Do microbes help or hurt you? (featuring Katrine Whiteson)

Daniel and Kelly talk to Katrine Whiteson (a Whiteson Prize laureate) about the complex relationship between humans and microbes See omnystudio.com/listener https://omnystudio.com/listener for privacy information.

Speaker names marked ? are inferred from speaking time and the show’s known hosts — they are not voice-verified.

• 0:00Daniel Whiteson?

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• 1:52Daniel Whiteson?

  Nobody likes getting colonized by microbial invaders. Those little guys swimming around inside you, messing up your body's normal function, hijacking your cells to make more themselves, meanwhile, giving you headaches, or sniffles, or stomach pains, or even worse. No, we want them out. We take medicine to kill them. Or we wait for our immune system to hunt them down and root them out, leaving us with pure, unpolluted human bits, right? Not really. Actually, the truth about our relationship with microbes is much more complex. They not only fight on our side sometimes, most of the time, we can't even tell who is on which side, or if there are even sides. Maybe it's more like a big microbial economy than a black and white battle. Today on the podcast, we're going to dig into the

• 2:37Daniel Whiteson?

  life of microbes and the role they play in keeping us healthy and sick. Do they help us? Do they hurt us? Or is the answer, as always, it depends? A word to today's parents, today's episode is getting a little gooey. We can't talk about microbes without talking about poo. It's always a conversational risk when talking to biologists. So keep that in mind if you're playing this episode with your little ones. I vote let them listen. There's pooer in knowledge. See what I did there? Either way, welcome to Daniel and Kelly's extraordinary microbial universe.

• 3:22Kelly Weinersmith?

  Hello, I'm Kelly Weiner Smith. I study parasites and space. And today we are talking about one of my favorite topics as a biologist, which is to say microbes and poop.

• 3:33Daniel Whiteson?

  Hi, I'm Daniel. I'm a particle physicist and I have poop in my freezer.

• 3:37Kelly Weinersmith?

  Oh, oh, that's a little too much. But all right. So what is the most unpleasant microbe related thing that's ever happened to you?

• 3:47Daniel Whiteson?

  You want to hear about every time I had diarrhea?

• 3:50Kelly Weinersmith?

  Maybe the one worst time is what I was thinking. I guess, no, maybe not.

• 3:54Daniel Whiteson?

  To hear about that.

• 3:55Kelly Weinersmith?

  Never mind, I'm backing off. For me, it was an infection that wasn't healing and that was unpleasant. We should go in a different direction. What else should I ask? Here's my question for you. What is your favorite thing to consume that increases the diversity of your microbiome, however temporarily?

• 4:12Daniel Whiteson?

  Well, as you'll hear in our conversation with Katrina in a minute, we are big fans of beans in the White's household. And so we're even members of the Rancho Gordo Bean Club, which means we have mailed to us every few weeks, a box of heirloom beans. And so we have all sorts of crazy beans. And basically, we have beans at every meal.

• 4:30Kelly Weinersmith?

  Wow. So you must have like the best bean recipes. Can you send some to me?

• 4:35Daniel Whiteson?

  Absolutely, yeah. We'll share some with you.

• 4:37Kelly Weinersmith?

  Because I gotta say, after this conversation with Katrina, I am starting to think about how beans can be incorporated into every one of our dinners, at least.

• 4:43Daniel Whiteson?

  Mm hmm. We put lentils on everything. They're in salad. They're in everything. They're fantastic. Yeah, we're big fans of beans. And our son loves beans too, which is a great outcome.

• 4:52Kelly Weinersmith?

  You didn't mention your daughter. Does she not love beans?

• 4:54Daniel Whiteson?

  She's not yet on the bean wagon. Yep.

• 4:57Kelly Weinersmith?

  You know, it's hard to get kids on the bean wagon, I imagine. Yeah.

• 5:01Daniel Whiteson?

  Well, you know, with lots of foods, you can start with like the easier version, you know? Like if you're gonna start drinking coffee, you put milk and sugar in it. I'm not quite sure what the easy way is with beans. Maybe put lots of cheese on top or something.

• 5:14Kelly Weinersmith?

  At tacos, it's gotta be tacos.

• 5:15Daniel Whiteson?

  Tacos, yeah, exactly. Anyway, today we are talking about really fun and really important topics. What's going on inside our bodies and on our skin about all those critters that are living with us or who are part of us?

• 5:29Kelly Weinersmith?

  And you asked our listeners a question to gauge how subtly they understand the importance of bacteria in our body. So you asked them, do microbes hurt you or keep you healthy? And here's what they had to say.

• 5:41Speaker 05

  Microbes in your body are what allow you to function at all. So yeah, they're helpful. Although some kinds of microbes are bad for you and they will hurt you.

• 5:53Speaker 06

  Both. There are good microbes and bad microbes. Providing the microbes in your body are kept under control in their number and their type, they can definitely help you. But if you get introduced microbes or the microbes get to a critical number, then they can also cause harm.

• 6:11Speaker 03

  Like most questions in biology, the answer is it depends. For example, your digestive system doesn't work without microbes. But if you have too many of the wrong ones, then...

• 6:24Speaker 02

  It doesn't work at all. We couldn't live without microbes in our body. I'm on to you now with your deliberately vague questions. So microbes in the body. I think what you wanted me to say was in the body, but not in the bloodstream. However, I think the research has changed on that. So I actually think you do have microbes in the bloodstream now. But by and large, yeah, they are good for you. I read somewhere that our bodies are whole ecosystems.

• 6:57Daniel Whiteson?

  So I would say that on the whole, the microbes are beneficial to us. They do both. They help you and they can hurt you if they metastasize, turn to cancer. Microbes in our body are good and help. But there might also be bad microbes that you could get that would make you sick. They can help or hurt or neither or either one depending on where it happens to be. I think the general rule of thumb is that the microbes that are in your body are there to help you.

• 7:30Speaker 03

  Whereas the microbes that are trying to get into your body from the outside are the ones you gotta worry about. I believe the great majority of them are benign and useful microbes compared to the rare unwanted intruders. Help, absolutely help. I can barely distinguish myself from my microbes. Finally, a question I can actually answer as a nurse. Uh, microbes in the body can be harmful or beneficial. It depends on the type of microbe, the quantity of that microbe, and the location of that microbe. Both because some are bad for your body like germs and some are good for your body like good bacteria.

• 8:13Speaker 03

  There are forty trillion microbes in your body compared to thirty eight trillion human body cells in your body.

• 8:23Kelly Weinersmith?

  The majority of the microbes are there to make you feel better. And then every once in a while, when the balance is out of whack, they get into stuff they're not supposed to and cause us a little bit of damage. But hey, what are friends for? Microbes span the gamut from being critical for functioning to being lethal.

• 8:45Speaker 05

  We might not exist without microbes. It's something like 10 times more microbes than human cells in the body. Um, they help with digestion and glucose metabolism, help absorb nutrients in the body.

• 8:59Kelly Weinersmith?

  Classic science answer, it depends. Oh, this is a false dichotomy. Microbes both hurt and help you.

• 9:07Daniel Whiteson?

  I think microbes in our body are the part of our body. These are great answers. Thank you very much to our list of volunteers. And remember, you can join them at any time. Just write to us to [email protected] and we will hit you up next time. Kelly, what did you think of these answers?

• 9:24Kelly Weinersmith?

  I liked, I can barely distinguish myself from my microbes. That made me smile. I wanted to learn more about the cancer and bacteria link. I don't know too much about that. Yeah. What about you? What was your favorite answer?

• 9:36Daniel Whiteson?

  I like the person who said that they're on to us with our deliberately vague questions.

• 9:41Daniel Whiteson?

  This whole thing is some kind of scheme. Yeah, I thought these were great. And they show that people have already a pretty nuanced understanding of microbes. They're not just pathogens. They're part of who we are and how we live and all of our futures.

• 9:55Kelly Weinersmith?

  All right. Well, I think it's time for us to dig in with the interview with our special guest today.

• 10:02Daniel Whiteson?

  So it's my pleasure to welcome back to the podcast Katrina Weitzin. She's the senior editor of the Weitzin Science Report, a quarterly journal. And she's the current holder of the Weitzin Endowed Fellowship for Actual Experimental Science, Not Just Computer Stuff.

• 10:15Speaker 05

  Whoa.

• 10:17Daniel Whiteson?

  Welcome to the pod.

• 10:18Speaker 05

  I don't think you guys understand what a big concession that was. There have been times at UC Irvine where there were three Weitzin labs. There was Daniel Weitzin, who you all know and love. Shimon Weitzin, his brother, who is a computer science professor at Oxford, but came and did a sabbatical here. And then there was the actual Weitzin lab, Katrina Weitzin, where there's like a physical lab and there's people in there growing microbes and glassware being autoclaved and stuff like that. It wasn't just like in the cloud, you know?

