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Cell: Enteric bacteria will change the activity of anti-cancer drugs
2018-03-12
The UCL University-led research analyzed the microbial processes of drug and nutrients in nematodes. The study showed that the activity of cancer drugs varies depending on the type of bacteria that live in the intestine. This finding highlights the potential benefits of manipulating the gut bacteria and diet to improve cancer treatment, as well as understanding the value of differences in drug efficacy among individuals.
This research article was published on the April 21st cell and uses a new high-throughput screening method to elucidate the complex relationships between hosts and the role of gut microbes and drugs.

Researchers respond to media interviews

The leader of the study, Dr. Filipe Cabreiro, said: “The therapeutic effects of patients with colorectal cancer are very different. We would like to know whether this may be caused by microbes changing the way the body treats drugs. We have developed a rigorous system that can be used in the host. Preclinical screening for drug interactions with microorganisms, or revolutionizing the design of bacteria for drug delivery."

Dr. Timothy Scott, the first author of the article, said: "We have forgotten that there are many organisms in our bodies that interact with food and drugs. So far, exploring the relationship between the host, the microbe and the drug has proved to be difficult. Usually isolated Microbiological methods are unrealistic, but using the in vivo methods we have now developed, we have some amazing insights into how drug activity can support or inhibit intestinal microbes."

Nematodes are an ideal model organism

The team developed a screening method based on nematodes. Nematodes are usually used as a simple model in the study of human metabolism, because it is simpler in evolution than humans but its relationship with microbes and human beings are comparable.

They screened 55,000 different conditions in the nematode by changing the bacterial gene and the drug type and dose. Computer analysis was then used to exhaustively analyze the genetic, dietary, and chemical effects of bacteria on the effects of fluorouracil. Fluorouracil is a common type of colorectal drug.

Fluorouracils act by preventing DNA production and prevent cells from dividing in an uncontrolled manner, which is a typical feature of cancer cells. They usually exist in the form of prodrugs, which means that the liver needs to break it down into active drugs. Although fluorouracil is a common cancer treatment drug, there is currently no universally accepted dose standard, and genetics of light cannot give an explanation of the patient's difference in drug response.

Some intestinal bacteria enhance the activity of colorectal cancer drugs

The extensive screening in this study used three different methods to confirm that the bacteria changed the activity of the drugs in the nematode. First, some bacteria help convert prodrugs into active drug forms and enhance drug activity. Second, bacteria affect the metabolic environment of cells, making them more prone to drug-directed cell death.

The team also found that the success of the combined treatment of cancer may be limited if host-microbe-drug interactions are not considered. For example, they found that metformin, an anti-diabetic drug, can reduce the effect of fluorouracil on worms by inhibiting the positive action of bacteria.

Dr. Cabreiro's conclusion is: "We have added a key missing ingredient in the drug's treatment of diseases - enteric bacteria. We plan to conduct in-depth research in this field to identify which microorganisms are responsible for drugs in the human body. The activity works and the regulation of dietary supplements can have a huge impact on the outcome of cancer treatment."

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