The Microbiome with Katrine Whiteson 2026-02-17 13:00:00.000 +00:00 David, I'm always amazed that at the end of the day, despite all of our technology, everything we're doing with speakers and electronics is still just magnets and copper wires. It's pretty remarkable when you think about all the intricate interactions and subtle divisions of labor that went into this thing that that you, the listener, are hearing in your ears right now. Um it's pretty mind blowing. Yeah, I just I think it's worth just pausing for a moment to appreciate that. Yeah, maybe we should have like a prayer, a meditative uh silence, yeah. Um but but during this silence, we can just reflect on the fact that this is a podcast. Yes. Um, and it's uh co-hosted by me, David Pinsoff, and uh my co-host Dave Petrozki. You said that like that might not be me, but it is me, right? That that would be you. I mean, unless there's another person named Dave Petrozowski who's been um showing up. There's only a couple of us. If you do a search, there's only a couple. There's no not many. So I think there's like five in the US. One of them, though, uh does GPS research. And so occasionally I get a graduate student application for somebody who's like interested in GPS technology on buoys in the Navy or something. And I I have to politely forward it along to the other David J. P. Trazewski, in fact. Yeah, I ironically, a person got lost looking for the GPS researcher. Yeah, exactly. First, first hoop not jumped through. Yeah. David, are there other David Pence offs? Uh not to my knowledge. It's a pretty rare last name, actually. Yeah. So is this all going in the intro? Is this going to be but are we eventually going to get to the title of the podcast? Uh what is the title? Uh it's Evolutionary Psychology the podcast. Yeah. Oh wait, we forgot to say actual evolutionary psychology by actual evolutionary psychologists. David, many times we have people on who do psychology or anthropology, um, but we're wading into new territory here with uh somebody who does work on the microbiome. Yeah. Um, it is the coolest, hottest topic in science now, if I could share that opinion. Do you agree? I feel like it's really an interesting topic. I have people are just uh I I have no idea what is the hottest topic in science other than artificial intelligence, which I think is. Well, yeah, that's a big one. But um I feel like I see microbiome stuff all the time. You know, uh probiotics. I feel like I see the stuff on on TikTok. The kids are talking about the microbiome. Are they? Yeah. Okay. Uh yeah. Well, you're in LA. We're in sleepy Santa Barbara, so we don't, yeah, we're like 10 years behind. Um I think this is the episode that uh sometimes people say, I wish the episodes had more practical advice for my everyday life. And if you want practical everyday advice for your life, I think this is the episode for you. Yeah, there's there's some really good practical advice. And also it's just a mind-blowing uh tour of what the microbiome is. Uh All the different details and facets of it. Like I found it absolutely fascinating. I feel like I learned so much listening to this. Um, I actually grocery shop differently, even though so I had seen so this is uh Katrina Weitzen, and she is um um at UC Irvine, and she gave a talk at the John Patton uh Memorial Symposium, and it just blew my mind. And so I wanted to invite her on the podcast and uh the work she's doing on the microbiome. She's like one of five labs doing this kind of work. It's incredible, cutting edge science with immediate real world implications. And again, it's coming from an evolutionary perspective, thinking about the ways in which our diet might be mismatched from the way that we're designed. Yeah. It's just incredibly mind expanding to think about the whole ecosystem of microbes that's living inside of you and how they've evolved symbiotically with us. And you know, we get into how you can often trace um the the genetics of a human better by looking at their microbiome than by looking at the human uh themselves and their DNA. Um uh it's just really fascinating stuff. Um, I think you'll really enjoy this one. Yeah. So uh enjoy along with your very, very large number of uh microbiomes that are also along for the ride as you listen to this episode. Yep. Enjoy. All right. Um, so today we have Katrina. Um, is it Whiteson? Is that Whiteson? Yeah. Whiteson. Um, I met you at John Patton's memorial seminar. Um, and I was just before we started recording, I was saying how just incredible um your talk was, and we got a chance to talk, and I think completely differently about which sounds like a boring thing, fiber. But but you study microbiome, you study your incredible, um just incredible research, and we want to get into it. But I want to start by asking the uh maybe as a lead-in to um John Patton. So you were can you talk us through how did you get involved working with John Patton? And what what is somebody who's studying microbiomes doing talking to John Patton. And how did you guys meet, or how did you start working together? What did you do? Great story and a great question. So when I so I started a lab at UCI in 2014, and I think I met John Patton within a couple years of that time. Um, right around the time I started my lab, uh the uh we recruited this um famous salivary scientist named Douglas Granger, and he started the salivary biosciences institute here. Wow, a salivary scientist. I was not even aware that such a field existed. And I'm there, I'm sure that uh Professor Granger has many titles beyond Salivary Scientist. Um, but he had a big research. I'm drooling to learn more about that. Salivating at the thought. Yeah. Yeah. In fact, they would do these workshops, and then you you'd get a mug that said something about saliva in really big letters, and then Eclastad is like drinking coffee out of this mug that says saliva on it. I can't imagine like the titles of papers in that literature. It just gotta be so funny. It's just like rife for a lot of spit ticks. Oh my gosh. So so John Patton um knew somehow was connected with Douglas Granger. I don't exactly know how they uh got to know each other, but um, but Douglas Granger, who was here ECI, facilitated my introduction to John Patton. And I remember we all met together, and John shared his story of the people he was working with in Ecuador and just the possibility that we could study the microbes living in the saliva samples, which then we extended to chicha, of course, and even to chica. What is what is chicha just for preparing? I don't think we've talked about I I don't know if we've talked about chicha. Uh yeah. I've heard some stories from Clark about chicha that were that were very fun, but it's worth um yeah worth repeating yeah yeah definitely. Um so chicha is a fermented beverage that people in Ecuador and other parts of South America make. And I mean, they really subsist on this bev on this fermented beverage, which is made by having the women of the household chew on um starchy root vegetables like yucca, and they chew the vegetable and then spit it into a vat, and it's like a communal activity, and then they let the vat ferment for a couple of days, and it gets to have mild alcohol content like a kombucha or a light beer. But the amazing thing about it is that people get something like 2,500 or 3,000 calories a day from drinking chicha. And it's it's like a water purification method, too. People really depend on it. Like when a hunting party goes on a trip for a few days, if they run out of chicha, everyone has this feeling of impending doom, like we're gonna die. And maybe they're right. If they drink water, they could get diarrheal illness. Like there's so many reasons why it's so important. Um, and anyhow, it's it's uh it's a fermented beverage that's really important to the food culture in Ecuador and nearby parts of the world. Amazing. So it's like a source of hydration. Uh yeah. Approximately. Sorry, sorry, David. Go ahead. Just out of curiosity, uh, what does it taste like? I for all the times I've spoken about it, I actually haven't tried it. I didn't go to Ecuador with John Patton. So I've just heard about it. I really should go. And yeah, that would be a good idea to go. I do personally brew kombucha at home, which I know is not the same thing, but you know. Um I do remember uh trying something that was advertised as chicha. I doubted it as the authentic thing. So I was in Nicaragua with my wife for our honeymoon at a resort, and they had something on the menu called Chicha. I doubt it's very similar to the one that um is actually made in these local communities. But um from what I remember, it was just kind of like really sour, kind of tasted like a sour beer. Yeah, I think it basically a sour beer is a great way to put it. And um actually Doghead Brewery, they made a single batch of chicha a few years ago that my grad student who worked on this project, he was really into brewing beer, and he I know he was really into that, but I didn't get to try it myself. Cool. So uh so John Patton, so we you the uh we cut you off, sorry. Yeah, we cut you off into the city. Too many exciting things to yeah. Well, I mean, there's a there's a lot to say, and you guys know John Patton was a talker, right? So I mean I've got I've absorbed a lot of his stories, even though I didn't go down there myself. I got to learn so much about it, you know. Yeah. So but what so for people who don't know, so I think like people know that, like, you know, John Patton was in Kanambo and we talked, we have talked to Brun Bowser about sort of what life is like there. Um, what what are you why? So we talked about saliva. What are you interested in? What did you and John realize you could do together that hadn't been done before? What were you guys doing? Yeah, great question. So um, you know, the people who live in Canambo are living in a there, it's a riverside community in Ecuador. There's no roads to cities. The people who live there, there's they subsist on chicha and whatever they can grow in their kitchen gardens and whatever they can hunt. Um so they are not eating processed food. So we live in a world where most of the industrialized world is consuming something like 70% of our calories are processed foods. They can't just like go to the vending machine and buy a Coke and so forth. And so John had been studying or, you know, working in Canambo since the 90s. And I think his initial draw there was because the community there has a very high homicide rate. So it started from a more anthropology perspective in that sense. But in the meantime, he was the one providing vaccines and antibiotics to this community because they really were quite remote. And I and I've talked to Brenda about that a lot too. I mean, I don't think it's that nobody had ever eaten any processed food. I think that does happen occasionally, but it's not a regular thing. And so that fascinated me because I'm very interested in understanding the human history of the microbes that colonize our bodies. And so we know that in the last century that has changed dramatically. And it's not just from one thing, but a combination of things like antibiotics and smaller family sizes and sanitation. And this really big one about the food we eat being so different. The way most of our food is processed, the fiber, the complex carbs that are hard to break down are often removed. And so as a result, our microbiomes have just shifted really, really dramatically. And it's connected to all these other diseases. So I mean, on the one hand, it's we've avoided infectious disease and our lifespans have increased. So that is worth celebrating. And actually, we don't appreciate it enough. I'm not sure if we think about that so much. But I mean, because of vaccination and antibiotics and these other measures, you know, lifespan has expanded incredibly. Children in the West and the industrialized world rarely die of diarrheal illness. Um, so that's obviously really good. But the other side of that coin is that we are now pro more prone to autoimmune diseases, allergies. And there's even more health conditions that we're starting to understand could actually be quite connected to our microbiomes, like some cancer types, like why are so many young people getting colon cancer? Like even Parkinson's disease and potentially Alzheimer's disease and other neurodegenerative diseases could be connected. So understanding you know what what things looked like in human history is really important. And from talking to John uh Patton I learned that the people in Canombo don't get acne and they don't get eczema and they, you know, their skin is perfect, and um, and they don't have a lot of these other allergy and autoimmune diseases that are becoming more common in our part of the world. So getting to understand um what the microbiomes look like in that community is really valuable, especially as it's changing so quickly. I'm certainly not the only person who's thinking about that though. There's actually a really cool global movement to try to preserve the microbes of human history. For example, there's a group called the Global Microbiome Conservancy. And they've even been trying to build a vault where they store samples from all different human communities. Um, it might be somewhere in Switzerland, and they're going to try to like save these samples. And the people who are part of the communities are partners in all of this research. So they've done a really good job of, or they're trying to do a good job of making it so that the science and the technology is being shared throughout the whole process. Wow. So that was the initial interest with John Patton. And he clearly had thought about it a lot himself, actually. He had a lot of really good ideas. And he was really interested in weaning the children there with breastfeed for a couple of years. And he was really interested in understanding how eating chicha, because also infants like toddlers were eating chicha from a pretty early age. So he was really interested in knowing like how the moment of weaning and getting chicha microbes into the system would affect health. Um and so actually in our study we ended up focusing on the women and children in Canambo. And hind to be honest, years