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Speaker A: 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 Doctor Justin Sonnenberg. Doctor Sonnenberg is a professor of microbiology and... |
Speaker B: Great to be here. |
Speaker A: 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, but I'm aware that our microbiome can be good for us, but we can... |
Speaker B: Yeah, I mean, essentially you're correct. I mean, we have all of these little microorganisms running around in our gut. I think just to start off with clarifying terminology, microbiome and microbiota quite often are referred to, are used to refer to our microbial community interchangeably. And I'll probably... |
Speaker A: Amazing. So we've got a lot of cargo, or maybe we're the cargo. Yes. |
Speaker B: Yeah. I mean, there have been people that have likened humans to just a really elaborate culturing flask for microbes, and that we've actually been designed, over the course of evolution, designed to just efficiently propagate this microbial culture from person to person, from generation to generation. So it... |
Speaker A: Interesting. I believe that our ph, or the ph of our digestive system, varies as you descend, as you go from mouth to throat and stomach. And you said that most of the microbiota are in the distal colon. Are there distinct forms of microbiota all along the length of the digestive tract and within these other... |
Speaker B: Totally, yeah. So it starts, like, with our teeth, and in our mouth and saliva, there's a oral microbiota. These microbial species are very different than the ones that you find in the digestive tract. They're usually built to deal with oxygen very well. They're in an area that is exposed to a lot of oxygen.... |
Speaker A: Very interesting. I imagine these microbiota have to get in there at some point. Are microbiota seen in newborns? In other words, where do they come from? And dare I ask, what direction do they enter the body? Or is it from multiple directions? |
Speaker B: Yeah, great question. 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 existential question in the field, like, where is this community assembling from? And the reason that it's such an interesting question is that a fetus, w... |
Speaker A: But, yeah, we should. |
Speaker B: Getting back to that original question of where do 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 we can certainly detect that signal. We certai... |
Speaker A: Incredible. You even said pets. So if a kid, if there's a dog in the home or a parakeet in the home, clearly they have a microbiome also, and potentially the child is deriving microbiota species from those pets. |
Speaker B: Exactly, yeah. And so the best studies that have been done have just looked at pets in the household as a factor and whether that changes 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 is the pet doing to change ... |
Speaker A: We will return to 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. It's a Havanese, right? |
Speaker B: Havanese. |
Speaker A: Incredible. What is your dog's name? |
Speaker B: Louis. Louis. Louis Pasteur. |
Speaker A: Louis Pasteur. How appropriate. Amazing dog. What a personality on that dog. The issue that I think a lot of people are probably wondering is, what is a healthy microbiome? What is it supporting? We hear that you need a healthy microbiome to support the immune system or metabolism or even the gut brain axis.... |
Speaker B: Yeah, 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 there are sessions at conferences, there are review articles being commissioned. There are all sorts of thought pieces about this r... |
Speaker A: 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? Or is it that there is a superior microbiome signature somewhere in our history or currently in the world? |
Speaker B: Yeah, I think that's a big question right now. I think there's a great quote from Dobchansky that says, nothing in biology makes sense except in the light of evolution. And these traditional populations are all modern people living on the planet now. But their lifestyle does represent the closest approximati... |
Speaker A: It reminds me of the. As a neurobiologist was weaned in the landscape of so called critical periods, where early life environment very strongly shapes 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 speci... |
Speaker B: Yeah, there's a big field that's emerging now that we refer to as kind of reprogramming the gut microbiome. And I think if we wanna conceptualize humans as this aggregate human microbial biology, most people have heard of CRISPR and the ability to potentially change our human genome in ways that correct gene... |
Speaker A: Very interesting. This multigenerational study reminds me of something that I was told early in my training, which was that it takes a long time for a trait to evolve, but not a long time for traits to devolve. |
Speaker B: Exactly. |
Speaker A: Which generally is true of human behavior, too, although it depends. We can all do better, nonetheless. |
Speaker B: Very interesting. |
