Is your gut microbiome preventing weight loss? | Dr. Suzanne Devkota and Prof. Tim Spector
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Welcome to ZOE Science and Nutrition, where world-leading scientists explain how their research can improve your health. We can all agree belly fat is stubborn, but it also stores excess energy, produces essential hormones. Too much could lead to serious health issues. Yet the constant barrage of messages to eliminate it overlooks the reason why it's there in the first place. New research reveals that gut bacteria may play a part.

Certain bacteria may make weight loss easier, while others contribute to obesity. For some, belly fat might even be a protective response to harmful bacteria that escape the gut. So could our gut bacteria be the key to achieving a healthy level of belly fat? Today's guests are at the forefront of this groundbreaking research. Dr. Suzanne Devkota is the Director of Microbiome Research at Cedars-Sinai Medical Center and a key figure in this rapidly evolving field.

She's one of a small group of scientists running cutting-edge studies on gut bacteria, how they impact disease, and how they might also heal us. She's joined today by another pioneer in the world of gut microbiome research, Professor Tim Spector. Tim is one of the world's top 100 most cited scientists, a professor of epidemiology, and my scientific co-founder at Zoe. You'll leave today's episode with a new perspective on belly fat and tips for supporting the bacteria living beneath it.

And if you're interested in learning about the foods that nourish your unique gut microbiome, you should check out Zoe's personalized nutrition program. Your Zoe program starts when you send us a stool sample, which we analyze with the world's most advanced gut health tests to understand the exact bacteria that you have in your gut

Our scientists have identified 50 bacteria linked with positive health outcomes and 50 linked with negative ones. We'll tell you which ones you have and exactly what to eat to feed the good ones. Why should you trust us? ZOE has the largest microbiome database on the planet and the most advanced home gut health test in the world. So you could be sure that your personalized nutrition program can help your gut help take care of you.

Visit zoe.com to get your at-home test kit and personalized nutrition program today. Now let's get on with today's episode with Dr. Suzanne Devkota and Professor Tim Spector. Suzanne, thank you for joining me today. Thank you.

And Tim, always fantastic to have you with us. Great to be here. So Suzanne, we have a tradition here at Zoe where we always start with a quick fire round of questions from our listeners. We have some very strict rules. You can say yes or no, or if you absolutely have to, a one sentence answer. And I can see you laughing because it is designed to be really hard for researchers. Are you willing to give it a go? Sure. Brilliant. And Tim, I know you know how to do this one. All right, starting with Suzanne.

Could gut bacteria cause belly fat to expand? Yes. Does belly fat play a role in our immune system? Yes. Tim, could too much belly fat increase our risk of disease? Yes, even if you're thin. And finally, Suzanne, what's the most surprising thing that you found in your research on the gut microbiome and belly fat? That bacteria actually can live in fat tissue.

And I know we're going to get into that and like your really amazing research. I think I want to begin though, by just recognizing that body fat is a very sensitive issue, right? We're constantly surrounded with marketing messages that it's shameful not to have a perfect body. Meanwhile, we also know that there are people all over the world who are still afraid of eating fat for fear that that fat is going to immediately be stored on their body and specifically on their belly. So this whole topic is definitely sort of full of this sort of anxiety. So I

so i'd love to just take a step back and sounds really obvious but what is belly fat

So belly fat, I mean, you can observe it externally. There's fat that just accumulates in the midsection. But when we talk about it, I think in medical and scientific terms, we're thinking the deeper layers. We really are looking at the fat that's attached to our internal organs. We call that visceral fat. And the fat, that visceral fat that's attached to the organs, when it expands with activity,

overnutrition and often in obesity, the risk for cardiometabolic disease significantly increases with more visceral fat accumulation.

The belly fat often that we might see externally can be what's called subcutaneous fat. And that's a completely different depot of fat that does different things metabolically. Cosmetically, we don't like it, but it actually is less harmful than the internal visceral fat attached to our organs.

If I understand right, you're saying I could have fat just sort of stored right under my skin. And even if that's on my belly, it's not necessarily hurting me so much. But I could also have it sort of deeper into my belly and it's sort of around these organs. Why is that bad? When we chronically eat too much and we gain fat...

we need that excess calories to go somewhere. If they don't go into fat tissue, they'll go into places like the liver or places that can cause some serious problems metabolically. And so the subcutaneous fat underneath our skin tends to be the place where the excess calories will go first. Fat expansion is a healthy process. It's not something that we want to advocate, but it is the body's way of maintaining a homeostasis.

