An incredible key study led by researchers at the University of Virginia in the United States has shown that dietary and gut bacteria have a profound effect on the efficacy and toxicity of chemotherapy drugs. The study, using a tick as a simplified microbiome model, showed how just one type of bacteria could multiply the toxicity of the drug, and the researchers concluded that the complexity of the interactions between drugs, diet and bacteria in humans was “astronomical.”
A review published last year in the journal Frontiers in Microbiology effectively sums up the evidence that supports a hypothesis that the gut microbiome plays a fundamental role in determining the efficacy of chemotherapy for cancer. Recent studies have shown how the pharmacological effects of a drug are directly affected by bacteria in the gut, and mediate the toxicity and efficacy of the drug.
Although there have been a number of observations that there is a strong link between the gut microbiome and the outcome of treatments in patients with various diseases, the new study aims to study its potential molecular processes.
To do this, the researchers used a tick model to simulate simple but special four-way interactions between diet, bacteria, drugs and hosts. Incredibly, the study found that dietary changes can directly alter the metabolism of microorganisms, increasing the drug’s toxicity to the host by 100 times.
“For the first time, we’ve seen that changing microbes or adding an amino acid to our diet can turn harmless doses of drugs into highly toxic drugs, and we can’t believe our eyes,” explains eyleen O’Rourke, author of the new study. “Understanding, with molecular resolution, what’s going on, needs to be screened by hundreds of microbes and host genes. The answer is an amazingly complex network of diet, microbes, drugs and host interactions. “
The biggest takeaway from the study was how complex the relationship between these drugs and the host-microbiome was, and how challenging the researchers were in cataloguing these interactions. The human microbiome is home to more than 1,500 different bacteria. Each microbe is metabolized in different ways with dietary ingredients and drugs, and each has its own unique microbiome.
In the study, the researchers concluded that “the complexity of drug-microbial-host co-metabolism in the body is astronomical.” This single and powerful work merely records a focused four-way interaction. The study highlights how powerful this overall effect is, and it does provide clues as to why some people respond better to chemotherapy than others. However, developing a treatment that harnesses the therapeutic potential of the microbiome will be a challenge, to say the least.
“By regulating the microbes that live in our guts, the potential to develop drugs that can improve treatment outcomes is enormous,” O’Rourke said. “However, the complexity of the interactions between diet, microbes, therapies and hosts we found in this study is surprising. We will require a lot of basic research, including complex computer modeling, to reveal how to fully exploit the therapeutic potential of our microbes. “
The new study is published in the journal Nature-Communications.