Gut Bacteria from Amphibians and Reptiles Show Complete Tumor Elimination

In contrast, a new study adopts a different strategy by isolating, culturing, and intravenously administering individual bacterial strains to directly target tumors, representing an innovative therapeutic approach.

Researchers at the Japan Advanced Institute of Science and Technology (JAIST; Nomi, Japan) now report a single-dose, bacteria-based therapy that eliminated tumors in mice and exceeded the activity of standard chemotherapy and immunotherapy. The approach uses a naturally occurring gut bacterium isolated from amphibians and reptiles. The bacterium, Ewingella americana, was identified by the research team after isolation from the intestines of Japanese tree frogs.

The research team isolated 45 bacterial strains from the intestinal tracts of Japanese tree frogs (Dryophytes japonicus), Japanese fire-belly newts (Cynops pyrrhogaster), and Japanese grass lizards (Takydromus tachydromoides). Systematic screening identified nine strains with antitumor activity, among which E. americana demonstrated the most pronounced therapeutic efficacy.

E. americana exerts antitumor effects through two complementary mechanisms that couple direct tumor targeting with immune activatio. As a facultative anaerobe, it selectively accumulates in the hypoxic tumor microenvironment and directly destroys cancer cells. At the same time, it stimulates host immunity by recruiting T cells, B cells, and neutrophils to the tumor site, triggering the release of pro-inflammatory cytokines such as tumor necrosis factor-α and interferon-γ that amplify antitumor responses and induce cancer cell apoptosis.

The remarkable tumor specificity of E. americana is characterized by selective accumulation in tumor tissue with no detectable colonization of normal organs. This specificity arises from synergistic features of the tumor microenvironment, including hypoxia that favors anaerobic bacterial growth and CD47-mediated local immunosuppression that creates a permissive niche for survival. In addition, abnormal and highly permeable tumor vasculature facilitates bacterial extravasation, while tumor-specific metabolic conditions support sustained bacterial persistence.

In a mouse model of colorectal cancer, a single intravenous dose of E. americana achieved complete tumor eradication, yielding a 100% complete response rate. This outcome significantly outperformed standard therapies, including an anti-PD-L1 immune checkpoint inhibitor and liposomal doxorubicin. The bacterial treatment was administered as a single 200 µL injection at 5 × 10⁹ CFU/mL, whereas comparator drugs were given in four 200 µL doses at 2.5 mg/kg. Results are reported as mean ± SEM (n = 5), with statistical significance assessed using a two-sided Student’s t-test (p < 0.0001).

Safety assessments showed rapid clearance from the bloodstream, with an estimated half-life of approximately 1.2 hours and no detectable bacteria at 24 hours. No bacterial colonization was observed in the liver, spleen, lungs, kidneys, or heart. Transient, mild inflammatory responses resolved within 72 hours, and no evidence of chronic toxicity was detected during a 60-day follow-up period. 

Future work will focus on validating efficacy across additional tumor types, including breast cancer, pancreatic cancer, and melanoma, while also optimizing administration strategies such as dose fractionation and intratumoral delivery. Investigators will further explore combination approaches to assess potential synergy with existing immunotherapies and chemotherapies. Collectively, the findings highlight unexplored biodiversity as a rich source of innovation for medical technology and a promising avenue for developing new treatments for patients with refractory cancers.

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Japan Advanced Institute of Science and Technology