How to Build, Maintain & Repair Gut Health | Dr. Justin Sonnenburg

1. 0:00 – 2:55

   Dr. Justin Sonnenburg, Gut Microbiome

   1. AHAndrew Huberman0:00

      (instrumental music) Welcome to the Huberman Lab Podcast, where we discuss science and science-based tools for everyday life. I'm Andrew Huberman, and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine. Today, my guest is Dr. Justin Sonnenburg. Dr. Sonnenburg is a professor of microbiology and immunology at Stanford School of Medicine, and one of the world's leading experts on the gut microbiome. The gut microbiome is the existence of trillions of little microorganisms throughout your gut, and by your gut, I don't just mean your stomach, I mean your entire digestive tract. Turns out, we also have a microbiome that exists in our nose, in any other location in which our body interfaces with the outside world. In fact, there's a microbiome on your skin, and while it might seem kind of intrusive, or kind of disgusting to have all these little microorganisms, they can be immensely beneficial for our health, meaning our hormonal health, our brain health, and our immune system function. Dr. Sonnenburg teaches us about the gut microbiome, how it's organized spatially, meaning which microbiota live where. He teaches us about these incredible things called crypts and niches, which are little caves within our digestive tract that certain microbiota take residence, and at that premier real estate, they're able to do incredible things to support our health. He also talks about the things that we can all do to support our microbiome in order for our microbiome to support our brain and body health. Dr. Sonnenburg co-runs his laboratory with his spouse, Dr. Erika Sonnenburg, and together, they've also written a terrific and highly informative book called The Good Gut: Taking Control of Your Weight, Your Mood, and Your Long-Term Health. Even though that book was written a few years back, the information still holds up very nicely, and today, he also builds on that information, informing us about recent studies that, for instance, point to the important role of fermented foods and the role of fiber in supporting a healthy gut microbiome. So, if you've heard about the gut microbiome, or even if you haven't, today, you're going to hear about it from one of the world's leading experts. He makes it immensely clear as to what it is, how it functions, and how to support it for your brain and body health. During today's discussion, we don't just talk about nutrition. We also talk about the impact of behaviors and the microbiome, behaviors such as who you touch, who you kiss, who you hug, whether or not you interact with or avoid animals, whether or not those animals belong to you, or whether or not they belong to somebody else. If all that sounds a little bit bizarre, (laughs) you'll soon understand that your microbiome is constantly being modified by the behavioral interactions, the nutritional interactions, and indeed, your mood and internal reactions to the outside world. This is an incredible system. Everyone has one, everyone should know how it works, and everyone should know how to optimize it, and today, you're going to learn all of that from Dr. Sonnenburg.

2. 2:55 – 4:16

   The Brain Body Contract

   1. AHAndrew Huberman2:55

      I'm pleased to announce that I'm hosting two live events in May 2022. The first live event will take place in Seattle, Washington on May 17th. The second event will take place in Portland, Oregon on May 18th. Both are part of a series called The Brain-Body Contract. For this series, I will discuss science, so I will discuss the mechanistic science around things like sleep, and focus, and motivation, physical performance, mental health, physical health, a large number of topics that I believe many people are interested in, and that certainly are important for our health and well-being and performance. In addition, I will, of course, describe tools and actionable items, most of which I have not discussed on the Huberman Lab Podcast or anywhere else. Presale tickets for these two events go live Tuesday, March 8th at 10:00 AM Pacific Time. We've made these tickets exclusively available to the listeners of the Huberman Lab Podcast, so they are password protected. To find them, you can go to hubermanlab.com/tour and use the code Huberman. Before we begin, I'd like to emphasize that this podcast is separate from my teaching and research roles at Stanford. It is, however, part of my desire and effort to bring zero-cost-to-consumer information about science and science-related tools to the general public. In keeping with that theme, I'd like to thank the sponsors of today's podcast. Our first sponsor is Athletic Greens, now called AG1. I've been taking AG1 since 2012, so I'm delighted

3. 4:16 – 8:30

   AG1 (Athletic Greens), ROKA, Helix Sleep

   1. AHAndrew Huberman4:16

      that they're sponsoring the podcast. The reason I started taking AG1 and the reason I still take AG1 once or twice a day is that it meets all my basic foundational supplementation needs. What I mean by that is it covers any vitamin and nutritional deficiencies that I might have 'cause I'm trying to be good about my nutrition and diet, but I don't always manage to get everything that I need, and I'm sure that there are a lot of gaps in there, so it covers those gaps. It also has probiotics, and as you'll learn in today's episode, and I've talked about on previous episodes, the probiotics are essential for a healthy gut microbiome. We need probiotics in order for our microbiome to thrive, and our microbiome supports things like gut brain health, indeed, things like metabolism, mood, hunger. It also supports the immune system. As you'll learn today, your gut microbiome actually manufactures neurotransmitters, the very chemicals that impact mood and brain function. Athletic Greens primes your system for a healthy gut microbiome, something that can be achieved with food and lifestyle factors, but is often hard to achieve with just food and lifestyle factors. If you'd like to try Athletic Greens, you can go to athleticgreens.com/huberman to claim a special offer. They give you five free travel packs to make it very easy to mix up Athletic Greens while you're on the road, and a year's supply of vitamin D3 K2. Vitamin D3 has many important biological functions that support your immediate and long-term health, and K2 as well is very important for things like cardiovascular health, calcium regulation, and so on. Again, if you go to athleticgreens.com/huberman, you can claim the special offer of the five free travel packs and the vitamin D3 K2. Today's episode is also brought to us by ROKA. ROKA makes eyeglasses and sunglasses that I believe are of the very highest quality. I've spent my lifetime working on the biology of the visual system, and I can tell you that the biology of the visual system has a lot of mechanisms in there, so that, for instance, if you move from a bright environment to a dim environment...... your visual system needs to adapt. One issue with a lot of sunglasses and eyeglasses is, you move from one environment to the next, and you have to take the sunglasses or eyeglasses off. You get a glare, or you have to adjust because of the way that the lenses are designed. With ROKA, they've taken the biology of the visual system into account, and so you never have to take them off and on in order to move from one environment to the next. They're also designed for movement and athletics, or you can wear them for just things like work, and going out to dinner, and so forth. They have a terrific aesthetic. They're extremely lightweight. In fact, I often forget that they're even on my face. I wear sunglasses when it's very bright, and when I'm driving in the sunlight. I wear readers at night. I hardly ever remember that they're on my face. They also won't slip off your face if you use them when running or cycling. The company was developed by two All-American swimmers from Stanford, so everything about these sunglasses and eyeglasses was developed with performance in mind in a lot of different situations and scenarios. If you'd like to try ROKA, you can go to roka.com, that's R-O-K-A dot-com, and enter the code Huberman to save 20% off your first order. Again, that's ROKA, R-O-K-A dot-com, and enter the code Huberman at checkout. Today's episode is also brought to us by Helix Sleep. Helix makes mattresses and pillows that are designed for your particular sleep needs. What I mean by that is, you can go to the Helix site, you can take a very brief two or three-minute quiz, ask questions like, do you sleep on your side, your back, your stomach, do you tend to run hot or cold through the night, maybe you don't know the answers to those questions, and then they match you to a mattress that's designed for your particular sleep needs. I match to the Dusk, D-U-S-K, mattress. I like a mattress that's not too firm, not too soft, I tend to sleep on my side. I sort of, in the, like, crawling soldier position, seems to be the most common position I sleep in, and that really works terrifically well for me. But you need to take the quiz to see which mattress works best for you. So if you're interested in upgrading your mattress, go to helixsleep.com/huberman, take the two-minute quiz, and they'll match you to a customized mattress. You can figure out how to get your optimal sleep, which is, as talked about on this podcast so many times before, sleep is the foundation of all mental and physical health and performance in any aspect of life. Sleep is key, and the mattress you sleep on is key to the sleep you get. After matching you to a customized mattress, you can get up to $200 off any mattress order and two free pillows. Again, if you're interested, you can go to helixsleep.com/huberman to get up to $200 off and two free pillows. And now for my discussion with Dr.

4. 8:30 – 12:49

   What is the Gut Microbiome?

   1. AHAndrew Huberman8:30

      Justin Sonnenburg. Justin, thanks so much for being here.

   2. JSJustin Sonnenburg8:33

      Great to be here.

   3. AHAndrew Huberman8:34

      Yeah. I am a true novice when it comes to the microbiome, so I'd like to start off with a really basic question, which is, what is the microbiome? I imagine lots of little bugs running around in my gut, and I don't quite like the image of that. Uh, but I'm aware that our microbiome can be good for us, but we can also have an unhealthy microbiome. So if I were to look at the microbiome at the scale that I could see the meaningful things, what would it look like, and what's going on in there?