later we were like, why didn't we just collect the samples from the men also? But I think it also would have been harder. It was part of the thinking that the women and children were uh the the master's students that John brought down with him were working really closely with them. So it was an easier set of samples to collect, I think. Yeah. amazing. I mean, I there's so many questions, and I'm such an amateur, and I think other people are amateurs listening too. So stupid, stupid questions. So one is where is the microbiome? And I think people have an have like a I have a cartoonish view, which is sort of what I learned in high school biology was we digest food. Um, it's sort of what our body does in absorbing nutrients. There was very little, at least when I was in school, talking about these uh other bacteria, or maybe there's like bacteria in the gut and they sort of help us digest our food. That's about the extent I know. So how is it that there's this whole you alluded to the importance of the microbiome, but please disabuse me of the notion that it's simple and insignificant. Um, you know, like what what is the microbiome? Where is it? How do you see it? How do you present it? Yeah, great question. That's a really important place to start. So, I mean, first of all, a microbiome is a community of microbes that live in a particular environment. So nothing is sterile, despite what you might read in medical textbooks about, you know, the lungs or urine or eyes being sterile. Nothing is sterile. There are microbes everywhere. And they're just really good at living in all environments. They were here, you know, for billions of years before we were. And they're really good at living in every condition. No oxygen, no problem. They've got like a metabolic solution for that, you know? So you have microbes everywhere. But what makes a pile of microbes different from a microbiome is that a microbiome is a community of specific microbes that can thrive in a particular environment. So the moist part of the inside of your elbow has a different microbiome than the dry skin on the front of your forearm because the environment is different. So different types of microbes are able to grow in those communities. And it's there's all it's not just about whether the microbes can get there. You know, you could imagine that dispersal is never a limitation for microbes because they're little and they can just fly along on the clouds or something, which is actually true. But um, but they don't just get everywhere. So dispersal is a limitation. In fact, why don't we have the microbes that our human ancestors have anymore? Well, that's because they're not we're not being exposed to them anymore. So it's not just like everything is everywhere. Um but uh but anyway so a microbiome is the community of microbes living in a particular environment and um our gut is the most dense place where most of the microbes in our bodies live, but we do have microbiomes in our oral cavity, in our, you know, there's nowhere that's sterile. Um, and so different microbial communities are useful indicators of health, and we are hopefully going to be better at manipulating them to improve our health in the near future. I mean, I could definitely imagine a future where, like vaccination, we ensure that children have certain microbes at certain points in development. And maybe that's going to really help us avoid some of the autoimmune diseases that are becoming more and more common. But those are still still research questions for sure. But as far as the gut goes, I mean, it's like a whole organ. You've got some, you know, it's akin to the size of your brain worth of microbes living in your gut. And microbes have really creative metabolisms. So, like you throw a new food substance in there, there's probably going to be a microbe in there that contains the right enzymes to break it down. And so we were mentioning fiber. When you eat fiber, which is carbohydrates that are slow to break down. So when you eat them, they don't get absorbed quickly. Like you eat white rice, it's gone in 30 minutes. You eat beans or another food that has a lot of fiber in it, the fibrous part of the carbs will persist in your digestion down to your colon where most of the microbes live. And then they'll be able to produ like when microbes get contact with those fibers, they produce really healthy molecular byproducts that are important for your immune system and your colon. Amazing. Fascinating. Uh am I am I correct that um our odors uh are also related to our microbiome? And that, you know, when we sweat, like say in our armpits, um, the bacteria that will grow and feed on that sweat will emit various gases, and that is in fact responsible for for the smell uh more than say the sweat itself. A hundred percent. Yeah, that is definitely true. So you have an armpit microbiome, and um, and some people develop microbes that produce more volatile compounds that have strong odors. And so that is definitely uh microbiome related. And in fact, there's a Belgian scientist who goes by Dr. Armpit and he has done a study where he did an armpit um transplantation where he he he got twins where one twin had trouble with BO and the other one didn't and he did an armpit transplant and it it involved the my skin microbes actually don't live just right on the surface they actually live like in the top millimeter of your skin so you kind of have to rough the skin up a bit but he did that and he um took microbes from the nice smelling twin and transplanted them to the one who was having trouble with BO and it was pretty successful is my understanding. Interesting. Uh and and certainly, you know, uh psychologically we we find the smell of body odor to be quite revolting um and disgusting. Um presumably that is because we are uh sensing a pathogen risk that these are rival bacteria that could potentially infect us. Do does that sound plausible or or wh what's going on there? That might be the case, but it's those the microbes that are causing those smells are usually not terrible pathogens or anything. I mean, a lot of the really healthy microbes, like the gut anaerobes producing those fibers, the smells, we also smell them every time we fart, right? And those smells are not good, but they're definitely health associated. So that's a really good question. I don't fully understand that. Um yeah, because BO smells tend to come from pretty healthy microbes. They're not really um pathogens you would need to avoid from my perspective. Yeah. So it sounds like there's been like there's like almost like in the way that germ theory happened, and before that, everyone was sort of blind to like the microscopic world. It almost I hear what you're saying is like there's like microbiome blindness in the sense of both the evolved psychology or or our evolved phenotype is designed around the fact that these microbiomes are recurrent part of our evolutionary history. But then also scientifically, in the same way, if you don't understand germ theory, then you're just like, yeah, let's just, you know, throw the do gross stuff, right? Because we don't know about germs. If we don't know about microbiomes in the modern environment, or we're not appreciating how they work or how our evolved biology interacts with them, then yeah, we might be doing all kinds of things that are quite bad for the microbiome. And it sounds like what you're saying is that by understanding the microbiome, there's a new slice of the world that's interventions, that's preventative, that's like healing people or preventing diseases or helping with health. Um, yeah, that's that's that's yeah. I mean a hundred percent. I mean, think about the era when we discovered antibiotics, it was like 1940s, it made a huge impact. So many World War II infections were had a better and different outcome than they would have if we hadn't made that discovery at that time. And we were so exuberant about antibiotics that we were just throwing them everywhere. I mean, we did the same thing with x-rays, really, actually, you know, like using them to measure shoe size. Oh my god, really? I didn't know about that. Yeah. If you went to like a really chic shoe store, they would x-ray your foot to get the size and like get the right shoe on there, you know. And uh anyway, so with antibiotics, kind of same thing. You're like anything that happened, you were given antibiotics, and we weren't thinking about the downside of hurting the microbiome because it wasn't even appreciated really. Um and so that I think we're better about now, although we still in the US use about 80% of our antibiotics for agriculture. So all of this careful vetting that we're doing, which we should do, of not giving people antibiotics for viral infections where they won't help and so on, will We'll only go so far unless we also change our agricultural policies. The agricultural thing is that uh I don't know much about that. Do you know more? Like is it is it preventative or yeah it's um it's prophylactic that antibiotics are often given because it helps farm animals grow more quickly. So pigs, cows, and chickens all will grow more quickly if they're given antibiotics, which is a pretty interesting experiment when you think about how we're also giving a lot of antibiotics to people. So maybe we're unintentionally fueling the obesity crisis with antibiotics. There's a lot of science questions there still that we don't know the answer to. There's multiple hypotheses about why farm animals grow more quickly when you give them antibiotics. And it's pretty interesting because it's true across vertebrates like cows, pigs, even birds. Um and a major hypothesis is that you put less energy into fighting infections when you have antibiotics on board. Um so that actually is pretty plausible. Um but there's other changes you could be making to your microbiome that could be changing how you process energy. yeah as well. One thing that I noticed, so we'll keep going on the John Patton story, but I want to interrupt it for a second because I realized from your talk that I didn't even know what fiber was. So you you explained that like fiber is like creaminess and avocado and lentils. It's not roughage. I had thought that roughage, like I think of like lettuce as fiber. Can you disabuse everyone? What is fiber and what's the difference between fiber and roughage? Deal, yes. Um, so fiber is the parts of carbohydrates that are big long chains that hum the linkages between those chains, human enzymes can't even break down. So that's a biochemical definition. That the that they're carbohydrates, they're like long chains of sugars, but the things connecting the sugars to each other cannot be broken by human enzymes at all. So without the help of microbes, they're just gonna stay intact and go through your digestion. There's also other names for fiber, like soluble as in dissolves in water, or insoluble as in does not dissolve in water. And there's a lot of like speculation about which ones are healthier. To be honest, I think they're all really healthy. And the key is just that we really need more fiber in our diet. So an average American is getting 10 to 15 grams of fiber a day when the the USDA recommends or like the daily government recommendations are 25 to 35 grams per day. But people in other parts of the world, like Kanambo, I don't know the fiber intake in Kanambo, but I do know in rural South Africa, in a comparable study, people were eating more than 70 grams of fiber a day without even trying. And so we're getting a lot less fiber. And like, where does it come from? Like, yes, some come you would get some fiber in lettuce, but just you would eat need to eat like 20 cups of fiber to get a pretty small 20 cups of lettuce to get a pretty small amount of fiber. So if you wanted to get, you know, most people have a gap in fiber of like 10 to 15 grams per day. And so if you look at the fiber content of foods that we're eating all the time, really my point about lettuce was just that you can't get enough fiber out of lettuce by eating like human amounts of lettuce. You'd have to go really overboard on the lettuce. Yeah, like so avocados are high in fiber, which I found so interesting because I before this also only knew that they were high in healthy fats. Yeah. Um, berries are really high in fiber, and so that's cool because they're so sweet, but they actually have a lot of fiber and they don't spike your blood sugar as much. Fiber can prevent blood sugar spike as well. So it's really good to be eating intact foods like fruits rather than juices because then you keep the fiber, for example. And you can buy frozen berries, so they're not that expensive. Um, another thing that is extremely high in fiber and not that expensive are dried beans and lentils. So a really good way to understand the fiber content is to look at the breakdown of the carbs on the nutrition label because it actually tells you how much fiber is there and then what the total carbs are. So you want to be looking at the total carbs and then the um the ratio with the fiber. So if you get white rice, it'll be like what zero to one grams out of 45 grams of the carbs are fiber. Brown rice, it'll be like four grams out of 40 grams of carbs are fiber. But uh beans, it'll be eight grams out of 15 grams of carbs in a half a cup are fiber. Half of the grams of carbs are fiber. So you can so quickly fill your fiber gap. Like if you just ate a cup of beans or lentils every day, you would fill your fiber gap. Um chia, chia seeds are like that too, actually. They're even better. Chia seeds, 10 out of the 12 grams of carbs in two tablespoons of chia seeds are fiber. So I've actually now done several studies, interventions. I did one in students and I did another one in breast cancer survivors where we had the intervention as two and a half tablespoons of chia seeds per day. And that's one of those studies ended a year ago, and I just did the like yearly follow up. And so many of the people in that study still eat two tablespoons of chia seeds every day. It's just like pretty easy to get yourself to do it. Um, it's funny because it's like a fad on the internet now, too. That wasn't so sometimes they're right. Broken clocks can be right twice the hour. Exactly. I I imagine