"Alade","year":"2020","journal-title":"Bull. Natl. Res. Cent."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1038\/nri2417","article-title":"Mammalian glycosylation in immunity","volume":"8","author":"Marth","year":"2008","journal-title":"Nat. Rev. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2091","DOI":"10.1007\/s00726-017-2494-2","article-title":"The role of methionine on metabolism, oxidative stress, and diseases","volume":"49","author":"Li","year":"2017","journal-title":"Amino Acids."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Yang, Y., Fukui, R., Jia, H., and Kato, H. (2021). Amaranth Supplementation Improves Hepatic Lipid Dysmetabolism and Modulates Gut Microbiota in Mice Fed a High-Fat Diet. Foods, 10.","DOI":"10.3390\/foods10061259"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Milton-Laskibar, I., Cuevas-Sierra, A., Portillo, M.P., and Mart\u00ednez, J.A. (2022). Effects of Resveratrol Administration in Liver Injury Prevention as Induced by an Obesogenic Diet: Role of Ruminococcaceae. Biomedicines, 10.","DOI":"10.3390\/biomedicines10081797"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"5039","DOI":"10.1128\/AEM.01235-16","article-title":"The microbiota of breast tissue and its association with breast cancer","volume":"82","author":"Urbaniak","year":"2016","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"106856","DOI":"10.1016\/j.phrs.2023.106856","article-title":"Expanding germ-organ theory: Understanding non-communicable diseases through enterobacterial translocation","volume":"194","author":"Boopathi","year":"2023","journal-title":"Pharmacol. Res."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Deplanche, M., Mouhali, N., Nguyen, M.-T., Cauty, C., Ezan, F., Diot, A., Raulin, L., Dutertre, S., Langouet, S., and Legembre, P. (2019). Staphylococcus aureus induces DNA damage in host cell. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-44213-3"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1945","DOI":"10.1016\/j.ccell.2023.09.012","article-title":"Tumor-resident Lactobacillus iners confer chemoradiation resistance through lactate-induced metabolic rewiring","volume":"41","author":"Colbert","year":"2023","journal-title":"Cancer Cel."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1356","DOI":"10.1016\/j.cell.2022.02.027","article-title":"Tumor-resident intracellular microbiota promotes metastatic colonization in breast cancer","volume":"185","author":"Fu","year":"2022","journal-title":"Cell"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1038\/nature09944","article-title":"Enterotypes of the human gut microbiome","volume":"473","author":"Arumugam","year":"2011","journal-title":"Nature"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Kashtanova, D.A., Tkacheva, O.N., Doudinskaya, E.N., Strazhesko, I.D., Kotovskaya, Y.V., Popenko, A.S., Tyakht, A.V., and Alexeev, D.G. (2018). Gut Microbiota in Patients with Different Metabolic Statuses: Moscow Study. Microorganisms, 6.","DOI":"10.3390\/microorganisms6040098"},{"key":"ref_24","first-page":"839","article-title":"Preliminary study on intestinal Flora in patients with breast cancer by Miseq high-throughput sequencing","volume":"40","author":"Abulaiti","year":"2017","journal-title":"J. Xinjiang Med. Univ."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1007\/s10096-020-04036-x","article-title":"Changes of intestinal microflora of breast cancer in premenopausal women","volume":"40","author":"He","year":"2021","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1138","DOI":"10.1158\/2159-8290.CD-20-0537","article-title":"A Procarcinogenic Colon Microbe Promotes Breast Tumorigenesis and Metastatic Progression and Concomitantly Activates Notch and \u03b2 Catenin Axes ETBF Promotes Breast Carcinogenesis","volume":"11","author":"Parida","year":"2021","journal-title":"Cancer Discov."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1080\/19490976.2015.1134082","article-title":"Formation of short chain fatty acids by the gut microbiota and their impact on human metabolism","volume":"7","author":"Morrison","year":"2016","journal-title":"Gut Microbes"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e2200470","DOI":"10.1002\/advs.202200470","article-title":"Microbiota in tumors: From understanding to application","volume":"9","author":"Xie","year":"2022","journal-title":"Adv. Sci."