   4. JSJustin Sonnenburg9:08

      Yeah, I mean, the, essentially you're correct. I mean, we have all of these little microorganisms running around in our gut. I think, you know, just to start off with clarifying terminology, um, microbiome and microbiota quite often are referred to, or used to refer to our microbial community interchangeably, and I'll probably switch between those two terms today. The other important thing to realize is that these microbes are, um, not just in our gut, but they're all over our body. They're in our nose, they're in our mouths, they're on our skin, and, um, so basically anywhere that the environment can get to, uh, in our body, which includes inside our digestive tract, of course, is, you know, colonized with, with microbes, and, um, the vast majority of these are in our distal gut and in our colon, and so this is the gut microbiota or gut microbiome, and, um, the density of this community is astounding. I mean, it really is, uh, um, if you get down to the scale of being able to see individual microbes, uh, you know, start off with a zoomed out view and you see something that looks like, you know, fecal material, the digesta inside the, the gut, and you zoom in and you start to, you know, get to the microscopic level and see the microbes, they are just packed, you know, side to side, end to end. It's a super dense bacterial community, almost like a, um, biofilm, you know, something that's just made up of microbes, to the point where, um, it's thought that, you know, around 30% of fecal matter is microbes, 30 to 50%. So, you know, it's, um, it's an incredibly dense microbial community. We're talking of, um, you know, uh, trillions of microbial cells, and all those microbial cells, if you start to get to know them and, and see who they are, um, break out in the gut probably to, um, hundreds to a thousand species, depending upon how you define, um, a microbial species. And then most of these are bacteria, but there are a lot of other life forms there. There are archaea, which are little microbes that are bacteria-like, but they're, they're different. Um, there are, uh, eukaryotes. So, you know, we commonly think of eukaryotes in the gut as, um, as, you know, something like, uh, a parasite, but, um, there are eukaryotes, there are fungi, there are also little viruses. There are these bacteriophages that infect bacterial cells, and so, um, and, and those actually outnumber the bacteria, like, 10 to 1, so they're just everywhere there, they kill bacteria, um, and so there's these really interesting predator-prey interactions, but, um, overall it's just this really dense, complex, dynamic ecosystem, and, and so, you know, we're, we're talking about the human as a single species, but we're also thinking of the human as this complex integrated ecosystem of hundreds to thousands of species interacting in concert to...... do all the fantastic things that we know happen in the human body.

   5. AHAndrew Huberman12:17

      Amazing. So we've got a lot of cargo, uh-

   6. JSJustin Sonnenburg12:19

      Totally.

   7. AHAndrew Huberman12:19

      ... or maybe we're the cargo.

   8. JSJustin Sonnenburg12:21

      Yeah. (laughs)

   9. AHAndrew Huberman12:21

      Who knows?

   10. JSJustin Sonnenburg12:22

       Yeah. I mean, there, there have been people that have likened, um, humans to just a really elaborate culturing flask for microbes, and that we've actually been designed, over the course of evolution, um, designed to, uh, just, um, efficiently propagate this microbial culture from person to person, from generation to generation. So it's a different way of thinking of the human body.

   11. AHAndrew Huberman12:45

       Interesting. I believe that our,

5. 12:49 – 16:00

   Gastrointestinal (GI) Tract & Microbiota Variability

   1. AHAndrew Huberman12:49

      uh, pH, or the, the pH of our, uh, digestive system varies as you descend, as you go from mouth to, you know, to throat and stomach. And you said that most of the, uh, microbiota are in the distal colon. Um, are there distinct forms of microbiota all along the length of the di- of the digestive tract, and within these other, um, interfaces with the outside world?

   2. JSJustin Sonnenburg13:12

      Totally, yeah. So it starts, like, with our teeth, and in our mouth, in saliva, there's a, uh, oral m- microbiota. Um, these microbial species are very different than the ones that you find in the digestive tract. They're, um, usually, um, you know, built to deal with oxygen very well, they're, you know, in an area that ex- is exposed to a lot of oxygen. They, of course, see different nutrients than, for instance, a colonic bacteria would see, and they grow quite often in, in mats that live, you know, on teeth. So they're their struc- they're very structured in terms of... And, um, and not, uh, moving around a lot, so they, they're very fairly stationary. As you move down the digestive tract, there are microbes in our esophagus and our stomach, but those are, you know, those communities are, are not very dense, and actually, not very well studied. We know of a very, um, you know, there's a very famous stomach bacteria known as Helicobacter pylori, which, um, can cause stomach ulcers, and cause gastric cancer in some, some, um, you know, uh, less frequent situations. But the, um, you know, this is, um, a, a very different m- um, different set of microbes, they have to be adapted to a different environment in the stomach, especially incredibly acidic environment. Um, but also very different in terms of their ability to interact with other microbes, just because the communities are less dense, they're less dynamic, um, there's less nutrients that stay there and passage through the community, so the, a lot of times, those communities are reliant upon nutrients derived from the host, as opposed to nutrients derived from our diet. As you move down out of the stomach into the small intestine, you start to see these communities which are the ones that are becoming more well studied. Um, small intestine is still a bit of a black box just because it's hard to access, and so there's some really cool technologies out there for using, for instance, capsules to do sampling as the capsule passes through the digestive tract, so that we have a better idea of what's going on in the small intestine. And then you get to the colon, and this is the community that's just so incredibly, you know, densely packed, um, doing a ton of... There, there's a ton of metabolic activity happening there, and, um, a bunch of interaction with the host, and that's the study, that's the, um, community that's really the best studied. Part of the reason for that is because stool is so easy to obtain compared to, for instance, something in the stomach or small intestine, and that stool is fairly representative. We know from studies that have been done using colonoscopies and so forth, stool is fairly representative of what's happening in the colon. So, um, dense, super exciting community, but also the best study just because it's the, the easiest to access in the lower digestive tract.

   3. AHAndrew Huberman15:57

      Very interesting. Uh,

6. 16:00 – 21:56

   Breast Feeding, C-Sections & Pets

   1. AHAndrew Huberman16:00

      I imagine these microbiota have to get in there at some point. Uh, are microbiota seen in newborns? Um, in other words, where do they come from, and dare I ask, um, what direction do they enter the body-

   2. JSJustin Sonnenburg16:12

      Yeah. (laughs)

   3. AHAndrew Huberman16:12

      ... or, or is it from multiple directions?

   4. JSJustin Sonnenburg16:14

      Yeah. Yeah, great question. So, you know, one of the burning questions that we can come back to at the end of this is, where does our microbiota come from, because it is this kind of, you know, existential question in the field, like, where, where is this community assembling from? And the, the reason that it's such an interesting question is that, um, you know, a fetus, when it's in the womb, it, that's actually a sterile environment. Um, there have been some studies that have looked at, um, whether there are microbes in the womb, and, and microbes colonin- colonizing the fetus at that point. Um, there's some debate about this, but overall, it looks like that's not a big part of the equation of microbial colonization. And, um, so each time an infant is born, it's this new ecosystem. It's like an island rising up out of the ocean that has no species on it, and suddenly, there's this, like, land rush for, you know, this open territory. And, and so the, you know- M- we know that infants go through this really complex process of microbiota s- assembly over the first days, weeks, months, years of life, and then, you know, you get into, um, switching to solid food two to three years of age. Um, there's some changes in, um, childhood, adolescence working into adulthood, but that first, you know, um, zero to, uh, one year is a super dynamic time with really, um, kind of stereotypical developmental changes in the gut microbiota that appear to, um, have the possibility of going wrong and, um, causing problems for inf- infants in some instances. But, you know, if you step away from that extreme side of things going wrong, there al- also are a lot of different trajectories that developmental process can take, because our microbiota is so malleable and so plastic, and those trajectories can be affected by all sorts of factors in early life. So an example is whether an infant is born by C-section or born vaginally, we know from, um, beautiful work that's been done in the field that, uh, infants that are born by C-section-... actually have a, um, gut microbiota that looks more like human skin than it does like either the va- the birth canal, the, the vagina microbiota, or, um, the mother's, um, stool microbiota. Babies that are born through the birth canal have initial colonization of vaginal microbes and of stool microbes from their mother. And so just these first days, whether you're born by C-section or through, or through natural childbirth, your gut microbiota looks very different. And then compound on top of that whether you're breastfed or formula fed, whether your family has a pet or doesn't have a pet, whether you're exposed to antibiotics, um, there are all these factors that really can change that developmental process and really change your microbial identity eventually in life. The reason that this is, um, that the field is playing, paying really close attention to this and studying this right now is because we know from animal studies that depending upon the microbes that you get early in life, you can send the immune system, or metabolism of an organism, or other parts of their biology in totally different developmental trajectories. So what microbes you're colonized or with early in life can really change your biology, and we can come back to that later. But-

   5. AHAndrew Huberman19:41

      Yeah. We should.

   6. JSJustin Sonnenburg19:43

      ... the, you know, the getting back to that original question of where your microbes come from, you'd think because you're born through your mother's birth canal or exposed to her skin microbes, that a lot of your microbes would come from your mother. But it actually turns out that, you know, we can certainly detect that signal, we certainly see maternal microbes in the infant, but there are a lot of microbes that are coming from other places. Uh, surfaces, other people, perhaps other caregivers, but perhaps, uh, strangers as well. So we acquire our microbes from a, a variety of sources. The first ones are, are from our mom or from our caregivers, from the hospital, but then we add to that tremendously over the first year or so of life.

   7. AHAndrew Huberman20:24

      Incredible. You even said, um, pets. So, uh, if a kid in a, uh, if there's a dog in the home or a parakeet in the home, that clearly they have a microbiome also, and potentially the child is deriving microbiota species from, from those pets.

   8. JSJustin Sonnenburg20:40

      E- e- exactly, yeah. And so the, you know, I, the, um, best studies that have been done have just looked at pets in the household as a factor, and whether that changes, um, you know, the group of infants that have a pet to look slightly different than the group of infants that don't have a pet. And then the question is, what, what is the pet doing to change those microbes? And some of it is probably actually contributing direct members of the microbiota. Actually, you know, we, um, I have a dog, that dog occasionally will lick my mouth without me like paying attention, you know, and that's probably introducing microbes. Um, we also know that, um, you know, pets are, are down in the dirt, they're, you know, outside, they're, you know, they're, they're being exposed to a lot of environmental microbes. And so just, um, you know, pets serving as a conduit for a bunch of microbes that we wouldn't otherwise come in contact with, um, is a, is a possibility as well.