Often when you might exceed your capacity to store it in subcutaneous fat, you will also start to build it in the deeper fat attached to the organs. And fat now when it's attached to organs that carry out critical functions in the body like the gut or the kidneys or even the heart, there's a cross-communication that we still don't fully understand between fat tissue and the organs that can lead to kind of knock-on effects systemically.

It's harder to use that fat as well, isn't it? So there's a difference between the superficial fat under your skin, which actually is more readily burnt when you're exercising, for example, than the deeper fat. It's harder to get it out of your system once it's there. So there's that difference in sort of temporary fat, if you like, and more...

hard to shift fat. Yeah. So fat's not one thing. It's not just one big glob of fat in our bodies. It's actually partitioned in our bodies in an interesting way. When was the last time that you listened to your gut? You know, there's a lot of misleading health advice out there. And a lot of what we're told about food is frankly wrong. It's time we listened to what's right.

Zoe scientists are gut health experts. We have one of the world's largest microbiome databases and most scientifically advanced at-home gut health tests. This lets us provide personalized nutrition insights and advice that you can't get anywhere else. Listening to your gut starts with an at-home test kit that includes a metabolic fitness test to help you understand your body's responses to food. But it also includes a gut health test that helps you understand the good and the bad microbes in your gut.

Then what happens is Zoe's app uses your test results to create a personalized program, helping you build life-changing nutrition habits step-by-step. Gut health is central for good health. So listen to your gut and give Zoe a try by becoming a member. The first step is easy. Go to Zoe.com and use the code podcast to get 10% off.

As a Zoe member, you'll get the comprehensive at-home test kit and the personalized nutrition program. So go to Zoe.com and get 10% off with the code podcast. Now, back to the show.

So I actually have a personal story about this and it's right back to the very early days of Zoe because I had never really thought about my fat at all. I'd always been told that actually I probably needed to like put some weight on and as part of the initial clinical trials that we were doing with Zoe in the early days when about a thousand participants come into hospital get lots and lots of measurements taken and one of them was this scan which is called a DEXA scan where

Very cool. It looks at what's inside your body. So I thought that was quite exciting and I thought that I was going to get a really fantastic clean bill of health. And actually, I remember as I did it,

the nurse doing this test being like really surprised and looking at it really carefully and then pass it on and eventually I got the results back a little bit later and I remember Tim explained to me that basically I'm like thin on the outside and fat on the inside and actually I had a lot of fat layered into like this visceral fat you're talking about which is the first time I'd ever heard that that term and this was very bad news you were a toffee

I know. Thin on the outside, fat on the inside. Yeah, which a lot of people are, and in a way, don't realize that they have poor metabolic health because of that. And it's quite genetic as well. So it's seen quite a lot in Asian populations where they don't have external signs of fat, but on the inside, it's really important. So yeah, you were a great example, Jonathan. And it was a big shock to me, to be honest. It's like one of the things that really...

kickstarted my personal desire to really follow all the nutrition advice that we've sort of been working through with Zoe over the last few years because I sort of got interested in this actually because I'd had food intolerances. I know we're going to talk a little bit about your own experiences.

But actually that had pushed me to eating this very classic Western diet, huge amounts of sort of refined carbohydrate. And I'd assumed that it was having no impact on me. So it was really amazing to sort of realize that I was not as healthy on the inside as I had thought. And that's the first time I'd experienced this. So I think, is that very unusual to only have this visceral fat and not have lots of visible fat everywhere else across your body?

It's not unusual. As Tim mentioned, there's definitely subgroups of individuals and tends to be, there's some genetic association as well of individuals who are very thin. You would never view them as, who have type 2 diabetes are thin, but they're storing the fat that they eat, or it's actually not the fat that they're eating, it's largely the carbs that they're eating in their liver or in their visceral fat depot. So they won't look thin.

overweight or obese, but they may be just as unhealthy on the inside. And that's an area of research that's really growing right now. Why are some people depositing their fat in this way versus the way we traditionally think about fat deposition? And I think we can learn a lot from comparing the two types.

