Essentials: Build a Healthy Gut Microbiome | Dr. Justin Sonnenburg

Welcome 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 opthalmology 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.

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. And I'll probably switch between those two terms today.

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. Basically anywhere that the environment can get to

mouths. They're on our skin. 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 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. You start off with a zoomed out view and you see something that looks like, you know, fecal material, the digest 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 bofilm 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 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

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. Most of these are bacteria. Um but there are a lot of

thousand species. Most of these are bacteria. Um but there are a lot of other life forms there. There are archa which are little microbes that are bacteria-like but they're they're different. Um there are uh ukarotes. So

you know we commonly think of ukarotes in the gut as um as you know something like uh a parasite but um there are ukarotes, there are fungi, there are

also little viruses. There are these bacteria phages that infect bacterial cells. And so um and and those actually outnumber the bacteria like 10 to one.

cells. And so um and and those actually outnumber the bacteria like 10 to one.

So they're just everywhere there. They kill bacteria. Um and so there there's these really interesting predator prey interactions. But um overall it's just this really dense, complex, dynamic ecosystem. >> Our 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? Um there have been some studies that have looked at um whether there are microbes in the womb and and microbes colon 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 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 brush

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 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. Infants that are born by C-section actually have a um gut

vaginally. 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 vag

the birth canal, the the vagina microbiota or um the mother's um stool microbiota. Compound on top of that whether you're breastfed or formulafed,

microbiota. Compound on top of that whether you're breastfed or formulafed, 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

antibiotics. Um there are all these factors that really can change that developmental process and really change your microbial identity eventually in

life. We know from animal studies that depending upon the microbes that you get

life. 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 trajectory. 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 are

population. And I will say that there's no single answer to this, but there are some really important considerations. 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

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. Through those studies, we really started to get the image that there is

health. 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. 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. 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

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 perturb herbed microbiota that's uh really predisposing

people to a variety of inflammatory and metabolic diseases. If my gut microbiome was um disbiotic, 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? Yeah, 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

the issue that I think 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 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-anibiotic 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

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 you know, one of the kind of simplest and nicest examples um of this

state. And you know, one of the kind of simplest and nicest examples um of this is a an experiment that um we performed uh with with mice where we you know,

we're 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 low- fiber diet. And we were basically asking the question that, you

know, if you switch to kind of a westernike 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 um in the

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 where by 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 remained um, something like

originally was. Let's say 30% of the species only 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. So, in

that case, it's 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 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

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

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

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. >> What's the idea about cleanses and

fasting as it relates to the health or the disbiosis 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. So if you're in the process of acquiring a really good microbiota and

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 going to 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

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.

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. It sounds to me that avoiding processed foods is a

good idea or heavily processed foods in general. And I mean, not that you know, the occasional consumption is is um necessarily bad, but consuming processed foods is just bad for the microbiome. Can we say that categorically?

>> For sure. Okay, 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

that. But the flip side of this, 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

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. your gut microbiota is just producing this vast array of

metabolism. your gut microbiota is just producing this vast array of fermentation endproducts 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, 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 Whitesman

metabolic syndrome. Actually, there's been beautiful work out of the Whitesman Institute on this. And then emulsifiers, these compounds that are put in processed foods to help them maintain shelf 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 mucous 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.

>> I do want to make sure that we distinguish uh 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 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

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. Um historically there are I think traditional populations that use these

taste. Um historically there are I think traditional populations that use these for instance to sweeten um you know 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 the studies still need to be done.

>> Do you actively avoid artificial sweeteners sucralose aspartame saccharine you personally? Yeah, you know, I do I I avoid them, but I'm not I 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 I'm a pretty flexible eater. I

don't believe that having an artificial, you know, having a diet coke um will, you know, somehow cascade into some terrible disease or something like that.

