Diet Interactions With Gut Microbes Affect Cancer Treatment Outcomes

According to a recent study, diet can affect the outcome of chemotherapy due to microbes in the gut that can trigger changes in a patient’s response to drugs. The results of the study showed that components of our daily diets, such as amino acids, can increase or decrease the efficacy and toxicity of drugs used for cancer treatment.¹

The results of this study have significant implications regarding the correct dosage for drugs and potential adverse effects of chemotherapy for each patient, according to the study. The results also may clarify certain changes in patient responses to chemotherapy that previously had unclear origins.¹

"The first time we observed that changing the microbe or adding a single amino acid to the diet could transform an innocuous dose of the drug into a highly toxic one, we couldn't believe our eyes," said Eyleen O'Rourke, PhD, assistant professor of Biology and Cell Biology at University of Virginia's College of Arts & Sciences, in a press release. "Understanding, with molecular resolution, what was going on took sieving through hundreds of microbe and host genes. The answer was an astonishingly complex network of interactions between diet, microbe, drug, and host."²

Using a lab model created with roundworms, the researchers found that changes in the diet could increase the toxicity of a chemotherapeutic drug up to 100-fold.¹

"The same dose of the drug that does nothing on the control diet kills the [roundworm] if a milligram of the amino acid serine is added to the diet," said Wenfan Ke, a graduate student and lead author of a scientific paper outlining the findings, in a press release.²

With more than 1000 species of microbes living inside each of us, there are many potential possibilities in terms of how these microorganisms may react to both diet and treatments. This knowledge opens up new pathways for research regarding how each of these aspects of human health in the gut interact with a drug, according to the researchers.¹

The roundworm model used in the study is also an extremely simplified version of the human microbiome, or collection of microbes in the gut. In their model, roundworms acted as the host, while non-pathogenic E. coli bacteria acted as the gut microbes. However, the relationship between diet, microorganisms, and host in humans is far more complex.¹

The researchers explained that with this new information, drug developers would need to take into account the effect of diet interacting with microbes during lab work assessing drug efficacy. For example, drug developers would need to consider whether diet could cause the microorganisms to produce metabolites that may support or hinder the efficacy of the drug being tested.¹

The researchers noted that with the complexity of these interactions remaining "astronomical" in scope, more research would be needed to realize the therapeutic potential of working with microbiota during treatment.¹

"The potential of developing drugs that can improve treatment outcomes by modulating the microbes that live in our gut is enormous," O'Rourke said in a press release. "However, the complexity of the interactions between diet, microbes, therapeutics, and the host that we uncovered in this study is humbling. We will need lots of basic research, including sophisticated computer modeling, to reveal how to fully exploit the therapeutic potential of our microbes."²

REFERENCES

• Ke W, Saba JA, Yao CH, et al. Dietary serine-microbiota interaction enhances chemotherapeutic toxicity without altering drug conversion. Nature Communications. 2020;11(1). doi: 10.1038/s41467-020-16220-w.
• Diet, gut microbes affect cancer treatment outcomes [news release]. University of Virginia Health System. June 5, 2020. sciencedaily.com/releases/2020/06/200605121420.htm. Accessed June 8, 2020.