Bacteria help fight against cancer

An international team of scientists led by researchers at the MRC Laboratory of Medical Sciences (LMS), Imperial College London and the University of Cologne have discovered that microbes associated with tumors produce a molecule that can control cancer progression and boost the effectiveness of chemotherapy.

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

New research, published online in Cell Systems, provides a significant breakthrough in this field, identifying a powerful anti-cancer metabolite produced by bacteria associated with colorectal cancer.

This finding opens the door to new strategies for treating cancer, including the development of novel drugs that could make existing therapies more potent.

The researchers used a sophisticated large-scale screening approach to test over 1,100 conditions in C. elegans. Through this, they found that the bacteria E. coli produced a molecule called 2-methylisocitrate (2-MiCit) that 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 within and around tumors) of patients was also able to produce 2-MiCit. To confirm the effectiveness of 2-MiCit, the team used two further systems; human cancer cells and a fly model of colorectal cancer. In both cases, they found that 2-MiCit showed potent anti-cancer properties, and for the flies could extend survival.

Professor Filipe Cabreiro, head of the Host-Microbe Co-Metabolism group at the LMS, and group leader at the CECAD Research Cluster in Cologne, explains the significance, “We’ve known that bacteria are associated with tumors, and now we’re starting to understand the chemical conversation they’re having with cancer cells.

“We found that one of these bacterial chemicals can act as a powerful partner for chemotherapy, disrupting the metabolism of cancer cells and making them more vulnerable to the drug.”

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

Dr. Daniel Martinez-Martinez, postdoctoral researcher at the LMS and first author of the paper, says, “Microbes are an essential part of us. That a single molecule can exert such a profound impact on cancer progression is truly remarkable, and another piece of evidence on how complex biology can be when considering it from a holistic point of view. It is really exciting because we are only scratching the surface of what is really happening.”

In collaboration with medicinal chemists, the researchers also modified the 2-MiCit compound to enhance its effectiveness. This synthetic version proved even more powerful at killing cancer cells, demonstrating the potential to develop new drugs based on natural microbial products.

Filipe adds, “Using the natural microbial product as a starting point, we were able to design a more potent molecule, effectively improving on mother nature.”

These exciting discoveries highlight how the cancer-associated microbiome can impact tumor progression, and how metabolites produced by these bacteria could be harnessed to improve cancer treatments.

These findings are also important in the context of personalized medicine, emphasizing the importance of considering not only the patient, but also their microbes.