Biomed Pharmacother. 2025 Sep 17. pii: S0753-3322(25)00753-X. [Epub ahead of print]192 118559
The host microbiota has emerged as a critical modulator of immunity and cancer pathogenesis, influencing not only tumor initiation and progression but also therapeutic responses. This review explores the multifaceted roles of commensal and engineered bacteria in cancer therapy, highlighting the underlying mechanisms of bacterial tumor targeting, immunomodulation, and synergy with immune checkpoint inhibitors. We summarize the contributions of key bacterial genera-such as Clostridium, Bifidobacterium, Listeria, Salmonella, and Escherichia-focusing on their direct oncolytic properties, delivery systems, and interactions with the tumor microenvironment. Clinical trials employing live bacteria, bacterial metabolites, and fecal microbiota transplantation are also discussed, emphasizing their translational potential and current limitations. Additionally, we explore how the microbiome has been recognized as an enabling hallmark of cancer, capable of influencing inflammation, immune evasion, and therapeutic resistance. Despite significant progress, challenges such as safety, delivery specificity, and regulatory concerns remain. Advances in synthetic biology, precision microbiome engineering, and personalized medicine offer promising strategies to overcome these barriers. By integrating microbial biology with immuno-oncology, bacteria-mediated cancer therapy (BMCT) represents a novel frontier with transformative potential in cancer treatment.
Keywords: Bacteria; Cancer; Immunotherapy; Microbial metabolites; Oncomicrobiomics; Polymorphic microbiome