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

0:00Welcome to Huberman Lab Essentials, where we revisit past episodes for the most potent and actionable, science-based tools for mental health, physical health, and performance. I'm Andrew Huberman, and I'm a professor of neurobiology and ophthalmology at Stanford School of Medicine. And now for my discussion with Dr. Justin Sonnenberg. Justin, thanks so much for being here. Great to be here. 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 think, you know, just to start off with clarifying terminology, microbiome and microbiota quite often are used to refer to our microbial community interchangeably.

0:43And I'll probably switch between those two terms today. The other important thing to realize is that these microbes are 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. basically anywhere that the environment can get to in our body, which includes inside our digestive tract, of course, is, you know, colonized with microbes. And 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 the density of this community is astounding. You start off with a zoomed out view and you see something that looks like, you know, fecal material that digests inside 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.

1:33It's a super dense bacterial community, almost like a biofilm, to the point where it's thought that, you know, around 30 % of fecal matter is microbes, 30 to 50%. So, you know, it's, it's an incredibly dense microbial community. We're talking of, you know, trillions of microbial cells. And all those microbial cells, if you start to get to know them and see who they are, break out in the gut probably to hundreds to a thousand species. 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 different.

2:15There are eukaryotes. So, you know, we commonly think of eukaryotes in the gut as, you know, something like a parasite. But there are eukaryotes, there are fungi, there are also little viruses, there are these bacteriophages that infect bacterial cells. And those actually outnumber the bacteria like 10 to 1. So they're just everywhere there. They kill bacteria. And so there's these really interesting predator-prey interactions. But overall, it's just this really dense, complex, dynamic ecosystem. Are microbiota seen in newborns? In other words, where do they come from? And dare I ask, what direction do they enter the body?

3:03There have been some studies that have looked at whether there are microbes in the womb and microbes colonizing the fetus. And there's some debate about this. But overall, it looks like that's not a big part of the equation of microbial colonization. And 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. There also are a lot of different trajectories that developmental process can take because our microbiota is so malleable and so plastic.

3:37And 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. Infants that are born by C-section actually have a gut microbiota that looks more like human skin than it does like either the birth canal, the vagina microbiota, or the mother's stool microbiota. 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, there are all these factors that really can change that developmental process and really change your microbial identity eventually in life.

4:24We 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 with early in life can really change your biology. How do I know if my microbiome is healthy or unhealthy? Context matters a lot. What's healthy for one person or one population may not be healthy for another person or population. And I will say that there's no single answer to this, but there's some really important considerations. Perhaps the best way to start talking about this is to go back to the inception of the Human Microbiome Project, which was this program that NIH started.

5:10They invested a lot of money in 2008, 2009 for really propelling the field of gut microbiome research. It was becoming evident at that point that this was not just a curiosity of human biology, that it was probably really important for our health. Through those studies, we really started to get the image that there is this tremendous individuality in the gut microbiome. And so it's really hard to start drawing conclusions after initial pass of that project of what is a healthy microbiome. But the other thing that we started to realize at the same time, there were studies going on documenting the gut microbiome of traditional populations of humans, hunter-gatherers, rural agricultural populations.

5:58and 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. And so, one possibility is that in the industrialized world, we have 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. But another possibility is that this is a microbiome that's gone off the rails, that it is deteriorating in the face of antibiotic use and all the problems associated with an industrialized diet, Western diet.

6:45And that even though the Human Microbiome Project documented the microbiome of healthy people, healthy Americans that what they really may have been documenting there is a perturbed microbiota that's really predisposing people to a variety of inflammatory and metabolic diseases. By now, I'm sure that many of you have heard me say that I've been taking AG1 for more than a decade. And indeed, that's true. The reason I started taking AG1 way back in 2012, and the reason why I still continue to take it every single day, is because AG1 is, to my knowledge, the highest quality and and most comprehensive of the foundational nutritional supplements on the market.

7:27What that means is that it contains not just vitamins and minerals, but also probiotics, prebiotics, and adaptogens to cover any gaps that you might have in your diet, while also providing support for a demanding life. Given the probiotics and prebiotics in AG1, it also helps support a healthy gut microbiome. The gut microbiome consists of trillions of little microorganisms that line your digestive tract and impact things such as your immune status, your metabolic health, your hormone health, and much more. Taking AG1 consistently helps my digestion, keeps my immune system strong, and it ensures that my mood and mental focus are always at their best.

8:02AG1 is now available in three new flavors, berry, citrus, and tropical. And while I've always loved the AG1 original flavor, especially with a bit of lemon juice added, I'm really enjoying the new berry flavor in particular. It tastes great, but then again, I do love all the flavors. If you'd like to try AG1 and try these new flavors, you can go to drinkag1.com slash Huberman to claim a special offer. Just go to drinkag1.com slash Huberman to get started. If my gut microbiome was dysbiotic, it was off early in life, can I rescue that through proper conditions and exercise? Or is there some sort of fixed pattern that's going to be hard for me to escape from?

