[MM4F] Both? Both is Good!

Arizona State University and science are recognizing researchers who address pressing problems. The ASU Science Prize for Transformational Impact honors early career scientists developing innovative solutions to today's biggest challenges. Hear from the inaugural winners on ASU's Lab Coat Optional podcast and visit science.org slash ASU to apply. This podcast is supported by the Icahn School of Medicine at Mount Sinai, one of America's leading research medical schools. The school is the academic arm of the Mount Sinai Health System in New York City. It's consistently among the top recipients of NIH funding. Researchers at the Icahn School of Medicine at Mount Sinai have made breakthrough discoveries in many fields vital to advancing the health of patients, including cardiology, cancer, immunology, neuroscience, and artificial intelligence. The Icahn School of Medicine at Mount Sinai. We find a way. This is a science podcast for August 20th, 2026. I'm Sarah Crespi. First this week, our summer interns are leaving. We have two diverse voices and science journalism interns here to talk about their work that they did this summer with the news team. And after that, I'm going to talk with researcher Leslie Chan about a pill that sends signals about the gut microbiome out through the breath. We are just wrapping up our summer intern season. We have two interns from our diverse voices in science journalism program, and they're going to talk about their time working in the newsroom and some of the stories they enjoyed writing. First, we have Laura. She had the pleasure of writing about the diarrheal disease outbreak happening in the U.S. My name is Laura Martina Gudelo. I am one of the diverse voices interns. Newsroom Science. So first of all, let's get it over with and say the name of this organism. Can you help out with that? Cyclospora cayetanensis. So they've been calling it what? Cyclospora. And cyclospora is the parasite. Cyclosporiasis is the illness. This diarrheal disease outbreak, foodborne illness in the U.S. It's only been happening since May, but it has made a lot of headlines. And some of those headlines are, why don't we know where this is? This is coming from and why can't we stop it? And so you did a really deep dive into that. Was that something that you were interested in going into the story? I was. Anything that is health related sparks my interest. And I know there was some doubts in the newsroom as to, oh, should we cover this? Because everybody else is already covering it. So with Martin, the global health editor, we decided that we would do an explainer because that's a different angle from what we had been seeing in other outlets. We're always looking for a science angle, and it's not that there's new research out there on identifying this disease or figuring out what it's doing to people. It's literally why is the detection so hard? And there's some scientific answers to that as well as political ones. Yeah, because people were focusing a lot on, oh, there has been, you know, of course, funding cuts and CDC suffering, which is true. But the interesting thing is that even if that hadn't been happening, tracing the parasite is so much more difficult than tracing a bacteria that like your baseline. It's really difficult anyway. Yeah, and there's not a good infrastructure for tracking this the way, for example, if there's an E. coli or a salmonella outbreak, which are both foodborne illnesses, there's a lot in place already to nail that down. Yes, exactly. Because historically, bacterial related foodborne illnesses have been tracked much more. And also they cause many more cases annually. So the focus was on them. And actually there is, for example. A database called PulseNet that helps with the DNA of E. coli or salmonella so that health officials can connect cases between different states. But that doesn't exist for parasitic diseases, as far as I know. This is not life threatening in almost every case. And people will just be like, I have a stomach bug and move on with their lives. It's only when it kind of gets to that hospitalization level that it gets reported. That's another one of the challenges is that, sure, you can say, oh, this person, this person has cyclosporiasis only when that person goes to the doctor and has their stool analyzed, which is not like maybe you have diarrhea and you stay at home and then you never get that analyzed. So it's probably an underestimation. There's also this difference between parasites and bacteria. So it's not just how we think about them, but also the biology of these organisms is substantially different. The former cyclospora person at CDC who is not there anymore, and that's one of the problems, but anyway, he explained that it's very challenging for them because they cannot grow the parasite in the lab. Cyclospora only reproduces in humans' small intestine. Basically, scientists are working with a parasite that they can find in your stool. And that is not a lot. You have very few organisms to go with. Also, their genome, cyclospora's genome, is 10 times bigger than that of Salmonella or, or E. coli. So they don't do whole genome sequencing. They just look for little markers in the genome that kind of connect the relationships between. Exactly. The eight marker test is still pretty good, but it's not whole genome sequencing. So it's harder to say like, oh, all of these cases from these people come from the same source because you don't have the