Scientists at the Japan Advanced Institute of Science and Technology (JAIST) have identified a naturally occurring bacteria from the intestines of Japanese tree frogs (Dryophytes japonicus) that demonstrated remarkable anti-cancer activity in mice. The findings, published in gut microbesintroduce a new approach to cancer treatment that uses live bacteria to directly attack tumors rather than simply altering the gut microbiome.
Unlike many previous studies that focused on changing the composition of gut bacteria or using fecal microbiota transplants, this research isolated individual bacterial strains, grew them in the lab, and administered them intravenously to attack tumors.
The team collected 45 bacterial strains from the intestines of Japanese tree frogs, Japanese fire-bellied newts (Cynops pyrrhogaster) and Japanese lizards (Takydromus tachidromoides). After examining the bacteria’s anti-cancer activity, nine strains showed promise. Among them, American Ewingella produced the strongest results.
A single treatment eliminated tumors in mice
In a mouse model of colorectal cancer, a single intravenous dose of American E. completely eliminated the tumors, producing a complete response (CR) rate of 100%. According to the researchers, the treatment outperformed standard therapies used in comparison, including immune checkpoint inhibitors (anti-PD-L1 antibody) and the chemotherapy drug liposomal doxorubicin.
The researchers emphasize that these findings are limited to mice, but believe the results provide an encouraging proof of concept for the development of new bacterial cancer therapies.
Dual attack on cancer cells
The bacteria appears to fight cancer through two complementary mechanisms.
First, American E. It directly attacks tumors. As a facultative anaerobic bacteria, it thrives in both oxygen-rich and oxygen-poor environments, allowing it to multiply within oxygen-deprived regions commonly found within tumors. Once there, the bacterial population increased approximately 3,000-fold within 24 hours of treatment, directly damaging the cancer cells.
Second, the bacteria stimulates the immune system. Their presence attracted T cells, B cells and neutrophils to the tumors. These immune cells then released inflammatory signaling molecules, including TNF-α and IFN-γ, which strengthened the immune response and promoted cancer cell death.
Why bacteria target tumors
One of the most surprising findings was that American E. It accumulated almost exclusively within tumors and did not colonize healthy organs.
Researchers believe that this tumor specificity is the result of several factors working together:
- The low-oxygen environment inside tumors encourages bacterial growth.
- Cancer cells produce the protein CD47, which suppresses local immune activity and creates conditions that allow bacteria to survive.
- The tumor’s blood vessels are unusually leaky, making it easier for bacteria circulating in the bloodstream to enter the tumor tissue.
- Tumor-specific metabolic changes provide nutrients that support bacterial growth.
Together, these characteristics allow bacteria to concentrate where tumors are located, avoiding normal tissues.
Favorable safety results
The research team also evaluated the safety of the treatment.
They found that the bacteria were rapidly cleared from the bloodstream, with a half-life of about 1.2 hours, and became undetectable within 24 hours. No bacterial colonization was detected in healthy organs, including the liver, spleen, lungs, kidneys, or heart.
The treatment only caused mild, temporary swelling that returned to normal within 72 hours. Over a 60-day observation period, the researchers found no evidence of chronic toxicity.
Expanding to other types of cancer
The study establishes proof of concept for the use of natural bacteria as anti-cancer therapy. Future research will examine whether the approach can be applied to additional solid tumors, including breast cancer, pancreatic cancer and melanoma.
The team also plans to optimize treatment methods using approaches such as dose fractionation and direct injection into tumors. The researchers will also investigate whether American E. It works even better when combined with existing chemotherapy or immunotherapy.
The findings also highlight the potential value of exploring biodiversity as a source of future medical treatments, offering the possibility of new therapeutic options for patients with difficult-to-treat cancers.
Glossary
- Facultative anaerobic bacteria: Bacteria capable of growing in both oxygen-rich and oxygen-poor environments, allowing them to multiply selectively in the low-oxygen conditions found within tumors.
- Complete Answer (CR): Complete disappearance of detectable tumors after treatment.
- Immune checkpoint inhibitor: Drugs that eliminate signals that cancer cells use to suppress the immune system, allowing T cells to attack tumors more effectively.
- CD47: A protein on the surface of cells that sends a “don’t eat me” signal to the immune system. Many cancer cells produce large amounts of CD47 to ward off immune attack.
The research was supported by the Japan Society for the Promotion of Science (JSPS) KAKENHI Grant for Scientific Research (A) (Grant No. 23H00551), the JSPS KAKENHI Grant for Challenging (Pioneering) Research (Grant No. 22K18440), the JSPS Program for the Training of Japan’s Top Research Universities (J-PEAKS) (Grant No. JPJS00420230006), the Japan Science and Technology Agency (JST) Program for Co-Creating Startup Ecosystems (Grant No. JPMJSF2318) and JST SPRING (Grant No. JPMJSP2102).