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Bacterial blockade
Date:7/25/2013

For decades, doctors have understood that microbes in the human gut can influence how certain drugs work in the body by either activating or inactivating specific compounds, but questions have long remained about exactly how the process works.

Harvard scientists are now beginning to provide those answers.

In a July 19th paper published in Science, Peter Turnbaugh, a Bauer Fellow at Harvard's Faculty of Arts and Sciences (FAS) Center for Systems Biology, and Henry Haiser, a postdoctoral fellow, identify a pair of genes which appear to be responsible for allowing a specific strain of bacteria to break down a widely prescribed cardiac drug into an inactive compound, as well as a possible way to turn the process off.

"The traditional view of microbes in the gut relates to how they influence the digestion of our diet," Turnbaugh said. "But we also know that there are over 40 different drugs that can be influenced by gut microbes. What's really interesting is that although this has been known for decades, we still don't really understand which microbes are involved or how they might be processing these compounds."

To answer those questions, Turnbaugh and colleagues chose to focus on digoxin, one of the oldest-known cardiac glycosides, which is typically prescribed to treat heart failure and cardiac arrhythmia.

"It's one of the few drugs that, if you look in a pharmacology textbook, it will say that it's inactivated by gut microbes," Turnbaugh said. "John Lindenbaum's group at Columbia showed that in the 1980s. They found that a single bacterial species, Eggerthella lenta, was responsible."

As part of that earlier study, researchers also tried but failed to show whether testing bacterial samples taken from a person's gut could be used to predict whether the drug might be inactivated.

"To some degree the research was stalled there for a number of years, and the findings in our paper
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Contact: Peter Reuell
preuell@fas.harvard.edu
617-496-8070
Harvard University
Source:Eurekalert

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