Gut bugs and diet affect how drugs work
Intestinal bacteria with a taste for certain drugs can dramatically affect how some people respond to different medicines, new research has shown.
Using the cardiac agent digoxin as a proof of concept, Harvard scientist Henry Haiser and his colleagues have found that a common bowel bug, called Eggerthella lenta, breaks down the drug, but only when levels of dietary protein are low.
This means that the levels of drugs getting into a patient's bloodstream could be strongly influenced by what bugs they carry and how these microbes respond to what the person eats.
In the current study, mice colonised with the Eggerthella bacterium had blood levels of digoxin that were twice as high when they were fed a high-protein diet compared with low-protein chow.
Dietary protein, and specifically the amino acid arginine, had the effect of turning off a subset of digoxin-metabolising genes in the microbes, the team found.
On the other hand, a diet low in protein, and hence arginine, led to the activation of this same group of genes and the ensuing deactivation of the digoxin within the intestine before it could be absorbed, resulting in low blood levels of the drug.
This shows, the scientists say in a paper in Science this week, that "a comprehensive view of pharmacology includes the structure and activity of our resident microbial communities and deeper understanding of their of their interactions with each other, with their host habitat and the nutritional milieu."
The next step, they suggest, will be use genetic techniques to examine the behaviours of the microbes in the guts of cardiac patients to see whether this can be used to guide more effective dosage regimes.