entire genetic information. And they're doing a lot of shuffling, unlike bacteria, which are just like, you know, cloning themselves, basically. Reproducing asexually. Because the parasite reproduces sexually. So genes are swapped. So you don't have the exact same genetic information, even if it comes from the same source. That's another challenge on top of everything. All right, Laura, this has been so fun to talk about. And I just want to ask you a little bit about what else you did on your, on your internship. You know, you've already worked at Outlet Scientific Reporting. You've been in school for this, you know, doing an internship at science. What did that bring to your arsenal of skills? So many things, but I would say first, it was my first experience in an American newsroom because I used to work in France. That was very exciting. And the adrenaline of the newsroom is great. Ideas flying around the entire day and like people just pitching stories and writing them and people editing and looking for editors and like everything is moving so fast. I like that adrenaline. I love the fact that I got to work with a lot of editors. I enjoyed working. And some health policy stories that I never had the chance to do before. So that was a first for me. And that was very interesting. Like NIH grant cuts. Also, the new CDC director. There's a lot of policy news to be had, right? Exactly. All right, Laura, thank you so much for talking with me. And I'm so glad that you were here this summer. And good luck with what happens next. Thank you. Laura Agudelo was born in Peru, raised in Colombia and moved to France to pursue university studies. After working as a health journalist and editor at a French clinical journal for family physicians, she attended MIT's graduate program in science writing. I asked our other diverse voices in science journalism intern, Mona Patterson, the same question. You know, she has a lot of experience in different parts of science and reporting. What did working at science in the newsroom this summer get her? A lot of my professional background comes from broadcast journalism. So building. Video packages and editing, which you approach those stories a bit differently than how you approach print and long form writing. And so the biggest thing that I'm taking away is just sort of what that whole ecosystem of the newsroom is like, how you work with editors. I just feel I've learned so much about that process. And that has made me a way stronger writer and gave me the skills necessary to continue writing after this internship and to learn more. So I'm just super excited and thankful. So you've brought a few stories that you worked on during your summer internship. One is on the vagus nerve, which I don't know if people know. This is a big deal in our body and it's just not something that gets a lot of attention. So what is the vagus nerve responsible for? So the vagus nerve is sort of this central component to how our body regulates itself. It does a lot of unconscious functions. So, for instance, it regulates our heart rate, our breathing. It regulates our digestion, our gastrointestinal system. So because it sort of controls all these different functions within these organs throughout our body, and it all comes from a central place, our lower brainstem, it starts as one branch that then branches out into a bunch of finer branches. And within those finer branches, there is a bunch of different nerve fibers. And so if you're trying to stimulate certain nerves, maybe that's going straight to the heart or to the lungs, it's really hard. Because of how intricate this network is. And so researchers have found with different therapies trying to stimulate or trying to reduce pain or epilepsy that it's been hard sometimes to target these certain areas because you're not really sure which nerves are going where. And so what do they do in this study to kind of get a better sense of where everything is? It was a huge thing for them to tackle because the vagus nerve is. - Up to like 200,000, fibers within this nerve that branches into a left and the right. So there's about like up to a hundred thousand nerve fibers in each of these branches. And so trying to figure out where they are and where they're placed around these organs is really difficult. And so the researchers use a bunch of different imaging techniques to try and figure out where they're going. And so they used ultrasound imaging to get this really basic understanding of the anatomy. And then they went in with micro CT, which is an x-ray imaging technique to trace the paths of these nerve fibers. We should point out that this is extracted from cadavers. So they did the imaging and all this micro CT, and now this next step's on the vagus nerves that have been extracted. Right. And so this last technique that they did, so at an even finer scale, the researchers made thousands of thin slices in these nerves that they had, and they exposed them to a bunch of different enzymes. And so they did a lot of research on how to do that. antibodies and these antibodies then bound to specific proteins within the fibers and stained them different colors. That process highlighted fibers that carried these specific neurotransmitters and that let the researchers know what function these fibers had, what organs they were communicating with. And so it was super interesting. A map is only useful if other people can see it, right? Is this something that other people have access to? And how might