there are a lot of internet fads related to this uh microbiome body of research. Um I would imagine there are a lot of misconceptions and and and there's a lot of misplaced hype. Uh I would be curious, since you're an expert in this field, if there are any things that you would like to correct, any things that you would like to debunk or set the record straight on, anything where people are getting too carried away with this stuff. Yeah, thank you for that opportunity. I mean I think the main one is that probiotics are really not what they say they are. So probiotics are like a $50 to $80 billion industry. And most of them claim that you're going to eat this, you know, tablet of microbes and it's going to become part of your microbiome. It's going to make your microbiome more diverse, and that's going to help your health in some way. But most of those microbes, first of all, are just representing a tiny sliver of the microbes in your microbiome. So they're not gonna increase your diversity. You're gonna like, if this were to be actually possible, you would be like skewing the diversity towards whatever was in the tablet. You wouldn't be like promoting diversity all around, you know? Um, and just they just don't they just don't stick. I mean, they just are transient and pass right through you. Most of them are not human microbes. They're like food microbes. They don't um they don't have adaptation to become part of a human microbiome. Um, they also are for the most part harmless, but there's actually times when they really can be not um just neutral, but they can actually cause harm. And for example, um, people who are undergoing cancer treatment, especially immunotherapies, if they take probiotics, it worsens the outcomes. It like literally makes you have worse chances of having a successful cancer treatment. And that's tragic because people are doing this to help their health and they don't understand that it's like just it's actually wrong. And then another case is after antibiotics. And I mean, you'll find many doctors who prescribe probiotics after antibiotics, thinking that it's going to like help restore your microbiome. But what happens is that then that probiotic is in there, taking up space in your gut in the moment that you want these other types of strains to be able to return. And so it actually slows the return to a normal healthy microbiome if you eat probiotics. Now it might not have long-term consequences. That might still be a pretty neutral outcome. And maybe it'll protect you from a pathogen. So there could be positive outcomes. But if you go and read the the actual guidelines coming from the physicians, they will correctly state that there's not enough evidence to to say that you should take probiotics after antibiotics. Wow. What should you do after antibiotics? Or what's the right metaphor for so if probiotics, like sticking the bugs themselves in doesn't work, what's the right metaphor? And what should you do after you take the antibiotics? Yeah, well, you eating fiber is actually the thing to do. And like to and actually, even before you take the antibiotics and while you're taking the antibiotics, if possible, getting fiber into your system. And I actually think eating fermented foods is really good too, which do have microbes in them. But and it's not that I think those microbes will engraft and become part of your gut microbiome. It's just that we know that people eating fermented foods and fiber have higher gut microbiome diversity and it can decrease inflammation when you eat fermented foods like that. So, you know, for example, let's say you knew you had to take antibiotics for like dental surgery or something. So it was planned. I would totally recommend eating really well, like in terms of getting the right amount of fiber, and you know, sleeping, all the things that you know to do right, they become even more important before you take antibiotics. And if you can do those things, then the disruption to your microbiome will be limited. Because basically, eating fiber when the antibiotics come in, it gives your microbes a place to hide out. So then they won't be able, like they won't be taken down in the same way. You're like giving them little territories to hide out in that the antibiotics won't get to. So then they'll still be there after the antibiotics are gone. That's amazing. And what about yogurt? I think like anecdotally, people I have this folk notion of like yogurt and the bacterian yogurt is like really good. Is that true? Yeah, I think that's true. I mean, I don't like nutrition is so complicated. I mean, we can't even agree if eggs are healthy. So I mean, I don't want to overstate the evidence we have, but um, but the evidence we have indicates that eating fermented foods together with fiber is the best thing we know to do. And that includes yogurt. And what's really interesting is that if you study the fecal microbiomes of people who have been eating fermented foods, it's not that you see long term that those yogurt microbes are part of the microbiome, But rather, I think it's like the molecules in the yogurt are nurturing the microbes that you want to have in your gut. And so probably there's like a whole level of diversity in our gut microbiomes that's below the limit of detection from the way we study them. But when you eat yogurt, the molecules in there will promote the growth of those bugs that we otherwise weren't detecting. And then they become more they then you it looks like your microbiome is more diverse. And it is because those bugs have become countable. Um, and it could be that you're getting the microbes from other humans around you. I mean, microbiomes are very much at a household level. So um, and like if you're doing animal studies, you have to take the cage effects into account big time because the mouse cage will all share the same microbes, and other cages will have different ones, and you'll think you're studying whatever intervention you're studying, but really you're just studying which cage each mouse is in. Wow. Wow, amazing. So the metaphor is like we're eating for billions, and we should feed our bugs. That's the bottom line. Yeah. Yeah, that's a good one. Feed the feed the right ones and don't feed the wrong ones. And so this is coming back to Kanambo then. So it sounds like the the thing that John was interested in, and that you and John were interested in, and you can tell tell us or correct this if this is wrong. Is this a natural experiment quickly changing of people eating a more quote unquote sort of maybe like evolutionarily recurrent type of diet without the processed food? So, what did you either do or what did you discover working with John? What what did you yeah? Yeah, well, exactly. We set up a study design that was at the household level because we know that microbes are shared in households. And this was really hard. And what John did was really impressive because we collected multiple samples from many people that lived in, it was 28 households that we were able to collect samples from. And we got saliva, chicha, and fecal samples from the women and children in those 28 households. And so as a result, we were able to see how much was shared at the household level, how different the households were from each other, how s how similar the mothers were to their children, for example, how similar the saliva microbes were to the chicha microbes, because the chicha is um begun by chewing on the root vegetable. So obviously it gets completely seeded by all the saliva microbes. And so we got to like watch the fermentation go. And actually another thing that the master's students working with John did was they grew their own batch of chicha and took time points so we could actually see the succession of the microbes in the fermentation. They took samples every day for four days from several different batches. So that was really cool. And then we got to see what was in the gut microbes in the people in Conombo. And that on its own, I mean, to be honest, that part I was just really interested to see what was there, both the saliva and the fecal microbes, just to see how they compared to there had been a few studies of global, a few global studies of populations that were less contacted. Like for example, the Hadza hunter gatherers had been studied. Actually, that just happened around the time John and I started this study. And um, and so there have been a few other studies around the world. And what people were finding was that the microbes in the in the gut microbiome were, first of all, just super diverse. So many microbes that are missing from the industrialized world are present. And many of those microbes are fiber degraders. So um, so there's this one microbe called prevatella. There's a lot of different kinds of previtella, but there's one that's in the gut that breaks down fiber, And it's basically missing in the Western world. Like when I do studies in my UC Irvine students in classes, we basically don't really have any previtella in any of our samples. But the people in Canambo, more than 50% of the we the way we studied the microbes was by cracking open all the cells, extracting the DNA, and sequencing it. So our readout is sequencing reads. And more than half of the reads mapped to this vanishing microbe called Previtella. So I mean, that to me was just amazing to see that that is still happening. And I think these microbes are really ancient. I think it's this is like a hypothesis, but it's possible that the microbes in the people in Kanambo have been passed down human to human since people lived in Africa. Like all of those migrations, people kept the microbes with them. And there's other evidence of that. Like there's this one stomach bug called Helicobacter pylori, where you can actually trace human migration better from the mutations in the Helicobacter pylori than you can from the mutations in the human genome itself. And actually, that might not be true anymore because now we have more sequencing capacity, but there was a period where that was it was easier to learn from the microbes than from the humans. Wow. And uh so anyway, just seeing those privatella in Kanambo to me had this really like just very profound implication that the microbes could have potentially traveled through all those generations of people out of Africa. Um and we were getting fiber in all those generations. And it wasn't until basically the 20th century when we started like taking the fiber out of flour and packaging up all of these tasty treats and taking antibiotics and all these other things we did in the 20th century. But that's you know, a couple generations of that, and we totally lost it. what what do you think are the the health implications for this research? Um because you know, as we know in the modern world we have all sorts of health problems, we have an obesity crisis. Um presumably some of this might be linked to uh differences in the microbiome we would have had ancestrally versus the microbiome we have now. What what do you think are the best um ideas from this line of research, the best implications we might take from it in terms of uh modern health problems. They're all science questions. So um so it's it's kind of early to to even know how to answer the questions. But um but like I mean I really do think that there will be a future it might be decades from now where we are more intentional about cultivating the microbes in our guts and in other maybe in other parts of our bodies too so that we uh uh promote immune development in the right way and avoid cancer development, for example. Um, and so you know, there's there's a lot of different angles this research is taking. Um, but for example, there's a bifidobacteria that breaks down breast milk that is present in that has been present through most of human history and that we have lost in the 20th century. Um and so that means sorry. So literally can you explain what that means? That like so babies born now don't have it? Babies born in, you know, industrialized parts of the world. So the US and Europe, for the most part, they are completely lacking this bifidobacteria that contains genes that can break down breast milk sugars, which should be called fibers, actually. So it's the same 15% of the energy in breast milk is in the form of essentially a fiber, a complicated carbohydrate that humans can't break down. And you need a microbe to break it down. Wow. And through most of human history, that microbe has been present in the human communities that babies are born into. And it's not even necessarily that it had to come from the mom. I mean, imagine living in a village where there's lots of babies around and you know, you just would have multiple opportunities for becoming exposed and colonized, exposed to and colonized by this bifido. And so we have lost that in the 20th century. So I that's a place to start because immune development is so critical in the early part of our life like that. So I could imagine a future where we are very intentional about making sure that babies get this, whether it's only this bifido, maybe we'll learn that there's other bugs that can play this role too. But that if we could more intentionally colonize the infant microbiome with the same types of microbes that humans have had through their history, that might help reprogram our immune systems to avoid these allergies and eczema and autoimmune diseases that have become more common. So that to me is like a really potentially near-term thing that could change. And I mean, it's already happening. There's research out of UC Davis that led to a company called Avivo, where they are selling this bifido. So to me, that's a real opportunity. It's interesting though, like when I have a friend who's pregnant and I'm like not wanting to proselytize and also there's not decades of research where you can say you know what kind of outcomes this will have, but it seems like a good idea to make sure that babies are exposed to this bifido. How do we know that this company is cultivating the right one? I mean, that's a million-dollar question, or it's actually probably a hundred million dollar question to do a clinical trial to answer that question. And then you'd want to compare different ones. I mean, that's