• 10:48Daniel Whiteson?

  Well, we're not here today to debate the philosophical question of whether stuff on the computer is actual science or not. That's just me trying to butter you up for the episode.

• 10:55Kelly Weinersmith?

  I think we should bring you back for that debate, though.

• 10:59Speaker 05

  I know that what Daniel does is real science. I don't mean that. I'm just, I'm just enjoying the joke, you know?

• 11:06Daniel Whiteson?

  I'm just glad to get that on the air while we have that recorded now.

• 11:08Speaker 05

  Oh, boy.

• 11:11Daniel Whiteson?

  So today, we've invited you on the podcast because we're talking about microbes and microbes in the body and whether they help you, whether they hurt you, what their role is. Are they part of us? Are they our friend? Are they our enemy? Are they our frenemy? How does it all work? And this is your area of expertise. So we're very happy to talk to you about it. But first, let's get people acquainted and make sure everybody is talking about the same thing. Like, when I say microbe, what does that mean to you?

• 11:35Speaker 05

  Well, microbes refer to life forms that are too small to see with the naked eye, but it can refer to like lots of different branches of the tree of life. So microbes can be viruses, which we even debate whether they're alive or not, but they're definitely the most biologically diverse entity on the planet. So viruses, bacteria, fungi-like yeast, other eukaryotic parasites, like nightmarish ones that cause diarrhea. But most microbes are not pathogens, even though most of what you hear about microbes are pathogens. Most microbes actually are living their lives. Their goal is never to cause disease. They're out for themselves, you know?

• 12:16Daniel Whiteson?

  They have goals? You mean like if you talk to them, they'd have like hopes and dreams?

• 12:19Speaker 05

  Well, I mean, I think all life forms have a basic goal of reproduction, whether they're like thinking about it or not.

• 12:26Kelly Weinersmith?

  Could you give us a bit of our history on the thinking about this? Like, did we always think it was bad to have microbes in our gut? Have we kind of gone back and forth on thinking they're good or bad?

• 12:35Speaker 05

  Yeah, I mean, definitely. Well, the first time we ever even saw a microbe was when Van Loon Hook ground his own microscopes. He was a draper in the Netherlands and he was grinding his own microscopes in order to look at the threads at the edge of the curtains he was making. But then, for fun, he just took a piece of dental plaque, like a glop out of his mouth, and looked at it. And he saw the little microbes jumping around. And he drew pictures of them. He called them animalcules. That's the first time we saw a microbe. At that point, I think our thinking was pretty neutral. I mean, it took us a couple centuries to even realize. That like washing hands was a good idea to prevent disease. Uh, so yeah, it was pretty neutral for a while, but then I'd say by the 20th century, once

• 13:17Speaker 05

  cock postulates and we understood that microbes cause disease. Then I think we were just expecting every time we turned a corner and discovered a new microbe that it was causing disease. And you might've heard of like Bubble Boy or in the 1950s, when we first developed notobiotic cultivation. We at that time thought like, wouldn't it be great if we could all be sterile? We really didn't imagine that the microbes were doing too much positive. With a few exceptions, like there were people who appreciated probiotics around the year 1900.

• 13:47Daniel Whiteson?

  We go back, I want to understand what is notobiotics and who is the Bubble Boy?

• 13:51Speaker 05

  Great. Notobiotics refers to cultivating animals in a intentional community of microbes. It doesn't actually have to mean sterile. It can often mean like intentionally cultivating, say a mouse with like 10 known microbes. And then like learning exactly how those microbes affect immune development and all other kinds of health outcomes. So notobiotics are a really important tool in microbiome science where we can intentionally cultivate mice or zebrafish or like pick your model animal of choice. We can't really do that with people though. With this exception of Bubble Boy, who was a boy who had severe immune deficiency. And I mean, kind of brilliantly considering the technology available at the time.

• 14:35Speaker 05

  His medical community, the doctors around him figured out how to keep him in essentially sterile conditions, like in a plastic bubble with oxygen pumped in. So that he was never exposed to microbes that would quickly kill him. There's a movie about it too. So that's pretty rare to have a human growing up with that little microbial exposure. But at that time, we thought like, oh, the more antibiotics, the more better. Just like pop them down, it'll probably help you. There was not really a feeling of loss that by taking antibiotics, you were destroying something.

• 15:06Kelly Weinersmith?

  And I feel like since then, we've gone in the opposite direction where whenever you're listening to a podcast, you get advertisements about bacteria that are so good for you. And have we sort of gone in the opposite direction? Are we finding a happy medium?

• 15:21Speaker 05

  That's a good question. I feel like the ads you hear. Are sometimes coming from the eighty billion dollar probiotic industry, which is not really resting upon too much evidence, to be honest. And so the kinds of things you hear in those ads are often not all that close to reality. So I guess it depends a little bit about which parts you're hearing about. I think the message that we shouldn't just pop antibiotics without any concern for the damage they can cause. I feel like that has gotten much better. So yeah, I think we have come to appreciate that taking antibiotics has a consequence that's not only positive. Although keep in mind that eighty percent of the antibiotics used in the United States at least are in agriculture. So our own human consumption can only have so much impact on avoiding the antibiotic resistance crisis.

• 16:06Daniel Whiteson?

  All right, so microbes are these little critters that are too small to see, which frankly feels to me like a little fuzzy. Like if I have terrible vision, are there some things that are microbes to me? Like if I can't see cats, do they count as microbes? Because I have like really bad eyesight. But as usual, it's biology, so it's fuzzy.

• 16:22Speaker 05

  No, I mean, it's definitely like, you know, if I had a slide, I could give you some images of the scale bar and the sizes of viruses and bacteria. Like your average bacterial cell is about ten times smaller than your average eukaryotic cell. Eukaryotic cells have a nucleus. Those are the kind of cells that make up our bodies. And there's also unicellular versions of them. But I mean, yeah, the point is just that they're tiny and they tend to be unicellular, too.

• 16:50Daniel Whiteson?

  I mean, some dogs are tiny, too. Around LA, people's purses, microbial dogs. All right.

• 16:57Speaker 05

  Those dogs have like four thousand times as many microbes in their guts is what I'm saying, though.

• 17:03Daniel Whiteson?

  I mean, toy dogs are pretty small. Anyway, you're the expert on it, so I'll defer to you. And so you've walked us through this history where we learned about microbes. Some of them cause disease, but now we have a more nuanced take. So tell us, like, if microbes are part of us, where on the body do they live? Where can I find microbes in my body?

• 17:24Speaker 05

  I mean, you can find microbes literally everywhere, whether it's your body or not. And so. That's actually a challenge. Sometimes I start my talks out with this challenge that like a key postulate of microbial ecology is that nothing is sterile. And then I try to think of maybe exceptions to that, like places where life really can't be sustained. But I mean, you could just check out any environment, deep sea, ocean vents, hot springs, you know, the outside of a spaceship, like.

• 17:54Daniel Whiteson?

  What about Uranus? Is Uranus sterile?

• 17:58Speaker 05

  Wow. Well, that depends a bit on the meaning.

• 18:04Daniel Whiteson?

  Answer it in however you like.

• 18:07Speaker 05

  Well, I think there are places that have very, very low microbial load and some materials that can't really sustain microbial life so well, like maybe glass, for example. But on average, you know, on your body, which was your question, we have really, really dense microbial colonization in our gut. Those are mostly microbes that can't survive with oxygen. Like they're called anaerobes, so they live without oxygen. Most of the microbes in your gut are anaerobes, which I just think is amazing because we obviously live in a world with oxygen. So it's kind of crazy how all these anaerobes colonize our bodies.

• 18:41Kelly Weinersmith?

  We're reverse bubble boys for the bacteria in our guts.

• 18:44Speaker 05

  Yeah, exactly. Even your teeth have really strict anaerobes growing on them. So your oral cavity is super, super densely colonized with microbes. Like the number of microbes per density is about the same in your oral cavity and in your gut and like in a soil sample where they're famous for being teeming with microbes. And in your oral cavity, there's just gradients of microbes that gobble up the oxygen at the surface so that shields the ones underneath so that the anaerobes can survive.

• 19:12Daniel Whiteson?

  Why do you say oral cavity instead of mouth?