So I'd love to sort of go from this to like your own research on belly fat, because you've found this amazing way in which it might actually interact with our gut bacteria in like a very surprising way. And I know you specifically studied people with Crohn's disease, and I'd love for you to explain what that is. And then I think also expand to how that might apply to the rest of us. But could you maybe just start at the beginning, like,

Why did you choose to study people with Crohn's disease? What is it? In graduate school, I was in an inflammatory bowel diseases lab. But my background is actually nutrition and metabolism. So I was formally trained in studying metabolic diseases. And it's a long story, but I ended up in an inflammatory bowel diseases lab. And I said, okay, how can I bring these two worlds together? And so we really wanted to understand nutrition,

in chronic intestinal inflammation, but studying it through the lens of the microbiome. And how can the diets we eat shape the microbiome and then either

potentially drive or prevent inflammation in the gut. That got me into IBD and I continued that work until through today. And I have learned a lot about, you know, no disease is one thing. You know, there's many different subtypes of disease and it's true in obesity and diabetes and it's true in IBD.

And so I think that has been a big fascination for me in understanding where nutrition and the gut microbiome can help stratify these different subgroups. And IBD is really two diseases. It's Crohn's disease and ulcerative colitis. They affect different parts of the GI tract. They manifest differently. And Suzanne, the GI tract is? Oh, the gastrointestinal tract. So really your GI tract is from your mouth to your anus, the whole tube.

And Crohn's can affect anywhere in the GI tract, from the mouth to the anus. Ulcerative colitis affects the colon primarily. And we're interested in studying both of those, but we focus a bit more on Crohn's disease. And lots of people listening to this won't be familiar with Crohn's disease. So could you just help to sound very simply like...

What is going on? Is it very common? The epidemiology of it is very interesting. How, where in the world, you know, how it manifests in different populations. It's definitely most prevalent in Western populations, although it is increasing in countries that are becoming more Westernized. And diet is one of the things that is pointed to for that. Diet and lifestyle. So all the things that come with living a Western lifestyle, sedentary and poor diet and processed foods.

There is a genetic component to it. So we say that with Crohn's and colitis, it's a multi-hit disease. Not one thing will cause it. You need more than one thing. Often, it's a combination of genetics, microbiome, unusual immune response, and the environment.

And it could be any two or more combinations of those items can trigger the disease. Beyond that, we honestly don't know. For every person who comes in with a new diagnosis, what caused it are usually very different. And so it's really hard to say this causes IBD. Okay.

And could you give us a sense of what it's like to be living with Crohn's? Yeah, it's pretty awful. So chronic inflammation, you'll feel it. You'll have pain. You won't want to eat. Often individuals who have Crohn's or colitis tend to be thin just because they're still trying to figure out what food triggers they have. They don't know. So they just avoid to avoid the pain. It's a common, you know, we would all do that, I think.

Although it is kind of changing, there is more and more co-occurrence of obesity with IBD, but typically IBD patients are pretty lean because of the food avoidance. Also, you have to go to the bathroom very often. You might go 10, 12 or more times per day. So you always have to think if you go in a social outing or anywhere you are, where's the bathroom? How do you explain it to your friends? People are not often very comfortable talking about bathroom habits, so as that added layer of social outing,

discomfort to that as well. And then you're trying different medications. We still don't know. There's no one medication that works for every person. So often when you're newly diagnosed, you'll try one, it works for a while, and then it stops working and you try another and then another. And it's, I think, creates a lot of frustration for patients. Yeah. And I used to see

When I was a rheumatologist, it's an autoimmune condition. So in this big family of diseases where the immune system is attacking itself, it's got the wrong messages and therefore you end up attacking your own intestine. And you also get skin changes. You can attack your own skin. And arthritis was quite common. So about 10% or something like that of these people get quite bad, what we call seronegative arthritis.

Yeah, lots of things going on and there's lots of inflammation as well. And that makes generally people very tired. So that's the other sort of clinical thing you see in these autoimmune conditions is that the whole immune system is just overexcited and working hard all the time, which gives everyone fatigue as well as these specific gut problems. Absolutely. And another interesting aspect is that

External environmental changes can cause flares. So periods of high stress can cause individuals to flare when they were managed through medication. International travel, jet lag, things like that can cause people to flare. And those are interesting aspects that we still don't fully understand. So firstly, it sounds really tough. Secondly, I'd like to go and talk about this study because I think what's interesting is both what you found in this study, but also sort of

your belief that it has sort of much broader relevance, not just for people who are suffering from Crohn's, but from everybody else. So can we get into the study? Can you tell us about it? The study came about by kind of accident, as many do. I had been interested in looking at bacteria and fat tissue under this broad umbrella of just...

do bacteria leave the gut and go into other places? Which is a difficult question to address scientifically because you're always trying to manage contamination and things like that. But it has been observed by many, many people that bacteria can be recovered independent of sepsis, traditional blood infections of bacteria. People have reported recovering bacteria from the liver and other places. And so...