they use it to kind of, you know, better understand the body or improve So the data set is out right now, and they're putting it together and they're making it interactive. And so that will be out soon. But the hope for this map is that it will help researchers and people who are creating new techniques and therapies to treat these sort of conditions that deal with the vagus nerve. It'll help them to better be able to stimulate these sort of nerve fibers and understand where to place certain devices. How different? How different is this person to person? I think I read in your story that they did it for 30 cadavers. Is that enough coverage to really understand what's going on with me and you? From the conversations that I had, it seems there will always be a level of variability between each individual. And so this map is just helpful in the sense that it's giving a better understanding of where exactly these nerve fibers are, because it has not been mapped to this extent before. Even though it is a map, it's a map of the body. It's a map of the body. It's a map of the brain. The researchers also feel that this variability will be able to help explain maybe why some procedures do work better for others and maybe don't work for other people. All right, Mona. Thanks so much for coming on. Thank you. Mona Patterson is a diverse voices in science journalism intern at Science, and we are so happy to have her here and sorry to see her leave. Mona Patterson graduated from Chapman University in 2025 with a broadcast journalism degree. She has previously interned at NASA's Jet Propulsion Laboratory and the Smithsonian Environmental Research Center. After this, she will participate in a fellowship at University of California, Irvine's Community Geoscience Initiative. Pros, find the right flooring for the job in Lowe's newly redesigned flooring showroom. Shop our expanded assortment of trusted brands and get up to 35% off style, collections, stain master, and stain master pet protect special order carpet. And while you're here, save $100 on a DeWalt 20 volt max six amp hour, two pack of batteries. Now just $179. Get more of what you need faster and save more where it counts from the ground up. Our best lineup is here at Lowe's. Valid through 826 while supplies last. Selection varies by location. This episode is brought to you by State Farm. Listening to this podcast instead of doom scrolling, smart move. Another smart move, getting help from one of State Farm's 19,000 local agents when you choose to bundle home and auto. Bundling, just another way to save with the personal price plan. Prices are based on rating plans that vary by state. Coverage options are selected by the customer. Availability, amount of discounts and savings and eligibility vary by state. Also out on the site this week, we have a feature story by Kai Kupferschmidt on how AI chatbots are becoming experts at changing people's minds. His story talks about how studies show that chat GPT and other AIs use a flood of facts and the occasional lie to persuade people. This is part of an ongoing series that Kai is working on on misinformation. So definitely worth checking out this feature and the previous two. From commentary this week, I'm going to call out this letter from Paul L. Fox. He's looking back at August 20th, 1976. So a month after Viking 1 landed on Mars. Fox was on the Viking Lander imaging team. And at that time, he was able to take the first picture of a sunset on another planet. From the journal side, we have a science paper by Malisko and colleagues, that's M-A-L-E-S-C-O-T, on how functional MRI imaging depends on a relationship between brain activity and blood flow. But in the study, they show that different activities like touch or pain evoked similar net neuronal activity, but dramatically different blood flow changes. This could have important implications for evaluating fMRI imaging data. I wanted to call it one more paper, this one from Science Advances. It's by Saxena et al. on potential survivable niches for microbial life on the lunar south pole. Basically, there are parts of the moon that they modeled and used survey data to kind of say, maybe these could be a safe place for microbes on the moon. Okay, back to the main show. We have researcher Leslie Chan talking about an ingestionary metabolic probe for the gut microbiome. Our gut microbes provide us with many things, but they can also cause us some problems. You've probably seen probiotics, prebiotics, these supplements that aim at fixing imbalances in the gut, but it's actually not easy to figure out what exactly is going on with these millions of microbes that live inside of us. This week on Science Advances, we're going to talk about a pill that would encounter certain enzymes from microbes in the gut, sends out a signal in the breath. It's an ingestible metabolic probe for the gut microbiome. Hi, Leslie, welcome to the Science Podcast. Hi, thanks for having me. Let's start back up at the problem that you were trying to solve, the activity you were trying to detect. Then we'll work our way over to how the pill works, and then we'll get into how this might be more generalizable or something we think of as a platform. What, in this case, were microbes doing that you were worried about or that you wanted to detect? What was the activity you're interested in? Our gut microbiome produces a lot of enzymes, and enzymes are just proteins that help catalyze chemical reactions. In this case, we were interested in