   9. AHAndrew Huberman21:36

      I'll tell you what, we will return to, uh, pets, and in particular, your dog. An amazing dog, by the way. I met your dog just the other day, and I had to force myself, I had to pry myself away from-

   10. JSJustin Sonnenburg21:46

       (laughs) .

   11. AHAndrew Huberman21:46

       ... it's a Havanese, right?

   12. JSJustin Sonnenburg21:47

       Havanese.

   13. AHAndrew Huberman21:47

       Incredible. What is your dog's name?

   14. JSJustin Sonnenburg21:48

       Louis.

   15. AHAndrew Huberman21:49

       Lou-

   16. JSJustin Sonnenburg21:49

       Louis. Louis Pasteur.

   17. AHAndrew Huberman21:50

       Louis Pasteur, ah.

   18. JSJustin Sonnenburg21:51

       Yeah.

   19. AHAndrew Huberman21:51

       How appropriate. Um, amazing dog. What a personality on that dog.

7. 21:56 – 26:30

   The Human Microbiome Project at Stanford

   1. AHAndrew Huberman21:56

   2. JSJustin Sonnenburg21:56

      Yeah.

   3. AHAndrew Huberman21:56

      Um, the, the issue that I, I think a lot of people are probably wondering is, what, what is a healthy microbiome, and what is it, what is it supporting? We, we hear that you need a healthy microbiome to support the immune system, or metabolism, or even the gut-brain axis. How do we define a healthy versus a unhealthy microbiome? Some people might know the unhealthy microbiome as dysbiosis, is the word that I, I encounter in the literature. But given that there's so many species of microbiota, and given that I think we probably each have a signature pattern of microbiota, how do we define healthy versus unhealthy microbiota? Is there a test for this? Um, later we'll talk about technologies for testing microbiota. There are a lot of companies now, a lot of people sending stool samples in the mail. Um, never look at the postal service the same way again, but they're, it's out there and it's getting analyzed. It... So how should I think about this? I, I can think about things like heart rate, heart rate variability, uh, BMI-

   4. JSJustin Sonnenburg22:56

      Yeah.

   5. AHAndrew Huberman22:56

      ... all sorts of metrics of health. How should I think about the microbiota? How do I know if my microbiome is healthy or unhealthy?

   6. JSJustin Sonnenburg23:02

      Yeah. It's a, it's a million dollar question right now in the field, and there's a lot of different ways of thinking about that, and I can talk about some of those. But I would say that, you know, um, there are sessions at conferences, there are review articles being commissioned, there are all sorts of kind of thought pieces about this right now, like, what is a healthy microbiota? What are the features that define it? And, you know, I think before diving into this, the important thing to, to realize is it's a complex topic. Um, context matters a lot. What's healthy for one person or one population may not be healthy for another person or population. And, um, the microbiota is, um, malleable. You know, it's plastic, it changes. Um, our human biology, which I think is, you know, h- how we think about health quite often, BMI and, you know, longevity, reproductive success, however you want to define it, um, it certainly, um, can accommodate a variety of configurations of gut microbiota, and we don't have, um, uh... You know, it's really hard to untangle, um, all of the different factors of what, what could be, you know, very healthy versus a little bit less healthy. Um, so, so I, I will say that there's no single answer to this, but there are some really important considerations. And, um, perhaps the best way to start talking about this is to go back to, um-... the inception of the Human Microbiome Project, which was this, um, program that- that NIH started. They invested a lot of money in 2008, 2009 for, um, really, uh, propelling the, um, field of- of gut microbiome research. It was, um, becoming evident at that point that this was not just a curiosity of human biology, that it was probably really important for our health. And they had all this wonderful sequencing technology from the Human Genome Sequencing, um, Project, and with the human genome complete at that point, they started turning that technology to sequencing our gut microbes. And, you know, it's important to contextualize the amount of information that they're trying to, um, document. The, you know, collective genome of our gut microbes is on the order of, um, 100 to 500 times larger than our human genome. So it's just in terms of the number of genes. So it's just this vast number of- of genes, and then if you start getting into some of the fine variation, it's, you know, scales by 10 to 100 fold. So really a huge amount of information they're trying to document. And- and the... and so it's a, uh... it was a wonderful investment, and it continues to pay dividends to this day. Um, but one of their goals of that project was to try to define what a healthy microbiome is, versus a diseased microbiome in different contexts. And so they started, um, enrolling a bunch of healthy people and a bunch of people with, for instance, inflammatory bowel disease and other diseases, um, and- and the idea was let's- let's document those microbiomes, what microbes are there, what genes are there, and then we can start to get a sense of what are- what are the commonalities of the- the healthy people, and- and what, you know... how- how can th- that go wrong in these different disease states. And, um, you know, they- they... there were some answers from that, but you, um... through those studies, we really started to get the image that there is this tremendous individuality in the gut microbiome, and, um, and so it's- it's really hard to, um, start drawing, um, you know, conclusions after initial pass of that project of what is a healthy microbiome.

8. 26:30 – 28:58

   Traditional vs. Industrialized Populations

   1. JSJustin Sonnenburg26:30

      But the other thing that we started to realize at the same time, there were studies going on documenting the gut microbiome of, um, traditional populations of humans, hunter-gatherers, uh, rural agricultural populations, and, um, those studies were really mind-blowing from the perspective of, you know, all these people are healthy, they're living very different lifestyles, and their microbiome doesn't look anything like a healthy American microbiome.

   2. AHAndrew Huberman26:57

      So does that mean that the healthy American microbiome is healthy, but only in the context of living in the United States and consuming what's consumed here? Um, or is it that there is a superior microbiome signature somewhere in our history or currently in the world?

   3. JSJustin Sonnenburg27:14

      Yeah. You know, I- I think that's- that's kind of a- a- a big question right now. I think, you know, um, there's a great quote from Dobzhansky that says, "Nothing in biology makes sense except in the light of evolution." And, you know, the- these traditional populations are all modern people, um, living on the planet now, but their lifestyle does represent, um, uh, you know, the- the closest approximation to how our ancestors, um, early humans lived. And- and so those microbiomes, and now we know from sequencing of paleo feces, the microbiome of these traditional populations is representative, more representative of the microbiome that we evolved with, that- that, um, potentially shaped our human genome. And so one possibility is that in the industrialized world, we have a- a different microbiome from traditional populations, and that microbiome is well-adapted to our current lifestyle, and therefore healthy in the context of an industrialized society, and there probably are elements of that that are true. Um, but another possibility is that this is a microbiome that's gone off the rails, that it is, um, you know, deteriorating in the face of antibiotic use, and, um, uh, all the, um, problems associated with a, um, industrialized diet, Western diet. Um, and that even though the Human Microbiome, um, Project documented the microbiome of healthy people, healthy Americans, that what they really may have been documenting there is a perturbed microbiota that's, uh, really predisposing people to a variety of inflammatory and metabolic diseases.

   4. AHAndrew Huberman28:54

      Mm-hmm. It reminds me of the, um... as a neurobiologist, you know, I

9. 28:58 – 35:10

   Resilience of the Microbiome

   1. AHAndrew Huberman28:58

      was weaned in the- in the landscape of so-called critical periods, where early life environment, uh, very strongly shapes the- the brain, and so many studies were done on animals raised in traditional cages with a water bottle and some food, maybe a few other animals of the same species. And then people came along and said, "Wait, normally these species in the wild would have things like things to climb over, and things to go through," and you provide those very basic elements, and all of a sudden, the architecture of neural circuits looks very different, and you realize that you were studying a deprived condition. Um, and earlier, you actually referred to, if I understood correctly, two critical periods for gut microbiome development. Um, is it, uh, fair to say that there are critical periods? Meaning if my... let's say my... let's aim it at me. If my- if, uh, my gut microbiome was, um, dysbiotic, it was off, um, early in life, can I rescue that through proper conditions and exercise? Or is there some sort of, um, fixed pattern that's going to be hard for me to escape from?

   2. JSJustin Sonnenburg29:57

      Yeah. The- the... there's a big field that's emerging now that, um, you know, we refer to as kind of reprogramming the gut microbiome. And, you know, I think if we want to conceptualize humans as this aggregate, y- human microbial biology, um, you know, most people have heard of CRISPR and the ability to, um, potentially change our human genome in ways that correct, um, genetic problems. Um, that's a wonderful technology, um, and has kind of put on the table, you know, genetic engineering for curing disease, but it's much easier to change gut microbes for a problem, just because that- that community is- is malleable. Um, the...... the issue that, I think, um, we're seeing in the field is that, uh, microbiomes quite often, whether they're diseased or healthy, exist in stable states. They kind of tend towards this, um, well that has gravity to it, in a, in a way, biological gravity, where, um, it's really hard to dislodge that community from that state. So even individuals, for instance, that get antibiotics, um, you know, you, uh, take oral antibiotics, the community takes this huge hit. We know that a bunch of microbes die, the composition changes, and, you know, that represents a period of vulnerability where pathogens can come in and take over and cause disease. But if that doesn't happen, the microbiota kind of works its way back to something that is not exactly like, but similar to the pre-antibiotic treatment. Uh, we know with dietary perturbations, um, quite often you'll see a really rapid change to the gut microbiome, and then this, it's almost like a memory, where it snaps back to this, something that's very similar to the original state, even though the diet remains different. And so there's this incredible res- what we refer to as resilience of the gut microbiome, and, and, um, resistance to change, or at least resistance to establishing a new stable state. So that doesn't mean it's hopeless to change an unhealthy microbiome to a, a healthy microbiome, but it does mean that we need to think carefully about, um, you know, restructuring these communities in ways where we can achieve a new stable state that will resist the microbial community getting pulled back to that original state. And it, you know, one of the really kind of simplest and nicest examples, um, of this is a, a, an experiment that, um, we performed, uh, with, with mice, where we, you know, were feeding mice a normal mouse diet, um, a lot of nutrients there for the gut microbiota, things like dietary fiber, and, um, we switch those mice, half the mice, to a, a low fiber diet, and we were basically asking the question that, you know, if you switch to kind of a Western-like diet, uh, low fiber, higher fat diet, uh, what happens to the gut microbiota? And we saw the microbiota change. It lost diversity. It was very similar to what we see in, um, in the difference between industrialized and traditional populations. But when we brought back a healthy diet, a lot of the microbes returned. You know, it was fairly... You know, there, there was this kind of memory where it went back to very similar to its original state. The difference is that when we put the mice on a low fiber, high fat diet and then kept them on that for multiple generations, um, we saw this progressive deterioration over the course of generations, whereby the fourth generation, the gut microbiome was a, you know, a fraction of what it originally was. Let's say 30% of the species only r- remained. Um, something like 70% of the species had gone extinct, or appeared to have gone extinct. We then put those mice back onto a high fiber diet and we didn't see recovery.