Speaker A: So I have a puzzle, or a bit of a conundrum around this notion of species of microbiota. So if the ph, if the acidity differs along the digestive tract, but is more or less fixed for a given location. Right. I mean, unless something is really off, the ph of the stomach is within a particular range, and the i... |
Speaker B: Yeah, super, super interesting. So I'll come back to the attachment question and kind of like, why they don't get washed out, because this is super fascinating question. And I think your initial point of the kind of regional differences in what's happening in terms of physiology, biochemistry along the lengt... |
Speaker A: Incredible. That raises a question about two things that are reasonably popular. One is this notion of cleanses from either direction. People will consume things by mouth to try and cleanse their digestive tract. There's a long history of this. I'm not recommending this. There's differing opinions on whether... |
Speaker B: Yeah, 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 for health or bad for health. I think the fasting, we're in a really interesting situation in industrialized world because we have so many problems associated with our digestive trac... |
Speaker A: Something like that, and adherence, I think one of the reasons for the popularity of intermittent fasting, time restricted feeding and sort of, what do they call them now? Exclusion diets, where you entirely exclude meat or you entirely exclude plants or whatever it is, that adherence is sometimes easier in ... |
Speaker B: Absolutely. And we've had gastroenterology fellows in our lab that come in and we kind of. I think that to kind of slice through the nuance of all this, there's a very simple recipe and a really well accepted kind of broad definition of what a healthy diet is. Kind of the mediterranean diet, plant based diet... |
Speaker A: It should completely exclude meat and fish and dairy. |
Speaker B: And he was saying, like, you know, people can add their own spins on this, but I think that the main rule is just start off with, you know, and it kind of gets back to Michael Pollan's mantra, eat food, not too much, mostly plants. You know, I think if you stick with kind of these simple rules and don't over... |
Speaker A: Yeah, thank you for that. I know a lot of people are interested in these kinds of elimination diets and intermittent fasting. Time restricted feeding seems to be getting some traction, in part because at some level, we are all doing this when we sleep. Most of us aren't eating while we sleep anyway. And adju... |
Speaker B: Eat food, mostly plants, not too much. |
Speaker A: Got it. |
Speaker B: Or, sorry, eat food, not too much, mostly plants. |
Speaker A: Got it. I hear this again and again. I know there are a number of people who do seem to do well on a lower carbohydrate, even some people who report feeling much better on a really strictly, almost meat, organ only diet. And the only reason I raise this is not, I don't participate in other. I'm one of those ... |
Speaker B: Yeah. Great. So a few notes. The first one has to do with the carbohydrates and restriction of carbohydrates, and some people feeling healthier when they cut carbohydrates out. My guess is this is my theory to be tested, that people feel better cutting carbohydrates out. Because the diet that we eat in the U... |
Speaker A: And protein and fat are essential for brain development, as far as we know. Right. So it sounds like the hadza, I hope I'm pronouncing that correctly. You said would prefer to eat meat and honey, but they happen to consume a lot of plant fiber as a consequence of what's available. One of the questions I have... |
Speaker B: For sure? |
Speaker A: Okay. |
Speaker B: Yeah, absolutely. |
Speaker A: So your low carb person, your zero carb person, your extreme vegan, no meat, whether or not you're all meat, organ meat, sounds to me as if the number one thing, maybe even, dare I say above, Chris's point about plants. Although I'm not going to challenge Chris Gardner on nutrition, I would be way outside th... |
Speaker B: Yeah. And I think that's completely compatible with what Christopher was saying. He was saying if you put prioritize getting a huge amount 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. So it's kind of the same as avoiding processed food... |
Speaker A: The mention of artificial sweeteners is interesting. I confess. It's a third rail on social talking about artificial sweeteners. There are two camps, it seems, or at least two camps. One that say artificial sweeteners are not detrimental at all, another that says they're very detrimental, mainly based on the... |
Speaker B: Very little. You know, a lot of those have a lot more bang for the buck. They're incredibly sweet. So it takes a really small amount for them to trigger a huge amount of sweetness. And so it's depending upon the mechanism of action by which these sweeteners that are not sugar are impacting our biology. It ma... |
Speaker A: Do you actively avoid artificial sweeteners? Sucralose, aspartame, saccharine. You personally? |
Speaker B: Yeah, you know, so I do. I avoid them, but I'm not, you know, so I work closely with my wife, Erica. As you know, we do. We run the lab together, and we 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'... |
