A gut bacterium from Japanese tree frogs outperformed two established cancer treatments in mice. Digest
Live bacteria can grow inside tumors and help attack cancer, but finding strains that combine strong anti-tumor effects with acceptable safety remains a major challenge. A new study tested whether gut bacteria from amphibians and reptiles could serve as novel candidates for new cancer treatments.
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Researchers isolated 45 gut bacterial strains from a Japanese tree frog, Japanese fire belly newt, and Japanese grass lizard, then selected nine for further testing after they caused no severe short-term toxicity when injected into the tail veins of mice. Each strain was then tested in mice with colon cancer cells implanted under the skin, and tumor growth was tracked for 40 days after a single injection. In a second tumor experiment, the researchers focused on Ewingella americana, isolated from the Japanese tree frog, because it was the only bacterial treatment that produced complete tumor regression without later regrowth. Mice received E. americana, anti-PD-L1 treatment (an immunotherapy that blocks a signal tumors use to suppress the immune system), liposomal doxorubicin (a chemotherapy drug carried in tiny fat-based particles), or a bacteria-free control solution. The bacterial treatment was given once at a dose of 1 billion live bacteria, while the two drug treatments were each given four times.
- In all five mice treated with E. americana, the tumors became undetectable by physical examination and did not return for at least 30 days. The same outcome occurred in one of five mice given anti-PD-L1 and none of the mice given liposomal doxorubicin or the control solution, although both standard treatments slowed tumor growth compared to control.
- Mice successfully treated with E. americana did not develop tumors after a second injection of the same cancer cells in a separate experiment. None of 10 mice previously treated with E. americana developed another tumor during the next 30 days, while 10 previously untreated mice did.
- E. americana grew rapidly inside tumors. Viable bacterial counts inside tumors rose about 3,000-fold from 3 to 24 hours.
- The administered dose showed a favorable safety profile. Researchers found no lasting abnormalities in blood tests or major organs, and bacteria were undetectable in blood by 24 hours. Short-term effects included early weight loss and a temporary inflammatory response. However, higher doses caused acute death.
To investigate how the treatment worked, researchers tested E. americana in lab-grown clusters of colon cancer cells and examined tumors from treated mice. The bacterium directly disrupted the cell clusters and killed cancer cells. Tumors of treated mice contained more immune cells, stronger inflammatory signals, and more apoptosis, a controlled form of cell death. Since E. americana can grow with or without oxygen, the low-oxygen conditions inside tumors may have helped it multiply there, concentrating its direct effects while also triggering an immune attack. This response may also have produced lasting immune memory, helping the successfully treated mice resist a second cancer cell injection.
Because the study used a mouse model of colon cancer, it cannot show whether the treatment would be safe or effective in people. Nevertheless, the findings suggest that gut bacteria from understudied animals may offer promising starting points for developing new cancer treatments. In Aliquot #141, I explore how everyday lifestyle choices influence cancer risk.