• 19:15Speaker 05

  Well, I mean, mouth is probably a better choice. I see what you're saying, but I guess I just got so used to writing papers about oral microbiomes and oral cavities and like in the human microbiome. My own project, there were 17 sampling sites in the oral cavity. There's symmetry, like your two back top teeth on each side of your mouth have more similar microbial communities compared to ones closer to the surface, having to do with like nutrient access. And so I think I'm just thinking about that when I say it.

• 19:42Kelly Weinersmith?

  We've gotten a little bit farther away from my favorite topic. So first I want to point out that Daniel was the first one to mention poop and butts in this episode.

• 19:50Daniel Whiteson?

  I win, I win.

• 19:51Kelly Weinersmith?

  You can't always blame the biologist, but I've been dying to ask you. So I heard that our bodies have so many microbes that we have more microbes in our body than we do cells. But then I heard that the balance of power changes immediately following a bowel movement because there's so many bacteria in our feces. What is the truth, Katrina? I have to know.

• 20:18Speaker 05

  Wow. Well, that's an awesome question and it's been a real topic of debate. And it's funny because it's like the intro slide to every microbiome talk for about 10 years was all about how there's 10 times as many microbial cells as human cells in an average human body. But then we redid our back of the envelope calculations. So now we call it front of the envelope and now the ratio is estimated to be more like one to one. But like both the numerator and the denominator are like highly in flux here. So I wouldn't swear the life of my children on these calculations or anything like that because it's really.

• 20:51Daniel Whiteson?

  Good to know. Wow.

• 20:54Speaker 05

  But like even just estimating the number of cells in a human body.

• 20:58Daniel Whiteson?

  Wait, sorry. Are there science conversations that you have that I'm not in where you are swearing the life of our children?

• 21:03Speaker 05

  No, definitely not.

• 21:06Daniel Whiteson?

  I mean, I gotta wonder now that I hear this.

• 21:08Kelly Weinersmith?

  Daniel, I feel like you're often on the show talking about dangerous situations you'd put the kids in for the sake of physics. I don't, I don't feel like you have to be high and mighty about this.

• 21:16Daniel Whiteson?

  I'm mostly talking about your kids, Kelly.

• 21:18Kelly Weinersmith?

  Oh.

• 21:19Speaker 05

  Wow, interesting.

• 21:21Kelly Weinersmith?

  I'm sending my kids to their grandparents' house when you guys come to visit next week.

• 21:27Daniel Whiteson?

  All right. So Katrina, you're telling us there's a lot of uncertainty. We don't really even know whether there are more human or microbial cells in our bodies.

• 21:34Speaker 05

  I'd say the balance is closer to roughly even. And I agree that when you have a bowel movement, the balance would shift because you would lose a lot of microbial cells. Every time, depending how much fiber you eat and if you have really big bowel movements or not, but um, no matter what, despite the number of cells, what we can always say is that the diversity of metabolisms in our body is heavily weighted towards the microbes. Because human cells can only pull off like a pretty small number of metabolisms, like the number of types of genes is pretty small in comparison to the number of types of genes that microbes carry. Each microbe can live in a totally different niche. Like there's

• 22:16Speaker 05

  microbes that live with no oxygen or microbes that can live with a little bit of oxygen. And they each carry very unique genes for breaking down all kinds of molecules. So like our metabolomic diversity is unquestionably much more coming from our microbes than from our human cells.

• 22:33Daniel Whiteson?

  All right. So I feel like we're transitioning from talking about individual microbes to talking about like communities of microbes. And you're telling us these live here and those live there. And you hear the word all the time these days, the microbiome.

• 22:44Speaker 05

  Yeah.

• 22:45Daniel Whiteson?

  So microbiome, just a description of like the microbial communities?

• 22:48Speaker 05

  Yes, exactly. So a microbiome is a community of the microbes we just defined in a particular environment. So the microbiome definition includes what the environment is. So like the kind of microbes that live in your gut where there's not very much oxygen is very different than the kind of microbes that live at the surface of the ocean where photosynthesis is a big deal. So it's about what type of life is sustained in that environment.

• 23:14Daniel Whiteson?

  So if I see like a bunch of ladies in LA with a hundred tiny little dogs that are so small that I can't see them. So those are all microbes and together they make a little microbiome.

• 23:26Speaker 05

  I mean, I can't really just say yes to that. And if you can't see the dogs, that means they're in your imagination. So then.

• 23:36Daniel Whiteson?

  They're philosophical dogs.

• 23:37Speaker 05

  You need some evidence to support your claim. I thought you were a scientist.

• 23:43Daniel Whiteson?

  I just do computer stuff.

• 23:45Kelly Weinersmith?

  It's good to know that next time Daniel and I have a conversation like this, it's okay to just say, I'm not humoring that.

• 23:54Daniel Whiteson?

  Oh, no.

• 23:55Speaker 05

  In theory, I see what you're saying and like only Los Angeles would support 100 people with microscopically tiny dogs. So that's kind of special to that environment. I see your point.

• 24:04Daniel Whiteson?

  So then I want to connect it back to something you said earlier. You were talking about the kinds of microbes that live in different parts of our bodies. Do we have like one microbiome, like one community of microbes? Or are there different communities of microbes that live like in my oral cavity and on my gut or on the tip of my nose?

• 24:20Speaker 05

  Yeah, there's really big differences in the types of microbes that live in your gut versus your oral cavity versus like the drier patches of your skin on your elbow versus the oilier patches of your skin in another part of your body, like your armpit, say. And also, super interesting, most of our bodies on the skin, we have a lot of diversity of bacteria. But on our feet, which are more moist, we actually have more diversity of fungi. And this is all in health. Anyway, if we start talking about transplants, which I imagine we will, there's fecal transplants, there's armpit transplants, there's ear microbiome transplants. And so getting a healthy community of microbes going is really important to our health. But even defining health, of course, is really hard.

• 25:04Kelly Weinersmith?

  Well, can we try to talk a little bit more then about what these microbes are doing for us? So you mentioned that a bunch of the metabolism that happens in our body is caused by bacteria. And that sounds like it could be helpful. So what are some things that our bacteria do for us?

• 25:18Speaker 05

  Oh, what a great question. So I mean, to be honest, a lot of this is still unknown. So that's what's so fun about our field. I'd say most of the things the microbes are doing, we don't know what they are yet. But things that they do, for example, are they can break down fiber. So when you eat fiber in your diet, actually, human metabolism can't handle that at all. But the anaerobes living in your gut, they're really good at breaking down fiber. And another example that I love is the sugars in breast milk. They should actually be called fibers as well. So in breast milk, about fifteen percent of the energy is in the form of sugars or fibers that human

• 25:57Speaker 05

  metabolisms just can't access at all, but the microbes can. And so this is a really important moment in human history, like what moment matters more than when a baby is born. Clearly, we wouldn't just throw fifteen percent of the energy that's in breast milk down the drain unless it was really sustaining something important. And that fifteen percent of the energy in the breast milk is sustaining specific microbes that can break down the breast milk sugars. And then when a diarrheal pathogen comes through and tries to take up residence in a baby gut, it doesn't have access to that secret nutrient source. And so a big protection mechanism for babies in parts of the world where diarrheal illness is still a really big deal

• 26:40Speaker 05

  is if you're breastfed and you have those microbes that can break down the breast milk sugars, then the, when salmonella comes through, it's just kind of like cupping and those special microbes like bifidobacterias that can break down the breast milk sugars dominate the baby gut. That's probably how most baby guts were organized while they were breastfed through human history.

• 27:00Daniel Whiteson?

  So let me see if I understand. You're telling me that basically the first step in digestion, like I eat a bowl of beans. It's not that my human mechanisms get involved and break the beans down, but like microbes are on the front line and they start the process breaking things down because I can't.

• 27:15Speaker 05

  The order of events there is a little different. Like, okay, so you're eating your beans. They get to your stomach. The stomach acid starts to break things down. Digestive enzymes come in from your pancreas and small intestine area. So actually, the first chomp at most nutrients is coming from earlier steps in your digestive tract. And actually, the microbial load is quite low. Like, we do have microbes in our stomach, but at not very high density. And same with our small intestine. But by the time you get to the colon, so you need to eat foods that don't get absorbed quickly earlier in your digestive tract to give your microbes access to them. So if you just eat White rice or processed foods, those get absorbed real quick in your stomach and

• 27:59Speaker 05

  small intestine. But if you eat things that take longer, then they get down to where the most dense community of microbes lives and then you can give those microbes a chance to break down the fibers.

• 28:11Daniel Whiteson?

  I'm sure Kelly has a question, but I just want to ask one quick follow up about the baby thing. You're telling me that human mothers produce something that babies cannot digest without microbes in their guts, which means of course that we've been doing this for a long, long time.

• 28:26Speaker 05

  Yeah.

