肠道微生物 z-bo 2020-10-07 288

　　Researchers at Princeton University have developed a systematic method to evaluate how the gut microbiota chemically transforms or metabolizes oral drugs, thereby affecting their safety and effectiveness.

　　The new method can provide a more comprehensive understanding of how intestinal bacteria metabolize drugs, and may help to develop more effective, more personalized drugs with fewer side effects... Previous studies examined how gut bacteria metabolize oral drugs. The new framework can immediately assess the entire human gut microbial community.

　　Mohammed S. Donia, assistant professor of molecular biology, said: "Basically, we cannot escape the complexity of the microbial stage, but we accept it. This method gives us a more comprehensive and realistic understanding of the drug metabolism of bacteria."

　　The research team used this method to evaluate the impact of gut microbes on hundreds of common drugs on the market. The intestine is the main part of the body to absorb tablets and drug solutions. Researchers have discovered 57 kinds of gut bacteria that can change existing oral medications, 80% of which have not been reported so far, revealing unknown drug-microbiome interactions, highlighting the possibility of this method of making these changes Conversion to an inactive state (reduce the effectiveness of the drug), conversion of the drug to a toxic form (contains (may cause side effects)

　　This framework can identify potential drug-microbiome interactions early in development, and notify drug changes by notifying drug changes. This method also helps to better analyze the toxicity and efficacy of drugs tested in clinical trials

　　There are hundreds of bacteria in the intestine. The composition (type of bacteria and type of bacteria) varies from person to person.

　　Donia pointed out: "The difference between people is why the study of individual bacterial species is to emphasize what makes it impossible to compare the drug metabolism of the microbiome between individuals. We need to study the entire microbiome of the intestine."

　　Researchers have found that some people's microbial flora has little effect on specific drugs, while the microbial flora of others has a significant effect. This indicates that not only individual species, but also bacterial communities also affect drug metabolism.

　　"Every person's microbiome is unique, and we can see this in research," said Dr. Bahar Jabdan. He is a graduate student in molecular biology and the lead author of the study. "We have observed three major categories of drugs. In our research, all microbial communities continue to metabolize drugs, certain microbes but not others metabolized by microbes. And drugs that are not affected by microbial-derived metabolism."

　　This method can be used to distinguish the microflora of each patient. For example, the framework can predict the behavior of specific drugs and have adverse effects. When predicted, it helps to suggest changes in treatment strategies. She is a graduate student of the Lewis-Sigler Institute of Comprehensive Genomics and one of the first authors of the study, responsible for calculation and quantitative analysis of data. "Bacteria in these microbial communities can help each other survive and affect each other's zymogram. Unless you do research in the microbial community, you will never be able to capture it."

　　The framework includes four steps to systematically assess the intestine. The influence of microorganisms on drugs. First, the researchers collected 21 stool samples from anonymous donors and classified the types of bacteria in each donor. They found that each donor has a unique microbial community that lives in the gut, and most of these individualized communities can grow on the laboratory culture system they developed.

　　Then they tested 575 FDA-approved drugs to see if they were chemically modified by any of the 21 cultured phages, and then some drugs in all the cultured phages. I tested it here and we found that from Metabolites derived from microorganisms that have not been reported, and metabolites found in humans that are related to side effects but whose etiology is unknown. They found that the microbial phase of the donor may have the same reaction to the drug, or only a part of the microbial phase may have the same reaction.

　　Next, I studied how certain modifiers change according to the cultured microorganisms. In order to understand exactly how the transformation occurs, they tracked the source of the chemical transformation, as well as the specific bacterial species and specific genes of these bacteria. They also showed that the microbial-derived metabolic reactions found can be replicated in mouse models. This is the first step in applying this method to human drug development.