Cell drug failure? The gut microbes are "making a fuss"! Reveal the potential of gut microbes to change the safety and efficacy of drugs.

Introduction: human intestinal microflora is the largest and complex microbial community in the human body, and is also an important metabolic organ of the human body.many oral drugs will be changed by human intestinal microbiota, which will affect the therapeutic effect of patients.however, there are significant differences in individual response to oral medication.this reveals the influence of intestinal microbiota on drug response, but the underlying mechanism is still unclear.recently, researchers at Princeton University have developed a systematic approach to assess how our gut microbiota can chemically transform or metabolize oral drugs in a way that affects the safety and efficacy of drugs.the new method provides a more complete picture of how intestinal bacteria metabolize drugs, and can help develop drugs that are more effective, have fewer side effects, and are personalized for individual microbiota. The study was published June 10 in the journal Cell.previous studies have examined how a single species of intestinal bacteria metabolize oral drugs.the new framework can simultaneously assess a person's entire intestinal microbiota.background and prospects of the study, Mohamed s. Donia, an assistant professor of molecular biology, said: "basically, we don't escape the complexity of the microbiota, but we accept it.this approach enables us to have a holistic, more realistic view of the contribution of microorganisms to drug metabolism."the team used this method to assess the impact of intestinal flora on hundreds of commonly used drugs on the market.the intestinal tract is the main part where pills and liquid drugs are absorbed by the human body.the researchers found that 57 cases of intestinal bacteria can change the existing oral drugs.80% of them have not been reported before, which emphasizes the potential of this method to reveal the interaction between unknown drugs and microorganisms.these changes include the conversion of the drug into an inactive state, which reduces the efficacy of the drug, while the conversion of the drug to a toxic form may cause side effects.this framework can help to discover drugs and inform formulation changes by identifying early developments in potential drug and microbial interactions.this method can also help clinical trials to better analyze the toxicity and efficacy of the tested drugs. the intestinal microbiota varies from person to person, and the gut is home to hundreds of bacteria. the composition of these communities, such as the type of bacteria and the number of each bacterium, varies from person to person. this difference between people highlights why studying a single bacterial species makes it impossible for individuals to compare drug metabolism in microbiota. what we need to study is the whole gut microbiota. "the researchers found that some people's microbiota had little effect on a given drug, while others had a significant impact on it, suggesting the importance of bacterial communities, not just single bacterial species, in drug metabolism. Bahar javdan, PhD student in molecular biology and co-author of the study, said, "everyone's microbiota is unique and we can see that in our research. we have observed three major categories of drugs. In our study, all microbial communities can metabolize drugs, drugs metabolized by some microbial communities, and drugs that are not affected by the metabolism of any microbial community. "this method is valuable for personalized treatment of each patient's microbiota. for example, the framework can help predict the efficacy of a drug, and if adverse effects are predicted, it is recommended to change the treatment strategy. Jaime Lopez, a Lewis Siegler graduate student in integrated genomics and co-author of the study, said, "this is a case of medical and ecological collision. We calculated and analyzed the data and found that bacteria in these microbial communities help each other survive and influence each other's enzyme profiles. if you don't study it in the microbial community, you'll never catch that. The framework consists of four steps to systematically evaluate the effects of intestinal microorganisms on drugs. first, the researchers collected 21 fecal samples from anonymous donors and classified the bacterial species in each individual. they found that there was a unique microbial community in the donor's gut, and most of these personalized communities could grow in the laboratory culture system they developed. next, they tested 575 FDA approved drugs to see if they were chemically modified by one of the 21 cultured microorganisms, and then tested some of the drugs with all the cultured microbial communities. here, they found microbial derived metabolites that have never been reported before, and metabolites related to side effects reported in humans, but their sources are unknown. they found that in some cases, all donor microorganisms had the same response to the drug, while in other cases, only a fraction of the microbial population produced the same response. then, they studied the mechanisms by which some modified drugs were cultured. to understand exactly how these transformations occur, they tracked the sources of chemical transformations to identify specific bacterial species and specific genes in these bacteria. they also showed that the microbiota derived metabolic reactions found in this way can be reproduced in mouse models, which is the first step in the development of this method for human drugs. reference: [1] [2] recommended reading: anti epidemic, translational medicine network content team report: new discovery: scientists have discovered T cell subsets, which can reduce the risk of respiratory allergy and asthma [essence review] Professor Wang Suxia shared the application of electronic microscopes in clinical disease diagnosis and Research (real hammer) first confirmed: high salt diet will be changed in. 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