• 28:26Daniel Whiteson?

  Right? And microbes probably evolved with us. But how do babies get those microbes? Like, do they get them from the mom? Is it during the birth? Is it during gestation?

• 28:35Speaker 05

  It happens after birth, but actually, there's probably many opportunities. When something's really important, it's good to have a lot of ways for it to happen. And so it's not just only at birth. It could be at birth, but I would imagine that in a village or a community in human history's past where there were a lot of young children, that this would be passed between siblings and friends. I mean, you just need to be in an environment where that microbe exists. So it doesn't only have to be at the moment of birth. It could be at the moment of birth, but it could also be really at any time in the beginning of life.

• 29:11Daniel Whiteson?

  All right. Well, that takes us all the way back into prehistory and the understanding of microbes. We're going to take a break and we're going to come back and we're going to talk about the present and the future of microbes.

• 29:31Speaker 01

  That sound? That's the National Squash League. Pro teams, the world's best players, and rallies so fast you'll forget to breathe. Season four is in full swing and every match streams free on YouTube. Big hits, bigger rivalries, and a front row seat from wherever you are. Watch every match for free on YouTube. Search National Squash League and hit subscribe or follow live updates on Instagram at NSL.Sport.

• 29:59Speaker 03

  Cash flow crunch? OnDeck's small business line of credit gives your business immediate access to funds, up to $200,000, right when you need it. Cover seasonal dips, manage payroll, restock inventory, or tackle unexpected expenses without missing a beat. With flexible draws, transparent pricing, and control over repayment, get funded quickly and confidently. Apply today at ondeck.com. Funds could be available as soon as tomorrow. Depending on certain loan attributes, your business loan may be issued by OnDeck or Celtic Bank. OnDeck does not lend in North Dakota. All loan amounts subject to lender approval.

• 30:29Speaker 05

  Hi, I'm Jenna Oshkowitz. You might know me from Glee. This is At the Table, the food allergy podcast, a show about food, connection, and what it really looks like to live with food allergies. Each episode, we hear stories from real people like Daniel.

• 30:44Speaker 01

  People would always think I was lactose intolerant, so I just kind of shortened my explanation to I'm deathly allergic, in a big way that defined a lot of my childhood.

• 30:55Speaker 05

  And while there are challenges, there are moments that remind you, you are not alone. One of the best guys that I dated, he made a point to memorize all my food allergies. So join us and hear their stories and more, because living with food allergies isn't just about what you can't eat, it's about still having your seat at the table. Brought to you by Genentech and Novartis. Listen to At the Table, the food allergy podcast, on America's number one podcast network, iHeart. Follow At the Table and start listening on the free iHeartRadio app today.

• 31:35Kelly Weinersmith?

  And we're back. And, okay, Katrina, I have a question for you that I get asked a lot, and I would love to know what the answer should be. So I study parasites that manipulate the behavior of their hosts. And often people will say, okay, I've heard that our brains have nerves that go down to our stomach and that bacteria do things like release serotonin and dopamine that can communicate with our brains. So are our behaviors controlled by our microbiome? Can our microbiome be like, you need to eat more beans or something? So to what extent are our microbes influencing our behavior? Well, I mean, a lot, for sure. There's definitely-

• 32:15Speaker 05

  A very strong gut-brain axis. And we've known that for a long time, even independent of the microbes. We know that a lot of our nervous and immune system is in our gut. And so 90% of the serotonin in your body is produced in your gut, for example. And it's with the help of neuroendocrine cells in our guts. But those cells are being manipulated by the microbes. So there's a really strong connection between the dense community of microbes in our guts and all of the different types of cells lining our guts that are interacting with our nervous system. So there is a very strong gut-brain connection, no question.

• 32:58Speaker 05

  And there's so much interesting evidence, which is hard to sort through, about how if you improve your diet, you can improve symptoms of depression. Or if you meditate regularly, you can improve your inflammatory state and your microbiome composition.

• 33:13Daniel Whiteson?

  Well, you're saying it goes both directions, not just microbes are influencing how we think, but your brain can like control the microbes somehow?

• 33:19Speaker 05

  I mean, when you say it like that, it sounds fantastical. But I mean, I literally just watched Joe Handelsman give a talk last week about how people who were meditating regularly had improvements in their microbiome. And defining an improvement is a really hard thing to do in our field. So, you know, ask more questions if you want. But yes, it goes in every direction because our microbe composition is influenced by the environment. And if you do things that help to change your stress levels and the types of inflammatory cells that your body is inhabited by, then that changes the environment and it changes which microbes are winning the battle of survival in your gut at that moment.

• 34:02Speaker 05

  And which microbes are there to break down the foods that you're eating. So yeah, there's a very tight connection between our guts and our minds. But we're really at the beginning of figuring that out. There's a few conditions that we are starting to have really good evidence, like for Parkinson's disease, there's symptoms in the gut arising well before other symptoms like constipation. And that was one of the clues that helped us try to disentangle how the microbiome is involved in Parkinson's disease development. I'm so curious. In 10 years, like what we're going to understand better. But there's really cool evidence emerging all the time.

• 34:41Daniel Whiteson?

  So you've mentioned several times that the microbes play important roles in digestion, et cetera. Do we know what like a good microbiome is like? Do we understand what your microbiome should be doing and what its composition should be? And is that true in the gut or in my nose or my ear?

• 35:00Speaker 05

  That is still a science question, and I think it's also maybe a philosophy question. Even just to define health is really interesting. Our field has had a lot of interaction with philosophers through the years to try to define what health is. For example, at the operation nearby in Tustin for the product Voust, where they harvest so-called healthy fecal spores from so-called healthy donors in order to treat the diarrheal pathogen C. diff. They have to decide who can be a healthy donor and they screen people and only 1% are considered eligible.

• 35:37Daniel Whiteson?

  To be clear, what we're donating here are BMs, right?

• 35:40Speaker 05

  Yes, so they get volunteers to come and poop on site four to six times per week. And then they harvest the spores out of their poop. And that is the product Voust, which is being used to treat C. diff. It's one of two FDA-approved microbiome therapies in the country right now.

• 35:54Kelly Weinersmith?

  It's got to be hard to schedule. Like you can't just do that on cue. My son seems to be able to, but he's the only one I've ever met who can do that.

• 36:01Speaker 05

  Yeah, I think they have like a big line in the morning. So people who can do that regularly. I remember asking in one of my classes once, like, who knows when they're going to poop every day? Like, is it like something you know when it's going to happen or is it like?

• 36:14Daniel Whiteson?

  You're asking people about this in class and probably like raise their hand to talk about their poop schedule?

• 36:19Speaker 05

  Well, it was when I had somebody from the company Voust visiting to speak and she had exactly the question you just had, Kelly. Anyway, there were some people who were like, how could you not know when you're going to poop? I always know when. People who are like, I would never be able to guess that. That's clearly like something that's different about each person. But you know, 1% of people are not the only healthy people. And I think that we need to think about what we mean by health differently. When I'm writing my ethics review approval documents for the studies that I do, I have a very expansive definition of what I think health is. And to me, health is someone who's out and about, living their life. Like, a student in my class is definitely considered healthy. Otherwise, they couldn't like show up and be a college student.

• 37:00Speaker 05

  If they have some allergy or some other kind of defined disease that's been diagnosed, in my mind, that doesn't like knock them out of the category of being a healthy person. And so that's a really difficult question to answer. But your question was, do we know what a healthy microbiome is? And that was actually what the goal of the Human Microbiome Project was. It started in 2006 and they got 300 healthy donors in the United States to give samples. And healthy was defined somewhat more inclusively, I think, than the 1% that were accepted in that other donation context. And the goal was like, what's the core human microbiome? Like, what are microbes that are shared between everyone? And the fascinating thing was that every time you added one more person to the study,

• 37:45Speaker 05

  the Venn diagram overlap got smaller and smaller until there was nothing left. So there were no core human microbes. Everybody is different enough that there just really isn't a core human microbiome, depending how you define it.

• 37:58Daniel Whiteson?

  So you're saying, for example, person A is totally healthy and living their lives and having great poops and doesn't have anything in common gut bacteria-wise with person B, who's also healthy and can eat beans and doesn't have terrible digestive problem?

• 38:13Speaker 05

  Yeah, people are extremely different from each other. If you only had two people, I bet you would find some overlap. But by the time you get to about 10 people, you probably don't have much overlap left anymore. And then really big differences occur when you look around the world. And so there's really cool patterns of people who live in less industrialized places where they eat more plants and less processed food. Their guts tend to be dominated by plant breakdown microbes that are good at breaking down fiber and probably have other properties too. Whereas if you look in the industrialized world, and this is like so scary to me, that most people in the industrialized world Have a lot of mucus breakdown bugs in their gut. So basically, we're starving our guts of fiber.