   3. AHAndrew Huberman33:45

      Mm-hmm.

   4. JSJustin Sonnenburg33:45

      So in that case, it's, uh, um, a situation where a new stable state has been achieved. Um, in that case, it's probably because those mice don't actually have access to the microbes that they've lost, and we actually know that we did a, the control experiment of, uh, mice on a high fiber diet for four generations. They maintain all their microbes. If we take those fourth generation mice with all the diversity and do a fecal transplant into the mice that had lost their microbes but had been returned to a high fiber diet, all of the diversity was reconstituted. So it was, um, you know, so your, your question of, like, how do we establish new stable states? How do we get back to a healthy microbiota if we have taken a lot of antibiotics or have a deteriorated microbiota? It's probably a combination of having access to the right microbes, and we can talk about what that access looks like. It may look like therapeutics in the future. There are a lot of companies working on creating cocktails of healthy microbes. But it'll be a combination of access to the right microbes, and, um, nourishing those microbes with the, the proper diet.

   5. AHAndrew Huberman34:46

      Very interesting. This multi-generational study reminds me of something that I was told early in my training, which was that, uh, it takes a long time for a trait to evolve, but not a long time for traits to devolve. (laughs)

   6. JSJustin Sonnenburg34:59

      Yeah. Yeah. Exactly. Right.

   7. AHAndrew Huberman35:00

      Which generally, um, is, is true of, uh, human behavior too, although, um, it de- it depends. (laughs)

   8. JSJustin Sonnenburg35:06

      Yes, yeah.

   9. AHAndrew Huberman35:06

      We can all do better, nonetheless.

   10. JSJustin Sonnenburg35:07

       Very interesting.

   11. AHAndrew Huberman35:08

       So I have a,

10. 35:10 – 42:04

    Regional Differences Along Your GI Tract

    1. AHAndrew Huberman35:10

       um, a, a, a puzzle, or I, I have a bit of a conundrum, um, around this notion of, of species of microbiota. So if the, if the pH, if the a- uh, acidity is, differs along, uh, the digestive tract, but is more or less fixed for a given location, right? I mean, unless something's really off, the pH of the stomach is within a particular range, and the-

    2. JSJustin Sonnenburg35:30

       Right.

    3. AHAndrew Huberman35:30

       ... the, the intestine, so forth, and certain microbiota thrive in, at a given station, a given location along the, the digestive tract, and the pH is sort of fixed, um, more or less, uh, I'm trying to figure out wha- what, what is allowing certain microbiota to s- stay in a given location. Why don't they migrate up or down? So are they pH sensitive, and that's what's, what they're selecting for along th- the tract? And, um, I'm also trying to figure out how these changes in food so robustly change the microbiome. It's, it... The way you describe it almost makes it sound like food is the, the variable that's going to dictate the quality of the microbiome, although I'm sure there are other factors as well. And then in the back of my mind, I, I don't know that I want to ask this question, but I really want to ask this question, which is, where are they in there exactly, and why don't they all get flushed out, right? (laughs)

    4. JSJustin Sonnenburg36:22

       Right.

    5. AHAndrew Huberman36:22

       Um, if, uh, 30% of, of fecal matter is, um, microbiota, um, then where are they living? Are they in... Are they along the, the lining, in the little microvilli of the intestine, and what are they attaching to and, and interacting with? Uh, we know there are neurons in there. Um, we kn- especially within the stomach. There's a lot of w- work now being done on the, the gut neurons and how they signal to the brain and so forth. But who are they talking to in terms of the, the host cells?

    6. JSJustin Sonnenburg36:51

       Yeah.

    7. AHAndrew Huberman36:51

       And, um, because if it's just from food, I imagine that they're in there having their good time, or, uh, or not, and then some are getting flushed out or not, but how do they actually stay in there?

    8. JSJustin Sonnenburg37:01

       Yeah.

    9. AHAndrew Huberman37:02

       Who are they attaching to? What are they talking about?

    10. JSJustin Sonnenburg37:04

        Yeah.

    11. AHAndrew Huberman37:04

        What are they doing for fun-

    12. JSJustin Sonnenburg37:05

        Yeah.

    13. AHAndrew Huberman37:05

        ... and so forth?

    14. JSJustin Sonnenburg37:06

        Yeah. Yeah.

    15. AHAndrew Huberman37:06

        Yeah.

    16. JSJustin Sonnenburg37:07

        Super, super interesting. So, um...... I'll come back to the attachment question and kind of like h- why they don't get washed out, 'cause this is a super fascinating question. And, um, you know, I think your, your, um, initial point of like the, the kind of regional differences in what's happening in terms of physiology, biochemistry along the length of the gut is really interesting. There certainly is a pH gradient along the length of the gut. There is, um, actually bicarbonate that's secreted into the small intestine to try to neutralize s- stomach acid. There also is bile that's secreted, um, that creates a, a different chemical environment and there are bile-loving bacteria that kind of live in that region of the gut. Um, and then, you know, there, there is an... a nutrient gradient, just because as food leaves the stomach it, um, you know, a lot of the simple nutrients are absorbed, and so you might see microbes in the small intestine, for instance, that are better at consuming simple sugars, but you won't find many microbes in the colon like that, because all the simple sugars have been depleted at that point. Um, and then the immune system is a big factor as well, and the immune system is incredibly active in the small intestine. Um, the small intestine is this really interesting challenge for the host, because it's a tissue that's been, you know, its purpose is mainly absorptive, and so there has to be flow of, um, a lot of things, you know, a lot of nutrients from the luminal contents into host cells, and so that means the barrier can't be as fortified. And so the, the immune system is incredibly active in the small intestine to make sure that microbes aren't getting s- so close, and if they are getting close, there's a response to them to put them back in their right location. Um, so there's, you know, a l- a- and, and then, you know, along this whole kind of architecture of the gut, there's the longitudinal gradients, um, things like, like pH and so forth. And, and I should say that, you know, pH starts to drop again in the colon because a lot of those microbes are fermenting things and producing acids, and so you actually end up with, uh, you know, the, the pH starting to drop, not as low as the stomach, but starting to drop again if there's a lot of fermentation happening in the colon. In addition, you also have a gradient from the host surface epithelium out to the, the middle of the gut, and that is likely the, the key for what is retained in the gut and how the community isn't washed out. So lining the gut, we have epithelial cells in the small intestine. They're largely absorptive. Um, in the colon, there's a lot of mucus production, and we sh- also see this in the small intestine, and this mucus lining is this, um, you know, substance that we secrete largely made of carbohydrate actually, and the purpose of that is to keep microbes in the right spot and to allow nutrients and water to be absorbed in the small intestine and large intestine. And so it's this meshwork that is supposed to keep out large things like bacteria and let in small things like, like nutrients. Um, that mucus layer is, um, it turns over more slowly than the luminal contents passing by. And so, um, if a microbe learns to hold onto that mucus layer, it can actually resist the flow of the, the contents of the gut.

    17. AHAndrew Huberman40:39

        I see.

    18. JSJustin Sonnenburg40:39

        And so there, there's a, uh, many microbes in the gut that are not just good at attaching to mucus, but also good at nibbling on it, at eating it. And, you know, there are these bacteria like Akkermansia muciniphila, mucus loving. It's, um... one of its main things it does is actually eat mucus in the gut. That's its lifestyle. And, and so there, there's, you know, an incredible, um, gradient of, of activity from the host tissue working your way out to the middle of the gut. What's amazing is some microbes actually do penetrate past the mucus and there are these invaginations in the intestine known as crypts, actually where the stem cells live that produce the epithelium, and there are microbial communities that can form in those crypts. And we don't know completely what their function is, but we've done some studies that appear to indicate that if you can localize to a crypt, you've hit the jackpot as a microbe for being able to maintain dominance in the gut. So if you sit in the crypt and something similar to you, another microbe that's similar to you comes into the gut, you can actually exclude that microbe. And the thinking is that it can't find a spot to resist being washed out of the gut. So there probably are these little niches close to host tissue in the mucus that are absolutely essential for, um, for resisting getting washed out with the, with the flow of all the contents.

    19. AHAndrew Huberman42:02

        Incredible.

11. 42:04 – 51:19

    Fasting, Cleanses & Gut Health

    1. AHAndrew Huberman42:04

       That raises a question about two things that are, uh, reasonably popular. Uh, one is this notion of cleanses, um, from either direction. People will consume things by mouth to try and cleanse their digestive tract. There's, there's a long history of this. Um...

