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High\u2010throughput sequencing has revealed the presence of low\u2010biomass bacteria, fungi, and viruses across diverse malignancies, establishing the intratumoral microbiota as a fundamental TME component. However, evidence remains fragmented across descriptive associations, unclear mechanisms, and early clinical interventions, limiting casual interpretation and clinical translation. This review dissects the host\u2013microbiota\u2013tumor axis from intratumoral origins and colonization to pattern\u2010recognition signaling, including TLR\u2013NF\u2010\u03baB and cGAS\u2013STING, and oncogenic networks such as Wnt\/\u03b2\u2010catenin, JAK\u2013STAT, and PI3K\u2013AKT. Moreover, it also discusses how microbial metabolites like short\u2010chain fatty acids, secondary bile acids, and tryptophan derivatives reshape immune cell phenotypes and tumor cell metabolism. We then synthesize evidence linking microbiota to immune checkpoint blockade, chemotherapy resistance, radiotherapy toxicity, diagnosis, and prognosis. Finally, we compare translational strategies, including fecal microbiota transplantation (FMT), engineered bacteria, oncolytic viruses, and bacteriophages, together with their safety and standardization barriers. By connecting molecular mechanisms with preclinical and clinical evidence, this review comprehensively provides a framework for causal, biomarker\u2010guided microbiota interventions.<\/jats:p>","DOI":"10.1002\/mco2.70994","type":"journal-article","created":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T06:52:12Z","timestamp":1789195932000},"source":"Crossref","is-referenced-by-count":0,"title":["Microbial Signals in Cancer: Dissecting Host\u2013Microbiota\u2013Tumor Interactions and Potential Therapeutic Strategy"],"prefix":"10.1002","volume":"7","author":[{"given":"Juan","family":"Lu","sequence":"first","affiliation":[{"name":"State Key Laboratory For Diagnosis and Treatment of Infectious Diseases National Clinical Research Center for Infectious Diseases Collaborative Innovation Center For Diagnosis and Treatment of Infectious Diseases China\u2010Singapore Belt and Road Joint Laboratory on Infection Research and Drug Development National Medical Center For Infectious Diseases 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