• 38:56Speaker 05

  And as a result, the microbes are like turning to us and just like eating the mucus that's produced by the cells lining our gut. So there's this bug called Akkermansia that's very common in the industrialized world. And bizarrely, it's even marketed as a probiotic because it has been associated with positive outcomes. But it's breaking down the mucus, which is the only thing between you and sepsis. You have like literally millions of cells of microbes in your colon. And there's one layer of cells, this epithelial lining of cells lining your gut. And if that barrier breaks down, the microbes get into your blood and that's a blood infection. That's called sepsis. That's deadly.

• 39:36Speaker 05

  And so your mucus lining that one layer of cells is a really important part of the barrier protecting you. And so weirdly, we have a lot of bugs that are breaking down that mucus. Maybe there's some kind of feedback there. I mean, these are all science questions. Maybe like the bugs breaking down the mucus stimulate its production and maybe that's like not all bad. But just the fact that it's so common in the industrialized world and missing in the parts of the world where people eat more plants, it kind of makes me want to have the plant type of microbiome, not the mucus breakdown one.

• 40:09Daniel Whiteson?

  So then where can we expect similarities between microbiomes? Like you and I live in the same house. You mostly use similar foods, use the same toilets. Do we have similar microbiomes? Do we expect them to be similar?

• 40:19Speaker 05

  Definitely. That's one of the biggest signatures in every microbiome study after the individual is the household and the family. So when you collect samples from people who live together, they have so much in common. And so that's a really, really cool way to do a study. Like my favorite way to do a study is with household controls. So you can compare people with the same background. And otherwise, to do longitudinal studies where you take samples from the same person through an intervention and then use their starting point samples as the baseline. Because if you try to do it cross sectionally where everyone is so different, it just doesn't work at all. And back to the household question, I mean, I really love studies that get into that. And I have a friend down in San Diego, David Pride.

• 41:02Speaker 05

  And he did a study once where he compared married couples who'd been living together for a long time with Craigslist roommates who moved in together. And after six weeks, they shared a quarter of the Viruses in their gut communities. So sharing a kitchen and a bathroom is enough to share a lot.

• 41:19Kelly Weinersmith?

  Huh.

• 41:20Daniel Whiteson?

  The Craigslist connection.

• 41:21Kelly Weinersmith?

  Yeah.

• 41:21Speaker 05

  Yep.

• 41:22Kelly Weinersmith?

  How much do our own individual microbiomes change over time? So if you looked at a family now or five years down the road, how consistent would their microbiome be?

• 41:31Speaker 05

  They're quite consistent through time in families and households, but they're evolving because, you know, microbes have high mutation rates. They don't correct themselves as much as ourselves do. So in a virus community, for example, there was one grad student who took samples from himself throughout grad school, which took a couple of years. And between the beginning and end of grad school, some of the viruses in their gut, I'm sure it was anonymous. So maybe I shouldn't say the name of the study, but anyway, some of the viruses had mutated more than 3% in their genomes, which is the definition of a new virus. Each of our guts is kind of like its own little chemostat, where evolution can keep happening. And so through time, enough mutations arise that it

• 42:16Speaker 05

  could even be considered a new species of virus that's emerging. The other thing that happens is like, say you travel and get diarrhea and really shake things up, or you take antibiotics, you can kind of like, get your community steering to take a sharp turn after things like that.

• 42:33Daniel Whiteson?

  Wait, walk us through what's happening there. Like when you get diarrhea or you get C. diff, what's going on there? Something is coming in and outcompeting the microbes in our guts? Or what's going on?

• 42:42Speaker 05

  Yeah, exactly. So oftentimes a diarrheal pathogen, what will happen is that they'll come in with some toxin or some like really big hammer that causes big changes.

• 42:55Daniel Whiteson?

  Meaning that it kills the other microbes?

• 42:57Speaker 05

  Or that it just triggers an enormous immune response, which brings in a lot of oxidative stress. And I was just telling you how the microbes in our colons hate oxygen. Well, inflammation is basically a pile of oxygen. So bringing in all Those inflammatory cells and molecules, that's a tough condition for a lot of the bugs that live in our gut. And then you'll have an outgrowth of the kinds of bugs that can tolerate oxygen. In fact, when you study the microbiomes of people who have a terrible gut infection, you don't often find that the bug causing the infection is the most numerous. This really surprised me, actually. I've done a few studies like this with cluster deadenosine infections here at the

• 43:40Speaker 05

  UCI Medical Center. And my naive expectation was that you would see like, oh, it's 90% C. diff. So they have a C. diff infection. But that's not what you see at all. You just see a bunch of bugs that can handle oxygen, basically. And then there's probably a small number of C. diff cells that are just dumping toxin that's causing all that inflammation.

• 44:00Daniel Whiteson?

  That's really mind blowing. I mean, especially if you start from the point of view of like, diseases are microbes that come in pathogens come in and colonize the humans. Now you're giving us a whole new way to think about what disease is. Now it's like microbial war, where what's really being damaged are not the human cells, but like the microbes on our side that were doing their job for us. So it's really, we're sort of like a host. We're just like the battleground for this microbial confrontation.

• 44:27Speaker 05

  Yeah, exactly. I really like the concept of a holobiome, which is the idea that, you know, you are your own genome and cells, and then you are host to a community of microbes, which comes from the environment that you live in. So all the microbes in the environment that you live in, and then some subset of them colonizes you. And so part of your environment is your diet, and part of it is like, how much time you spend playing with dirt. So like, your exposure to microbes, who your roommates are, you know, stuff like that. Like, sometimes people ask me, well, how can I get a healthy microbiome if I don't have one yet? And like, one piece of advice would be to get a really healthy roommate who you knew how to help.

• 45:12Daniel Whiteson?

  You're gonna cause a lot of stress here. People are gonna blame their diarrhea on their roommates now.

• 45:16Speaker 05

  No.

• 45:17Daniel Whiteson?

  If you only did the dishes, then I wouldn't have diarrhea.

• 45:21Kelly Weinersmith?

  Or maybe you cleaned the bathroom too much. I needed your good microbes. Maned them for that. So I've got a question about how we even quantify microbiomes. So bacteria, you know, they can undergo conjugation. So they swap genetic material with each other. In just the course of a couple of years, viruses are becoming new species because they're mutating so much. How do you define a species when things are changing so quickly? And how do you compare between individuals when there's all this variability?

• 45:50Speaker 05

  Yeah, what a great question. And like, I've been in this field long enough that I've watched the pendulum swing back and forth on how we make those definitions. Sometimes it's driven a little bit by technology. But, um, you know, basically, there have been people thinking about microbial communities for more than a century. So it like, it goes back to, there was a Ukrainian microbial ecologist who was studying pond scum in Switzerland. And he made these columns called Winogradsky columns, which had, you know, just what I was talking about with the oxygen gradients, where you'd have oxygen-loving bugs at the top, and then their waste products become the treasure of the next layer of microbes, which need less oxygen and have different strategies for metabolism.

• 46:33Speaker 05

  So those layers of microbes, you could even consider them to be the unit of selection that matters. And so it could be defined functionally, almost. Since the mid 20th century, we started having molecular techniques for probing all of the microbes in a community. And this all started with environmental microbiologists. All the human clinical microbiology people were too busy isolating one pathogen at a time and throwing anything that they didn't define as a pathogen down the drain as like irrelevant normal flora or something like that. So the environmental microbiologists got really good at these really cool molecular techniques, starting with less resolution. So they had to define a species based on the information they could get.

• 47:14Speaker 05

  So we started like digesting common genes, like ribosomal genes, and using restriction enzymes that we got out of hot springs and putting them on gels. And then like, if the bands on the gel looked different, then that would be defined as a different species. So probably we're talking like, a few percent difference in genome, because we were only looking at one gene. One gene is exactly the same. There could still be millions of years of evolution separating those two organisms. Then we got much better. Now we can sequence everything. And so when I first started in this field around 2008 or so, we defined a bacterial species as being 3%

• 47:56Speaker 05

  different from the next in this one ribosomal gene. And that was how we defined a species. Since then, as our techniques have gotten better, we've leaned towards using even tighter definitions. So we could, you know, look at organisms that are almost identical and only have one nucleotide difference. And then we would start to define that as the taxonomic unit that mattered.

• 48:20Daniel Whiteson?

  Because these guys reproduce asexually, right?