    2. JSJustin Sonnenburg42:18

       Yep.

    3. AHAndrew Huberman42:19

       I'm not recommending this. There's differing opinions on whether or not this is good or bad. And the other is, um, fasting or time-restricted feeding. Uh, the reason, uh, I ask about time-restricted feeding is my understanding is that after a prolonged period of fasting, there's some, um, auto-absorption or, um, digestion of one's own, uh, digestive tract that then gets renewed. In other words, you... your intestine and stomach start eating its own lining to some extent in the absence of food. So what do we know about cleanses? Oh, and then I suppose there's cleanses from the other direction too, right, which, uh, less popular, but, um, uh, I've never run the statistics, but I, um... but certainly exist out there. Uh, what are... what's the idea about cleanses and fasting as it relates to the health or the dysbiosis of the microbiota?

    4. JSJustin Sonnenburg43:07

       Yeah. You know, there hasn't been a lot of high quality science in this area, and so it's really hard to conclude whether these are good or... good for health or bad for health. The... you know, I think the, the fasting, uh...You know, we're, we're in a really interesting situation in the industrialized world, because we have so many problems associated with our digestive tract, and that probably has to do with our, um, highly processed diet, and perhaps having a microbiota that's fairly perturbed as well. And so, you know, um, whether doing things like this are good or bad, um, it, it's really hard to define, because we may be starting off in a fairly bad state anyway. There are so many diseases that we're dealing with, metabolic syndrome, inflammatory bowel disease, that just put a massive portion of the population in a very different category than people that are thinking about, "How do I maintain health? How do I live a long life?" Um, from starting off in what we consider a fairly healthy state. And so things like, you know, fasting, um, and, and a lot of other therapies that have been developed in the field, um, you know, I think ketogenic diet may be kind of in this category as well, there can be tremendous benefits in terms of, um, their impact in the context of metabolic syndrome and for people that are battling, um, you know, eating a continual bad diet or something like that. So it-

    5. AHAndrew Huberman44:37

       And adherence. I think one of the pop- one of the reasons for the popularity of intermittent fasting, um, time-restricted feeding, um, and sort of ex- what do they call them now, exclusion diets, where you entirely exclude meat, or you entirely exclude plants, or whatever it is-

    6. JSJustin Sonnenburg44:53

       Right.

    7. AHAndrew Huberman44:53

       ... is the- that adherence is sometimes easier in the all or none. Um, as neurobiologists, we think of it as a go/no-go circuitry. (laughs) It's harder to make, uh, uh, decisions, uh, nuanced decisions often about food than it is to just eliminate entire categories of food. Not eating, for many people-

    8. JSJustin Sonnenburg45:11

       Yeah.

    9. AHAndrew Huberman45:11

       ... is easier than eating smaller portions.

    10. JSJustin Sonnenburg45:13

        Yep.

    11. AHAndrew Huberman45:14

        Um-

    12. JSJustin Sonnenburg45:14

        Yep. Yeah, yeah, and, and I-

    13. AHAndrew Huberman45:16

        So some of it, I think, is neurobiological and psychological. (laughs)

    14. JSJustin Sonnenburg45:19

        A- absolutely. And we've had, you know, gastroenterology fellows in our lab that come in and we kind of, you know, I think that to kind of slice through the nuance of all this, there's a very simple recipe and a really well accepted, um, kind of broad definition of what a healthy diet is. You know, kind of the, the Mediterranean diet, plant-based diet, um, is, you know, there's just a ton of data that, um, particularly people of European ancestry, but there's a l- you know, a pretty broad acceptance that if you eat mostly plants, for most people, that's gonna be very healthy, to the point where, um, you know, a, a, a wonderful colleague of ours, Christopher Gardner, who's studied diet, um, his whole life, um, trying to establish what a healthy diet is, and people was giving advice. I saw him giving advice to a, um, dietician who was trying to get all the rules of, like, what, what she should be recommending to, um, people that she deals with that are interested in a healthy diet. And she said, "So the, number one, I'm gonna say plant-based fiber is probably super important, and that should be, you know, very high on the list." And she goes onto number two, and he said, "Stop." He said, "If people do number one well, you don't need to know any other rules." I mean, it's basically like if you can have a high-fiber plant-based diet, um, for most people at least, you know, talking about the bucket of people that are already in a healthy state, you don't really need to think about other things, because you can't eat too much meat, you can't eat too many sweets. You've already eaten a huge amount of plant-based fiber. Your gut is full, you're not gonna be hungry. Um, and, and it kind of takes care of worrying about what should I eat or what, what shouldn't I eat? Just eat a ton of whole plant, you know, whole grains, legumes, um, vegetables, uh, fruit that's h- that's high-fiber based, not high sugar.

    15. AHAndrew Huberman47:02

        Does it completely exclude meat and fish and dairy?

    16. JSJustin Sonnenburg47:05

        He, and he was saying like, you know, people can add their own spins on this, but I, I think that the, the main rule is just start off with, you know, and it kind of gets back to, to Michael Pollan's mantra, you know, um, eat food, not too much, mostly plants. So, you know, I think if you stick with kind of these simple rules and don't overthink, like, "Should I have this? Can I eat eggs? Can I eat..." you know, just kind of stick to these simple rules, it makes it very approachable. But I agree, like, so these gastroenterology fellows that we've had in our lab say that they... it's really hard. We, we kind of say to them, "Why won't you give this dietary advice that's really well known?" And they just said, "Well, it's, it's really hard to get people to change their diet unless you're doing either a, a go/no-go sort of thing, like, uh, or eliminating something." So, you know, if ca- carrots are giving you problems, don't eat carrots. And that's a very simple, easy instruction to follow, but, um, doesn't really deal with the root problem of why can't you eat carrots, because you should be able to eat carrots. Most people can eat carrots. And, um, and so I, so I think that, you know, there, we, um, yeah, we, we, when we're, when we're thinking about things like, um, fasting and, you know, all these different dietary regimes and cleanses that people do, um, we, we have to step back for a moment and say, "Okay, well, what, what are really the, the big high-level rules that we should take home?" And then if you are experiencing problems and you want to think about how to deal with them, it's good to go to an evidenced-based method where there's actually data to back it up. The, you know, the, the data in the field really shows that with, like, fasting, uh, particularly if you go to, like, animals that hibernate or things like that where there's really extended fasts, you actually have, um, a microbiota come up that's, uh, that blooms in the absence of, of food coming in through diet. (clears throat) That's really good at, at eating mucus. So you have, um, you know, bacteria that's, that specialize in eating nutrients derived from the host because there's no other nutrients to live on. Now, whether this is good or bad, we don't know, but it, it seems like, um-... the, you know, consumption of mucus in excess is a problem from the standpoint of microbes getting too close to host tissue and inciting inflammation, which is what we see in animal models when we deprive of dietary fiber. We see these mucus utilizers become abundant and inflammatory markers start to come on, so, so fasting short term might be fine, probably, um, you know, there's definitely benefits that are seen metabolically. Um, in terms of what it means for long-term health from the standpoint of the gut microbiota, I would say we don't have the answer to that yet. In terms of the, you know, the cleanses, and the flushes, and all this, uh, personally, I, I think it's a terrible idea. I mean, we know that like if, um, s- you know, in studies that are being done now to reprogram the gut microbiota, to install a completely new microbial community, the first step is to wash away the resident microbial community that's there. So if you're in the process of acquiring a really good microbiota and you know how to do that, then the- the flushing everything out is great. Um, otherwise, what is happening is you're kind of leaving rebuilding of the community to chance, like what is it? And so, um, you know, what- what microbes are gonna colonize, who's going to take up space after you do this flush or cleanse, and, um, you know, that I think it's a- a little bit like playing Russian roulette. You may end up with a, a good microbial community in there afterwards, you may not. Um, you certainly want to pay close attention to what you're eating while you're doing the reconstitution of the community after you do something like that.

    17. AHAndrew Huberman50:43

        Yeah. Uh, thank you for that. I know a lot of people are interested in these kinds of elimination diets, and intermittent fasting, um, slash time restricted feeding seems to be getting some traction in part, because at some level we are all doing this when we sleep. W- most of us aren't eating while we sleep anyway, and, um, adjusting the numbers seems, um, more accessible for a lot of people. We have a lot of colleagues at Stanford who I- I know happen to follow that regimen, um, or a time restricted feeding regimen, but, um, also, um, whose follow the more traditional meal spacing as well, of course. The- uh, one of the things that I

12. 51:19 – 1:01:24

    Dietary Differences

    1. AHAndrew Huberman51:19

       wonder about as we talk about, um, primarily plant based with some, you know, what did you say the Pollan thing was, it was eat, uh, mostly plants, um, and then s- maybe some meat, but not too much-

    2. JSJustin Sonnenburg51:29

       Yeah.

    3. AHAndrew Huberman51:29

       ... or- or not too much?

    4. JSJustin Sonnenburg51:30

       Eat food, mostly plants, not too much.

    5. AHAndrew Huberman51:32

       Got it. Um-

    6. JSJustin Sonnenburg51:32

       Oh sorry, eat food, not too much, mostly plants.

