Microbial Signals in Cancer: Dissecting Host-Microbiota-Tumor Interactions and Potential Therapeutic Strategy

Cancers develop within a host ecosystem in which kinds of factors such as gut and tumor-resident microbiota influence the tumor microenvironment (TME) and therapeutic response. High-throughput sequencing has revealed the presence of low-biomass 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-microbiota-tumor axis from intratumoral origins and colonization to pattern-recognition signaling, including TLR-NF-κB and cGAS-STING, and oncogenic networks such as Wnt/β-catenin, JAK-STAT, and PI3K-AKT. Moreover, it also discusses how microbial metabolites like short-chain 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-guided microbiota interventions.