• 48:23Speaker 05

  Yeah, they reproduce asexually, but they have pretty high mutation rates. They don't like correct all their mistakes. So, you know, for a virus, every progeny is a mutant, basically.

• 48:35Speaker 05

  Like, I mean, think about that for flu or COVID. Like, I think there were actually really great visualizations about that since the pandemic that helped that become obvious to everybody, which is so interesting, right? If every time a virus makes a copy, it's a new mutant. Some of those just fall flat, but that's not the strategy. The strategy is like, most of them do okay, some of them do amazing.

• 48:56Daniel Whiteson?

  Well, hey, look, I'm sure those virus parents love all their little mutants.

• 49:01Kelly Weinersmith?

  All right, so let's take a break and think about the mutants in our life that we love. And when we come back, we'll talk more about the microbiome.

• 49:22Speaker 01

  That sound? That's the National Squash League. Pro teams, the world's best players, and rally so fast you'll forget to breathe. Season four is in full swing, and every match streams free on YouTube. Big hits, bigger rivalries, and a front row seat from wherever you are. Watch every match for free on YouTube. Search National Squash League and hit subscribe or follow live updates on Instagram at NSL.Sport.

• 49:49Speaker 01

  Cash flow crunch? OnDeck's small business line of credit gives your business immediate access to funds, up to $200,000, right when you need it. Cover seasonal dips, manage payroll, restock inventory, or tackle unexpected expenses without missing a beat. With flexible draws, transparent pricing, and control over repayment, get funded quickly and confidently. Apply today at ondeck.com. Funds could be available as soon as tomorrow. Depending on certain loan attributes, your business loan may be issued by OnDeck or Celtic Bank. OnDeck does not lend in North Dakota. All loans and amounts subject to lender approval. Hi, I'm Jenna Oshkowitz. You might know me from Glee. This is At the Table, the food allergy podcast, a show about food, connection, and what it really looks like to live with food allergies.

• 50:31Speaker 01

  Each episode, we hear stories from real people like Daniel. People would always think I was lactose intolerant, so I just kind of shortened my explanation to I'm deathly allergic, in a big way that defined a lot of my childhood. And while there are challenges, there are moments that remind you you're not alone. One of the best guys that I dated, he made a point to memorize all my food allergies. So join us and hear their stories and more, because living with food allergies isn't just about what you can't eat. It's about still having your seat at the table. Brought to you by Genentech and Novartis. Listen to At the Table, the food allergy podcast, on America's number one podcast network, iHeart. Follow At the Table and start listening on the free iHeartRadio app today.

• 51:25Daniel Whiteson?

  All right, so we're back, and we're talking to Professor Katrina Whitson of the Whitson Research Institute about the microbes in our body, how they influence our world and shape our lives. And we're talking about the links between microbiome and health. And in a minute, I want to ask you about what we can do to impact our microbiome. But you've sort of laid out this picture that like, these things are in our guts. We don't really understand why they're so different from person to person. We can't even really define health. We don't understand necessarily what microbiome you need to have healthy function. But we know that there's a connection between microbiome And health, right? And I've heard about people talk about connections between like the microbiome and like Alzheimer's or microbiome and autism and microbiome and

• 52:07Daniel Whiteson?

  all sorts of things in our lives. How much do we know about the impact of the microbiome on these conditions?

• 52:13Kelly Weinersmith?

  Can I super fast interject? I love that Katrina is president of the Weitzin Institute, but I do feel like we've never actually mentioned that Katrina is also a professor at UC Irvine and has her own lab. Have we given her actual credentials at some point?

• 52:28Daniel Whiteson?

  She does have a secondary affiliation at UC Irvine.

• 52:31Kelly Weinersmith?

  Okay, all right. So she is incredible in lots of ways. But okay, all right, sorry. Go ahead with the question.

• 52:37Daniel Whiteson?

  That's nice of you. Well, I mean, yes, we have observational evidence associating microbiomes with health on a lot of different fronts. And I mean, just it's hard to even know where to start. But one place I could start is that when I started my lab at UC Irvine in 2014, right when microbiome was becoming big in the literature and everybody was excited about it, I had 100 labs contact me wanting to collaborate in that first year. I think I had one grad student just beginning to join my lab. We obviously couldn't do 100 collaborations. So I ended up joining forces with an ecologist here, Jennifer Martini, and we started a microbiome center. And in the last 10 years, I have gotten to study easily 100 different types of microbiomes. Like, name a type of body sample you could

• 53:22Daniel Whiteson?

  think of. I've probably got some in our lab freezer, and I've probably studied its microbiome. And that goes for like, lots of different kinds of creatures, including sharks that eat seaweed from Donovan German's lab, for example. So we have been going around and like, watching what the microbiomes look like, and taking notes and associating that with health. So a lot of the information we have is observational. So we still have, in the future, a need to do more interventional studies where we ask, what, how does the microbiome change when you manipulate it in a certain way? You know, now we kind of know that microbiomes are associated with obesity and cancer and so forth. But then what do we do about it? That's kind of like the next 10 years of challenge. And there's a few glimmers of

• 54:06Daniel Whiteson?

  really, really exciting outcomes that make me think it's going to be possible. So like, for example, cancer treatment is an area that I think has a lot of room for big improvement, where my colleagues at MD Anderson, Jen Wargo, for example, have done studies showing that when melanoma

• 54:25Speaker 05

  Patients are getting immunotherapy, which usually only succeeds about thirty percent of the time. And the thirty percent of people who have a successful immunotherapy tend to have a certain kind of microbiome. Well, it turns out if you do a fecal transplant from someone whose immunotherapy succeeded into someone whose immunotherapy failed, that you increase their chances of a good outcome. Or if you ask how much fiber people ate, people who ate more than twenty grams of fiber per day have double the progress free survival when they're doing immunotherapy. And now they're even doing intervention studies where they're getting people on immunotherapy to eat fiber and they're watching to see if that increases their healthy outcomes. And that's not published yet, but I'm very optimistic.

• 55:08Speaker 05

  So those are the kinds of things I could see happening in the future. We even know that vaccine efficacy depends on fiber intake. So like, if you want to have a good response to a vaccine, eating well and having enough plant fiber to support your gut microbes and keep your immune system going will actually make you have a more robust response to a vaccine.

• 55:28Daniel Whiteson?

  See, I knew tacos are good for you. I always knew that.

• 55:31Speaker 05

  Exactly.

• 55:32Kelly Weinersmith?

  What are you putting in your tacos? Why are your tacos high fiber?

• 55:35Daniel Whiteson?

  Beans.

• 55:35Kelly Weinersmith?

  Oh, oh, I see. Not all tacos have beans in them, Daniel.

• 55:39Daniel Whiteson?

  Um, real tacos? Are you having like weird Virginia tacos with no beans in them?

• 55:43Kelly Weinersmith?

  I guess so. Yeah, I guess so.

• 55:46Speaker 05

  Even Texans put beans in their chili.

• 55:48Daniel Whiteson?

  I know, exactly. No, no, Texans have no beans in their chili. That's very important, Katrina.

• 55:54Speaker 05

  Okay, well.

• 55:55Daniel Whiteson?

  All right. So you've mentioned a few ways that we can impact our microbiome. Let's dig into those in detail. So you've talked a couple of times about fecal transplants, and people are probably wondering like, what are you talking about here? When I think about transplant, I think about taking a kidney out of one person's body and putting it in somebody else's body. Now I'm trying to think about what a fecal transplant means. Like, walk us through this. What's going on here? How does this work at all? What do we know about it?

• 56:18Speaker 05

  Okay, well, fecal transplants refer to taking a healthy microbiome from one person and trying to give it to another person. We have been doing this since ancient times. So more than a thousand years ago in China, people were using what they call golden soup to treat diarrhea.

• 56:38Speaker 05

  And actually, since I teach about this in my big classes, and I've heard so many good stories. From my students who bring up, oh yeah, my family's from the South and we used to do cow patties tea to treat diarrhea.

• 56:51Kelly Weinersmith?

  What?

• 56:51Daniel Whiteson?

  Really?

• 56:52Speaker 05

  Yeah.

• 56:53Daniel Whiteson?

  Southern hospitality, there you go.

• 56:54Kelly Weinersmith?

  Yeah, you guys have a lot to look forward to when you come to visit.