I'd love to talk about fiber and fermented foods because you and Chris had a what I think is a really interesting and exciting paper comparing inflammatory markers of people who ate a certain amount of fiber or certain

amount of of these fermented foods. 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 goes back to this 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 amilarate 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

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 um is not really very effective in the context of inflammatory western diseases, autoimmune diseases, metabolic syndrome, uh heart diseases and inflammatory

disease. You know, the list goes on and on. And so we started to think a lot

disease. You know, the list goes on and on. 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

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 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

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 um 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 to develop an inflammatory disease. Our flagship study, we wanted to understand if we put people on a high-fiber diet um how would that affect their microbiome

and immune system? And if we put them on a high fermented food diet, a diet rich in live microbes and all the metabolites that um are present from fermentation in 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. 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 uh diet um they were

day? the people that were eating the high fermented food uh diet um they were instructed to basically eat um you know foods that you could buy at a grocery

store that were naturally fermented and contain live microbes. Yogurt, kefir, uh sauerkraut, kimchi. We instructed people to eat nonsweetened yogurts. Um, a huge

sauerkraut, kimchi. We instructed people to eat nonsweetened yogurts. Um, 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 like 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 is difficult, but people really should try to stay away from those um fermented foods that are

loaded with sugar. And that's what we instructed people in this study. 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 Ferrris's book, The

quite costly. Um, I'll just refer people to a resource in Tim Ferrris's book, The Four Hour Chef. He actually gives an excellent recipe for making your own sauerkraut, which basically um involves cabbage and water and salt, but you have

to do it properly because you can grow some um not necessarily uh 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, you know, if you can get your

salt. If you're willing to follow the protocol, you know, if you can get your hands on a scobby, kombucha is another one that's super simple. It's >> you can grow your own.

>> 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 this it's a scobby, a symbiotic community of bacterian yeast that you, you know, you brew tea, you add sugar to it, and you put the scobby in and you

wait a week or two depending upon the temperature and you then you just, you know, move the scobby over to a new batch and you you're old. You what the scobby was in is kombucha and it's it's wonderful. >> So, how much fermented food were they

consuming in servings, ounces? um 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 um during the height of the intervention

possible. More is better. People um 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 the package that they were they were

buying. You know, for kombucha, it' be like a six to eight ounce glass um

buying. You know, for kombucha, it' be like a six to eight ounce glass um sauerkraut, like a half cup or something like that. And same with yogurt. The 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 um 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. Um but we um know in the context of the gut and for people living in the industrialized world, higher diversity is generally

better. Um we know that there's a spectrum of diversity. People with

better. Um we know that there's a spectrum of diversity. People with

higher diversity generally are health 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. Um we so we did the um this massive immune profiling and we see

fermented foods. Um we so we did the um this massive immune profiling and we see you know a couple dozen immune markers inflammatory markers decrease over the course of the study. So we multi we u measure these at multiple time points

throughout the course of the study and there's kind of this se step-wise reduction in things like interlucan 6 and um you know interlucan 12 a variety of kind of famous inflammatory mediators um 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, so kind of exactly what we would hypothesize would lead to

inflammation. So, so kind of exactly what we would hypothesize would lead to less propensity for inflammatory disease over time. That's a a huge extension of a very short study.

>> But did people say they were feeling better um in any way? And if so, what did you observe? And again, we're highlighting these as an data.

>> You 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 um set of effects that are actually kind of emanating from the gut brain axis and and I should say you know the the list of this goes on and on. There are people who claim that their complexion improves and that their

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 if you can affect your inflammation. you c we know that you can affect your cognition. We

know that you can affect your you know your your skin and and inflammation that's occurring on your skin. So so I really think that there is a basis for a lot of those anecdotes. It may just be hard to see in a short study and in um a

small you know a small cohort of people over a short period of time. you know,

we also have a um a standardized um uh stool measure that people use and there was um you know, kind of less constipation, better bowel movements over the course of both of these interventions. So, it did seem like bowel habits improved, which um a lot of

interventions. So, it did seem like bowel habits improved, which um a lot of times can lead to better moods, but that we weren't able to to measure that.

