A joint research team from the Gwangju Institute of Science and Technology (GIST) and Seoul National University Hospital (SNUH) has identified a beneficial bacterium in the endometrium that may help activate anti-cancer immune responses and suppress recurrence in endometrial cancer, suggesting a possible new direction for microbiome-based cancer treatment.
A joint research team, led by Professors Park Han-soo at GIST (left) and Lee Maria at SNUH, has found that Bacillus megaterium in the endometrium may activate anti-cancer immune responses and help lower endometrial cancer recurrence. (Credit: SNUH)
Endometrial cancer is the fourth most common cancer among women in the U.S. In patients with metastatic or recurrent disease, conventional chemotherapy alone has limitations in improving treatment response and survival. Although previous studies have suggested that the microbiome may affect cancer development, progression and immune regulation, the role of microorganisms inside endometrial tissue in anti-cancer immunity has remained unclear.
To examine the relationship between microorganisms and host immune responses, the joint research team, led by Professors Park Han-soo of the Department of Biomedical Science and Engineering at GIST, who also serves as CEO of Genome & Company, and Lee Maria of the Department of Obstetrics and Gynecology at SNUH, performed multi-omics analysis of endometrial tissue from patients with endometrial cancer and benign uterine diseases.
Multi-omics analysis integrates genomic, transcriptomic, proteomic and metabolomic data to identify biological interactions linked to disease.
The analysis showed that Bacillus megaterium was more abundant in endometrial cancer patients who had a lower risk of recurrence and longer survival.
The researchers then examined how the bacterium could trigger anti-cancer immune responses at the molecular level. They found that Bacillus megaterium carried cutC, a key gene required for the production pathway of trimethylamine N-oxide, or TMAO, a metabolite associated with immune activation.
Further analysis of endometrial tissue and blood samples from cancer patients showed that higher levels of the beneficial bacterium were correlated with higher blood TMAO concentrations. The findings suggest that the bacterium may contribute to anti-cancer immunity through the TMAO metabolic pathway.
(Credit: SNUH)
The team also confirmed that the bacterium breaks down choline, a nutrient found in food, and connects this metabolic process to immune activation. According to the researchers, TMAO generated through the bacterial choline metabolism pathway stimulated type I interferon signaling, which in turn activated T cells that attack cancer cells.
Type I interferon is an important immune signaling molecule produced in response to viral infection or tumor development. It helps the immune system recognize cancer cells and activate T cells while also contributing to anti-tumor immune responses.
In cell experiments and imaging analysis, the application of Bacillus megaterium enhanced immune cell-mediated anti-cancer responses, suppressed the proliferation of endometrial cancer cells and increased immune cell infiltration around cancer cells. The research team also observed increased expression of immune response-related genes, including type I interferon-related genes, in the group treated with the bacterium.
A similar immune-activating effect was seen when TMAO was applied alone, supporting the view that the bacterium may strengthen anti-cancer immune responses through metabolic regulation.
The researchers said the findings show that Bacillus megaterium may improve immune cell function and promote inflammatory cell death through its metabolic activity, raising the possibility of developing new microbiome-based treatment strategies for endometrial cancer.
“This study is the first case to systematically identify, at the single-strain level, a pathway through which anti-cancer immunity is induced by tracking bacteria, metabolites and host immune responses within the same patient cohort,” Park said. “It is meaningful because it suggests the possibility of an entirely new microbiome-based combination treatment strategy for endometrial cancer patients who show limited responses to existing anticancer drugs or immunotherapies.”
Professor Lee also said, “The long-term patient tissue and serum cohort allowed us to provide a new microbiome-based explanation for why some patients experience recurrence while others do not.”
Lee further explained that the team plans to conduct additional validation in patient groups from multiple institutions and diverse ethnic backgrounds, and expand the research into in vivo studies, including patient-derived cell models and animal studies, to accelerate clinical application.
The results were published online in
Microbiome
, an international journal in microbiology, on April 20.
Lee Han-soo
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