8:44Yeah. There's a big field that's emerging now that, you know we refer to as kind of reprogramming the gut microbiome and the issue that i think we're seeing in the field is that microbiomes quite often whether they're diseased or healthy exist in stable states they kind of tend towards this well that has gravity to it in a way biological gravity where it's really hard to dislodge that community from that state so even individuals for instance, that get antibiotics. You take oral antibiotics, the community takes this huge hit. We know that a bunch of microbes die, the composition changes, and that represents a period of vulnerability where pathogens can come in and take over and cause disease.

9:33But 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. We know with dietary perturbations, quite often you'll see a really rapid change to the gut microbiome. And then it's almost like a memory where it snaps back to something that's very similar to the original state, even though the diet remains different. And so there's this incredible, what we refer to as resilience of the gut microbiome and 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 healthy microbiome, but it does mean that we need to think carefully about 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.

10:30And one of the kind of simplest and nicest examples of this is an experiment that we performed with mice where we, you know, we're feeding mice a normal mouse diet, a lot of nutrients there for the gut microbiota, things like dietary fiber. And we switched those mice, half the mice to a low fiber diet. And we were basically asking the question that, you know, if you switch to kind of a Western like diet, a low fiber, higher fat diet, what happens to the gut microbiota? And we saw the microbiota change It lost diversity. It was very similar to what we see in the difference between industrialized and traditional populations.

11:11But when we brought back a healthy diet, a lot of the microbes returned. 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, we saw this progressive deterioration over the course of generations where by the fourth generation, the gut microbiome was a fraction of what it originally was. Let's say 30 % of the species only remained 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.

11:56So in that case, it's a situation where a new stable state has been achieved. 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 the control experiment of 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 your question of 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.

12:42And 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 nourishing those microbes with the proper diet. What's the idea about cleanses and fasting as it relates to the health or the dysbiosis of the microbiota? Yeah. I mean, we know that like, 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.

13:16So if you're in the process of acquiring a really good microbiota and you know how to do that, then the flushing everything out is great. Otherwise, what is happening is you're kind of leaving rebuilding of the community to chance. Like, what is it? And so, you know, what microbes are going to colonize? Who's going to take up space after you do this flush or cleanse? And, you know, that I think it's a little bit like playing Russian roulette. You may end up with a good microbial community in there afterwards. You may not. 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.

13:55It sounds to me that avoiding processed foods is a good idea. Or heavily processed foods in general. And I mean, not that the occasional consumption is necessarily bad, but consuming processed foods is just bad for the microbiome. Can we say that categorically? For sure. Yeah, you're exactly right. And we can break down, 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, the plant-based diet, if you're eating a bunch of complex, you know, fibers that feed your gut microbiota, your gut microbiota produces these substances called short-chain fatty acids, things like butyrate.

14:37And 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. Your gut microbiota is 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. Now, processed foods, I think is this other dimension where you have all of these weird chemicals, artificial sweeteners, weird fats, a lot of refined, simple nutrients.

15:15The 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 emulsifiers, these compounds that that are put in processed foods to help them maintain shelf stability so things don't separate. And so all the moisture content is retained appropriately. 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.

15:50And in animal models, we know that can lead towards metabolic syndrome as well. So 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. I do want to make sure that we distinguish artificial sweeteners from non-caloric plant-based sweeteners. Do we know anything about plant-based non-caloric sweeteners or low-caloric sweeteners? 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.

16:24And so it's depending upon the mechanism of action by which these sweeteners that are not sugar are impacting our biology, it may be that those are actually less negative or more healthy than the ones that are artificial just because it requires less of them in the food for us to perceive that sweet taste. Historically, there are, I think, traditional populations that use these, for instance, to sweeten different foods that our bodies just kind of know how to deal with those compounds better than the ones that are synthetic. But I think the, you know, the studies still need to be done. Do you actively avoid artificial sweeteners, sucralose, aspartame, saccharin, you personally?

17:09Yeah, you know, I do. I avoid them, but I'm not, you know, I think that just doing things in moderation makes it a lot 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 a pretty flexible eater. I don't believe that having an artificial, you know, having a diet Coke will, you know, somehow cascade into some terrible disease or something like that. I'd like to take a quick break and acknowledge our sponsor, Juve. Juve makes medical grade red light therapy devices. Now, if there's one thing that I've consistently emphasized on this podcast, it is the incredible impact that light can have on our biology and our health.

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18:28Personally, I use the Juve whole body panel about three to four times per week for about five to 10 minutes per session. And I use the Juve handheld light both at home and when I travel. If you'd like to try Juve, you can go to Juve, spell J-O-O-V-V.com slash Huberman. Right now, Juve is offering a special holiday discount of up to$600 off select Juve products. Again, that's Juve, J-O-O-V-V.com slash Huberman to get up to$600 off. I'd love to talk about fiber and fermented foods because you and Chris had what I think is a really interesting and exciting paper comparing inflammatory markers of people who ate a certain amount of fiber or a certain amount of these fermented foods.

