Drugs and gut bugs
Researchers are starting to uncover how medications affect bacteria in the gut, and vice versa.
The bacteria that inhabit the digestive tract do more than just help to break down food. Scientists are increasingly discovering that having a healthy and diverse community of gut bacteria is essential to overall health. Changes in these communities may increase the likelihood of harmful inflammation and diseases like obesity.
Medications may alter the gut bacteria; for example, antibiotics used to treat infections may wipe out beneficial bacteria in the digestive tract. Other drugs like nonsteroidal anti-inflammatory drugs (NSAID), which are sold over-the-counter to treat headaches and by prescription to treat pain, are known to damage the lining of the digestive tract. However, it was not clear how this affects the communities of bacteria in the gut.
Xue Liang and co-workers have now used genome-sequencing tools to determine which types and quantities of bacteria are normally present at various points along the digestive tract of healthy mice. The mice were then treated with an NSAID called indomethacin, which shifted the composition of intestinal bacteria towards a community that promotes inflammation.
Liang and co-workers then treated mice with antibiotics before giving them indomethacin to reduce the overall number of gut bacteria. These bacteria-depleted mice showed altered metabolism of indomethacin, and reduced blood levels of the drug, as evident in the production of fatty molecules called prostaglandins in the body. This is because the interactions between the gut bacteria and indomethacin modifies the inhibitory effect of indomethacin on enzymes known as COX-1 and COX-2. This may explain why some drugs work better in some people than others, as different people have different bacteria in their guts.
In the future, Liang and co-workers aim to investigate whether the communities of gut bacteria would be differently influenced by specifically inhibiting the action of either COX-1 or COX-2, given that drugs that inhibit COX-2 cause fewer gastrointestinal complications. There are also plans to explore whether alterations in the communities of gut bacteria are a driver or a passenger in gastrointestinal ailments, following ingestion of indomethacin. Previous work has shown the influence of the host molecular clock on gut bacteria. Therefore, Liang and co-workers will also ask if taking indomethacin at different times of day might improve how well the drug works and cause fewer side effects in animal models and eventually in humans.
To find out more
Read the eLife research paper on which this eLife digest is based: “Bidirectional interactions between indomethacin and the murine intestinal microbiota” (December 23, 2015)
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