this drug-metabolizing enzyme, or DME, called beta-glucuronidase, which reactivates drugs in the GI tract. Oftentimes, when we take drugs, the liver will detoxify the drug by adding certain chemical groups. Once those modified drugs are expelled into the GI tract to be expelled in stool, it encounters beta-glucuronidase from the gut microbiome, which then reactivates the drug locally in the intestine. When you have these high local concentrations of active drug, the unintended consequence is that it causes toxicity to intestinal tissues. That's what we want to detect is that sort of activity that's causing the toxicity. This is things like chemotherapy. You're giving somebody a drug, and it's taking an effect in the body, and then the body goes to clear it, and some microbe down there in the gut is turning it back on and making you sick. How would you normally go and try to find out if this was happening? What are the other approaches that people have tried in the past? Stool-based assays are possible, but they're, again, stool-based and require multiple steps. It's not like one microbe makes this one enzyme. A bunch of different microbes could make it, so even a genetic scan would necessarily tell you what the activity is like. Exactly. So it might tell you if the gene is present, but it doesn't tell you if it's active, if the beta-glucuronidase is expressed and active. So essentially, the probe is picking up the activity at the very end of this expression and any sort of modifications that might alter activity. How exactly does the pill work? Are you presenting this enzyme with some kind of tasty target molecule? The probe itself is comprised of ingestible compounds. So it's a sugar molecule that the enzyme recognizes, and it's a volatile organic compound or gaseous reporter. The gaseous reporter we use is generally recognized as safe and actually used as a food flavoring. Both combined actually create this ingestible probe, and so once it's ingested, it'll travel through the stomach, through the small intestine, and then the large intestine intact until it is essentially broken down by the beta-glucuronidase enzyme. Once it's broken down, it releases the reporter, which is cleared in breath. Yeah, I was surprised by this. So a lot of people will ask me, oh, so is the reporter just like burped up? Where do gases go when you make them in your gut? Right, exactly. But the way that it traffics to breath is actually it diffuses across the intestinal lining into blood circulation. And then in the lungs, we have these capillary beds where we have pulmonary gas exchange. So then the. reporter diffuses from the blood into the lungs and is then exhaled. We don't have to test burps or farts. We can test. No, not yet. Maybe in the future. That is very cool. When you tested this in mice, you're going to feed them this chemical that when broken up by the enzyme gives you the reporter. What were you most concerned about or the hurdles you wanted to make sure you get over when testing this in an animal model? We wanted to make sure that the probe was stable in transit through the GI tract. Yeah, like the stomach, dangerous. Right. Dangerous. Exactly. The stomach has a lot of different enzymes. It also produces and it has very low pH. So we want to make sure that the probe is only broken down by the enzyme. So that level of specificity is important for actually detecting the enzyme activity that we're interested in. Other things we were wary of or we knew to be careful of is we're completing these preclinical studies in mice. So they're very different than humans. So they have very low volumes when they're breathing, although their breathing rates are much more rapid. So we also have to think about the sensitivity side of things. We just are bigger volume. Right. Right. That's super interesting. So what did you use to detect the molecule in the breath? We used mass spectrometry, and that is basically a tool that detects molecules through mass space detection. So our reporter is a specific. Molecular weight. And we can specifically detect that compound in breath. One other thing I was concerned about with this difference between humans and mice is that their gut microbiomes might be very different than ours. Like, are we sure this will kind of translate? That's a fair question. Their microbiomes are very different from ours. What we were very fortunate with is that their microbiomes also have beta glucuronidase expressing microbes. And so as models for that activity, they actually. Were very suitable because they had those enzyme activities already present in their gut. How quick is the turnaround from eating a pill and getting a breath result? For this work. For a tiny mouse. Yeah. For this work, it is in the two to four hour window range. Once the probe itself is cleaved, it takes on the order of minutes for the reporter to traffic from the where it's cleaved to breath. So what that means is the breath collection time is dependent on when the. Probe enters the large intestine, which is where the gut microbiome mostly resides for humans. For example, usually these sorts of probes will enter the large intestine after the 90 minute mark. So an hour and a half in, then we might start breath collection. For our preclinical studies, we found that they entered the gut between hours two and three. Is the readout from this probe useful for different disorders, you know, past how microbes might be affecting chemotherapy toxicity? The beta glucuronidase activity