Gut Bacteria May Affect Response to Chemotherapeutic Drugs

The type of bacterial species in the gut microbiome may impact the response to chemotherapy for the treatment of colorectal cancer, according to a study published in Cell.

Although patients may have the same type of disease, the treatments can differ dramatically.

“Two twins, genetically identical, who have colorectal cancer could potentially respond very differently to the same treatment because of their microbiome,” said investigator Marian Walhout, PhD. “If we can learn how bacteria affect the efficacy or toxicity of chemotherapies, it’s not hard to image developing personalized medicine built on probiotics that could improve the clinical benefits of some cancer treatments.”

For the study, investigators used the roundworm Caenorhabditis elegan—–a transparent, microscopic worm often used in genetic studies––to determine how different bacteria may augment or depress cancer drugs.

The C. elegan were fed a diet of either E. coli or Comamonas bacteria. They were then exposed to different chemotherapy drugs, including the antimetabolite floxuridine (FUDR), to assess changes in the phenotype and genotype. FUDR is commonly used to treat colorectal cancer.

The results of the study showed that roundworms fed a diet containing E. coli were more sensitive to treatment with FUDR compared with worms fed a Comamonas diet. Depending on the dose of FUDR, these worms had dead offspring or were completely sterile. However, worms fed a diet of Comamonas produced live offspring at the same doses.

Worms fed the Comamonas diet needed to be exposed to a concentration of FUDR that was 100 times greater than worms fed E. coli to induce sterility.

For the effect to be produced, the bacteria needed to be alive to actively metabolize the drug or to produce a metabolite when exposed to FUDR.

“Because these are bacteria already in your microbiome, any pill or treatment you take orally would be exposed to the bacteria and the efficacy of the drug may be modulated by different bacteria,” said investigator Aurian Garcia Gonzalez.

The investigators used genetic screens to identify which bacterial genes were responsible for increasing or decreasing drug efficacy in C. elegan.

“This isn’t a model that indisputable demonstrates a therapeutic finding but the implications are quite interesting nonetheless,” Walhout said. “Using the humble worm and powerful genetic tools, we can potentially use probiotics to develop a personalized medicine that might maximize the benefit of some chemotherapy treatments.

“Any bacteria that can be fed to a worm can be tested and any drug that has an observed phenotype can be tested. This gives scientists a huge space to test because of the thousands of combinations of drugs and bacteria that could conceivable be tested. We hope this study inspires more people to look at this space, and explore the use of our findings to clinical settings in the future.”