>> What sorts of interesting things did you observe in the fiber group? data seem to be telling us that if you start off with a diverse microbiota, maybe one that's better equipped to degrade a wide variety of of dietary fiber, you're more

likely to respond positively to it. If you have a very depleted gut microbiome, you're not as likely to be able to respond to it. And thinking back to that experiment that we talked about before with the multigenerational loss of of

fiber fermenting microbes in in mice that were fed a western diet. Um it it may be that many of us in the industrialized world have a microbiome that's so depleted now that even if we consume a high fiber diet at least for a

short period of time we don't have the right microbes in our gut to degrade that fiber. And this has actually been observed by other groups. beautiful

that fiber. And this has actually been observed by other groups. beautiful

study out of University of Minnesota looking at immigrants coming to the United States and you know within 9 months but certainly over the course of years immigrants that come here lose um a lot of the diversity in their gut

microbiome but a lot of the fiber degrading capacity in their gut microbiome too. So it could be that over time this becomes a one-way street and

microbiome too. So it could be that over time this becomes a one-way street and it's hard for us to recover um the the microbes that that actually can degrade the fiber. And I think that this probably intersects with sanitation in

the fiber. And I think that this probably intersects with sanitation in our environment and the fact that we don't have access to new microbes that might help us degrade the fiber that we actually um you know have lost these microbes and they're in some ways irreoverable without deliberate reintroduction of fiber degrading

microbes. >> Well, you have children. Did you do you encourage them to uh interact with pets

microbes. >> Well, you have children. Did you do you encourage them to uh interact with pets and dirt and >> absolutely stuff in the environment provided that stuff wasn't immediately toxic?

>> Yeah, exactly. Certainly just with infectious diseases in general, it's really important to be aware of um you know the the possibility for compromising your health through the spread of germs. And so that that is

just you know handashing is important and we have to be careful with you know um the the spread of germs. But I do think that um you know the sanitation sanitization of our environment um has gone overboard with the you know um

various things being impregnated with antibiotics you know shopping carts and things like that and toothbrushes and you know it's it's like antibiotics and and um you know things for killing microbes are are everywhere. And when we

were raising, you know, when our daughters were young and we were we were making these decisions, the calculations that we would make were really um one uh how likely are they to encounter a disease-causing microbe? If we've been

out, you know, on a hike or in our garden, you know, just kind of working in the dirt or whatever, maybe it's not as important to wash your hands before you have lunch, even if there's a little bit of dirt on them. um if they've been in a public playground where maybe there's um other kids with germs or

maybe even chemicals like pesticides and and herbicides that are being used um maybe it's more important than to wash your hands. You know, certainly if you've been in the grocery store or on the subway, probably a good idea to wash your hands, but I so I think you really need to think about kind of the the

context of it. And um exposure to microbes uh from the environment is likely an important part of um educating our immune system and keeping the proper balance in our immune system and it's just a matter of figuring out the right way to do that safely.

>> What what's the thought about probiotics for for the typical person that's not recovering from a round of antibiotics or that um has been prescribed them?

>> The So I think the the first thing to say is buyer beware because it's a supplement market. It's largely unregulated and that means that there

supplement market. It's largely unregulated and that means that there are a lot of bad products out there and a lot of products that um even though they're not intended to be bad, just don't have great quality control. There

have been several studies that have taken off the uh over-the-counter just kind of off-the-shelf probiotics, surveyed what's in there based on sequencing, and shown that they what is in there does not match what's on the

label. So there there are places that probiotic companies can send their

label. So there there are places that probiotic companies can send their product to have it independently validated. So you want to look for that sort of validation on on a product. Um there also are names that are just very

wellknown and um you know it's uh you know their reputations are on the line. So they probably invest a little bit more in quality control than maybe

