Summary:
Microorganisms are increasingly understood to play a role in how cancer develops, progresses, and responds to treatment. This experimental study investigates whether bacteria could be used as a cancer therapy, focusing on the gut microbiome as a key source. The gut contains a large number of microbes that help break down food, support the immune system, and protect against harmful organisms. These microbes also produce substances that can affect how the body functions and how the immune system responds. Research suggests that the types of bacteria present in the gut may influence tumour growth and how well treatments, particularly immunotherapy, work. This may occur through changes in inflammation and immune activity (such as how the body detects and attacks abnormal cells, including cancer). This study examined a different approach to treatment by using naturally occurring bacteria instead of genetically modified ones, which can have safety concerns. Nine bacterial strains were isolated from the gut of amphibians and reptiles, as these species may host unique types of bacteria. The strains were tested in preclinical models to assess whether they could kill cancer cells, target tumours, stimulate immune responses, and remain safe. Their effects were compared to standard treatments such as chemotherapy and immunotherapy. One strain, Ewingella americana, showed strong anti-cancer effects. It reduced tumour growth by directly killing cancer cells and by activating immune cells that help attack tumours. In this study, it performed better than standard treatments in experimental models and showed low toxicity, meaning it caused minimal harm at effective doses. Overall, this study suggests that gut bacteria, particularly from less-studied species, may offer new options for cancer treatment. However, further research is needed to confirm that these findings are safe and effective in humans.
Abstract:
The utilization of gut microbiota in cancer therapy has attracted considerable attention as an emerging therapeutic frontier. In this study, we systematically evaluated the antitumor effects of nine bacterial strains isolated from the intestines of amphibians (Dryophytes japonicus and Cynops pyrrhogaster) and a reptile (Takydromus tachydromoides). Among the isolates, Ewingella americana exhibited remarkably potent cytotoxic activity with selective tumor-targeting ability characteristic of facultative anaerobic bacteria. Mechanistic investigations revealed that E. americana functions through a dual-action mechanism: direct tumor cell killing and robust activation of host immunity, leading to enhanced T cell, neutrophil, and B cell-mediated tumor attack. Treatment with E. americana significantly outperformed standard therapies, including anti-PD-L1 antibody and doxorubicin, in tumor regression studies. Importantly, comprehensive safety evaluations in murine models demonstrated that the gut-derived E. americana strain exhibits minimal pathogenicity and exerts no significant adverse effects at therapeutically effective doses, contrasting favorably with genetically modified bacterial therapeutics. Comparative analysis revealed superior therapeutic efficacy of E. americana over conventional treatments while maintaining an excellent safety profile. These findings suggest that gut microbiomes of lower vertebrates harbor numerous uncharacterized bacterial species with exceptional therapeutic potential. Our study establishes a foundation for developing naturally occurring, non-pathogenic bacterial therapeutics and underscores the critical importance of microbial biodiversity in advancing cancer treatment strategies.
Article Publication Date: 10/12/2025
DOI: 10.1080/19490976.2025.2599562
