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People sometimes suffer from the toxic side effects of drugs that help many others. Yale scientists have identified a surprising explanation: the intestinal microbiome.
The research, published February 8 in the journal Science, describes how bacteria in the gut can turn three drugs into harmful compounds.
"If we can understand the contributions of the microbiome to drug metabolism, we can decide which drugs to give to patients, or even modify the microbiome, so that patients get a better response," said Michael Zimmermann, co-author principal, postdoctoral researcher in the laboratory of the experienced author. Andrew Goodman of the Department of Microbial Pathogenesis and the Institute of Microbial Sciences.
Goodman, Zimmermann, Maria Zimmermann-Kogadeeva, lead author and Rebekka Wegmann, currently PhD student at ETH Zurich, studied an antiviral drug whose degradation product can cause serious toxicity and showed how intestinal microbes transform the drug into a harmful compound. They then administered the drug to mice carrying a bacterium whose drug-processing power was insufficient and measured the levels of this toxic compound. Using these data, they developed a mathematical model to successfully predict the role of intestinal bacteria in the metabolism of a second antiviral drug and clonazepam, an anti-epileptic and anti-anxiety medication. .
The study found that intestinal microbes were responsible for producing 20 to 80% of the circulating toxic metabolites derived from the three drugs.
The new model can potentially identify those most at risk of side effects from many drugs and help researchers adapt new approaches to minimize this risk to individuals, say the researchers.
"This approach could potentially be applied to other drugs," said lead co-author Zimmermann-Kogadeeva, also a Goodman lab postdoctoral fellow.
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