Speaker A: Crave, you know, this classic scientist. Scientists love the pastry in the afternoon and the coffee. Yeah, in the old days, it used to be a cigarette, too, right? |
Speaker B: Right, exactly. |
Speaker A: When I started my training, a lot of people still smoked. |
Speaker B: Yeah, right. |
Speaker A: And it was only during my postdoctoral training that they eliminated smoking on campuses, and productivity took a trough for a while, and until these people developed other tools to focus their attention. |
Speaker B: Exactly, exactly. So there is this kind of need, and then once you have an ingrained behavior and maybe things that are addictive, it becomes incredibly difficult to break that habit. And so I would say gradually, over the course of five or more years, we have migrated our diet away from sweet foods to, um, ... |
Speaker A: 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 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... |
Speaker B: Yeah. You know, it's a very good question, and I don't mean to suggest that those things are 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, unless it's done with, like, some sort of, unless it's done in an informed... |
Speaker A: Yeah, 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 the inflammatome, so inflammatory markers of people who ate a certain amount of fiber or a certain amount of these... |
Speaker B: Yeah, absolutely. Yeah, yeah, yeah. Great. Yeah. Wonderful. And an important note there is the one you pointed out, that this is an incredible collaboration with Christopher Gardner's lab and a bunch of people, Erica Sonnenberg, helped lead the study. And then tons of, like you were saying, postdoc staff and... |
Speaker A: They house themselves. You don't have to pay. You don't have to pay for their housing. That's true for those that can afford housing, of course. |
Speaker B: Yeah, sadly, just for that portion of the population. So Christopher's group are masters of working with human populations. And then the other wonderful thing that we have at Stanford is this human immune monitoring center run by Mark Davis and Holden Maker. They started this beautiful center for allowing pe... |
Speaker A: Could you give us some examples of what those diets look like? And were you changing their basil diet, or were you just adding things on top of what they were already eating? It's hard to change people's diets. It's very hard to trust that they actually do it, and they're nothing sneaking and. |
Speaker B: Totally. Yeah. And so we. And, you know, we've started the center for Human Microbiome Studies at Stanford for doing a lot of these studies, and a portion of the studies we do focus on supplements, probiotics, microbes delivered in pill form, prebiotics, which are purified forms of fiber. And in those cases,... |
Speaker A: And I'm really glad you pointed this out, because you can find sauerkraut on the non refrigerated shelf that is indeed non fermented. A lot of fermented foods that are available in the US can be high in sugar. So was there any instruction as to getting people to make sure that they were consuming yogurts tha... |
Speaker B: No, it's super important point. We instructed people to eat non sweetened yogurts. I think a huge pitfall in this area is you can have a yogurt loaded with bacteria, the base of what's healthy, and then a ton of, like, artificial flavoring, and sugar loaded on top of that. Manufacturers put a ton of sugar in... |
Speaker A: And beer was not included. Right. The number of people that asked when I did a brief thing on social media about this study, and, uh, hopefully I got it right. I think I did. Um, but people just ask about beer. I'm not a drinker, so for me, beer has no appeal anyway. But beer is fermented. Correct. But were ... |
Speaker B: With their normal dietary habits? But that did not count as a fermented food. |
Speaker A: Kombucha was as I said kombucha was. |
Speaker B: And kombucha can have small amounts of alcohol in it. But, you know, we. Yeah, kombucha actually was one of the major things that people drank during the, or consumed during the fermented food phase. And the deal with beer is that there may be beneficial properties of the microbial communities in naturally f... |
Speaker A: I will get to the results of the study in just one moment. But I want to say, a lot of people shy away from the high quality fermented foods because they can be quite costly. Um, I'll just refer people to a resource. In Tim Ferriss book, the four hour chef, he actually gives an excellent recipe for making yo... |
Speaker B: But, you know, if you can get your hands on a scoby, kombucha is another one that's super simple. |
Speaker A: You can grow your own. |
Speaker B: You can, you can just make your own. And it's super easy to do. I make it. I constantly have a batch of kombucha going at home. And it's just, you know, it's a scoby symbiotic community of bacteria and yeast that you, you know, you brew tea, you add sugar to it, and you put the scoby in and you wait a week o... |