that we focus on here has directly been implicated in GI toxicity from this cancer therapeutic. More broadly, these activities or this particular activity has been implicated in the recycling of potential carcinogens in the body as well. So you can imagine that any sort of foreign molecule that is introduced into the body, even if it's introduced with good intentions like drugs, there has to be a certain amount of activity that is involved in the body. There has to be a way for the body to expel these compounds. And so beyond drugs, there are potential carcinogens that enter the body. And if we have this enzyme that reactivates them after the liver DMEs have detoxified them, then you're essentially creating this loop in which we have this reintroduction or recycling of the carcinogen in the body. So beyond drug-induced GI toxicities, this has implications in how carcinogens make a difference in the body. might be recycled in the body and could eventually cause cancers. The liver is basically tagging things and saying, you're not active anymore. You're going to get out of here. This enzyme is undoing that generically. It's not just targeting a specific drug. It's targeting that bond that the liver is creating to kind of protect the body for excreting this molecule safely. It can be generalized in that way. Exactly. Could other enzymes, other molecules be tracked this way? This is very specific what's in the paper. We know the enzyme and you're able to get its substrate, which is something that is not toxic, attach it to something that's not toxic, and then that bond is broken by the enzyme and you get your signal. Is this something that you can kind of build on and target other functional molecules in the gut for breath testing? For this one paper, we're focusing on a drug metabolizing enzyme, but we know that the gut microbiome produces many other types of enzymes that have implications for other diseases, like our ability to digest dietary sugars, our ability to prevent inflammation in the gut. What that means is that we can modify these probes quite easily to detect other enzymes so that we can use these breath signals that we're producing to potentially detect other types of GI diseases, to look at other potential harmful or helpful activities from the gut microbiome, and so forth. Beyond the gut microbiome, we can also pick up host enzyme activity, so human enzyme activities, to essentially use those as biomarkers for other GI diseases. Wow. So this is kind of, you can imagine a panel of digestible probes that gives you back a panel of breath that tells you a little bit about the profile of what's going on in your gut. Exactly. This sort of approach is relatively new. It's this emerging paradigm that we call induced volatilomics. So usually breath contains thousands of distinct volatile organic compounds already, but there's been difficulty in identifying which of these volatile compounds are actually indicative of disease. Our approach is, instead of relying on these naturally occurring volatiles, is there a way to induce the exhalation of volatiles that we essentially use as breath biomarkers? So that's more broadly the strategy that we're using for many types of diseases, not only GI diseases, but lung diseases and diseases of other tissues and organs. Okay, Leslie, but we never ended up talking about yogurt and probiotics. So you kind of touched on this at the beginning, where you mentioned now there are a lot of microbiome modulating therapies that are coming out. Like, a lot of us take prebiotics and probiotics. There are a lot of nutraceuticals, not necessarily FDA regulated, to try to help us create a healthy gut microbiome. And now we also have fecal microbiota transplants, or FMTs, to help treat certain diseases, like C. diff infections. So these sorts of tools are important so that we can have some sort of way to assess efficacy of these treatments that we're saying are helping our gut microbiome. So now we have maybe more quantitative measures to validate these ingestibles that are supposedly helping our gut microbiome. Absolutely. That's great. Thank you. Leslie Chan is an assistant professor in the Wallace H. Coulter Department of Biomedical Engineering at Georgia Tech and Emory School of Medicine. You can find a link to her Science Advances paper at science.org/podcast. And that concludes this edition of the Science Podcast. If you have any comments or suggestions, write to us at [email protected]. To find us on podcasting apps or on YouTube, search for Science Magazine Podcast. Or, as always, you can listen on our website, science.org/podcast. This show was edited by me, Sarah Crespi, and Kevin MacLean. We had production help from Podigy. Our music is by Jeffrey Cooke and Wenkhoi Wen. On behalf of Science and its publisher, AAAS, thanks for joining us. I didn't like what you said, Odin pauses, about the future. This is the love story of real-hinge couple Odin and Edward, written and read by me, Curtis Garner. Listen to the free audiobook now. You listen to us to hear about new discoveries in science. But did you know we're a part of the American Association for the Advancement of Science? AAAS is a nonprofit publisher and a science society. When you join AAAS, you help support our mission to advance science for the benefit of all. You can become a AAAS member at the Silver level or above to receive a year's subscription to science and an exclusive gift. Join today by visiting AAAS.org/join. That's AAAS.org/join.