• 56:59Speaker 05

  I mean, this is something you would only do when you're in dire straits, right? But if you've been having diarrhea and you weigh 65 pounds and you can't walk, you might be up for trying something bizarre to survive, you know? And so actually, a modern time story comes from the Mayo Clinic in Minnesota, where a woman who had a C. diff infection, C. diff is typically caused by taking antibiotics and decimating your healthy microbiome, which makes it easy for C. diff, which forms spores in your gut to rear its head and make toxins and cause diarrhea. And it can get really recurrent and difficult to treat. And the standard of care, ironically, is more antibiotics, which caused the problem in the first place. So a woman at the University of Minnesota at the Mayo Clinic,

• 57:43Speaker 05

  her doctor had this, you know, it's kind of crazy idea, like, let's take a fecal sample from her husband and transplant it into her and see if we can help this situation get better. And her symptoms improved within a day. She went from having had diarrhea every 15 minutes and she was in a wheelchair and was like unlikely to survive to the next day, her diarrhea was resolved.

• 58:05Kelly Weinersmith?

  It's incredible.

• 58:07Daniel Whiteson?

  I think you're skipping over some of the crucial steps involved. Like, when you talk about this fecal transplant, are we talking about the northern route, the southern route? Like, how do you get it from him into her?

• 58:15Speaker 05

  Yes, good question. You've heard me say my northern and southern route joke. Well, I mean, your digestive tract is a tube, so you have a couple of entry points.

• 58:26Daniel Whiteson?

  She's so polite.

• 58:29Speaker 05

  And so to do a fecal transplant, you can take a healthy sample, put it in the blender, and then get it into a nasal gastric tube down into your stomach from the northern route. Or you can do it more Like an enema into the bottom part of your digestive tract. You can also make capsules and you would need to swallow about twenty or thirty glycerin capsules that have poop in them to have an impact, which reminds me of a favorite story. Stanley Falco at Stanford in the nineteen fifties was a hospital technician as a young man. He's now like every now, he was one of the fathers of the hygiene hypothesis. But as a young man, he was helping a surgeon who had this idea that they could hide

• 59:14Speaker 05

  healthy fecal samples from before a patient had surgery in their ice cream. And they could eat that postoperatively as they were waking up because a lot of people were getting diarrhea from the antibiotics they were getting in the surgical ward. And without telling them, they had them eat ice cream with these fecal glycerin caps in there. And it was working great, like nobody was getting diarrhea. But when the director of the hospital found out, he fired them.

• 59:39Kelly Weinersmith?

  I mean, yeah, yeah.

• 59:42Daniel Whiteson?

  No more brownie chunk ice cream for you.

• 59:45Speaker 05

  But they have all recovered and that thinking got them really far. So that was actually very ahead of their time to be doing that in the nineteen fifties. But then it was around twenty ten or so that this story in Minnesota I told you about emerged. And then since then, it's become like really a sought after treatment for C. diff, but very hard to regulate. It's kind of similar to blood donation. Like, we haven't figured out how to make synthetic blood. And it's still a quest. And similarly for fecal material, it's a quest to figure out like what is even in there, which parts of it are needed to make a fecal transplant successful.

• 1:00:19Daniel Whiteson?

  So what's happening is that like my microbiome is devastated, which is why I have diarrhea. I'm getting somebody else's community that comes in and then grows into some healthy community. That's the idea?

• 1:00:29Speaker 05

  Well, that might have been initial thoughts on what the idea was. But interestingly, in the last fifteen years, we've tried dissecting the poop into its various components. And so fascinatingly, we've discovered that many of the different components are enough to work as a fecal transplant. So you can filter the poop and only give the liquid supernatant, which has molecules and maybe viruses, but certainly not bacterial cells. And that's enough to cause a successful so-called fecal transplant. We call it a filtered fecal transplant and that still works. Or you can just isolate the spores out. Those are cells for sure. And give that as a treatment. That's the FDA approved treatment for the product

• 1:01:11Speaker 05

  Voust. Or you can take a whole fecal community. There's a Swedish poop from the 1990s that has been cultivated anaerobically ever since then.

• 1:01:20Daniel Whiteson?

  Historic poop?

• 1:01:22Speaker 05

  Yes. And my students are like, hey, that poop is older than me.

• 1:01:28Daniel Whiteson?

  Whenever I use the bathroom, I never imagine it's going to go down in history, but this one really did.

• 1:01:32Speaker 05

  Yeah, this one poop has saved like probably thousands of lives. This one poop has been cultivated anaerobically for many years. And so presumably, none of the initial molecules from that poop are present, but just the progeny of all those generations of microbial growth. And that has been enough to cure C. diff in many, many different people. So to be honest, it's still a science question, like what you actually need to make a fecal transplant work. There also have been famous failures. There were phase three clinical trials of cocktails of microbes that people put together in the pharmaceutical industry, thinking that that would work and it didn't. So there's a je ne sais quoi about the poop that just works perfect.

• 1:02:16Kelly Weinersmith?

  So you mentioned that when you've got the liquid supernatant without any of the bacteria in it, but you've got their metabolic excretions plus viruses, it works fine.

• 1:02:27Speaker 05

  Yeah.

• 1:02:27Kelly Weinersmith?

  Does that suggest it's the viruses that actually matter?

• 1:02:30Speaker 05

  What a cool question. I love that question. I don't know the answer, but it has been shown in like a number of different ways. There was a group in Germany in Kiel that showed this with the viruses with the filtered fecal filtrate. And then there's a group at the University of Copenhagen who have done really extensive studies in this really cool model of baby piglets. And their goal is to be able to help preterm infants in the NICU. And it's such a good idea because it would be very dangerous to give live microbes to preterm babies whose guts are in really bad shape. But if you could do it with the viruses, you might be able to create an environment that helps the gut microbiome develop successfully. And like babies in the NICU have really bad outcomes with their guts, like a third become

• 1:03:14Speaker 05

  septic, a third get necrotizing enterocolitis. And a third have what they call healthy outcomes, but I mean, they're really in dire straits. And so I love what the group at the University of Copenhagen is doing because they're starting in a model of baby piglets, which is pretty similar to a human model. And I am optimistic that it won't take too long before they'll feel like it's safe to try it in babies, because the room for improvement there is just enormous. So that to me is like a really, really cool way that we could improve health.

• 1:03:43Daniel Whiteson?

  So if you get a transplant from somebody else, they have a different microbiome. It's no guarantee that it's definitely going to work for you. Is the ideal transplant a donation from yourself? Like if you're out there having good poops every day, should people put some of that in the freezer for the day when they have surgery or diarrhea?

• 1:04:00Speaker 05

  I really like that idea. It's certainly been a topic of conversation in our household.

• 1:04:06Daniel Whiteson?

  Don't dig around in our freezer unless you want some surprises, by the way.

• 1:04:09Speaker 05

  Well, not your favorite part of our freezer, I know, but I appreciate your open mindedness.

• 1:04:16Speaker 05

  And by the way, when my students have to put fecal samples in the freezer for our studies, we joke about like the right way to do that. And like, if your roommates don't like the idea, just empty out a box of strawberry popsicles or like chicken nuggets. And you could just hide your samples in there. And if they're trying to steal a popsicle, I mean, that's on them.

• 1:04:35Daniel Whiteson?

  Oh, they're going to get a popsicle, it's just not going to be strawberry.

• 1:04:39Kelly Weinersmith?

  After this conversation, I'm never going to look at popsicles again.

• 1:04:45Daniel Whiteson?

  Poopsicles, yeah.

• 1:04:46Speaker 05

  So the question was, could we do like auto, like self fecal transplants and have that work? And that has been studied in a lot of different contexts, also for like recovery from antibiotics. If you really know that you're healthy, like maybe everybody should be banking their own sample at some point in their life when they just were digesting really well and they were 18 and had like been eating really well for the summer or something. Save a moment of that glorious part of your health in the freezer so you could restore yourself to it. I like that idea. I've proposed this for different kinds of contexts. Like, one time I wrote a proposal about helping people who were gonna have to have radiotherapy for cancer. And often, people get essentially diarrhea and other really rough consequences of the radiation treatment.

• 1:05:31Speaker 05

  So the idea was to restore their health to what they were before the treatment. But somebody who has cancer might have cancer promoting properties in their own fecal microbiome. So you could inadvertently bring them back to getting cancer again. I mean, this has been studied extensively, like, this kind of approach has been used. There was a big study in New York City of people who were getting bone marrow transplants for blood cancers, where they did transplants from peoples before fecal sample in order to try to help them avoid getting... I mean, people get terrible infections after getting cancer treatment. So this is an area, again, kinda like the preterm babies, there's like a ton of room for improvement there. But the concern is that you would cause cancer again.