line. So they probably invest a little bit more in quality control than maybe some of the other lesserk known names because there's such a huge range of products and because each person is their own little caper when it comes to

the microbiome. It's really hard to know um whether there are great products for

the microbiome. It's really hard to know um whether there are great products for a given indication. And the really good advice that I've heard is try to find a study that supports in, you know, a really well-designed study. And this is

very hard for people who aren't scientists to evaluate, but so, you know, if you're experiencing a medical problem or want to consult a doctor, um, the, you know, that that might be helpful. But finding a study where a

specific probiotic has successfully done whatever it is you're looking for and then sticking with that probiotic is really the best recipe for as a as a place to start in this space, I think. >> And what about prebiotics? Because there

are a number of um reasons why I can imagine that prebiotics would be beneficial.

>> The studies that have been done on prebiotics, the it's really kind of a a mixed bag of results. The um there have been studies done with um purified fibers where you actually see microbiota diversity plummet over the course of the

study because um you get a very specific bloom in a small number of bacteria that are good at using that one type of fiber and that's at the expense of all the other microbes that are in the gut. And so, um, so it's really hard to replicate

with purified fiber what you'd get, for instance, at a salad bar in terms of the array of complex carbohydrates that you would be exposing your microbiota to.

And I think the kind of um uh broad view of this in the field is that consuming a broad variety of plants is and and all the the diverse fiber that

comes with that is probably better in fostering diversity in your microbiota than purified fibers. Now, there are um again a lot of people who benefit from purified fibers either for GI motility um or or for other aspects of of GI

health problems that they've been experiencing. Again, I think it's the type of thing where you have to um try to find the thing that that's right for you. But there um there also are studies that suggest that if you layer rapidly fermentable

you. But there um there also are studies that suggest that if you layer rapidly fermentable um fibers on top of a western diet, you actually can um result in in weird

metabolism happening in your liver because you have this incredibly rapid fermentation of fiber along with a lot of fat um coming into the system. At

least that's the that's the theory. And in a mouse study that was published a few years ago, they actually see that a subset of the mice develop hepaticellular carcinoma when they're fed a a highdose prebiotic liver cancer

on top of a um on top of a western diet. So whether that's representative of human biology, we don't know. But um you know purified fibers are definitely very different um both in terms of the diversity of structures but also in

terms of how rapidly they're fermented in the gut because um you know if you are eating plants the complex structures there really slow the microbes down in terms of fermentation and you end up with a slow rate of fermentation over

the length of your colon as opposed to this big burst of fermentation that can happen if you eat something that is highly soluble and and easily accessed by the microbes.

>> So, you've covered a tremendous amount of information and I'm incredibly grateful. Where can people find out more about the work that you're doing? Uh, we

grateful. Where can people find out more about the work that you're doing? Uh, we

can certainly provide links and you have a book on this topic. So, could you tell us about the book where we can f learn more about the Sonnenberg lab and the work that you're doing? Um, maybe people will even try and enroll in some of these studies.

>> Um, yeah. So, uh, Erica, my wife and I wrote a book called The Good Gut. And um

that that really was a um response to how we were changing our lives in response to to being in the field being very familiar with the research seeing that a lot of our friends that weren't studying the gut microbiome but were very wellinformed many of them scientists were not doing the same

things we were doing and it was very clear that it was just the um lack of information funneling out of the field to other people. And so we wanted to um make that accessible to people who are not microbiome scientists. And then you

know in terms of kind of connecting with our research certainly there's the center for human microbiome studies at Stanford which is kind of our home base for doing a lot of these dietary interventions. We list the studies there um give more information on what we're doing and then we have a lab website too

that people can go to and read more about our research and we're always looking for participants for our studies. Thank you so much for your time and for the work you do and I hope we can do it again. >> Thanks Andrew. This was a great conversation. >> Terrific.

conversation. >> Terrific.