{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T06:06:29Z","timestamp":1784700389003,"version":"3.55.0"},"reference-count":119,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>\n                    Brain metastases (BrM) develop within a highly specialized central nervous system niche shaped by the blood\u2013brain barrier\/blood\u2013tumor barrier, brain-resident stromal cells, myeloid populations, and distinct metabolic constraints. Emerging studies suggest that bacteria-related signals can be detected in primary and metastatic brain tumors; however, their biological meaning remains incompletely defined. In particular, low-biomass brain tissues are highly vulnerable to reagent contamination, environmental carry-over, batch effects, and bioinformatic misclassification, making it essential to distinguish molecular bacterial traces from viable intratumoral bacteria or a\n                    <jats:italic>bona fide<\/jats:italic>\n                    tumor microbiome. In this review, we propose a graded conceptual framework that separates bacterial signals\/elements, intratumoral bacteria, and intratumoral microbiota\/microbiome according to evidentiary strength. We summarize current evidence for the spatial and cellular localization of bacteria-related signals in BrM and discuss potential source models, including primary-tumor carry-over, hematogenous dissemination, gut microbiota\u2013derived metabolites, oral microbial input, and bacterial extracellular vesicles. We further examine how these signals may interact with the BrM tumor microenvironment by influencing tumor-cell stress adaptation, myeloid inflammatory niches, antigen-presentation pathways, vascular-barrier remodeling, and metabolic reprogramming. Particular attention is given to the emerging gut\u2013brain\u2013metastasis axis and to cancer-type-specific contexts in breast cancer, lung cancer, and melanoma brain metastases. From a translational perspective, bacteria-related signals in BrM may eventually contribute to biomarker development, patient stratification, and therapeutic modulation of the microbe\u2013host axis. Nevertheless, current evidence remains insufficient to conclude that BrM broadly harbor stable, active, and clinically actionable microbial communities. Future progress will require multi-source matched cohorts, longitudinal sampling, stringent low-biomass contamination control, absolute quantification, spatial validation, functional models, and explicit separation of microbial presence, viability, and causality. A rigorous evidence-based approach will be essential for moving this field from intriguing associations toward biologically interpretable and clinically meaningful applications.\n                  <\/jats:p>","DOI":"10.3389\/fcell.2026.1893882","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T05:52:52Z","timestamp":1784699572000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Bacteria-related signals in brain metastases: evidence boundaries, tumor-microenvironment remodeling, and translational prospects"],"prefix":"10.3389","volume":"14","author":[{"given":"Guicheng","family":"Kuang","sequence":"first","affiliation":[{"name":"Department of Neurosurgery, West China Hospital, Sichuan University","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhenghaonan","family":"Qiu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, West China Hospital, Sichuan University","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lingxiao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, West China Hospital, Sichuan University","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinjian","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, West China Hospital, Sichuan University","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hang","family":"Ji","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, West China Hospital, Sichuan University","place":["Chengdu, Sichuan, China"]},{"name":"West China School of Medicine, Sichuan University","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, West China Hospital, Sichuan University","place":["Chengdu, Sichuan, China"]},{"name":"West China School of Medicine, Sichuan University","place":["Chengdu, Sichuan, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1038\/s41572-018-0055-y","article-title":"Brain metastases","volume":"5","author":"Achrol","year":"2019","journal-title":"Nat. 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