a really uh tough question, but it's something that we have power to do something about. So I really like that that it's uh actionable. Um, and then you know, you were asking questions about what other kind of near term health impact that this research could have. I mean, that's what I love about the suggestion about fiber, because it's really very likely to help and it's unlikely to hurt, you know. Um, so if you can get yourself to eat more fiber, And there now have been many intervention studies showing that even short term, you will push your microbiome towards a healthier state by eating more fiber. And I guess another piece of advice is to start slow. I mean, fiber can cause constipation, maybe anti-intuitively. You need water when you're eating fiber. So when we do these fiber interventions in the classes here, I have grad students TA ing the students, and they have to be like college counselor or sorry camp counselors getting the students to drink enough water and stuff. And uh so you know start slow. It's not that it has to be immediate, but you know, think of it like a year-long project. Like if you were going to the gym and wanted to lift heavier weights, you would start slow and build up. And so if you can do that with fiber, it's very likely to help your health. Um it could be helping not just immune related, but it could help prevent cancer, for example. I mean, if there's any diet, I mean, if you look at all the meta-analyses of tons of different studies, there's a lot of agreement that eating more plants and eating more fiber will help your health. And so I think it's just important to come up with something that you actually like that you can get yourself to do that will get you 10 or 15 grams of fiber per day. And um especially if you're having to take antibiotics or cancer therapy or to be honest, really any kind of drug or even microplastics. You'll you're protected from microplastics when you're eating fiber because it forms this matrix that will kind of help expel anything you take in like that. So it's a feels like a pretty easy way to to protect your health. And yeah, I mean that's that's kind of the edge of our knowledge. There's tons of research studies going on to try to in more detail understand the impact of the microbiome on many different cancer types and immune diseases, inflammatory bowel disease, for example. And there's definitely progress happening, but usually it takes decades before basic research knowledge makes it into people's lives. And I'm always heartened by that when I think about how much progress we've made in our fields, because it's only been about like maybe 10 or 15 years that this has been an active area of research. And if you look at the cancer immunotherapy example, for that one took about 50 years before the initial basic science discoveries and between the time when those were made and when the treatments became available. And actually the RNA vaccine that we had for COVID, that involved 20 years of basic research. And if we hadn't had that, we would never have been able to make the vaccine so quickly. And it was accelerated by the people who made that happen for all of us because there was such a demand for it. Yeah. so I'm curious about this link between um the microbiome and and specific diseases and disorders. So I can sort of intuitively understand why having a less diverse microbiome would make your digestive processes less effective, make you less able to extract the proper nutrients that you need out of food, um, and that I could understand how that could lead to health problems. But I'm a little less clear about what the causal pathway would be to something like, say, cancer. Like uh or um the auto uh the auto-dimmune autoimmune diseases, um, I could sort of understand why that would make sense and that your immune system is trained on the microbiome. Is that the idea? Um, but with with cancer, that's a little less clear to me what what the link would be there. Could you could you talk through some of the possible causal pathways that might uh be working here? Yeah, I mean I we are definitely like at the edge of human knowledge here. So some of the studies are more observational still. Yeah. Um, but you know, for example, let's take colon cancer as an example because it's adjacent to the location of all those gut microbes. When you are eating enough fiber, then the microbes in your colon are taking the fiber and producing these actually quite smelly volatile molecules. They're called short-chain fatty acids. And like some of them are household items that you're familiar with, like acetate, Butyrate. These molecules are the favorite fuels of the cells lining the colon. So they're used to running on acetate, and butyrate's the most abundant and probably the most important one. So if you're eating fiber and the microbes are turning it into butyrate, then those cells are running on their favorite fuels. So the metabolism of those cells is like going in the right direction. And now here's where my own knowledge is. Um, I don't have a lot more knowledge of each of these pathways, but I have colleagues, for example, who have devoted their careers to understanding, you know, particular types of metabolic signaling in the cells that live in our colon. And if that goes awry, then the chances that one of those cells will be able to take off in a cancerous direction increase. So if you keep the those cells in a healthy state, it um it helps to promote all the features that you want out of your cells. I mean, what is cancer? Cancer is when one cell becomes a renegade and takes off in a crazy direction with a crazy genome and unneighborly practices that just don't respect the cellular boundaries around them. And so if you are not fueling the cells lining your colon with the molecules that they have become accustomed to throughout our evolution, then you are making it easier for those cells to go off in a crazier direction. Um is it is part of it. Um but I mean the correlations exist for distant cancer types. And so, and actually, another thing that I should have said first is that one of the most important functions of our immune system is to survey and prevent cancer cells from taking off. And so this actually is probably a more important mechanism that when you keep your immune system humming along at its best possible function, then that will help promote the, you know, the surveillance and removal of precancerous cells. I did not know that. Wow, fascinating. That's crazy that I didn't know that. Yeah. Yeah, that is actually kind of crazy. And so so the the immune system could actually uh kill the the precancerous cells before they they take off just as they would another microbe pathogen? Yeah. Oh I mean that is a huge and like you know very very important function of our immune system. And think about when like maybe you have friends or colleagues who have had to take immunosuppressants either because of um an inflammatory bowel disease or after organ transplant or there's reasons that people have to take drugs that suppress their immune function. And one of the most um important consequences of taking immunosuppressants is increased cancer, like the increased likelihood of cancer developing, because then you don't have your immune system there to help protect you. Wow. And my understanding is that the immune system obviously, I mean, it was interesting to me and it's obvious in retrospect, but talks to the gut. So for example, like I mean, uh, nut allergy, or or for example, if if if uh if a substance is detected in your gut, your immune system learns that that's food and not something to attack, for example, like in a simple way. Um so so is that right that the immune system is this sort of contingent evolved system that's surveying the contents of the gut, surveying everything? And and sort of is is that right? Yeah, that's definitely right. And um yeah, I mean, actually, there's a a book I recommend if you guys get if anybody listening gets interested in the fiber stuff. And there's a doctor in South Carol Carolina named Will Buschemitz, and he wrote a book called Fiber Fueled. And in this book, his goal is that everybody should be able to work towards eating everything. And it's such a cool way of putting it because everybody has all these food intolerances. And he's a gastroenterologist. He's come across people with all kinds of sensitivities. And a major reaction to those sensitivities is avoidance because who wants to be having reactions to their food? I mean, that's terrible. So it's very understandable that you avoid the foods that cause reactions. And there will be exceptions to this, like gluten for celiac disease or lactose intolerance and so forth. But in general, if you work towards it and have low amounts of exposure repeatedly through time, it's a reasonable goal that most people should be able to eat most things. And that's part of what you were just bringing up with the way that your immune system is sampling all the molecules in your gut. Because yeah, you have a ton of immune cells in your gut. You actually have a ton of nervous system cells in your gut too. Yeah, the most neurons. I remember that from neuroscience, and it was just sort of passing through, but it's always been like, why is that? More neurons outside of your brain are in your gut than anywhere else. Yeah, that's amazing. So all this stuff about butterflies in your stomach and so on. I mean, we really do have a lot of sensing capacity in our gut. We also have a network of neuroendocrine cells that produce all kinds of hormones and other important molecules. So, like 90% of the serotonin in our bodies is produced by cells in our gut. And they are human cells, but they are adjacent to this massive network of microbial cells. So that's another way that eating fiber will impact your health because by eating fiber and keeping those microbes humming along on their favorite fuels, all the meta all the metabolic byproducts are feeding the immune cells and the nervous system cells, the neuroendocrine cells in your gut. And that will push those cells towards, you know, giving you all the different good stuff. And when I just came across, like I didn't know what that stuff was, that's because that's the edge of scientific knowledge. Really, I mean, there's like a few molecules we've studied really well, like serotonin, which there's still plenty of mysteries around that one, but at least we can name it. A lot of these molecules are undiscovered by science, like truly. Like when I even when I get a sequence data set back, I can only identify usually like 30% of the data that comes back. The rest is just unknown. It's not that it's garbage, it's just that we haven't ever studied it before as a scientific community. And for molecules, that number is even higher. So like when I take a sample and run it through the state of the art, you know, how do you catch all the different molecules in a sample type of equipment? Maybe like five or 10% of the molecules can even be identified. So there's a lot of communication going on there that we don't understand yet. But I still think the advice that we could have given you a generation or two ago to like eat foods that your grandmother recognizes as food, or eat foods that you can read what the ingredients mean. So it's not something crazy and processed or like Michael Pollins, like eat food mostly plants, not too much. I still think that will honestly be the best advice for a long time, no matter how fancy our molecular identifications become. You know yeah. Um, one of what is the effect? So I think like um when I moved from Germany back to the US, I noticed that there's a lot more enriched flour, which as I understand it, is different than just milled flour, and then a lot more sugar in things. Um those are cheap things to make. What is the effect of sugar or enriched flour or or alcohol, for example, like high concentrations of alcohol on our microbiome? Well, I mean, everything affects our microbiome. So the answer will always be that there is an effect. Um, and then it starts to become more context dependent for that person and how much and so forth. So, I mean, you know, I personally am interested to know if people can mostly eat terribly, but then just like sprinkle some fiber on top, and then that will solve the problem. Or is that really still gonna be hard on your microbiome, and it's important to remove some of the more negative aspects of our diets. And I think that's a science question. But I mean, overall, eating all this processed stuff is probably not great for us, especially in larger quantities. Um, the way that food is processed in Europe and the US, there's some really big differences. Um, also in those strains of wheat. So you you've probably heard lots of anecdotal stories like I have of people who can't eat wheat in the United States, but they go to Europe and they can eat pasta in Italy and they can eat bread in Germany. And nobody quite understands why. And there's a bunch of hypotheses like the strains of wheat in the US have more gluten in them. So that's actually not a processing issue. It's just like the strains that have chosen to grow here. And that gluten helps with the texture being nicer, I guess. So that's the motivation, but maybe that's why people have a harder time eating gluten in the United States or eating wheat in the United States. Um there's so many nuances in the processing that I'm honestly not an expert in. But it still makes the advice stand to try to just like eat whole foods to the extent that you can. Yeah. And that feels like it's fighting I mean, the there's just this issue of profitability. Like Dave and I have talked about how as much as independent or individual people want to do things and we can wag our fingers at people. And I'm not saying we're doing this. Yeah. But it's it for me, it's tempting to sort of be like, you should be eating your fiber, which is like a joke, right? But um as a trope. But it's this thing of you know, going to the store, um, or what even if everybody wants there to be like whole, fresh foods that are healthy, cheap, abundant, you know, not high in pesticides. These are we're feeding our kids and our grandkids and our future. Um, there's still just structural