• Gut bacteria affect how drugs work, research finds


    CHANGES in the usually benign microorganisms that live in a person’s digestive tract brought on by antibacterial or antibiotic drugs likely have an effect on how the body responds to medication, including side effects the patient might suffer, a new medical research in Japan has discovered.

    Researchers at the Kumamoto University carried out the study, and published their findings in the journal Molecular Pharmaceutics.

    Antibacterial and antibiotic drugs are often prescribed for the treatment and prevention of bacterial infections and often taken with therapeutic drugs to prevent recurrence of infection. Unfortunately, the drugs affect not only harmful bacteria, but also the naturally occurring bacteria in the intestines, the study explained.

    To determine what changes were caused by the drugs, the researchers examined protein changes in the liver and kidney as a result of antibacterial drug consumption. Changes in these proteins have a great influence on drug efficacy and side effects since they are responsible for the metabolism and transport of many drugs, and are also affected by changes in the intestinal flora.

    The research was conducted using three groups of mice: An experimental group of germ-free mice which were free of intestinal bacteria since birth; a group of mice that had received antibacterial drugs for five consecutive days; and a control group of mice with naturally occurring intestinal flora.

    The researchers detected significant changes in the levels of proteins involved in drug metabolism and transport in the liver and kidneys of the mice, which could have implications for drug formulation and dosing, as these proteins are very similar to those found in humans, the study concluded.

    “The most significant drug-metabolizing enzyme that decreased was cytochrome P450 2b10 (Cyp2b10),” said Professor Sumio Ohtsuki, who led the research project. “Not only was the amount of the enzyme reduced nearly 96 percent, but the metabolic capacity of the drug in the liver was also reduced by approximately 82 percent. Cyp3a11, a similar type of enzyme, was also reduced by about 88 percent.”

    The human equivalent of these two enzymes, CYP2B6 and CYP3A4, are reported to be related to the metabolism of more than half of the pharmaceuticals on the market, Ohtsuki noted.


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