Linking gut microbe to tumor suppression
Published in Cell Reports Medicine, the study helped pinpoint a specific gut bacterium that can boost the body’s ability to fight melanoma.
The research showed that Bacteroides uniformis and the metabolites it produces can help suppress tumor growth. The bacterium converts the amino acid tryptophan into indoles, which boosted anti-tumor immunity in mice. The findings open the door to future microbiome- and diet-based strategies that could help more cancer patients respond to immunotherapy.
To determine whether the same mechanism might be relevant in people, researchers also analyzed samples from cancer patients receiving immunotherapy. Investigators found increased levels of enzymes used to produce indoles in those responding well to the therapy, suggesting the same phenomenon was contributing to patients’ outcomes.
“When I think about the role of the microbiome in cancer therapy, I see an opportunity to better understand why some patients respond well to treatments such as immune checkpoint inhibitors while others don’t,” the senior author said. "Our study advances that idea by identifying a specific microbe and the metabolites it produces as one potential reason why patients respond differently to immunotherapies."
The researchers were able to distinguish the important effects of tryptophan degradation. Only the indole-producing bacterial strain produced anti-tumor immunity. When a genetically modified Bacteroides uniformis that could no longer convert tryptophan into indoles was introduced to the germ-free mice, the anti-tumor effect disappeared, and tumors developed normally.
“Previous research established that gut bacteria affect the immune system and can help fight cancer,” said a co-lead of the study. “Our new findings are an important step forward because they give us a specific metabolite that can be used for future therapies.”
The findings suggest that manipulating the gut microbiome — or providing beneficial bacterial metabolites directly — could someday help improve responses to cancer immunotherapy.
"Our idea is that down the road, we could design microbiome- or diet-based interventions that provide beneficial microbes or the dietary substrates they need to enhance a patient’s response to immunotherapy,” the author said. “What’s especially exciting is that this approach has the potential to extend beyond melanoma because indoles play an important role in improving immune responses to other types of cancers as well."
https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791(26)00338-1
https://sciencemission.com/Tryptophan-degradation-by-intestinal-Bacteroides
