Bacteria hidden inside tumors can help fight cancer

Most people are familiar with the microbes found on our skin or in our gut, but recent discoveries have revealed that tumors also host unique communities of bacteria. Scientists are now investigating how these tumor-associated bacteria affect tumor growth and response to chemotherapy.

New research, published online in Cell systems on September 10, 2025, provides a major discovery in the field, identifying a powerful anti-cancer metabolite produced by bacteria associated with colorectal cancer. This discovery opens the door to new strategies for treating cancer, including the development of new drugs that can make current treatments more effective.

The researchers used a sophisticated, large-scale screening method to test more than 1,100 cases in a type of microscopic worm called… C. elegans. Through this, they found that E. coli bacteria produced a molecule called 2-methylisocitrate (2-MiCit) which could improve the effectiveness of the chemotherapy drug 5-fluorouracil (5-FU).

Using computer modeling, the team demonstrated that the tumor-associated microbiome (bacteria found in and around tumors) of patients was also able to produce 2-MiCit. To confirm the effectiveness of 2-MiCit, the team used two other systems; Human cancer cells and a fly model of colorectal cancer. In both cases, they found that 2-MiCit showed strong anti-cancer properties, and could extend the flies’ survival.

Professor Philipp Cabrero, Head of the Microbial Combined Metabolism Group at the LMS, and Group Leader at the CECAD Research Group in Cologne, explains the importance of this discovery: “We knew that bacteria are associated with tumors, and now we are starting to understand the chemical conversation they have with cancer cells. We found that one of these bacterial chemicals could act as a powerful partner in chemotherapy, “Which disrupts the metabolism of cancer cells.” Cancer cells make them more susceptible to the drug.”

The study revealed that 2-MiCit works by inhibiting a key enzyme in the mitochondria (the structures inside cells that generate energy for cellular functions) of cancer cells. This leads to DNA damage and activates pathways known to reduce cancer development. This multi-pronged attack weakens cancer cells and works synergistically with 5-FU. This combination was significantly more effective in killing cancer cells than either compound alone.

“The microbiome is an essential part of who we are,” says Dr. Daniel Martinez Martinez, a postdoctoral researcher at LMS and first author of the paper. “The ability of a single molecule to have such a profound impact on cancer development is truly remarkable, and further evidence of how complex biology is when looked at from a holistic point of view. It’s really exciting because we’re only scratching the surface of what’s really going on.”

In collaboration with medicinal chemists, the researchers also modified 2-MiCit to enhance its effectiveness. This synthetic version has proven to be more potent in killing cancer cells, demonstrating the potential for developing new drugs based on natural microbial products. Philip adds: “By using the natural microbial product as a starting point, we were able to design a more effective molecule, effectively improving upon Mother Nature.”

These exciting discoveries highlight how the cancer-associated microbiome influences tumor development, and how metabolites produced by these bacteria can be harnessed to improve cancer treatments. These findings are also important in the context of personalized medicine, as they underscore the importance of taking into account not only the patient, but also their microbiome.

This study was primarily funded by the Leverhulme Trust, the Wellcome Trust/Royal Society, the German Research Foundation DFG, and the Medical Research Council.