selection dynamics of like what's profitable. Um, you know, and even as you said, like the probiotic thing, like it's a huge market. And like, I don't know, are people going to make a lot of money if you're like eat beans? You know, like so um in thinking about the discrepancy between what you see when you go to a store versus what we know scientifically, yeah. Like, should are we fighting the fact that profitability is in the way, or is that a a false choice? And is there a way to make align profitability with what's healthy for us? Um I know I feel better. I I I'm willing to pay, for example, like I feel better when I eat healthy. And feeling better is a different thing than like something just like tastes good sort of right like so yes yeah yeah often feel awful when after eating you know the the junk food that I crave you know so it's definitely a trade-off yeah I mean processed food is addictive I mean truly addictive the same way that other addictions that we treat really seriously um and have therapies for in our country processed food uh is certainly in the same category so I mean it's it's there's a lot of barriers to to helping people avoid becoming addicted to processed food. I mean, that's just basically a normal thing in our society that you're addicted to processed food and it's around everywhere. Our food environment makes it basically impossible not to be addicted to processed food is is my experience of someone that's lived here most of my life. And I mean I've lived in European cities too. It's you're still having tons of access to processed food. I mean, that's just how the modern world is right now. Yeah. So I don't know how we remove the processed food addiction part, but I mean, it doesn't have to be expensive to get enough fiber. So that's always the the message in my classes is that, you know, here's five things that you all know what they are, and they are not expensive. And so the barrier really is not cost. Um, it might be time, but I think it's more about just like having it be part of your routine. Yeah. So I I that's really my message is that, you know, pick something that you actually like and that you can get yourself to do and just try to do it every day. And even if you're still a little addicted to processed food, at least you'll have the fiber in there too. And I think that's better than not doing it. I mean, right now we I there's a Starbucks out the window behind me right now, where they sell 20,000 frappuccinos every month, or it might even be more than that by now. And it is so much sugar. I mean, the amount of sugar a person eats in a day today is more than the amount of sugar a person would eat in a year 300 years ago. Like sugar used to be this precious commodity. Like the queen would have a key to the room that had the sugar in it, and nobody else could go in there. And it was a very um, you know, people were still addicted to it if they could get could get their hands on it, but it just wasn't like everywhere in their environment the way it is here, especially drinking it. People just get so much sugar that way. So I guess if I could say two things, it would be like not to drink sugar, because you just get so much of it so fast. And I mean, just find something else that you like to drink, but that doesn't have 60 grams of sugar in a cup or whatever, because it's like a crazy amount of sugar you get that way. And then the other one is just to pick something with fiber in it that you like. So if it's beans, I mean, it's actually not that hard to buy a crock pot at the thrift store for 10 bucks. And on Sundays, you cook up a pot of beans and then you just like eat a cup of them one day each week. Somehow you put them in your salad, you bring them with you for lunch, like whatever it is. that's to me kind of doable. Or like for berries, which are quite expensive when they're fresh, they're not expensive when they're frozen. So maybe you like smoothies. So put some frozen berries in your smoothie with some chia seeds in the mornings. And then like all day you'll have this feeling like you did something right, you know, like you got your fiber. Yeah. And berries are much cheaper than a Starbucks coffee. I mean, you're you're in Europe. I was used to like maybe one euro or two euro for a coffee out of a good espresso machine. And like coming back to the US, I'm like, I I refuse to spend. So I just like have a coffee machines around. Like, you know, not everybody can do that. But yeah, if you can, yeah. Berries are cheap compared to um coffee. Yeah. You're right. I mean, people are willing to spend a really large amount of money on coffee. It's a good point. Or like boba or whatever sugary drink they're into. Another thing is you can make kombucha at home, um, which is I mean, maybe that's like a fringe activity. It's hard for me to tell anymore. But but I mean it's actually not that hard and it's pretty fun and it tastes good. And um, and that's like a way to have a kind of unusual, fun, nice beverage that's a little bit sweet, but it's not gonna have like when you when you make kombucha, you start out with about a cup of sugar in a gram, uh sorry, a gallon of black tea or whatever tea you're using. But then you give the microbes like a week to m to eat down a lot of the sugar. So by the time you drink it, it's actually not that sweet, but it's flavorful. So and kombucha has taken off in the probiotics industry. So in terms of making profit, I mean there's actually quite a few of these beverages. Like even the Super Bowl ads are full of ads for that poppy drink that has the fiber in those poppy drinks is inulin. And that is a plant fiber. Um, so I mean, it's is that as good as making sure you're eating whole foods every day? Like probably not, but it is fiber. I mean, I I I'll take any fiber. I think that counts in the positive category and those have become very profitable. Yeah. Yeah. Because of your you oh sorry, David, just because of your talk. I mean, I actually feed my son since I started talking berries and um uh soups with with beans and lentils, and he loves it. But I'm just like and I just feel like I'm constantly I'm like, this is great. Like and it's it's super easy. Um and uh yeah, so thank you. Like I would not have known it if I if you didn't I I love I didn't hear that talk. Yeah. That's really cool. Yeah. Um I I feed my daughter one of my daughter's favorite snacks is just canned beans with like a little bit of salt sprinkled on them. That's like she it's her go to thing. So I'm very glad to hear that that's that's good for her because she just coincidentally really likes it. Her daughter's awesome, David. She likes horror movies and canned beans. This is awesome. She's well that's really cool. Yeah. Yeah, no, I'm I'm a very proud father. Uh I I wanna make sure I'm getting the the causal pathway here of why processed foods are bad. So is it because uh companies put in preservatives to keep the food from spoiling so it could be transported uh to vast distances? Um and those preservatives, while good at keeping the food from spoiling, at the same time are damaging to the the microbiome because i while they prevent, you you know, bad bacteria from growing on the food, they also kill the good bacteria w uh in us when we eat them. Is that the logic of how we're that's one part of the logic, although it's actually not the part I'm the most worried about. To me, the major problem is that one pretty universal step in all processed food is removing the fiber. Okay. And so basically you're simplifying the food to be a pile of sugar, essentially. So um so I mean, white flour is still better than just pure cane sugar in terms of how it will affect your blood sugar and what will be left for your microbes to eat in the colon. But but when you process food and you remove the fiber, it means that there's nothing left for your microbes to eat. Like your microbes depend on getting fiber to your colon, um, which is where they live. The the most density of microbes is in the last part of your descending colon. The it uh in good circumstances, you'll have like 10 to the ninth bacteria per gram in your in that last part of your colon. Whereas in your stomach, it's like 10 to the two, you that's hardly anything because it's so acidic. And then that number, the density of microbes kind of grows at as you go down the colon until you get to the descending golden. And that's where like the overwhelming majority of the microbes in your body live right there. Yeah. So if you eat processed foods where the fiber has been removed, you are giving those there, there's nothing there for the microbes to eat. And so one signature of the gut microbiomes of people in the industrialized world are microbes that eat gut mucus, which is an indicator that there's no fiber in there. And the microbes have turned to eating the mucus that your human cells are producing to line the colon. That mucus layer is like what's between you and all the bacteria. You want a really, really thick mucus layer for a lot of reasons. It's like a sign of immune health in many ways. But you know, if you if that barrier breaks down, then you end up with what we call a leaky gut, which means you're prone to sepsis, and it means you're which is a blood infection, and it means you're prone to just all these molecules getting into your blood, or like have you ever known someone who was having appendicitis or a urinary tract infection and they started hallucinating? And that's because the molecules in their gut were leaking out and interfering with their brain function. So you want that barrier to be really strong. Like one of my favorite stories in all these years of stories I've gotten to hear about microbiomes was from a Swedish mucus biologist. Um, and he took a he snuck a field mouse into his lab and he'd been studying the mucus layer in lab mice his whole life. And then he looked at this field mouse, and the mucus layer in there was like way thicker, way more complicated. And so that field mouse out in the world, having all of its exposures, was able to develop a really, really good thick mucus lining of its gut. So humans eating processed foods are basically like the lab mice. Like we aren't giving our microbes the fuels they need and the our bodies the exposures they need to build up a really good protective mucus layer in our gut, like that. Yeah. Interesting. So in other words, it's not sugar per se that's bad. It's sugar that's stripped of its fibrous content. Exactly. Which is bad. Yeah. And it's this oh yeah, sorry, go ahead. Like juice versus or like an orange with all the fiber in it versus juice is a really big difference. Like if you look if you gave a bunch of people a glass of orange juice versus an orange and measured their blood sugars, you would see the juice spikes everybody and the fiber um buffers the spike. Got it. So why why are food companies uh stripping sugar of its fiber content? Is it just that it give gives a more concentrated dose of sweetness or like what what is the reasoning there? Well I mean just think about the difference between a croissant made from white flour and you know something that's really whole grainy and good. And I mean I personally like whole grain like I prefer it um but but it's not the standard. I mean, if you go into the grocery store and most of the aisles of food, which are based on what food companies think people will become addicted to. I mean, they have they have done a lot of research on what people like to eat and what they will become addicted to and buy more of. And they that has landed them on foods that have very little fiber in them. So I mean, it's it's just simpler. And I mean, actually, the initial reason is kind of interesting because one of the first times we started stripping wheat of fiber was around the time of the Great Depression. And another and it's it's because the whole wheat it goes bad more quickly. And so if you remove the fiber, which of course removes a lot of the nutrients, the fiber, um, sorry, the flour will not go rancid as quickly. And so during the Great Depression, I remember learning that they were processing a lot of the wheat flour and putting it on unrefrigerated trucks and taking it to like the dust bowl, basically, and making sure people had food, which obviously was a really good idea. But um, but that was uh that was a bit of a turning point, I think, in when we started having this like massive industrialized scale fiber removal happening of our wheat. Yeah. And I like I and I keep always having my like Germany experience, but like coming back to the US after 10 years away, my my overarching experience is like I feel like we're children, like all the bread at the grocery store is enriched or refined flour. In Germany, none of it is like you can't buy something that has if you read enriched flour, it means that they took the fiber out and they're just adding like stuff back, usually. Like it's not usually whole grain. Um, but the weird thing is when people visit Germany, or like if I like buy German bread and I give it to people, people love it. And people always say, I wish I could buy this here. I've had so many conversations with people across the political divide. Yeah. You know, like even, you know, like even visiting family back home, like places that where you wouldn't think. And people like, oh my God, I wish like I could get German bread here. I I even wonder like just this is an aside, but I even wonder if like the way people test food preferences is wrong in the sense of like it's like what David said is like something might taste good in a second, but then like you're like, ooh, do I want to eat more of that? Or do I want to come back to that or eat it a lot? And I actually don't know the answer to this, but like if you just bring people in and you're like, give them A, B, C, D, and E, and you're like, which do you prefer? That's different than which do you feel better eating day in and day out? Which do you prefer coming back to after you've felt the effects of it for a couple of hours or a couple of days or a couple of weeks? And I don't know if they're measuring that. So like even from like a very like market-based capitalist perspective, I actually wonder if like the way people are measuring desirability of food