    7. AHAndrew Huberman51:35

       Got it. Um, you know, and, uh, in, uh, just I- I have, I hear this again and again, I know there are a number of people who do seem to do well on a lower carbohydrate, um, you know, and even some people who report feeling much better on a, like, really strictly almost meat organ only diet, and the only reason I raise this is not, uh, I don't participate in any other kind, I'm in a- I'm one of those omnivores, uh, that out there. Um, I do eat some meat. Um, and I do eat plants as well. But the reason I raise this is that earlier you were talking about, um, communities that may have microbiota that are, um, healthier than ours, or at least different than ours, and there are communities in the world that, uh, that subsist largely on animal products, or for which unprocessed animal products are considered the richest nutrient foods in those communities. Protein is very scarce, in- ancestrally protein was- was more scarce, so eggs and meat and things of that sort. So could there be a genetic component? In other words, if we fast-forward 10 years and we actually can make sense of all this human genome stuff, are we going to find that someone who has, um, Scandinavian, uh, roots, or somebody who has South American roots, or somebody who descended from a different tribe will do better on one particular diet versus another, and thereby, or I should say, and in parallel with that, that their gut microbiome will have different signatures that are... so your microbiome might thrive on plants and mine might thrive on organ meats? And as I say this, um, I'm not a big consumer of organ meats, I'm just laying this out for sake of example.

    8. JSJustin Sonnenburg53:09

       Yeah. No, I- I- yeah, great. Um, so, um, a few notes. Uh, the first one has to do with the carbohydrates and restriction of carbohydrates, and some people feeling healthier when they- they cut carbohydrates out. My guess is, (clears throat) and this is- this is my theory, um, to be tested, um, that people feel better cutting carbohydrates out because the diet that we eat in the United States and in industrialized countries, the carbohydrates are largely crap. They-

    9. AHAndrew Huberman53:42

       Processed.

    10. JSJustin Sonnenburg53:42

        ... they're processed.

    11. AHAndrew Huberman53:43

        Right.

    12. JSJustin Sonnenburg53:43

        They're- it's like starch, simple sugar. Um, it's things that contribute to glycemic index. It's- it's these sugars that- that we eat. They make it to our small intestine, they get chopped up into simple sugars, absorbed into our bloodstream, and we have a ton of glucose then coursing through our veins, which we know is bad and can lead to things like diabetes. Um, if the carbo- (clears throat) the carbohydrates that were in our diet were complex carbohydrates, dietary fiber, and we like to refer to the subset of dietary fiber that the microbiota can actually access as microbiota-accessible carbohydrates.

    13. AHAndrew Huberman54:21

        Mm-hmm.

    14. JSJustin Sonnenburg54:21

        And the reason that we like that term is it has the word carbohydrate in it, and it's, um, to point out that not all carbs are bad, it's just there are bad carbs, or carbs that are bad if you consume them in too high a quantity, things like, you know, uh, table sugar and simple starches, but there are good carbs as well, and these microbiota-accessible carbohydrates are the complex ones that we can't digest and fuel, um, our gut microbiota. Our gut microbiota can ferment them. And, um, so the, you know, I thi- I think, um, we probably all would be better off with less of the carbs that we're typically served, but most of us, and probably the vast majority of us, would be better off by consuming a lot more carbs that were complex, that were microbiota-accessible. Um, and I'll come back to why that's important in terms of our biology. There's some mechanisms that are known as to why those complex carbohydrates are so important for our health for most of us. Um-... I think this aspect of human genetic adaptation to diet is super interesting. And then layer on top of that, gut microbiota, (clears throat) adaptation to diet, which is another layer of this that, um, is also fascinating. It's very clear that over very short periods of time, humans can adapt to differences in their diet. Lactase persistence is kind of the classic example of this. Just over the past 10,000 years, um, humans, you know, certain groups of humans have adapted to being able to consume dairy, um, by taking this enzyme lactase that normally is just expressed in most of the world's population early in life, to be, (clears throat) be able to metabolize lactose in breast milk. Um, by extending the expression of that throughout life, now you can consume milk for your whole life. And so that is an example of specific populations of humans, um, human genome, genetically adapting to diet in a very short period of time. And this, there are other examples of this, and undoubtedly this has happened, um, throughout the world to various aspects of diet. So certainly, um, it's important to remember that there will be, um, different diets that are better for different groups, based on what genes you, you harbor and have in your, in your human genome. The other aspect on top of that is that, um, you know, there, there are, um, good examples of the gut microbiome adapting to cultural differences in diet. And the classic example of this is the degradation of seaweed. So we know that, um, most Americans, if you eat sushi and, and there's nori there, and you, you eat, um, some of this, this seaweed, it has a dietary fiber in it known as porphyrin. That porphyrin will shoot through most of us untransformed. Inert substance, uh, you know, it'll do other things like retain water and serve as kind of something like cellulose, not be, um, fermented at a high level. Um, if somebody from Southeast Asia that's always consumed, um, seaweed and is part of a culture that consumes seaweed eats seaweed, they have a gut microbe that can now metabolize porphyrin. And so there are these very specific gene transfer events where the genes for breaking down porphyrin have been imported into the microbiome of many people in Southeast Asia to, um, you know, we can think of it as helping digest porphyrin, but it's really just a microbe that's found a niche, found a way to make a living in the gut by consuming something that's common in the diet there. So there are these different layers. There are human genetic adaptations and there are microbiome adaptations that are cultural and, and based on people's geographic location, um, but, you know, the, there's no escaping the fact that for much of human evolution, the vast majority of people that are on this planet had ancestors that were hunter-gatherers, foraging, consuming huge quantities of plant material, just because that's, that's what was there. And so one of the groups that we study, the Hadza hunter-gatherers in Africa, um, and I, I should, um, take a moment just to say that, you know, um, our research and, and research of many people in our field and other fields rely on study of indigenous communities, and it's really important to, um, think of these communities as, um, you know, our equals. They're modern people on the planet, they have interesting lifestyles that are informative with regard to certain aspects of, of human biology, um, but in many cases, they also are, um, you know, leading a vulnerable existence. And so we really take great care in our research program, and it's important for people to realize that, um, you know, these populations take part in our research because they're wonderful research partners, and (clears throat) , we need to be mindful of kind of thinking about how, um, yeah, both we talk about them and, and use our data that, that has, um, been gained through their, um, generous contribution to our research program. The Hadza hunter-gatherers, it's estimated, consume on the order of 100 to 150 grams of dietary fiber per day, and that's in stark contrast to the typical American that consumes about 15 grams. So somewhere 10, 7 to 10-fold decrease in the main nutrient that feeds our gut microbiome in the American diet. The, the Hadza are, um, you know, one example. There are diff- many different foraging populations, but the vast majority of these populations consume huge amounts of dietary fiber, because plants are the reliable, consistent source that, you know, if you, as a, um, hunter-gatherer, go on a hunt, usually that hunt is unsuccessful. You know, I think the data are that, you know, one out of 20 to 30 hunts are successful in landing actually big game. For the Hadza, they have, you know, birds that they shoot, and small animals, but quite often, um, day after day, they're relying upon, uh, berries, tubers, baobab fruit. You know, they're, they're relying on the plants in their environment. And actually, if you, um, go to the data and look at what their food, food preferences are, their food preferences are actually meat and honey. So they don't eat a high-fiber diet because they love fiber. They eat a high-fiber diet because that's what's available and consistent, um, for them to, to survive. But, you know, our brains are wired for caloric density, and so if you took a, a Hadza and put them in a restaurant in the United States, they would make the same crappy decisions that we make because we, you know, all want sugar and fat and calories. It's how our, our brain is wired.

    15. AHAndrew Huberman1:01:01

        And protein and fat are essential for brain development as far as we know, right? So the, so it sounds like the, the Hadza, I hope I'm pronouncing that correctly, uh, d- you said would prefer to eat meat and honey, but they do con- they happen to consume a lot of plant fiber as a consequence of what's available. The, um, one of the questions I, I have as it relates, um, to all of this is it,

13. 1:01:24 – 1:07:03

    Simple vs. Complex Carbohydrates, Processed Foods

    1. AHAndrew Huberman1:01:24

       it sounds to me like...... there is no question from the pure vegan all the way to the extreme opposite, which would be pure meat diet, um, that avoiding processed foods is a good idea.

    2. JSJustin Sonnenburg1:01:40

       Yeah.

    3. AHAndrew Huberman1:01:40

       Or heavily processed foods, in general. And I mean, not that, uh, you know, the occasional consumption is, is, um, necessarily bad, but, um, whether or not one is thinking about one macro nutrient profile or another, it sounds like consuming pro- processed foods is just bad for the microbiome. Can we say that categorically?

    4. JSJustin Sonnenburg1:01:58

       For sure.

    5. AHAndrew Huberman1:01:59

       Okay.

    6. JSJustin Sonnenburg1:01:59

       Yeah, yeah. Absolutely.

    7. AHAndrew Huberman1:01:59

       Whether or not, you know, so you're a low carb person, you're a zero carb person, you're extreme vegan, no meat, whether or not you're all meat, organ meet, sounds to me as if, uh, the number one thing, maybe even, dare I say, above Chris's, uh, uh, point about plants, although I'm not going to challenge Chris Gardner on, on, on nutrition.

    8. JSJustin Sonnenburg1:02:17

       (laughs)

    9. AHAndrew Huberman1:02:17

       I would be w- uh, way outside the lane lines to do that. But is it to avoiding processed foods-

    10. JSJustin Sonnenburg1:02:22

        Yeah.

    11. AHAndrew Huberman1:02:23

        ... is paramount.

    12. JSJustin Sonnenburg1:02:24

        Yeah, and I think that's completely cr- compatible with what Christopher was saying. He was saying if you put, prioritize getting a huge amount of, of whole plant based food with a lot of fiber first, you're not going to have room for eating a lot of processed food.

