Drug Response Could Be Affected by Intestinal Flora

Among the numerous effects intestinal flora has on health, findings from a recent study suggest that it can affect drug response as well.

Researchers discovered that changes in intestinal flora from antibacterial and antibiotic drugs, or other natural changes, can effect a person’s drug response and susceptibility to side effects, according to a study published by Molecular Pharmaceutics. In the study, researchers analyzed protein changes in the liver and kidney that are responsible for drug metabolism and transporting drugs, which can influence efficacy and side effects.

In the study, researchers used 3 types of mice:

• germ-free mice born without intestinal bacterial
• mice receiving antibacterial drugs for 5 days
• control mice with natural intestinal flora

Researchers used proteomics to analyze changes in the proteins in the liver and kidney of the mice.

“The most significant drug-metabolizing enzyme that decreased was cytochrome P450 2b10 (Cyp2b10),” said lead researcher Sumio Ohtsuki, PhD. “Not only was the amount of the enzyme reduced nearly 96%, but the metabolic capacity of the drug in the liver was also reduced by approximately 82%. Cyp3a11, a similar type of enzyme was also reduced by about 88%. The human enzymes corresponding to these 2 enzymes, CYP2B6 and CYP3A4 are reported to be related to the metabolism of more than half of the pharmaceuticals on the market.”

Researchers also found that the breast cancer resistance protein (Bcrp1), which transports cancer drugs, had a reduction of 50% in the livers of both groups of experimental mice. For patients with cancer, antibacterial drugs can be prescribed to prevent infection from bone marrow suppression.

“The results of this study show that many drugs may be affected by changes in the intestinal flora,” said Dr Ohtsuki concluded. “In the future, if it is confirmed that similar mechanisms exist in humans, we expect our research to lead to optimal dosing and a reduction in drug side effects.”