The next time you pop a pill, know that the microbes in your gut might get to it before you do. Some people harbor a strain of bacteria that inactivates a common cardiac drug, a finding that could explain why people have different reactions to some medications.
“Microbes have long been known to ‘steal’ drugs by converting them into inactive forms,” says Peter Turnbaugh of Harvard University, who led the study. But picking out the specific culprits among the gut’s throngs of bacterial suspects has been a challenge for scientists, he says.
Turnbaugh’s team focused on microbial interactions with the cardiac drug digoxin. Made by the foxglove plant, digoxin has been used for more than 200 years to treat irregular heartbeat. More than 30 years ago, scientists discovered that some patients harbor a common gut bacterium, Eggerthella lenta, that could convert the drug to an inactive form, dihydrodigoxin. But researchers were confounded by the observation that some E. lenta carriers still had the active drug in their blood.
Turnbaugh’s team decided to dig into E. lenta’s genes. The results, reported in the July 19 Science, reveal a small cluster of E. lenta genes responsible for nixing digoxin. The researchers found that not every strain of E. lenta turns on the drug-dampening genes.
Turnbaugh’s team then found that the amino acid arginine prevents the microbe’s digoxin-destroying genes from turning on. When the researchers gave digoxin to mice that had E. lenta in their guts, higher levels of the active drug appeared in mice on a high-protein diet (containing arginine) than in mice that went without protein.
“This is a really fantastic piece of work,” says Ian Wilson of Imperial College London. The study finally provides a solid explanation for the differences among E. lenta carriers, Wilson says. “The effects [of digoxin] will be a combination of the strain, the diet, and whether that person is on antibiotics.”
These drug-bug interactions could make microbial genes just as important as a person’s genes for predicting how a drug will affect someone, says Matthew Redinbo of the University of North Carolina at Chapel Hill. “Your blood work is a vanishing fraction of what we should be measuring before giving a drug.”