    13. AHAndrew Huberman1:02:37

        Yeah. Yeah.

    14. JSJustin Sonnenburg1:02:38

        So it's kind of the same as avoiding processed food.

    15. AHAndrew Huberman1:02:40

        Right.

    16. JSJustin Sonnenburg1:02:40

        So I think that those are exactly the same rule, and I think that, yeah, that you're exactly right, and we can break down w- you know, there's a lot of data of why different components of processed food are so bad for us and so bad for our microbiome, and I can talk about a few examples of that. But the flip side of this is this mechanism of, you know, and, and again, thinking about the spectrum of a plant based diet versus a meat based diet, um, you know, there's, uh, a lot of data to tell us that, uh, meat or, or ketogenic or high fat diet may have big benefits in terms of short term metabolic health. That's typically how people think about that diet. Um, there's also a lot of heart disease that's linked with that as well. There's good literature for that, which is something to, for people to, to look at and be aware of. The plant based diet, if you're eating a bunch of complex, um, you know, fibers that feed your gut microbiota, your gut microbiota produces these substances called short chain fatty acids, things like butyrate. And it's known that these short chain fatty acids play really essential components, both in terms of fueling colonocytes, enforcing the barrier, keeping inflammation low, regulating the immune system, regulating metabolism. And so, you know, m- a lot of people think of dietary fiber as this inert substance that passes through, makes us feel full maybe for a little bit, but we get hungry afterwards right away. If you're eating a lot of fiber that's feeding your gut microbiota, your gut microbiota's just producing this vast array of fermentation end products that then get absorbed into our bloodstream and have all of these tremendous cascading effects that appear to be largely beneficial on our biology. And so to think about that paradigm of simple carbs versus complex carbs, in the case of simple carbs, you end up with high blood sugar, you know, something that will spike your insulin and, you know, have all kinds of weird metabolic effects. In the case of complex carbohydrates, you'll end up with very low blood sugar, because most of those have low glycemic index and a bunch of short chain fatty acids that are having regulatory rules. So, so just to, to round out that, that topic, I think there is a reason to think that, you know, maybe not appropriate for absolutely everyone out there, but I think the vast majority of people, particularly given the statistics of what we know people eat in the United States and in industrialized countries, most people would reap tremendous health benefits from eating more whole, plant based dietary fiber. Now, processed foods I think is this other dimension where you have all of these weird chemicals, artificial sweeteners, weird fats, um, you know, a lot of refined simple nutrients. The simple nutrients we've talked about, but we know that, for instance, artificial sweeteners can have a massive negative impact on the gut microbiome and can lead us towards metabolic syndrome actually. There's been beautiful work out of the Weizmann Institute on this. And then em- emulsifiers, these compounds that are put in processed foods to help them maintain shelf s- stability so things don't separate, and so, um, you know, all the, the moisture content is retained appropriately. Um, many of these are known to disrupt the mucus layer, and as soon as you start disrupting that barrier, that can lead you in the direction of inflammation, and in animal models, we know that can lead towards metabolic syndrome as well. So there's, there's components of processed food that are, when studied in isolation, known to have a direct negative impact on gut biology and the microbiota.

    17. AHAndrew Huberman1:06:02

        Yeah. The mention of artificial sweeteners is, is interesting. I, I confess, uh, it's a third rail on social m- talking about artificial sweeteners. There are two camps it seems, or at least, um, two camps, one that say artificial sweeteners are not detrimental at all, another that says they're very detrimental mainly based on the mouse studies, and then there are people in the middle that are... I put myself in that category. I drink the occasional diet soda. I don't consume them in large volume, but I'm sort of in the, the middle there. However, um... And so I just throw that out there, because I know immediately people s- um, are jumping on that. But I will just mention there's some recent data fr- out of, um, Diego Borges' lab at Duke University that the neurons that live in the gut mucosa, these neuropod cells, can actually distinguish between artificial and, um, true sweet, uh, sugar versus artificial, uh, sweeteners, um, based... They send different patterns of neural signals up to the brain, and the brain circuitry seems strongly impacted. So I think as the data emerge, we're hearing more and more of these artificial sweeteners, um, either are problematic or at least are signaling

14. 1:07:03 – 1:12:44

    Artificial & Plant-based Sweeteners

    1. AHAndrew Huberman1:07:03

       different events in the, in the gut. Uh, I do want to make sure that we distinguish, uh, artificial sweeteners from non-caloric plant based sweeteners.

    2. JSJustin Sonnenburg1:07:13

       Yeah.

    3. AHAndrew Huberman1:07:13

       Um, and this is based on a mistake that I've made over and over again on the podcast (laughs) where I'll just kind of lump artificial sweeteners, um, into one big category, and say, and then I'll mention stevia. So what about plant based sweeteners-

    4. JSJustin Sonnenburg1:07:25

       Yeah.

    5. AHAndrew Huberman1:07:25

       ... that are not artificial, they weren't manufactured in a laboratory, like saccharin or sucralose or aspartame?

    6. JSJustin Sonnenburg1:07:30

       Right.

    7. AHAndrew Huberman1:07:30

       What... Do we know anything about plant based non-caloric sweeteners or low caloric sweeteners?

    8. JSJustin Sonnenburg1:07:36

       ... ve- very little. You know, a lot of those have, um, a lot more bang for the buck. They're, they're incredibly sweet, so it takes a really small amount for them to trigger a huge amount of sweetness. And, um, and so it's depending upon the mechanism of action by which these, um, sweeteners that are not sugar are impacting our biology. It may be that those are actually, um, you know, less negative or, or more healthy than, um, the ones that are artificial, just because it requires less of them in the food for us to perceive that sweet taste. It may also be that because they're... You know, I don't think that everything is, that's natural is better necessarily than things that are artificial. Um, but it may be that because of, um, you know, kind of evolutionary exposure to these compounds in our diet, um, historically there are, I think, traditional populations that used these, for instance, to sweeten, um, you know, uh, sweeten different foods, um, that our bodies just kind of know how to deal with those compounds better than the ones that are synthetic. Um, but I think the, you know, w- the studies still need to be done.

    9. AHAndrew Huberman1:08:40

       Do you actively avoid artificial sweeteners? Sucralose, aspartame saccharin? You personally?

    10. JSJustin Sonnenburg1:08:45

        Yeah, you know, uh, so it... I, I do. I, I avoid them, but I'm not... I, you know, um, so th- y- um, I work closely with my wife, Erica, as you know. We do... Uh, we run the lab together, and we, um, you know, wrote this book, The Good Gut, where we kind of document our journey in changing our lifestyle, dietary habits, choices we make based on the research as we've gotten to know it in the gut microbiota over the past 15 years. And, um, you know, I, I think that one of the lessons that we've learned is that just, uh, doing things in moderation makes it a lot, um, easier, and doing things slowly makes it a lot easier. And so, so there are very few rules that I have that are hard and fast. I'm, I'm a pretty flexible eater. I don't believe that having an artific- you know, having a Diet Coke, um, will, you know, somehow cascade into some terrible disease or something like that. Um, I, I try to avoid them. I don't really like the flavor of them. I'm, I'm super sensitive to the, the nuances of the flavor, even with the, you know, stevia and mogro sites from monk fruit and stuff like that. I just really... The off flavors are really hard for me to deal with. But, um, so, so... But I also, in this journey of changing our diet, like when we started off in microbiome research, I was in the habit of, you know, in the afternoons having a sweet, a muffin or a cookie or something like that. And when we started to realize that w- w- you know, we should be eating less sweets and eating more dietary fiber, this was an incredibly difficult change for me to make. I was just wired to kind of crave, you know, this-

    11. AHAndrew Huberman1:10:18

        Classic scientist.

    12. JSJustin Sonnenburg1:10:19

        Y- y- yeah (laughs) .

    13. AHAndrew Huberman1:10:19

        S- scientists love the, the pastry in the afternoon-

    14. JSJustin Sonnenburg1:10:22

        Right, totally.

    15. AHAndrew Huberman1:10:22

        ... and the coffee.

    16. JSJustin Sonnenburg1:10:23

        Yeah, yeah.

    17. AHAndrew Huberman1:10:23

        And in the old days, it used to be a cigarette too. You know?

    18. JSJustin Sonnenburg1:10:25

        Right, right, exactly.

    19. AHAndrew Huberman1:10:26

        When I started my training, a lot of people still smoked.

    20. JSJustin Sonnenburg1:10:29

        Yeah, right.

    21. AHAndrew Huberman1:10:29

        And it was only during my postdoctoral training that they eliminated smoking on campuses, and, and productivity took a, took a trough for a while-

    22. JSJustin Sonnenburg1:10:37

        (laughs)

    23. AHAndrew Huberman1:10:37

        ... and until these people developed other tools to, uh, to focus their attention, and-

    24. JSJustin Sonnenburg1:10:41

        E- exactly, exactly. So there, there is this kind of, like, need, and then once you have an ingrained behavior and maybe things that are addictive, it becomes incredibly, um, difficult to break that habit. And, um, and so I would say, you know, gradually over the course of like, you know, five or more years, we have, um, you know, migrated our diet away from sweet foods to, um, things that are, are less sweet. Um, and it's, you know, it's been a journey. It's been a slow process. Um, but we've gotten to the point now where we've just retrained our palates, and it's amazing how this happens now, where I'll have something that, you know, is something that I would have used to have, like, daily, and it's unpalatable. I, like, I just can't deal with the sweetness of it. And, and so I avoid... I certainly avoid artificial sweeteners, but I also avoid just sweet things in general that have sugar in them, um, just because they... Now, they... You know, as originally I was ma- I was trying to be disciplined and trying to change my diet, but now they just don't taste good to me.

