Cell: How do gut microbes affect drug safety and efficacy?

, June 25, 2020 --BioonBiovalleyBIOON /-- Researchers at Princeton University have developed a systematic approach to assess how the microbiome in our gut chemically converts or metabolizes oral drugs, affecting their safety and efficacynew methods provide more complete images of how gutbacteriametabolize drugs, and may help develop more effective, less side effects, personalized drugsThe study was published June 10 in the journal Cellprevious studies have looked at how a single species of gutbacteriametabolize oral drugsThe new framework can assess a person's entire gut microbiome at oncePhoto Source: Janie Kim"Basically, we don't shy away from the complexity of the microbiome, we embrace it," said Mohamed SDonia, an assistant professor of molecular biology at theof Published in CellThis approach allows us to gain a general and more realistic view of drug metabolism"
research team used this method to assess the effects of gut microbes on hundreds of common drugs on the marketThe intestine is the main part of the body where pills and liquid drugs are absorbed by the bodyresearchers found 57 gutbacteriacould alter existing oral drugsEighty percent of them have not been previously reported, underscoring the potential of the method to reveal unknown drug-microbiome interactionsthese changes include converting drugs into inactive conditions (which reduce severity) to converting drugs into toxic forms that can cause side effectsthe framework can help drug discovery and inform formula changes by identifying potential drug-microbiome interactions early in developmentThis approach can also help to better analyze the toxicity and efficacy of the drug being tested in theofclinical trialsgut is home to hundreds of bacteriaThe composition of these communities -- the type of bacteria and the number ofeachbacteria -- varies from person to person"This human-to-human difference underscores why a single bacteria species makes it impossible for individuals to compare the metabolism of microbiome sespressos," Donia said We need to study the entire gut microbiome "
researchers found that the microbiome in some people had little effect on a given drug, while others had significant effects on the microbiome, demonstrating the importance of bacterial communities -- not just a single species -- for drug metabolism "Everyone's microbiome is unique, and we can see that in our study," said Bahar Javdan, M.D He is a graduate student in molecular biology and co-author of the study "We looked at three broad categories of drugs -- drugs in our study that were consistently metabolized by all microbial communities, drugs that were metabolized by certain microorganisms and not other microbes, and drugs that were not affected by any microbial-derived metabolism." this approach is valuable for personalizing the microbiome of each patient For example, the framework can help predict the behavior of a drug and suggest a change in treatment strategy when it predicts adverse effects "This is a case of medical and ecological conflict," Jaime Lopez said She is a graduate student at the Lewis-Sigler Institute for Integrated Genomics and one of the first authors of the study, which calculated and quantitatively analyzed the data "
bacteria in these microbiomes help each other survive and affect each other's enzyme spectrum If you don't study it in the microbiome, you'll never capture it "
the framework consists of four steps to systematically assess the role of gut microbes in drugs first, the researchers collected 21 fecal samples from anonymous donors and classified the types of bacteria in each donor They found that each donor's gut lived with a unique microbiome, and that most of these personalized communities could grow in the laboratory culture systems they developed Picture Source: Next, they tested 575 The FDA approved drugs to see if they were chemically modified by one of the 21 cultured flora, and then tested for a portion of the drug with all cultured flora Here, they found microbial-derived metabolites that have never been reported before, as well as metabolites that have been reported in humans to be associated with side effects but whose origin is unknown They found that in some cases the donor's microbiome had the same reaction to the drug, while in other cases only a portion of the microbiome had the same reaction then they looked at the mechanisms by which some of the modified drugs were cultured with microbial changes To understand exactly how transformation occurs, they tracked the source of the chemical transformation and the specific types of bacteria and the specific genes in these bacterial They also showed that microbial-derived metabolic reactions found in this way could be reproduced in mouse models, the first step in the development of human drugs (BioValleyBioon.com) references: Study sifs sitor s for the gut microbiome to alter drug safety and efficacy
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Personalized mapping of drug metabolism by the human gut microbiome ," Cell (2020) DOI: 10.1016/j.cell.2020.05.001
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