When I joined Cedars-Sinai in the gastrointestinal department, I was presenting some of our mouse work on bacterial translocation, actually in obesity.

And there was a colorectal surgeon in the audience who we work with closely today who said, what about creeping fat? And creeping fat is this very, and we'll talk about a little bit more, but this unusual manifestation of visceral fat attached to the gut that is unique to Crohn's disease. And it expands and wraps around the intestine when there is inflammation inside the intestine. It's been this long surgical mystery, but surgeons, when they

have to do surgery on a patient to remove part of their intestine, they look for this fat wrapping as a demarcation for where they should cut. And I said, well, that's really interesting, but where would I get these patients and these samples? And

And he said, well, I can get them for you. I see them every week. And that started probably an eight-year collaboration with Phil Fleschner. And we've collected probably over 200 patients. COVID slowed that down a little bit, but collected surgical samples from individuals who are going in to get part of their intestines removed. And people

People have been observing this for a long time. We know there's chronic inflammation going on. Could it be that microbes in the intestine are...

you know, leaving the gut because of this chronic barrier disruption. The intestine, when it gets inflamed, the barrier that keeps everything in the gut becomes loose and quote-unquote leaky. Normally, should any bacteria be coming out of my gut and going into the rest of my body? Well, that's something interesting that we found through this study is actually bacterial translocation is very normal.

in all of us. It happens. But when you have a normal working immune system, it's really of little consequence. You clear them and it's no issue. We would find bacteria in the fat of healthy tissues as well. You're saying in a normal healthy person, actually, some of the bacteria is like sneaking through the gut and into the sort of surrounds of my gut all the time. But it's just that my immune system is sort of zapping it before it goes off and

causes some horrible infection or something. Is that? Correct. Yes. And it's very different types of bacteria and healthy individuals that are translocating than what we see in our IBD patients. So it's a factor of having a competent immune system and actually different bugs that tend to be more quote unquote benign from our experience.

Bacteria are not trying to cause disease. A lot of what we study are accidents, being at the wrong place at the wrong time, but it persists and you get disease. Microbes really aren't trying to harm their host. It doesn't benefit them, but things happen. We might change our diet suddenly because we travel, and that can cause short-term defects in our gut barrier. It's not major consequence. We self-repair, but you can get these periods of leakiness

through simple things that we do in our day-to-day life. And those are probably the moments when bacteria translocate. But we really don't see, when we look at that tissue, any abnormalities like what we see in our Crohn's patients. So tell me what you found at the end of these eight years and all these samples. What was the discovery? So the big mystery was how does fat tissue on the outside of the intestine change?

know where this inflammation is on the inside of the intestine because the fat's only wrapping there. If you go just two centimeters over to the healthy gut, there's no fat wrapping there. So there's this migration and there's some signal, some communication between the gut and the fat.

And as a microbiome researcher, I said, could it be that microbes are the signal, whether microbes directly translocating or some byproduct from the microbiome seeping into the fat tissue? And so we asked, okay, let's take fat tissue from these patients. We had the gut and we had the fat attached. We sampled from the gut by sequencing and by cultivation in parallel because we wanted to see not just...

is there dead bacteria? We want to see if there are live bacteria there. So we would cultivate in parallel from the gut and the fat. And we were absolutely stunned to find the sheer numbers and diversity of different bacteria living in the fat tissue. And these were all organisms that live in the gut. So these were not skin bugs. These were not mouth bugs. These were the same bacteria that we're also recovering from the intestine. So

The fat tissue is not a normal home for bacteria. We confirm they are coming from the gut, but clearly some will go and die and some will go and survive. And we're really fascinated in the ones that are able to go and continue living.

And the work that we have continued from our originally published study is really diving deep into looking at these organisms that are surviving in fat tissue. And what we're finding is they have a very different genetic makeup than other bacteria in the gut. Namely, they have a much larger number of lipid metabolizing genes. So they can use fat more readily when presented with an environment that's rich in fat.