• 1:06:16Speaker 05

  So maybe a healthy donor is safer. And then I hear your question, well, what if the healthy donor is really different than you? Well, another thing that happens is, it's rare that we follow up our studies long enough to really see what happens. But there was one study of autistic children where they did fecal transplants from a stranger, like a healthy donor, not a family member. But then they followed up for two years, both the kids with autism and a healthy sibling in the same household. And I loved that they did this for two years. This is Rosie Crossman Lake Brown at Arizona. And they found that, at first, the autistic children who received the fecal transplant from a stranger donor, their guts were more similar to the healthy donor.

• 1:06:59Speaker 05

  But after two years, their gut microbiomes resembled their siblings more. But they did have higher diversity. So it's almost like the fecal transplant kickstarted the capacity to carry a higher microbial diversity. But then, all those strains got replaced by strains that were available in the household. So the household influence is really important. And it makes me wonder, like, when people get married, there's gonna be a battle of the microbiotas, and somebody's gonna win. And that hasn't really been studied that much, you know?

• 1:07:32Daniel Whiteson?

  Till diarrhea do its part.

• 1:07:35Daniel Whiteson?

  Can we talk about the probiotic industry you mentioned earlier? It's $80 billion and I feel like I see pills and powders and yogurts promoting probiotic this and probiotic that. What's in those and what's your take on whether they're likely to do anything?

• 1:07:50Speaker 05

  Well, that's a really big question. It is a really big industry. I was even just comparing the size of the probiotic industry and the antibiotic industry. And I think the probiotic industry might even be a bigger moneymaker than antibiotics, but it's close. But I mean, that's amazing to me. $80 billion, like that's close to the GDP of many nations. And so whether it could work is one question. And yes, the idea of a probiotic makes sense. I mean, if you could get the right bug to the right place at the right time, that's a great idea. It could definitely work. When we say probiotic, that includes fermented foods like yogurt and kombucha and kefir and miso. And those, we actually can see really kickstart diversity in our guts.

• 1:08:34Speaker 05

  Not necessarily because the bacteria in those products are colonizing our gut, but they can kickstart diversity in a good way. Most people, when they take a probiotic and many packages claim that it's gonna directly increase your microbiome diversity. I think a lot of people, when they eat a probiotic, imagine that now that bug is happily living in their gut and they just like got their community a little happier. Now, most probiotics actually don't do that. Most are transient. So if you are taking those pills and then you measure people for a week, you'll see a washout period and after a week or so, it'll be gone, which is probably not what people imagine. You also might not want the probiotic to stick.

• 1:09:15Speaker 05

  So I always remember the story of a startup in San Francisco where they evolved probiotics that were good at binding to mucus with the idea that they could persist in the gut, but they forgot about gum mucus and everybody got cavities in their little study.

• 1:09:31Daniel Whiteson?

  I'm not laughing, that's sad.

• 1:09:33Kelly Weinersmith?

  Biology is so complicated.

• 1:09:35Speaker 05

  I know.

• 1:09:37Speaker 05

  So on average probiotic packages, you know, they don't have to have evidence for the claims they make on the packages. So they can say some pretty fantastical things. And actually in my microbiome class this quarter, we had a probiotic sus score, like a suspicion score activity where everybody had to go find a probiotic with crazy claims on the package and then try to investigate the claims and like what evidence there was for them. And there was not usually a whole lot of evidence. And the students had amazing comments afterwards that were like, man, if I saw a celebrity claiming that a probiotic worked, I just would believe it. It never occurred to me to like investigate the evidence. And I'm like, you guys are science students. I'm glad if you're learning that.

• 1:10:18Kelly Weinersmith?

  Yeah, it's important.

• 1:10:20Speaker 05

  Yeah. So, you know, just off the top of my head, you know, there's probiotics out there that are named like happy hoo-ha and they claim to improve your vaginal microbiome. Or like, you know, anyway, there's some pretty funny ones. But there are some probiotics that are well investigated and people are doing studies with them. And sometimes they're not sharing the evidence in order to protect their IP. So it's complicated. But the way the industry is regulated is just that the probiotics have to be generally regarded as safe or grass, which is not a very high standard. I mean, it's a high standard in the sense that like this thing's not going to kill you. That's good.

• 1:11:00Kelly Weinersmith?

  Might give you cavities.

• 1:11:01Speaker 05

  Might give you cavities or might just do absolutely nothing. And I mean, the supplement industry even beyond probiotics is an enormous industry and there's very few claims. And it's pretty hard to know. I mean, even for, you know, ourselves, like Daniel and I, we have a son who's an athlete and he's always, you know, really willing to do what it takes to be healthy. And so we've had a lot of conversations about what we understand about what's in a supplement versus what we understand about what's in a food. And, you know, with the tools we have in our own households, we can't really assess the safety of food or supplements. That's why we need infrastructure and institutions that help us understand that. But a lot of the things that we can buy in packages might have stuff that's dangerous

• 1:11:45Speaker 05

  in them and we have to be really careful. So my general instinct is to lean towards food and.

• 1:11:53Speaker 05

  You know, the advice to generally not eat things that your grandparents wouldn't recognize as food, or maybe it has to be our great grandparents now, because a lot of the processed foods that are available to us these days with tons of ingredients we can't even pronounce, it could be really damaging our health.

• 1:12:10Daniel Whiteson?

  Mm hmm.

• 1:12:11Speaker 05

  It's not like I have really great evidence for every single one, but I think that leaning towards eating things that you can recognize tends to work the best for the evidence that we have right now.

• 1:12:21Daniel Whiteson?

  And earlier on, you mentioned fiber and beans. Why is fiber something good to eat? I mean, if you're not gonna do a poop transplant and you're not buying Happy Hoo-Ha or whatever, if you're just gonna try to do this through like healthy eating and food, tell us why fiber is important.

• 1:12:35Speaker 05

  Definitely. So fiber is the part of carbohydrates that doesn't get digested very quickly. It's longer chains of carbohydrates that your human enzymes can't even access. So the way to figure this out is if you look at an nutrition label, it'll list the total carbs and then it'll list the subset of the carbs that are fiber. So for a piece of white bread, it might be like nineteen grams of carbs, one gram of fiber. Wheat bread might be nineteen grams of carbs, five grams of fiber. Okay, cool. So now we're talking like, you know, nearly a quarter of the carbs in that piece of bread is fiber. It's gonna be slower to hit your blood sugar levels. It's gonna persist in your digestive tract down to your colon where all the microbes live and give them some food. So that's pretty good.

• 1:13:19Speaker 05

  Now let's talk about beans and lentils. Half of the carbs in beans and lentils are in the form of fiber. So if you eat a cup of black beans or Old Navy beans or lentils in a day, you'll get probably ten or twenty grams of fiber out of the thirty or forty grams of carbs. That's half of your fiber needs for the day. So the daily recommended allowance of fiber in the US is twenty-five to thirty-five grams per day. And we're usually getting half of that. Most Americans are getting 10 to 15 grams per day. So we all need to think about how to fill our fiber gap. You always hear about how we're not eating enough protein. I mean, to be honest, we're probably eating plenty of protein in the United States, but we really are not eating enough fiber. If you eat fiber, you are fueling the microbes in your colon.

• 1:14:02Speaker 05

  And then if you do experience some kind of stress, whether it's antibiotics or diarrhea or just like literally stress that causes inflammation and oxygen descending upon you and making it harder for those bugs to thrive in your colon. When you have fiber in there, you've given the bugs a place to hide out. So you can weather the storms of any kind of other fluctuations in your life better and keep the microbes happier. So like, if you did know you had to take antibiotics, I would definitely really recommend making sure you're eating enough fiber. And fermented foods actually are another really good contributor.

• 1:14:36Daniel Whiteson?

  All right. So that's scientific evidence that chili should have beans in it.

• 1:14:42Daniel Whiteson?

  We settled that age old question.

• 1:14:43Speaker 05

  I mean, I don't think there's anyone who would disagree that if you wanted to protect your microbiome, having beans in your chili would be a good idea.

• 1:14:52Kelly Weinersmith?

  All right, everybody. So tonight, grab your beans and your bino and hopefully Katrina White son will be back on the show in not too long. Thanks for spending some time with us today.

• 1:15:01Speaker 05

  Awesome. Thank you.

• 1:15:09Kelly Weinersmith?

  Daniel and Kelly's Extraordinary Universe is produced by iHeartRadio. We would love to hear from you.

• 1:15:14Daniel Whiteson?

  We really would. We want to know what questions you have about this extraordinary universe.

• 1:15:20Kelly Weinersmith?

  We want to know your thoughts on recent shows, suggestions for future shows. If you contact us, we will get back to you.

• 1:15:27Daniel Whiteson?

  We really mean it. We answer every message. Email us at questions at danielandkelly.org.

• 1:15:34Kelly Weinersmith?

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• 1:15:43Daniel Whiteson?

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