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"973","DOI":"10.1126\/science.aay9189","article-title":"The human tumor microbiome is composed of tumor type-specific intracellular bacteria","volume":"368","author":"Nejman","year":"2020","journal-title":"Science."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1128\/iai.23.2.403-411.1979","article-title":"Translocation of certain indigenous bacteria from the gastrointestinal tract to the mesenteric lymph nodes and other organs in a gnotobiotic mouse model","volume":"23","author":"Berg","year":"1979","journal-title":"Infect Immun."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1007\/978-1-4615-4143-1_2","article-title":"Bacterial translocation from the gastrointestinal tract","volume":"473","author":"Berg","year":"1999","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1016\/0016-5085(94)90110-4","article-title":"The prevalence of gut translocation in humans","volume":"107","author":"Sedman","year":"1994","journal-title":"Gastroenterology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"eabo2003","DOI":"10.1126\/sciimmunol.abo2003","article-title":"Immune checkpoint blockade induces gut microbiota translocation that augments extraintestinal antitumor immunity","volume":"8","author":"Choi","year":"2023","journal-title":"Sci. Immunol."},{"key":"ref_34","first-page":"306","article-title":"The mathematical theory of communication","volume":"14","author":"Shannon","year":"1997","journal-title":"MD Comput."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1007\/s002489900050","article-title":"Temporal changes in the bacterial communities of soil, rhizosphere, and endorhiza associated with field-grown cucumber (Cucumis sativus L.)","volume":"34","author":"Mahaffee","year":"1997","journal-title":"Microb. Ecology"},{"key":"ref_36","first-page":"373","article-title":"Systematic analysisi of disordered microbiota in tumor tissues and intestine of breast cancer patients","volume":"35","author":"Wang","year":"2023","journal-title":"Chin. J. Microecol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Xuan, C., Shamonki, J.M., Chung, A., DiNome, M.L., Chung, M., Sieling, P.A., and Lee, D.J. (2014). Microbial dysbiosis is associated with human breast cancer. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0083744"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1038\/sj.icb.7100155","article-title":"Clinical relevance of TLR2, TLR4, CD14 and FcgammaRIIA gene polymorphisms in Streptococcus pneumoniae infection","volume":"86","author":"Yuan","year":"2008","journal-title":"Immunol. Cell Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1046\/j.1365-2184.1999.3210049.x","article-title":"Correlation between cholesterol esterification, MDR1 gene expression and rate of cell proliferation in CEM and MOLT4 cell lines","volume":"32","author":"Batetta","year":"1999","journal-title":"Cell Prolif."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1166","DOI":"10.1080\/21505594.2022.2097417","article-title":"Delivery, structure, and function of bacterial genotoxins","volume":"13","author":"Du","year":"2022","journal-title":"Virulence"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1551","DOI":"10.1086\/652763","article-title":"Treatment of infectious mastitis during lactation: Antibiotics versus oral administration of lactobacilli isolated from breast milk","volume":"50","author":"Arroyo","year":"2010","journal-title":"Clin. Infect Dis."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.trecan.2020.01.019","article-title":"Mutagenesis by microbe: The role of the microbiota in shaping the cancer genome","volume":"6","author":"Barrett","year":"2020","journal-title":"Trends Cancer"}],"updated-by":[{"DOI":"10.3390\/microorganisms13112593","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2025,7,10]],"date-time":"2025-07-10T00:00:00Z","timestamp":1752105600000}}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/13\/7\/1632\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,19]],"date-time":"2025-11-19T09:14:49Z","timestamp":1763543689000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/13\/7\/1632"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,10]]},"references-count":42,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,7]]}},"alternative-id":["microorganisms13071632"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms13071632","relation":{},"ISSN":["2076-2607"],"issn-type":[{"value":"2076-2607","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,10]]}}}