By DONNA RACHEL EDMUNDS

Changes in diet can increase the toxicity of a chemotherapeutic drug by up to 100-fold.

What we eat has a direct effect on the outcome of medical treatments such as chemotherapy thanks to the interplay between our diets and the microbes in our gut, new research from the University of Virginia has found.

Common elements of our diets can both have positive and negative effects on drugs in terms of both their effectiveness and toxicity – and even changes as small as the addition or removal of one amino acid can have a significant impact, researchers found. Doctors have long known that a patient’s diet can influence treatment, but the scientists were astonished to realize just how much difference small changes to diet can make.

“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, of UVA’s College of Arts & Sciences, the School of Medicine’s Department of Cell Biology and the Robert M. Berne Cardiovascular Research Center. “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.”

The human body contains more than 1000 different species of microorganisms which play an active role in processing the food we eat and the nutrients we absorb. Changes in our diet influence the health of the microorganisms, which in turn influences how the nutrients in our food, or any other substance we ingest such as medicinal drugs, are absorbed into and used by the body.

Delving deep into this elaborate web of interactions, researchers created a simplified model of the multibiome – the vast community of organisms – found in people in order to study how changing one variable rippled through the whole system. They did this through studying roundworms, to mimic the human host, which carried a non-pathogenic E. coli bacteria to represent the microbes in the human gut.

Using this model, they found that changes in diet can increase the toxicity of a chemotherapeutic drug by up to 100-fold. “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 new scientific paper outlining the findings.

The findings have far-reaching implications on the whole field of medicine, and could mean that doctors in the future prescribe not only drugs, but also detailed dietary guidelines and tailor-made microbe cocktails to maximize the efficacy of the treatment on the patient.

And although researchers have noticed that diet can affect treatment outcomes before, this study marks the first time that the underlying molecular processes have been fully investigated, paving the way for a more accurate understanding of the relationships in play.

“The potential of developing drugs that can improve treatment outcomes by modulating the microbes that live in our gut is enormous,” O’Rourke said. “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.”