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又到了每周一次的 Nature Podcast 时间了！欢迎收听本周由Benjamin Thompson和 Shamini Bundell 带来的一周科学故事，本期播客片段讨论肠道菌群对口服药物的影响。欢迎前往iTunes或你喜欢的其他播客平台下载完整版，随时随地收听一周科研新鲜事。 音频文本： Host: Nick Howe Ugh, I’ve got such a headache. Host: Shamini Bundell Big night last night? You have no tolerance for alcohol. Host: Nick Howe You can talk. Host: Shamini Bundell Better take some aspirin. Host: Nick Howe Aspirin never works for me. Host: Shamini Bundell So, you’re rolling on the floor after half a pint of cheap ale but have a high tolerance for aspirin? Host: Nick Howe Yeah, it is kind of weird, but people do have big differences in their responses to all sorts of drugs. Things like gender, age, size – they all seem to have an impact, and this week in Nature, there’s another idea. Interviewee: Michael Zimmermann Our hypothesis was that the microbiome might play a role. Interviewer: Nick Howe This is Michael Zimmermann, a microbiome researcher from Yale University. Since most oral drugs are absorbed in our gut, Michael wondered if the diverse microorganisms that live there could be a major reason people can react so differently to drugs. Michael’s been asking one core question. Interviewee: Michael Zimmermann Can microbes metabolise clinical drugs? Interviewer: Nick Howe Michael took 271 different drugs and incubated them with 76 different kinds of bacteria commonly found in the human gut. Interviewee: Michael Zimmermann The results were quite striking. We found that out of the test of 271, almost two thirds of those tested drugs could be metabolised by at least one of the bacterial species and strains that we tested. Interviewer: Nick Howe Drugs were disappearing from the petri dishes, which meant they must be getting altered in some way by the bacteria – in other words, metabolised. And metabolising drugs may change their efficacy or make them stop working completely. Michael wanted to identify which genes in the bacteria could be responsible for all this metabolisation. So, he and his team took one bacterium that was metabolising lots of drugs and chopped up its genome. Then they inserted the chunks of DNA into a bacterium that previously had no effect. If the modified bacteria could metabolise a drug, then the piece of DNA that had been inserted was responsible. Interviewee: Michael Zimmermann We were able to identify a total of 30 gene products from the microbiome that collectively metabolised 20 different clinical drugs. Interviewer: Nick Howe Seeing things in a petri dish is one thing but seeing them in complex organisms is another, so Michael wanted to test these findings in animals. He used his new knowledge of drug-busting genes to manufacture strains of bacteria that metabolised the drugs and strains that couldn’t. He inserted each of these strains into mice that previously had no gut microbes at all and then gave the mice the drugs. Interviewee: Michael Zimmermann We found that the drug reaches the lower intestine where most of the bacteria live and we also found that the genes that we tested also converted the drug in the mouse. Interviewer: Nick Howe The test in mice used single bacterial strains. But humans all have unique cocktails of microorganisms in their guts. With all those microbes interacting, could this also be happening in humans? Michael looked for signs of drug metabolism in faecal samples from a range of healthy people. Interviewee: Michael Zimmermann And what we find there is actually first of all, there was quite a big difference between communities from different individuals. So, some communities, microbial communities, metabolised certain drugs very quickly, whereas others were very slowly or even incapable of metabolising a given drug. Interviewer: Nick Howe The abundance of the genes Michael had identified in the human samples was a good predictor of how quickly certain drugs would be metabolised. For other drugs, though, it was the presence of a particular species or strain of bacteria that had the biggest impact. Melissa Herbst-Kralovetz, a microbiome researcher not associated with this study, thinks this may pave the way for doctors to choose the most effective drug for individual patients. Interviewee: Melissa Herbst-Kralovetz These bacterial genes that metabolise particular drugs, we can use that as a way to predict whether a patient is going to respond or not respond to a particular drug as well as potentially if they will have toxic side effects. Interviewer: Nick Howe Up until now, most studies have shown correlations between the microbiome and the effectiveness of drugs, but this study is one of the first to dig into how these associations work. Melissa was impressed by the effort to draw causal links. Interviewee: Melissa Herbst-Kralovetz It’s really exciting how comprehensive this study was and how they utilised a lot of different methods and incorporated these mechanistic experiments to better establish this causal link between how the bacteria are metabolising these drugs. Interviewer: Nick Howe Better understanding the causal links in drug responses may mean scientists are able to do more with our gut microbes. Interviewee: Melissa Herbst-Kralovetz Unlike out host genome, the gut microbiome is modifiable through diet, antibiotic usage, faecal microbiome transplant, and this could really have important implications for expansion or contraction of the metabolic functions of that community. Interviewer: Nick Howe That was Melissa Herbst-Kralovetz from the University of Arizona in the US. You also heard from Michael Zimmerman from Yale University, also in the US. You can read Michael’s paper over at nature.com.ⓝ Nature Podcast每周为您带来科学世界的全球新闻故事，覆盖众多科研领域，重点讲述Nature期刊上激动人心的研究故事。我们将话筒递给研究背后的科学家，呈现来自Nature记者和编辑的深度分析。在2017年，来自中国的收听和下载超过50万次，居全球第二。 |
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