is wrong. I don't know this, but this but they must also be measuring it based on what people buy. I mean, those products would go out of business. Like the fact that there is a waterbread section in every store means that people are buying wonder bread. Like I think, you know. Yeah, yeah. I don't know. I always wonder that too. Just as I'm going through the store and I see a whole section of stuff that I'm like, gosh. This is garbage. I might like yeah, my yeah, my head is like this is garbage. You're feeding people garbage. Yeah. It's garb. Like it's literally it's like not food. Yeah. Yeah. But I but also it depends on how you grow up. And so you know, you have to respect that, but also figure out how to help people eat better, like in every situation, you know. Yeah. Like whatever that's money. I mean, people just to be slightly political, like people talk about redistribute redistribute redistribution of wealth. Yeah. But if you're if you're making money off of selling people unhealthy food, totally. I'm paying for somebody that person's profit, I'm paying for that's money coming, you know, if they get cancer or if they they're obese or whatever and they have health effects and colon cancer or, you know, their kids unhealthy, whatever, we're all paying for that, you know. So that's a redistribution just as much as anything else. Yeah. That's a really interesting point. I never thought about that. Yeah. So uh I mean, it could be that um when you strip away the fibrous content, it becomes easier for your body to just quickly extract the energy from the food. Whereas if there's a lot of fiber in it, as we know, if fiber sits in your gut for a long time, it takes a long time to extract all the nutrients from it. And so it could be that if you know, maybe we're making calculations where if we need the energy right now and we're discounting the future, then more processed foods with less fiber content are going to be more appealing to us because we're more concerned about getting that energy boost right now versus accumulating a healthy microbiome in the long run. I don't know. I mean, I I'm sure Daniel Nettle has lots of opinions on this because he does research on uh how poverty affects uh uh uh temporal discounting and diet choices and obesity. And so that that could be playing a role that if you're discounting the future more and and you have more of a need for immediate energy and perhaps storing fat for future food insecurity, uh, that that could contribute to this. Yeah, I totally see that point. And I mean, even just in terms of getting through the day, you know, it's more convenient to eat processed foods. You don't have to cook them. I mean, it just all around just takes less resources. That's true. Yeah. Um, but yeah, the the blood sugar, the point about the time for digestion has really big blood sugar impacts. And so um it's it is a good trick to know that if you include fiber in your meal, um it will be much easier for your body to weather the sugar spike storm. And so I think a lot of people don't know uh very much about that and that that could could help people make decisions because they might not realize what the consequences are. If everyone's just addicted to processed foods and not thinking about it from that perspective, it's harder to make choices like that. Yeah. It's it's just it's funny because like it's sort of like cooking, you know, like cooking with care and love and ingredients that matter is the solution. And that's like a hard thing when people are busy. Or I mean it's not that hard, but it you can you can imagine it's just sort of like exercise and sleep. You know, it's sort of like, you know, it's it's uh it's simple, straightforward, not the easiest thing, maybe not the most profitable thing. Yeah. But but it's but it comes back to like taking an evolutionary approach. Like I, you know, we we talk a lot about there's things you just wouldn't think of if you don't take an evolutionary approach. If you don't take the idea that we're really complicated and we evolved around a lot of invariances in the environment, including the kind of food we're eating. And there's a lot of ways in which we're better. Like we're not killing each other. We don't have to like, you know, as you said, like zoonotic infection is much lower. Um, but but but it sounds like we just we're learning about this whole new area where we can um we might have been doing high, high cost, low benefit, dumb things. And if we learn more about this new part of our phenotype that we didn't really know much about, we still don't know much about, we can do some low-cost, high benefit possible. Yeah, I mean, in the same way that we were just popping the antibiotics, thinking that were there was only a positive outcome from that. eating white flour has consequences we might not have really been aware of as we were making that choice, you know, in processed foods without the fiber. And I mean, we're I mean, we're PhDs in evolutionary sciences, we're learning stuff real time. And I mean, most people don't have the luxury of having that training. And I mean, why would you think? It's like it's bread, right? Like bread is bread is bread, right? Yeah. Calories are calories are calories. Um, and the idea that that's not true, you know, most people don't have the luxury of learning that's not true, and there's not a lot of incentive right now. Yeah, it sounds like to disabuse people of that idea. Yeah, the other one that I think is kind of an important um piece of knowledge is the difference between mirrorac and metamusal. So a lot of people have constipation, and even kids, I know families where the kid is getting mirrorac every single day to help with constipation. Mirlax it comes is polyethylene glycol. It's not uh fiber at all, it's um it's a molecule that causes some goopiness the same way that fiber does, it draws the water out of the system, but it also the way it impacts your microbiome is actually quite negative. And so, for example, if you give mice antibiotics and then you compare mirlax, which is polyethylene glycol, versus metamucil, which is made from psilium husks. Metamucil is actually fiber. Metamucil is like, you know, it's processed a bit, but it's still fiber and it came from plants. If you give mice antibiotics and then you give them either mirloc miralax or metamucel, the mice that get mirrorax will get a terrible infection and very likely die from sepsis. Whereas the um the uh mice that get the mirror the metamucle, which is the orangey flavored version of psyllium husks. And I mean, you can just buy psyllium husks too. That's fiber, and those mice will do better. So even just like from a treating constipation in the hospital or at home or whatever perspective, like you can really change your infection outcomes by knowing that piece of information. Like a lot of doctors I know don't know that. Wow. So very very cool stuff, uh uh and and interesting and useful. Um I'm curious, I want to go back to this uh brain in our guts, because I find this quite mysterious. Uh what do we have neurons down there and what are they uh what are they doing? Like w what kinds of computations are these gut neurons doing? Why do we have so many neurons down there? I'm curious uh if you have any ideas on this question. I mean, I have mostly questions myself, but you're at UCLA and I can tell you that like some of the best people in the world thinking about these questions are also at UCLA. So I I mean you maybe you want to invite one of them on and like I want to listen to that interview. But um Yeah. So I mean, what are some reasons we would have neurons in our guts? I mean, I don't know. I really don't know. I mean, I I can feel it myself, like the whole thing about butterflies in your stomach, or um, you know, using our guts as part of our intuition for for like how we feel about things. I mean, I have experienced that myself, but I don't I I also know that societies can be very tricked by um what they know about their organs, like you know, maybe you've heard how in Egypt everyone thought that their brain was their thinking center was in their heart. Yeah. I always think about what that must have felt like. I mean, I don't know what they thought was going on in their brain, but apparently they just when they were m um preserving bodies, they would just throw their brains away. They didn't even think that was important. So here we are kind of learning something massive about our own bodies that we have all these neurons in our guts, and are they doing? I mean, clearly they're gathering information and sending that information back to our brains. I really like this idea that, or I mean, I think it's really important to understand that you have these neuroendocrine cells that are producing hormones that affect your well-being in every possible way. And so if you are eating foods that promote a healthy microbiome, then you're going to promote healthy communication with those neuroendocrine cells. One of the biggest discoveries in this area is that we have microbes that can transport serotonin. And this it UCLA is a center of this research. Elaine Shaw's lab has made a lot of these discoveries. And we found it, I've done an Alzheimer's disease research project, and we found the same thing. that these microbes can transport serotonin. And in my mind, it could also be that when those microbes are being sustained, they are signaling to the neuroendocrine cells to also produce more serotonin. So it's like a loop. And so I think part of how this is all working, and the reason you have so many nervous system cells in your gut is that your brain wants to like have some impact on the production of these hormones and the location of their production is your gut. So it's like a communication system. Wow. And um, and when you have the right microbe there transporting the serotonin, it's probably releasing signals. This I don't think this is known yet, but um, you know, it's probably releasing signals that tell the neuroendocrine cells like, hey, get get us some more of that serotonin going, please, you know, and then that has impact on your well being for lots of known and unknown reasons. So the gut is a is a hormone factory. Or it's the fuel for the hormone factory. Yeah, there's other locations of hormone production, so it's not the only one. Yes, it is an important one. Fuel, right? It's yeah, wow. Yeah. You can think of it as like, you know, the the the trucks containing the materials to build the power lines. Exactly. You know, it's like there needs to be some communication between the power lines and what materials they need to sustain themselves and the and the trucks that transport the, you know, those materials. Yeah. And like if the trucks all get flat tires, then somebody needs to like talk about that or figure out, or you know. Yeah. It's a really good metaphor. Yeah, doing like the take a step back and be an adaptationist about like if if there's an organism, what are the functions that have to be hooked up to the material delivery system? And what would you want to know about what materials are being delivered, which ones are low, which ones are high? I mean, I find the whole thing about like craving food to be magical. Like, how does my body know right that I want cantaloupe? Like, how does my like what in me sort of knows there's something missing that it's in cantaloupe that somehow the system that knows what a cantaloupe is, which is outside my body, some part like I find this magical. Yeah, I mean that to me, I've always wondered how much truth there is in that. I think I've I've also always been very interested in that question. And I don't really know how much how much truth is in it, but it's very interesting. I mean, we also we s we now have like urban cases of scurvy, for example, where people are just like eating toast even of course we do, yes. And I mean, of course and maybe they really don't have access to fresh foods and so that's like a societal problem and not an individual problem. But I mean to me is amazing that p it'll be difficult to diagnose because it's uncommon, but um but that actually happens and so yeah yeah I is there is there research like this is for all of us does anybody know like the feeling of like I feel good after getting exercise or I feel good after eating this kind of food is there's is there research on that like it feels like in the Venn diagram of psychology and physiology and microbiology like as a psychology professor you know I teach intro psych yeah I mean I I I took a motivation class and that talked about like hunger and thirst maybe I'm ignorant but yeah do does it I don't know, does anybody know? Like, is there is there research on like the feeling good you get when you eat well or you get exercise and like what's up with like is is there? Yeah, I mean here at UCI we have a physiology department and there's people that work on um the post exercise high and like the molecules that are released with exercise. So I on that side I definitely know. I don't know as much about that on the food side, but I mean there is a lot of food research. Yeah. So I don't know. Do you know, David? I I honestly have no idea. Yeah. It's just it's uh there's just so many questions, such a vast field to I mean, even just like the subtlety of our food cravings. Like I often have like a strong craving for pickles or something or or whatever, and like uh and I I feel gross after like eating something that's like really greasy and heavy and I just wanna you know get go into a food coma is the is the expression. But other foods that they don't have that effect on me. And the like just these subtle uh effects that that specific kinds of foods have on us. I feel like it's such an understudied and important topic. Yeah. Or just even the difference between cats and dogs, where like cats don't overdo it, and dogs are more like us, and they'll just like eat themselves to death. Although, although I had a cat who is a main part main coon, and boy, she would eat the The vet was like, it was like, yeah, you can't give her all the food she wants. Like, you can't do outlips. Um, we before uh um, you know, we were we're not at the end yet, but we're getting closer to the end. I do want to ask you, you mentioned