A research team of Prof. Eijiro Miyako at the Japan Advanced Institute of Science and Technology (JAIST) has discovered that the bacterium Ewingella americana, isolated from the intestines of Japanese tree frogs (Dryophytes japonicus), possesses remarkably potent anticancer activity. This ground-breaking research has been published in the journal Gut Microbes.
While the relationship between gut microbiota and cancer has attracted considerable attention in recent years, most approaches have focused on indirect methods such as microbiome modulation or faecal microbiota transplantation. In contrast, this study takes a completely different approach: isolating, culturing, and directly administering individual bacterial strains intravenously to attack tumours, representing an innovative therapeutic strategy.
The research team isolated a total of 45 bacterial strains from the intestines of Japanese tree frogs, Japanese fire belly newts (Cynops pyrrhogaster), and Japanese grass lizards (Takydromus tachydromoides). Through systematic screening, nine strains demonstrated antitumour effects, with E. americana exhibiting the most exceptional therapeutic efficacy.
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Remarkable Therapeutic Efficacy
In a mouse colorectal cancer model, a single intravenous administration of E. americana achieved complete tumour elimination with a 100% complete response (CR) rate. This dramatically surpasses the therapeutic efficacy of current standard treatments, including immune checkpoint inhibitors (anti-PD-L1 antibody) and liposomal doxorubicin (chemotherapy agent)
Dual-Action Anticancer Mechanism
E. americana attacks cancer through two complementary mechanisms:
- Direct Cytotoxic Effect: As a facultative anaerobic bacterium, E. americana selectively accumulates in the hypoxic tumour microenvironment and directly destroys cancer cells. Bacterial counts within tumours increase approximately 3,000-fold within 24 hours post-administration, efficiently attacking tumour tissue.
- Immune Activation Effect: The bacterial presence powerfully stimulates the immune system, recruiting T cells, B cells, and neutrophils to the tumour site. Pro-inflammatory cytokines (TNF-α, IFN-γ) produced by these immune cells further amplify immune responses and induce cancer cell apoptosis.
- Hypoxic Environment: The characteristic hypoxia of tumour tissues promotes anaerobic bacterial proliferation
- Immunosuppressive Environment: CD47 protein expressed by cancer cells creates local immunosuppression, forming a permissive niche for bacterial survival
- Abnormal Vascular Structure: Tumour vessels are leaky, facilitating bacterial extravasation
- Metabolic Abnormalities: Tumour-specific metabolites support selective bacterial growthTumour-Specific Accumulation Mechanism
E. americana selectively accumulates in tumour tissues with zero colonisation in normal organs. This remarkable tumour specificity arises from multiple synergistic mechanisms:
Excellent Safety Profile
Comprehensive safety evaluation revealed that E. americana demonstrates:
- Rapid blood clearance (half-life ~1.2 hours, completely undetectable at 24 hours)
- Zero bacterial colonisation in normal organs, including the liver, spleen, lung, kidney, and heart
- Only transient mild inflammatory responses, normalising within 72 hours
- No chronic toxicity during 60-day extended observation
This research has established proof-of-concept for a novel cancer therapy using natural bacteria. Future research and development will focus on:
- Expansion to Other Cancer Types: Efficacy validation in breast cancer, pancreatic cancer, melanoma, and other malignancies
- Optimisation of Administration Methods: Development of safer and more effective delivery approaches, including dose fractionation and intra-tumoural injection
- Combination Therapy Development: Investigation of synergistic effects with existing immunotherapy and chemotherapy
The researchers conclude that the study demonstrates that unexplored biodiversity represents a treasure trove for novel medical technology development and holds promise for providing new therapeutic options for patients with refractory cancers.
Source: JAIST
