Release date: 2017-06-08 In the search for personalized treatment, many studies have focused on differences in individual genomes. However, there is growing evidence that individuals' responses to drugs are not only affected by genes, but that our unique microbial communities—the bacteria and other microbiota that live in the body—are the key to determining efficacy. Researchers now have evidence that healthy people can metabolize certain drugs in different ways, depending on their microbial composition. The findings were presented at the American Society for Microbiology meeting in New Orleans on June 4. Bacteria that settle in the human body "eat" any nutrients around them, whether it is the food in the host diet or the medication they take. However, if a microbe metabolizes a drug to a useless or toxic compound, then eating it will cause us trouble. Leah Guthrie, a computational biologist at the Albert Einstein College of Medicine in New York, has studied data on irinotecan, a drug commonly used in the treatment of colon cancer, which causes severe diarrhea in some patients. Previous studies in mice have found that a bacterial enzyme called beta-glucuronidase can modify the chemical structure of irinotecan and other drugs. Under normal conditions, the liver detoxifies the drug-adding group through the glucuronidation process. But this bacterial enzyme removes the added group and breaks down the drug into a toxic compound. Intestinal flora affects the absorption of drug toxins by patients To understand whether an individual's gut flora affected their metabolism, Guthrie and her colleagues collected fecal samples from 20 healthy people. They used irinotecan to process the sample and measure the compounds produced by the interaction of the bacteria with the drug in the sample. The team found that four of the samples contained high levels of irinotecan metabolic toxins, but there were no significant differences in the types of bacteria found in the samples. When the researchers analyzed the proteins synthesized in the stool samples, they found that those with more bacterial metabolites contained strains that produced more beta-glucuronidase. The levels of protein that transport sugar to cells in these individuals are also significantly higher, suggesting that they are more likely to absorb toxic compounds and develop gastrointestinal problems. Researcher Libusha Kelly, a microbiologist at the Albert Einstein College of Medicine, said researchers are planning to collect samples of cancer patients using irinotecan to determine if this is the case. Matthew Redinbo, a structural biologist at the University of North Carolina at Chapel Hill, is also studying irinotecan, which he believes is a good study of the interaction between intestinal bacterial enzymes and drugs. Redinbo said: "Our most in-depth exploration is to observe intestinal enzymes and study them like human enzymes." Redinbo says the liver removes chemical groups by beta-glucuronidase to treat many drugs used by patients: this means that the effects of microbes are far-reaching. His work in mice has found that some beta-glucuronidase can perform similar modifications to anti-inflammatory drugs, including ibuprofen, which can cause intestinal toxicity during long-term use. There are often individual differences in the therapeutic effects of drugs on some diseases, such as cancer. Image source: Nature There are still many unknown effects of intestinal microbes on drugs. Emily Balskus, a biochemist at Harvard University in Cambridge, Mass., has found that dozens of gut bacteria seem to modify therapeutic drugs, including some to treat Parkinson's disease and anxiety. Bacterial interference may also help explain why animal models do not always predict human drug toxicity because the animal's gut microbes are different from humans. However, there are still many problems. Only a handful of enzyme-destroying enzymes have been discovered, and it is unclear how much intestinal bacteria differ in the human population. For example, a paper published in the June 2 issue of Science magazine pointed out that the anti-HIV drug tenofovir for vaginal gels is not effective for women who have Gardnerella in the vagina. The bacteria quickly break down the drug into inactive compounds, but scientists don't know how the process works or whether it can stop it. In the end, Balskus said, clinicians may be able to screen people's microbes to determine if they are effective for them. If their gut microflora looks a bit problematic, doctors can prescribe some enzyme inhibitors or change the patient's diet to provide an alternative source of food for the bacteria. A study showed that dietary intervention in mice successfully prevented intestinal bacteria from degrading a heart disease drug called digoxin. Redinbo wants to try this technology on humans. He started a biological company and plans to apply for a clinical trial license. In this experiment, the researchers will give cancer patients beta-glucuronidase inhibitors and irinotecan. Still, more research is needed to learn more about the interaction between bacteria and drugs. Therefore, it takes a long time for this treatment to be used by a doctor. 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