By: David A Fein, MD
An interesting study from Kumamoto University in Japan suggests that changes in the bacteria that normally reside in our gut may have a big impact on how your body metabolizes the medications you take.
By weight, we are mostly made of human cells. But if you go by the number of cells you are walking around with, you are far more bacterial than human. Until recently, it was thought that most areas of the body were sterile and that in those spaces where bacteria normally colonize (such as the skin, mouth, nose, colon), the bacteria were mainly just passive passengers taking advantage of an indifferent host. Instead, it is increasingly becoming apparent that there is substantial interaction between our bacterial population and how our organs function. For example, feed the gut bacteria of fat mice to normal weight mice and you quickly fatten up those mice. Those bacteria appear to have an effect on regulating the appetites of the mice.
In the current study researchers looked at three groups of mice. One had normal gut bacteria, one had been given antibiotics for 5 days to alter their bacterial population and one group was kept free of bacteria from birth.
The results showed that the levels of important enzymes in the liver of the mice were severely reduced when the intestinal bacteria were altered or reduced. In some cases, the enzymes were reduced by as much as 96%. The affected enzymes correspond to 2 cytochrome enzymes in the human liver, CYP2B6 and CYP3A4. Those enzymes are involved in the metabolism of more than half the pharmaceuticals currently on the market. A reduction in the activity of those enzymes in the human liver could dramatically alter blood levels of many common medications.
In some cases, reducing the activity of those enzymes could render a drug almost completely useless. For example, Plavix is commonly used as a blood thinner to help prevent heart attacks, strokes and to prevent clots from occluding a stent. However, Plavix has no activity in the form in which it is taken. It must first be metabolized into the active drug by those same liver enzymes. If their activity is reduced, the amount of active drug in the blood will be much lower.
In addition, Bcrp1, a protein that transports many kinds of cancer drugs, was reduced by more than 50% in the livers of the mice with absent or altered bacterial populations. Since antibiotics are often administered to cancer patients during chemotherapy to help fight infections when their immunity is reduced, it is possible that the changes in gut bacteria that result may influence how their cancer drugs are metabolized.
It remains to be confirmed whether this effect occurs in humans. The science of understanding how we interact with the bacteria call us home is still in its infancy and is evolving rapidly. It is increasingly clear that that those bacteria play some important roles in regulating normal physiology.