    25. AHAndrew Huberman1:11:41

        Yeah, likewise. I completely lost my appetite for sugar at the turn of the last year, and I don't know how to explain it. But I... The way I, um... Even though I don't have an a- a mechanistic explanation, I just, I say I like sweet people. I don't like sweet food anymore. I just don't. I have not lost my appetite for, um, fatty foods. I love ch-

    26. JSJustin Sonnenburg1:11:59

        (laughs) .

    27. AHAndrew Huberman1:11:59

        ... cheese and, uh, certain, certain meats for me. Uh, I blame my Argentine lineage. I-

    28. JSJustin Sonnenburg1:12:04

        (laughs) .

    29. AHAndrew Huberman1:12:04

        ... is, uh, is... I gravitate towards them. But in any case, um, avoiding processed foods, probably avoiding sugars, emulsifiers, these kinds of things, uh... And, uh, for people listening or watching, we're not setting up strict guidelines here. We're just, um, bouncing around the, uh, the carnival that is the microbiome and, and nutrition, because I think that these... We hear this, uh, everywhere, "Eat this, don't eat that," or, "This is best for microbiome or worst for microbiome." But I'm hearing fiber again and again, so we're gonna come back to fiber. But I want to make sure that we, um, close the hatch on this issue of fasting and cleansing. Based on your answer earlier, it sounds to me like it is not necessary to do a

15. 1:12:44 – 1:14:50

    Cleanses: Useful? Harmful?

    1. AHAndrew Huberman1:12:44

       cleanse or fast prior to an attempt to repopulate the microbiome. In other words, if I want to make my mi- microbiome healthier, it sounds like I don't have to try and flush all the, the-

    2. JSJustin Sonnenburg1:12:54

       Yeah.

    3. AHAndrew Huberman1:12:54

       ... the current microbiota out of there first. Is that correct?

    4. JSJustin Sonnenburg1:12:57

       Yeah, y- y- uh, you know, it's a very good question, and I don't mean to suggest that those things are (clears throat) known to be terrible, or I would just say, like, this, you know, the studies haven't been done. And to me, wiping out this microbial community, um, unless it's done with some sort of... Unless it's done in an informed way, and we don't really have the information for how that would be done, it just seems like, um, you know, playing the lottery a little bit.

    5. AHAndrew Huberman1:13:21

       Okay.

    6. JSJustin Sonnenburg1:13:22

       And so, so I, I think, you know, I don't want to say that those are... It may be that when the study is done, those are shown to be amazing, but I just don't think we have the data to know that yet, so it's somewhat of an arbitrary thing.... um, if somebody you know out there feels way better when they do this and are not experiencing problems with it, then maybe it's the right thing for them. But I certainly can't- can't say that it's something great to do. I- I- I can imagine a future where, um, as the microbiome gets incorporated into this, you know, emerging paradigm of precision health, you go into a clinic, somebody types your microbiome and says, "Oh, there's a- this huge, massive misconfiguration, you have all these engrafted bacteria that live, that are residents in your gut microbiome, that are ascending out molecules that are not good for your health. It would be good if we do a mass reprogramming of it." The way that we do that is we flush your gut and we actually give a light antibiotic treatment to try to kill everything that's there, and then we repopulate with this other consortium of microbes that we've studied and know are healthy, know are compatible with your human genome and can be reinforced with a diet that we know is good for you. We'll install those microbes, we'll help you along in the diet to note, so you know how to nourish those microbes and that will be the way that we'll reconfigure your gut microbiome. So, you know, I can't imagine a future where that sort of flushing or cleansing is part of something for repopulating the gut, but right now it seems a little half-baked to me. Yeah.

16. 1:14:50 – 1:20:17

    Your Microbiome & Your Immune System

    1. JSJustin Sonnenburg1:14:50

    2. AHAndrew Huberman1:14:50

       Great. I'd love to talk about fiber and fermented foods, because you and Chris had a really, what I think is a really interesting and exciting paper at the end of last year about comparing, um, the inflammatome, um, so inflammatory markers of people who ate a certain amount of fiber or a certain amount of- of these fermented foods. This study is amazing for several reasons, but, um, almost as amazing is how diverse the interpretation of this study was in the media. If ever there was a study that was, um, kind of hijacked by different priority schemes out there-

    3. JSJustin Sonnenburg1:15:31

       Yeah.

    4. AHAndrew Huberman1:15:32

       ... um, it's this study. So you performed the study, uh, with Chris and your post-docs and graduate students and staff. What are the major conclusions and what sorts of directives, if any, emerged from this study? And I'll just preface this again by saying, if I wasn't clear, some news report said, "Ah, this means fiber is not important."

    5. JSJustin Sonnenburg1:15:52

       Yeah.

    6. AHAndrew Huberman1:15:53

       And then others said, "This means fermented foods and fiber are important." And others said, "Fermented foods are the thing and the only thing." It- it was all over the place.

    7. JSJustin Sonnenburg1:16:02

       Yep.

    8. AHAndrew Huberman1:16:03

       And, um, one of the reasons for doing this podcast at all is so that we can go straight to the people who perform the work.

    9. JSJustin Sonnenburg1:16:10

       Fantastic.

    10. AHAndrew Huberman1:16:10

        And even though I'm not- certainly not an expert in microbiome, give you the opportunity to share with me and me to ask the kinds of questions that have... I have zero agenda. I do like sauerkraut. I do drink the occasional (laughs) , uh, kombucha. Um, I do like low sugar, not so sweet forms of fermented foods. So I would be delighted if fermented foods are good for me, but I have no stake in the fermented food industry.

    11. JSJustin Sonnenburg1:16:34

        Yeah, absolutely.

    12. AHAndrew Huberman1:16:35

        Yeah.

    13. JSJustin Sonnenburg1:16:35

        Yeah. Yeah. Great. Um, yeah, wonderful. And- and an important note there is- is the one you pointed out that this is an incredible collaboration with Christopher Gardner's lab and, um, you know, a bunch of people. Um, Erica Sonnenburg helped lead this study and then- and then tons of, like you were saying, post-doc staff and, um, other people at- at Stanford and then wonderful participants that, um, were- were part of this study. So a- a huge team effort. Um, l- let me take... Before I dive into that study, let me take a step back because I think the reason that we did this study and- and kind of Christopher's group and- and our group has- has started to, um, pursue this line of- of looking at dietary interventions and how they impact our microbiome, how they impact human biology, goes back to this, um, kind of epiphany that we- we had while studying the gut microbiome, because I think when we started studying it at Stanford, we were thinking about it as this kind of newly appreciated aspect of our biology, almost like, um, finding an organ that we didn't know was there and starting to think about like all the drug targets that were there. Can we go in with small molecule drugs and think of ways to manipulate this community to ameliorate disease? And, um, this is largely the mindset of Western medicine and largely born out of the era of infectious disease. Um, you wait for an infection to start, a bacterial infection, you treat with antibiotics and, you know, that's the way medicine is practiced and that's become less successful over time as we've moved into this era of inflammatory Western diseases and, um, you know, with the exception of the- the current pandemic that's, you know, sweeping the world, um, you know, largely moved out of the era of infectious diseases, at least infectious bacterial diseases, that this paradigm of waiting for diseases to appear and come into the clinic, um, is not really very effective in the context of inflammatory Western diseases, autoimmune diseases, metabolic syndrome, heart diseases and inflammatory disease, you know, the list goes on and on, and, um, and so we started to think a lot about like, how can we get out in front of this? How can we think about like preventative ways of dealing with this crisis of metabolic and inflammatory diseases? And this tremendous beautiful body of literature started to come forward in the field, uh, about 10 years ago that showed that the gut microbiome is absolutely critical to modulating our immune status. So if you change the microbiome, you can fundamentally change how the immune system operates, and we know that the immune system is the- at the basis of a lot of these diseases, inflammatory chronic diseases. And so it- it brought up this possibility that maybe the fact that we're not nourishing this community well enough, maybe the fact that it's deteriorated over time, um, due to all of the things that go along with an industrialized lifestyle, antibiotics and so forth, um, maybe we have a microbiome right now in the industrialized world that is setting our immune system at a set point, simmering inflammation that's driving us towards these inflammatory diseases. And wouldn't it be wonderful if we could figure out how to, um, uh...... use diet specifically, but just kind of learn the rules of how to reconfigure both the composition and function of our gut microbiome so that inflammation was different in our bodies, so that each one of us was less likely to go on and de- develop an inflammatory disease, leading to better, you know, longevity and health, um, over the course of our life. And, um, so we, we were, you know, studying this in- actually in mouse models, and realizing that, um, you know, we really

17. 1:20:17 – 1:32:13

    Dietary Fiber & Fermented Foods

    1. JSJustin Sonnenburg1:20:17

       needed to start doing human studies. We needed to, um, start studying microbiome in humans. And because we were studying diet, we knew that this was something we could go in and do right away. We didn't have to apply for FDA approval for a drug before we could do a human study. We could just start doing human dietary interventions, longitudinally monitoring the immune system and the microbiome, and starting to put the pieces together of what is it in diet that can change our microbiome in a healthy way, help us define what a healthy microbiome is, and monitor the immune system in great detail. And so there were really two critical components of this, in addition to our microbiome expertise. One was Christopher Gardner's group. Um, we wanted to do these human studies, but we're absolutely terrified of humans. We work with mice. Humans are terrifying, um, in many ways, but-

    2. AHAndrew Huberman1:21:06

       But they house themselves. You don't have to pay-

Episode duration: 2:14:38