A research team led by Prof. Eijiro Miyako at the Japan Advanced Institute of Science and Technology (JAIST) found a bacterium in the intestines of Japanese tree frogs that showed exceptional anticancer efficacy in mice.
The findings, published in Gut Microbes, mark a pivotal shift in microbiome-based cancer therapy. While much recent research has focused on fecal microbiota transplantation and microbiome modulation, this study pioneers a novel strategy: using living bacteria themselves as anticancer agents.
The scientists collected specimens from Dryophytes japonicus (Japanese tree frog), Takydromus tachydromoides (Japanese grass lizard), and Cynops pyrrhogaster (Japanese fire belly newt), isolating 45 distinct bacterial strains. Using 16S ribosomal RNA gene sequencing and molecular phylogenetic analysis, they identified nine distinct bacterial species for further study. Among them, Ewingella americana emerged as the most promising candidate.
Indeed, in a mouse model of colorectal cancer, a single intravenous dose of E. americana completely eliminated tumors in all treated animals, achieving a 100% complete response (CR) rate. Its antitumor activity substantially exceeded that of the standard treatments tested in the study, including an anti-PD-L1 immune checkpoint inhibitor and liposomal doxorubicin chemotherapy.
Extensive safety studies in murine models found that E. americana had minimal pathogenicity and caused no significant adverse effects at therapeutically effective doses.
How it works
E. americana functions through a dual-action mechanism:
Direct Cytotoxic Effect: Being a facultative anaerobe, E. americana can survive and proliferate in the characteristically hypoxic and immunosuppressive environment found inside solid tumors. This allowed the bacterium to grow 3,000 fold within 24 hours, selectively accumulating and colonizing tumor tissue, where its growth, together with the immune response it triggers, likely contributed to the observed tumor regression.
Robust activation of host immunity: After damaging the cancer cells, E. americana rapidly recruited immune cells into the tumors, suggesting that the treatment triggered an immediate inflammatory response that reinforced its antitumor effects. T cells, B cells, and neutrophils infiltrated the tumor tissue and released inflammatory signaling molecules such as TNF-α and IFN-γ, further enhancing the immune response and promoting cancer cell death.
Excellent Safety Profile & Immune Memory
Beyond its outstanding efficacy, what strikes the most about E. americana is its ability to exclusively target tumors without colonizing healthy organs. This is due to several factors in place within the tumor microenvironment.
Hypoxia: Solid tumors are poorly oxygenated, creating conditions that favor bacterial growth.
CD47 expression: Cancer cells over-express CD47, a “don’t eat me” signal that suppresses local immune clearance and help bacteria survive within the tumor.
Leaky blood vessels: Tumor vasculature is unusually permeable, making it easier for bacteria circulating in the bloodstream to enter tumor tissue.
Nutrient-rich environment: Tumor-specific metabolic abnormalities provide nutrients that support bacterial survival and proliferation.
The research team also evaluated the treatment’s safety profile. The bacteria were rapidly cleared from the bloodstream, with a half-life of approximately 1.2 hours, and became undetectable within 24 hours. The treatment caused only mild, temporary inflammation, returning to baseline within 72 hours. Over a 60-day observation period, the researchers found no evidence of chronic toxicity.
Perhaps most remarkably, the treatment appeared to leave behind an immune memory. Thirty days after E. americana had eliminated their tumors, the cured mice were injected again with the same cancer cells. Not one developed a new tumor, while every untreated control did, suggesting that the treatment had trained the immune system to recognize and reject the cancer upon a second encounter.
Next steps
The study successfully established proof of concept for using naturally occurring bacteria as a cancer therapy. Future research will focus on determining whether the treatment is also effective against other solid tumors, including breast cancer, pancreatic cancer, and melanoma.
The team will also explore safer and potentially more effective ways to deliver the treatment, including dose fractionation and intratumoral injection. Researchers will also investigate whether E. americana produces stronger anticancer effects when combined with existing immunotherapy or chemotherapy.