19:11Let me take, before I dive into that study, let me take a step back because I think the reason that we did this study goes back to this kind of epiphany that 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 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 this is largely the mindset of Western medicine and largely born out of the era of infectious disease.

19:48You wait for an infection to start a bacterial infection. you treat with antibiotics and 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 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 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.

20:25And 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 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 at the basis of a lot of these diseases, inflammatory chronic diseases. And so 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 due to all of the things that go along with an industrialized lifestyle, antibiotics and so forth.

21:17Maybe 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 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 to develop an inflammatory disease. Our flagship study, we wanted to understand if we put people on a high fiber diet, how would that affect their microbiome and immune system?

21:59And if we put them on a high fermented food diet, a diet rich in live microbes and all the metabolites that are present from fermentation and foods, how would that change microbiome and immune system? The idea was in the case of the high fiber diet, just increasing plant-based fiber. So can you eat more whole grains, more legumes, more vegetables, nuts, get the fiber up in the range of, you know, from 15 to 20 grams per day, up to over 40 grams per day. So can you kind of double or more the amount of fiber that you eat per day? The people that were eating the high fermented food diet, they were instructed to basically eat foods that you could buy at a grocery store that were naturally fermented and contain live microbes.

22:45Yogurt, kefir, sauerkraut, kimchi. We instructed people to eat non-sweetened yogurts. A huge pitfall in this area is you can have a yogurt loaded with bacteria, kind of the base of what's healthy, and then a ton of artificial flavoring and sugar loaded on top of that. Manufacturers put a ton of sugar in after the fact to kind of mask the sour taste of fermented foods, which is hard for some people to become accustomed to. Getting used to that sour flavor is difficult, but people really should try to stay away from those fermented foods that are loaded with sugar. And that's what we instructed people in this study.

23:21A lot of people shy away from the high quality fermented foods because they can be quite costly. I'll just refer people to a resource in Tim Ferriss' book, The 4-Hour Chef, he actually gives an excellent recipe for making your own sauerkraut, which basically involves cabbage and water and salt, but you have to do it properly because you can grow some, not necessarily lethal, but some somewhat dangerous bacteria if you don't scrape off the top layer properly. But he gives beautiful instructions for how to do this in vats. You can make large amounts of truly fermented sauerkraut just from cabbage, water, and salt if you're willing to follow the protocol.

23:59You know, if you can get your hands on a SCOBY, kombucha is another one that's super simple. You can grow your own. 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, a symbiotic community of bacteria and yeast that you, you know, you, you brew tea, you add sugar to it and you put the SCOBY in and you wait a week or two, depending upon the temperature. And you, then you just, you know, move the SCOBY over to a new batch and you're old, you know, what the SCOBY was in is kombucha and it's, it's wonderful.

24:31So how much fermented food were they consuming? Eating servings, ounces, how many times a day, early day, late day? The general instructions were for people to eat as much fermented foods as possible. More is better. People during the height of the intervention phase were up over six servings on average per day of fermented foods. So kind of two servings at each meal. And the, you know, ounces or weight or size, it really depended on what the fermented food was. And we just told them to stick to what was a recommended dose on the package that they were buying. for kombucha would be like a six to eight ounce glass sauerkraut, like a half cup or something like that.

25:12And same with yogurt. The big signal really was in the fermented food group. We saw all the things that you would hope to see in a Western microbiota and Western human. We saw this increase in microbiota diversity over the course of the six weeks while they were consuming the fermented foods. We can't always say that higher diversity is better when it comes to our microbial communities. We know there are cases, for instance, bacterial vaginosis where higher diversity is actually indicative of a disease state. But we know in the context of the gut and for people living in the industrialized world, higher diversity is generally better.

25:49We know that there's a spectrum of diversity. People with higher diversity generally are healthier. If you can push your diversity higher, you're in better shape. And so we saw that increase in diversity. And then the major question is what happened to the immune system as these people were increasing their gut microbiota diversity through the fermented foods. So we did this massive immune profiling and we see a couple dozen immune markers, inflammatory markers, decrease over the course of the study. So we measure these at multiple time points throughout the course of the study. And there's kind of this stepwise reduction in things like interleukin-6.

26:27and interleukin-12, a variety of kind of famous inflammatory mediators. And then even if you go into the immune cells and you start looking at their signaling cascades, we see that those signaling cascades are less activated at the end of the study compared to the beginning of the study, indicating an attenuation of inflammation. So kind of exactly what we would hypothesize would lead to less propensity for inflammatory disease over time. That's a huge extension of a very short study. Did people say they were feeling better in any way? And if so, what did you observe? And again, we're highlighting these as ANIC data.

27:05You know, tons of people say they have more energy, they think more clearly, they sleep better. And it's really hard to uncouple like, is this because, you know, these people have taken charge now of what they're eating and just feel better in general for being in control of kind of what they're doing? Or is there this cascading set of effects that are actually kind of emanating from the gut-brain axis. And I should say, you know, the list of this goes on and on. There are people who claim that their complexion improves and that their, you know, allergies, and there's probably all sorts of ripple effects.