something about phages and amazing work you're doing on that. Can you talk a little bit about what is a phage and what are you doing with them to uh help people? Yeah. Thank you. Um, so phages are viruses that infect bacteria. And so basically, every cell on the planet has viruses infecting them. So we hear about the famous viruses like HIV and COVID, but they're rare. Most viruses are not pathogens, but there are viruses everywhere. So every single one of these bacteria that we've been talking about in our microbiomes probably has about 10 viruses infecting it. Wow. That's very comp it's things are complicated. Yeah. We're just we're just Russian dolls of things inside of things. Oh my God. Exactly. Russian dolls of sometimes it's almost like I wish I wasn't a Darwinian worldview person. Just like everything is simple and like it's like, oh my God, like the have the bacteria have this whole world of yeah that's crazy. And that's wonderful. But yeah, please well it's I mean it helped it's viruses like really help make the world work. You know, viruses can evolve quickly, they can like bring new traits really quickly. Like if you give antibiotics to somebody and then you measure all the antibiotic resistance genes that have emerged out of that system, a lot of them come from viruses moving between cells and sharing that trait. And then it's like that trait became pretty important right then because the antibiotic is coming through and gets selected for. And so then all of a sudden every bacteria that could take on a virus that could help it get that trait is the one that would survive. You know, so you could see how there's like sweeps of selection pressures where the viruses bring traits that are like the money move that makes them survive, you know. Yeah. So viruses are like the closest thing to like pure natural selection almost. They're just like this like really uh supernaturally selected minimal phenotype things, like almost. Yeah, I mean maybe they literally they're just selfish genes, that's all they are. Yeah. So as a result, I mean, just there are all these viruses, bacterial viruses, and um and they are the enemy of our enemy sometimes. So if you have an infection with a pathogen and antibiotics aren't working anymore, you could use a virus, a phage, to kill that bacteria. And it's not a new idea. It's actually been known since before we had antibiotics. And so before we had antibiotics, people were using phages to treat infections. When Elizabeth Taylor was filming Cleopatra in England, she got a staph infection and they treated her infection with a phage and she survived. And there's like a lot of stories like that. And actually, in the former Soviet republics, that type of treatment continued. And so when antibiotics became big in the US and Europe, there was less access in the USSR, and people kept going with phages. So, for example, at the Eliava Institute in Tbilisi, Georgia, phages are produced to treat infections, and that's like the most normal way to handle bacterial infections in that part of the world. So it's like really continued. We have some evidence, or I mean, kind of a lot of evidence, but it's not been formally clinically researched from all of that activity. And then as more and more antibiotic resistant infections have started to emerge in our part of the world, there's been a resurgence of interest in the phages. And so I started studying them more like from an ecology perspective, like what kind of viruses are there in people, like probably 10 or 15 years ago. But then I started getting requests from people who had terrible infections, like, can you find a phage that will infect my bacteria? And so the student the students here at UC Irvine are very enthusiastic about the prospect of helping someone in a wonderful way. And so basically, I've had this team of students hunting phages against infecting pathogens for like more than 10 years. And so we get wastewater samples from local SoCal wastewater treatment plants. And wastewater actually is a wonderful summarized source of information about all of the human infections and bacteria. So there's tons and tons of phages in wastewater. And this is a this is a common approach. There's dozens of labs around the world doing this. And so we'll get the pathogen from the clinical microlab, we'll hunt a phage out of the wastewater. We're usually able to find a phage, and now we have several hundred in our freezers from all this year, all these years of searching. So now when we get a new isolate in, we check our freezers first. And if none of those work, then we'll go hunt a new phage. And now we also I have a cold room with like a collection of wastewater, and the same way some people collect wine, we did wastewater. And we know Riverside 2020, right? Or something like that. Yeah. No, for real. Like there's this one sample from Escondido in 2020 that always has stenotropomonas phages in it. So when we can't find a stenophage, we're like go back to that one. And then, you know, the students have sometimes the students have connections to different wastewater treatment plants. Like one of them had a dad who worked at one, or another student. Amazing. Yeah. And then they'll like know how to get a new kind of wastewater into the system for us. So you're like a phage sommelier. You're like, you're like, yeah. I think we should do Escondino 2020 for this. Maybe that's a good place to start. Yeah. And actually we had when the pandemic hit, we had wastewater from the Orange County Sanitation District that we had collected every two weeks for the year before the pandemic started. And it got us into a whole wastewater sequencing project, um, which is a different story. But um and that really has persisted. Now there's actual wastewater surveillance happening at a national level with like real relatively good infrastructure. It's pretty cool. Wow. And just to clarify, so all this, the main mechanism is just differential reproductive success. So you basically expose something, you're like, this is the um the thing, the bacteria we want to destroy. Um we sort of just see uh if there's something that sort of can differentially infect it or affect it. Right. Like if you if you have a bacterial community, an infection growing in your body and the antibiotics are not are not working. So the bacteria is resistant to the antibiotics, but you find a phage that can infect that bacteria, you treat the person with that phage, the virus will infect the cells and pop them open and kill them. Right. And even if it doesn't kill all of them, what what I hope for is just like a bit of a boost. So like sometimes we find that there's synergy where when you combine the antibiotics and the phages, the antibiotics work a little better too. So maybe like as a team, they can do the infection better. And then you've got your immune system. Yeah. So between the antibiotic, the phage, and the immune system, you now have like a new handle on the infection, basically. Dream two. Yeah, exactly. How do you how do you so you have a sample of the bacteria and you have wastewater, how do you tell which phage is or how do you get the how do you go from wastewater and your sample? What's that? Yeah, great question. So we grow up the bacteria that we want to be able to infect. And then we add a little bit of wastewater to it. And then we it we filter the wastewater so there's less bacterial cells and there's more smaller viruses in there. And then we pour an agar plate that you've probably seen an image of before. And there's like some details that you have to like kind of change the texture of the agar to make the phages be able to show up. But then what you'll end up with if you succeed, the next day you'll come in and you'll find a white bacterial lawn that has little clearance zones, little circles, and those represent a phage eating the white bacterial background. So if you come in and we call it a plaque. So if you come in and you've done your plaque assay and you see some plaques, some little clearances where the phage killed the bacteria, that's your phage. And it's usually like a big mix the first t time, and then you have to like purify it a bunch of times to try to get it down to being one phage. Right. So you're it's art it's artificial selection. So you're basically just saying, like, look, here's the victim hopefully yeah the bacteria and you're just making little battlefields and then you're just sort of like is there something that is I'm gonna look to see that actually kills this that's replicating based on the fact that it's killing it and that's how you discover it. Yes, exactly. Cool. So you're artificially selecting. Yeah. And then from there, I mean, the amazing part is that there aren't just like companies manufacturing phages right now. And it and antibiotics have a weird economics to them. Um, they're not chronic medicines. Like blockbuster meds are like statins or you know, Ozempic, something people will need for a long time. So the they're chronic and can be profitable. Antibiotics are these acute treatments and pharma has not been investing in them because they don't pay back the RD. And the government hasn't really been investing in them very much either. So there's been a real lag in antibiotic discovery in the last couple of decades. Meantime, the infections are getting worse and worse. And so like the predictions for how many antibiotic-resistant infections we're going to have in the next couple of decades are like staggering. Like more people will die from antibiotic-resistant infections than cancer by the next decade or two. So there's like a lot of motivation to find alternatives. And the phages are an alternative, but they're still a little bit homemade. Like we don't have them at an industrial scale at all. So literally, labs like mine, like academic labs, I am not a pharmaceutical person. I'm like a I normally teach undergrads micro, you know what I mean? And um people in my lab will produce the phage. Um, and we'll follow we you each phage will be really finicky and we'll have to come up with a kind of specific protocol that that particular phage will cooperate with. And then we'll write down our method and send it to the FDA and ask them if they approve us to use this treatment. And we also take the phage and send it for third-party sterility and endotoxin testing so that it's not just our lab saying, like, yep, we think it's sterile, you know. Yeah. Um, and then and then that's in the United States, there's three or four labs doing this. And I'd say in the last five or ten years, like less than a hundred people have received treatment like this. Um, but we have we've we did one case last year and we have like about 20 cases that were like in the middle of trying to produce phages for people. And a case means like what's the one case like it's literally somebody who is like, I have a a disease or an infection that I can't I that I don't know that the yeah, what is can you yeah, what is Yeah, definitely. So um it a case is we we asked for the cases to be more chronic. Initially, we were taking on these really acute cases where someone was about to die from an infection, and then my students would stay all weekend to find a phage and they would find one and then the person would die and nobody helped anybody. And it we did isolate phages that way, but I just realized this made no sense that we weren't actually helping anyone. It was like we were giving false hope to the family, and the students were like over heartbreaking. It's heartbreaking. Heartbroken at the end of it, exactly. So I changed tax about a year ago and I said that we would accept chronic cases. So we would accept cases where it would be okay if it took us a year to produce the phage, because in reality, that's what it takes. And so um, so the case we did, we actually made it all the way through and actually got to help someone last year was um a woman who had sinusitis and nose infection for 10 years. And actually, your sinuses are amazing. They like go way back into your head. And she had staph in there for 10 years. She kept getting fevers. So she would just, she was living her life with like getting a terrible fever every week or two. And the antibiotics weren't really, they would maybe help a little, but then the fever would be right back. Um, and so the infectious disease doctor identified her as a good candidate because it was chronic, but it was really affecting her life. And so it was worth the risk of trying something new. And so we got the staff isolate from the clinical microlab. And actually, this that was a really hard phage to find. Like I think we looked for about six months unsuccessfully. And I have this one star student who trained a new medical resident one week. And on that medical resident's first try, she found the phage. So they're either she was lucky with whatever piece of wastewater she was using, or she just had slightly different technique, or you know, we'll never know. Um, and we named the phage Ludmilla, and then we spent about six months coming up with all the methods for producing it and getting it checked and everything, and then we submitted paperwork to the FDA, and that was a couple months. Um, and then we had to get approval from the hospital here at UCI and the ethics board, and that was a couple months. So I don't know, it's like it's hard to see where a year went, but I actually made a timeline and you can see just like what dates things happened. There were just months between a lot of these steps. But finally in July, we had permission, and I remember the day the student who had produced the phage Ritwick is his name. He like went and bought a fresh cooler and he he got fresh lab coats and anytime he opened the fridge that we bought a special fridge that only this phage could go into and he he only opened it twice, I think. And he'd put a fresh lab coat on and get the phage out of that fridge and put it into the brand new cooler. We were like trying to just be really clean about everything, you know. And uh and he drove it over to the hospital, and the pharmacist uh mixed up the right dose, um, which was actually another whole project of getting the pharmacy to be okay with how we were doing things. So each step just took a lot of organization. Um, but