Speaker A: I love it. I would love it if members of this audience would start to make their own kombucha and sauerkraut. I've been having so much fun. I don't do it, but, you know, it's done in our home. I don't. I don't go anywhere near the food production. It's for everyone's benefit. So how much fermented food and t... |
Speaker B: Yeah. So we had a wonderful dietitian instructing people for this. And her name is Dalia Perlman. And she really was the key, and is the key for many of our studies for getting people to eat differently. And the general instructions were for people to eat as much fermented foods as possible. More is better. ... |
Speaker A: Great. So what were the results? |
Speaker B: Yeah, so the results astounded us in a way, but then thinking more deeply, and it'll be evident even after I explain it in the context of this conversation, likely why we saw the results. We saw the results were astounding because our hypothesis going into this was that the high fiber diethye was going to gi... |
Speaker A: How long was this study again? |
Speaker B: So the complete protocol, I think, was 14 to 17 weeks or something like that. The actual intervention phase consisted of a four week ramp and then a six week maintenance period. So the intervention itself was ten weeks, but there were six weeks of really kind of hardcore high levels of fiber or fermented foo... |
Speaker A: Yeah, and I'm glad you mentioned the ramp, because my experience with fermented foods is that it can be beneficial to give the system an opportunity to acclimate. I mean, if you consume a giant bowl of sauerkraut, it's not going to be the worst day and night of your life, but you'll know you did totally just... |
Speaker B: Totally. And so both with the fermented foods and the fiber, it's well known that this kind of gradual ramping is a really important way of mitigating bloating and other kind of digestive discomfort that can happen when your microbiome reconfigures and starts fermenting more and changing community members. S... |
Speaker A: I love that my weird behavior is inadvertently being studied at Stanford medicine. I want to just mention something about the gut shots. Those are sold as a drink. Those also, just for certain listeners in different budgets, they can be very expensive. If you really think about some of them are exceedingly e... |
Speaker B: Yeah, very. I mean, very potent from the standpoint of fermentation, but also very salty. So, you know, there's a lot of effects that can. |
Speaker A: Don't do what I do, at least not at the outset, but so that is an experienced warning. So they did this, as I recall, there was a swap condition or there was a halt condition. So you did controls, right. It wasn't just comparing groups. You had individuals who were initially in one group or the other move to... |
Speaker B: Correct. |
Speaker A: Well, so we stop and then return. |
Speaker B: Yeah, we actually just did a stop and followed them during a washout phase. And the ideal situation for dietary interventions like this are to do crossover studies, as you're suggesting. We've recently completed a ketogenic versus mediterranean diet intervention. |
Speaker A: Are those data published yet? |
Speaker B: Not yet, but Christopher's been tweeting a lot of these data, and there's a paper in revision right now. So if you go to Christopher Gardner's Twitter feed, you'll be able to find him reporting some of the early results of this study. |
Speaker A: Give us a snippet of. Was there a super. Just give us a. You don't have to tell us which one. But was there a superior condition of either mediterranean versus ketogenic? |
Speaker B: So the metabolic effects of these. It's a beautiful study. I should let his group comment on that. The microbiota data we actually are just generating now. So the study that he's had, his group has put together from this is largely independent of the microbiota data. And now we're doing a more in depth analy... |
Speaker A: We'll return to that. |
Speaker B: But it's a super exciting study because it is one of these where people eat a certain way. And what's really beautiful about this is we even got food delivered for part of the intervention, so we had complete control over what they at least had available to eat. And then the second phase, they, um, they, um,... |
Speaker A: Great. We will provide a link to the study in the caption. And thank you for that Very ClEar and Thorough description from one of the investigators involved in the study. It's great to go direct to the source. Anecdotally, were there improvements in mood in resistance to colds and infection during the course... |
Speaker B: Totally. |
Speaker A: So did people. I certainly noticed that when I'm eating more fermented foods or there's probiotics in drinks I consume and so forth, that I feel, quote unquote, air quotes, completely subjective. I feel better. I wish there was an objective measure of feeling better, but I seem to think more clearly, sleep b... |
Speaker B: Yeah, totally. You know, we. As part of this effort to look at how dietary interventions affect our. Our health and wellbeing and so forth and microbiome and immune system, we interact with a lot of people who have read our book or kind of have become microbiome enthusiasts and have implemented a lot of thes... |
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