The Role of Bacteria in Drug Responses

It may soon be possible to predict the capacity of your gut’s bacteria to metabolize certain drugs, and that could help doctors prescribe the drugs that are the safest and most effective just for you.

Yale researchers have identified human gut microbes that metabolize more than 150 medicinal drugs, highlighting the role bacteria play in determining how well you respond to medications. They have also pinpointed the genes from these microbes that are responsible for many of the drug-metabolizing activities. They published their results in the June 3, 2019 journal Nature.

The metabolism of drugs was once thought to be exclusively the role of organs such as the liver, which carry out the important task of turning chemical compounds into water-soluble molecules to help their elimination from the body. This process is crucial to determining the effectiveness and safety of clinical drugs. The drugs need to stay in the body long enough to have an effect, but not long enough to accumulate and potentially become toxic.

Studies of the body’s metabolism of drugs typically do not assess the contribution of the microbiome. To map the connections between gut microbes and medical drugs, Yale researchers investigated how 76 different kinds of bacteria from the human gut chemically modified 271 drugs. Almost two-thirds of these drugs were metabolized by at least one of the bacterial specimens tested.

The researchers then constructed genetic libraries of the selected drug-metabolizing gut bacteria, which allowed them to systematically identify many of the genes responsible for the chemical transformation of the drugs. They found that the number of these genes varies widely across the gut microbiome of healthy human volunteers. In some cases, these differences explain why some gut microbiomes metabolize drugs rapidly, while others modify the same drugs slowly or not at all.

“We hope this study provides a useful first step in understanding the microbiome contribution to drug metabolism,” said co-lead author Michael Zimmermann, postdoctoral fellow in the  lab of senior author Andrew Goodman of Yale’s Microbial Sciences Institute and the Department of Microbial Pathogenesis. “We think these approaches could shed light on how the gut microbiome also modulates our response to non-drug compounds, such as dietary nutrients and environmental agents.”

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