then the person finally got to try this phage, uh, she put it into her um nasal rinse every evening, like essentially with a neti pot, but with distilled water, and added the phage to that, and then she rinsed every night for six weeks. And then the treatment ended last September. And I just learned on like two days ago that the fevers have remained gone. Like the fevers have not come back. So that to me is like I wasn't like a month later, I was glad she was doing better, but I wasn't like sure we had helped. But now that it's been almost half a year and she still doesn't have the fevers, it feels like that was just really good news that I mean, of course, I understand the infection can come back, but it'd be nice if this effort had some impact. And um and yeah, so I think that she hasn't had to take antibiotics again and her inflammation is much better and she hasn't had the fevers come back. She went on a trip to Italy, I heard. Amazing. So really live in, that's good. You got to have some of the the better uh uh uh flour is is the difficulty it sounds like it was it was it sounds like you're taking on a lot of costs to do this that you wouldn't need to is that because there's not infrastructure to do this and because you're basic because you're a basic scientist in a good way, like we're big we're basic scientists too. Yeah, you're you're doing this extra. This is like you're at the the the pointy end of innovation. And ideally in the future, there would be mechanisms to offload this regulation work and the production work, but it's just because you're so new, this is so early days that you have to do everything. Yeah, in some ways. In other ways, we've known about this for a hundred years. And so why are there not companies doing this? That just has to do with the way our medical system is organized, that there isn't really room for an operation like this. I mean, it's it's a bit crazy. It's not going to be profitable. Um, the reason I'm able to do it mainly in this case is because of this amazing student who cared so much about doing it? He's he he started working in my lab as a high school student and he's about to graduate college. So he had a lot of time to learn all these skills. And to be honest, he is the driving force that the reason that this happened, because it was a lot of work for him. Um and it's the kind of work where if I tried to hire someone to do that work, it would cost a lot more money than I could ever get to pay them because there aren't like research grants to pay someone to do this. But um, but most of the labs doing this have some secret source of money that they figured out because it's not a typical research grant, or they're just kind of using their research grants on the side to get this kind of work done. Um, so that yeah, it's hard to get funding for it. We just applied for a big ARPA H grant um to build a network across the country that would help um give phages to people more quickly. And we'd be, you know, we we would like to figure out how to build a network like that better. Do you feel like the regulations are reasonable given the costs, or or is it just that the regulations are unwieldy and designed for larger entities that might have more money than you? You know what I mean? Like yeah, I honestly the the FDA's compassionate exemption route is functioning pretty well, in my opinion. And in fact, um, yeah, we had an experience in the middle of all those amendments where they disagreed with one of the steps in one of our protocols, or I don't know if disagree is the right word, but they were like not gonna approve it. But then they just like had an alternative suggestion that worked great. So it wasn't it didn't stop us. So I actually felt like that was pretty functional. Like I was worried that we were gonna do all that work and then it was just gonna be rejected and down the drain or something. So I actually thought they worked pretty well with us. Agreed. But I think science funding in general is in a bit of a crisis right now. Like it's kind of a strange system that you guys are obviously very familiar with. But you know, you get a job in a university. If you're lucky, your own salary is paid. But to actually do any science, you need funds to support staff and re resources for your lab and like where those funds come from is those sources are like all disappearing all the time. Yeah. So you know it's just it's hard to get to do stuff with science these days. Yeah. And it's just but it's and just to put the period on it, you literally change somebody's life. I mean, doing this basic science, it's really amazing. Yeah. Yeah. That is a really cool thing about this about the microbiome field in general, that it's like right at the edge of translation and like we know enough to be able to do things that are actually directly causing a treatment for someone. Yeah. So yeah, that is pretty cool because a lot of basic science you don't get to see the outcome for decades. Yeah. Do you have a good John Patton story? Oh gosh, what a good question. Oh, I probably have a lot. Um well, I mean, maybe I'll just leave, I'll just share one. Like he would often come by our lab and talk, and he'd stick around for hours and we loved it. It was very fun to talk to him. In fact, he came to one of my students' defenses, the student who worked on Chicha, Andrew Oliver, and he was full of so many stories. But I guess one thing I'll just say is that John Patton invited my graduate student Andrew Oliver down to Canambo to help collect the samples. And I was really, you know, I was encouraging. I was like thinking about if I could do it myself, but I had little kids at the time and stuff. And if you go there, you're like remote for the whole summer kind of thing. It's like yeah, Brenda made it very clear. Yeah, like it's a it's a serious thing. Yeah. To it's a serious commitment. Yeah. At minimum, that's a that's an understatement. Yeah. Yeah, exactly. Um, and so and so John was describing the chicha and how it's like kind of fibrous and you'd get like chunks of it stuck in your teeth, and you know, how it had a really strong flavor and stuff like that. But that if you go into someone's house, you have to drink the chicha. I mean, you you really um there's no there would be no polite way to decline chicha without causing like some serious um, you know hurt feelings. And so anyway, he's like both trying to convince Andrew Oliver that he should come, but also sharing all these like stories that made it seem like it was gonna be pretty tough to survive. So Andrew declined to go down there after hearing all about flavors and chunks in the chicha. Yes. The downstream consequences of offending people. David, I don't know if you m remember this differently, but my memory is the the cheerful greeting from the canoe to somebody's house is I'm not gonna kill you in the night, you know, something to that extent. Like that's the best case, that's the best communicative event. That's like a friendly communicative event. I'm not gonna kill you in your sleep. I feel like I want to use that. That's really funny. Yeah. It's it's it's actually more alarming than saying nothing. Well, maybe. Maybe not. Maybe if you like, oh, was there a possibility that you would? Oh yeah, if you were actually worried about that, that would be a good idea. But yeah, no, for us, right? That's like I didn't even think of that. Yeah. So uh is there anything we should have asked you? We we usually have to ask that question before. Oh, that's nice of you to ask. No, you guys asked great questions. I got to um be on my fiber soap box for sure. Thank you. Great. Yeah. It's incredible. I literally, yeah, I just cannot. I mean, yeah, there's there's uh there's a small category people whose talks like forever change the way I think about the world, and and you are in that category. Um and it's just it's incredibly cool work. It's a bonus that it's, I mean, you could from a basic perspective, it's a bonus that there's this incredible real-world consequences to like what should you buy at the store this week to like possibly help people. And then from the applied perspective, it's cool that it's an evolutionary thing. Like, you know, this is an evolutionary podcast, and it's nice that um this is uh the kind of thing you wouldn't think of if you weren't coming from an evolutionary deep time perspective. Um so no matter how you look at this, it's just really cool work. So thank you for doing it. And I I hope that um people just rain more funding on this because unlike so many things, it's so useful basically, but also really helpful um in an applied perspective. So just thanks for coming on and and thanks for doing this. Yeah. Thanks so much for inviting me. Yeah. And thank thank you for restoring my my faith and my sense of inspiration and hope about the power of science to help us uh understand the world and actually help people. So Yeah. Uh and eat some beans this week or lentils or or um or fruit or uh berries. Yeah. Yeah, get get that fiber or the chia seeds. I'll have to take it. All right. All right. Thank you, Katrina. Yeah, thank you very much. So David, uh to sum up the ratio of carbs to fiber, um, don't what uh what which is the one? The poly don't polyethylene glycol, which doesn't sound good. It actually sounds like um antifreeze. Antifreeze, that's what it is. It's ethylene glycol. Um okay. But polyethylene glycol is the stuff that uh you should not use, but the psyllium husk or the derivatives are. I'm just sort of reviewing. Oh, the other thing to say is like berries often are very high in pesticides, so it's good to get organic berries if you can, if you're gonna feed them to kids, especially. Yeah, berries are great. Beans are great. Chia seeds to get some fiber. Avocados high in so we're we're sponsoring all those uh whole foods and then Yeah, this episode is brought to you by uh avocados. Yeah, uh exactly. Oh yeah, and Miralax. We're I we're um we're not um uh Miralax Boo Miralax. Yeah, boomerlax, we're we're unadvertising Muralaks, which I mean. Yeah, and what was the the the good one? Was Metamusil, right? Yeah, I think it's Metamusil. We're we're we're really I never metamusil I didn't look. We know what we're talking about. I think it's Metamusle. Like, yeah, I mean really it's just psyllium husk. It just gets some organic psyllium husk and yeah, psyllium. Yeah, just doum Murphy. Uh is a great actor. I don't know who that is. Oh, he was the uh the scarecrow in uh Batman Begins. Okay. He's in a lot of things, but that's what I'm saying. Oh, that guy. Oh, yeah, yeah. He's got like a creepy face. Yeah, he's Oppenheimer. Yeah, he's Oppenheimer. That's probably more relevant, but my memory for some reason is is more tuned to one of those. What did you think of that movie? Oppenheimer I thought it was a little boring. I don't know. I thought it was overrated. Okay. All right. Personally. I mean, I watched it on the plane. I don't really have time to watch movies except when I'm flying. Yeah, that's a good airplane movie. Yeah. Yeah, I don't know. I don't know. I my expectations were high and they were not met. I appreciated that it wasn't super unidimensional. I appreciate movies that at the end of the movie you don't think, oh, I wish I was that person or I lived at that time. Yeah, I definitely don't wish I was Oppenheimer. Yeah, Yeah. There's some original recordings of Oppenheimer that are worth listening to. Um one of the good things about YouTube and the internet is you can actually listen to people. Norbert Wiener, too, like the original cybernetics guy. Like you can actually listen to some of these people talking. Yeah. That's cool. I wish I could listen to a recording of Charles Darwin. That would be awesome. Yeah, maybe. Yeah. Maybe he had a bluegrass band or something. Charles Darwin on the steel guitar. Yeah. I I mean, I bet he'd be very good. Yeah. Would you is that Darwin? Is that one of your um if you can meet a historical figure? Oh yeah. Absolutely. Top of my list. Okay, really? Oh yeah. Okay. I mean, to just tell him like all the stuff that's happened since he wrote on the origin of species, and like tell him all the evidence that has confirmed and uh deepened and enriched his theory, like just to watch his eyes light up, that would be awesome. Yeah. And he's just like he's just a great scientist. If you read On the Origin, you know, descent of man, like expression of emotions in man and animal, like he he's a really meticulous thinker. I mean, yeah, he got a lot of stuff wrong, but like I don't know, just uh he's a great mind and and a beautiful writer too. Like Yeah, yeah, yeah. That last passage of On the Origin, the the grandeur in this view of life. Yeah. It's a beautiful passage. All right. Well, on this note, um, I don't know, you know the spiel, you know. Please like and subscribe and tell some about this podcast and Yeah, Patreon, send us an email, write a review, all that all that bullshit. Does Darwin do people um do leave reviews of like on the origin of species? do you think? Um, I don't know. I haven't checked the the Amazon list. Has there ever been a biopic about Charles Darwin? Not that I'm aware of. I would love to see a biopic of Darwin. I think there's a voyage of the Beagle. I think the BBC did something. Oh, really? Yeah. Anyway. All right. Well, I mean, I my one of my favorite um books is uh back in the day. I read uh The Moral Animal by Robert Wright. Uh that's a lot of people's intro gateway drug to Yeah, a lot of their gateway drugs. Um and uh what the best shtick of that book is he weaves in a biography of Darwin with with the chronicling of evolutionary psychology, and he sort of psychoanalyzes Darwin through the lens of evolutionary psychology. It's a really great shtick. I as you can tell, I actually never read that one. I was one of the ones I did not read. It's really fun. I mean, you know, there are a few few parts that don't hold up so well, but like it's it's a really fun read. Yeah. No, many of the evolutionary psychologists that I respect very highly uh got got their it got it got their hooks into them through that book. So yeah. Aaron Sell, I think was another one. Yeah. No, it's a great book. Yeah, cool. All right. We'll see you guys next week. See ya, David. Bye.