Suzanne, just help me to understand that for a minute. I think first of all, you're saying you did all this analysis and the answer is these bugs were still living in the fat outside of the gut. So they're like happily there, munching on, well, if this was me, me, effectively, is that what you're saying? Yes. You're fat. You're fat. And so they're like, especially when you said they're like lipid optimized, that science speak for like they eat fat.

fat particularly? They can use fat for fuel. Yeah. So they literally manage to escape from the gut, get into your fat, and then they just start eating you from the inside out, which sounds like it might be this amazing new drug, but I'm guessing it's not where you want it or in the right way, you know, before anyone is suddenly thinking this is... Right. It actually does the opposite thing. So bugs are not reducing your fat by eating it. First of all, you have

way more fat than the bacteria that are in there. So that's a big job. Don't worry, Jonathan. It's not all going to disappear. I wasn't worried about that. I was just thinking that before. You're blowing my mind here, so I just want to make sure I understand. Well, what we actually found is a feedback mechanism. So the fat, what it is actually doing is...

responding to the presence of microbes. So microbes, as I mentioned earlier, do not belong in fat tissue. And so the immune cells and the fat, you know, the stem cells and the fat and so on, when they see the bacteria there,

Part of the—and this is what we've been working on in the lab for some time—is the fat is actually acting like the body's Band-Aid. It is saying, okay, there's a source of microbes coming in. There's a breach somewhere. Let's migrate to that spot and—

grow around it. Okay, so as long as the microbes are actually stimulating this band-aid-like response. So it's, and because the way we discovered that was when we looked in the blood of these patients, we did not see bacterial products in the blood. They looked like healthy people. So Suzanne, you're basically saying that I'm actually going to grow more fat to sort of wrap around this bacteria that's where it shouldn't be, almost like sort of encase it. Encasing to protect the body from having bacteria spread everywhere.

And so this visceral fat attached to organs, what we're proposing is that it's not just

a VAT for excess calories when we overconsume. It's actually, fat is this very dynamic response of active tissue that's doing more in our bodies. One of the things, one of the other things it may be doing is responding to bacteria to protect the body. So it's part of the immune system, really. Yeah, and you could view it that way. Because I think this is a huge change in our idea of what fat is. And not only do we know it's metabolically active, but

But actually, it's a key part of our defense and immune system that it can deal with infections. And we've never thought of it in that way. And every year, we find out the immune system is actually more complicated than we gave it credit for. So it's yet another way in which our body reacts differently.

to threats of infection or autoimmunity. So yeah, that's really fascinating. And when we look at the immune milieu, the immune environment of the fat tissue, it looks completely different than healthy tissue. And it looks quite different than obese tissue as well. But we are studying that as well from gastric bypass patients, trying to see if what we're observing is...

more universal than just applied to Crohn's disease. But we definitely see immune cells aggregating throughout the fat tissue almost as like the sentinel sites for mobilization against further bacterial stimulation. A lot of really interesting adaptive immune cells that typically are not there. And are these microbes one that, as well as liking fat, do they like the inflammation? Because generally fat cells produce inflammation

these inflammatory chemicals, don't they? So we don't know if they like the inflamed environment, but we do know they have several immune evasion strategies so they can handle the inflamed environment much better than their counterparts. Do you think there's anything to learn from what you're seeing in these Crohn's patients about the way that this fat is not just this sort of passive store?

Is there anything to learn from that for the rest of us? I mean, that's one of our big questions. We think, yes. If you carry forward this hypothesis that fat is acting like a Band-Aid in our body, anywhere where you'll have a breach, you'll have some degree of fat expansion. And we've just been really interested in talking to surgeons, talking to other clinicians in different fields, in nephrology, kidney docs,

people who do heart transplants, and we ask, you know, what does the fat look like around these other organs? And we get, for example, in docs who do the kidney transplants, they always say the kidneys that have more fat wrapped around them, those individuals always do worse with their transplant. And so...

You shouldn't really have microbes in your kidneys, so it may not be as much of a direct microbial translocation. It could be a microbial signal. I don't know yet. But there is some relationship between this fat wrapping around other organs as well that has to do with what's going on in the organ itself. And so we are trying to collect samples from individuals so we can better understand the microbial component of this. And we did a podcast on...

and colon cancer and gut cancer. And one of the things that was mentioned, this is a podcast we did a little while ago, was some suggestion that potentially there might be bacteria being implicated in cancers that were not directly in the gut, but elsewhere. And I'm just listening to you talk about this translocation I've never heard of before, which is

very cool name. Is there any reason to believe that these bacteria might ever be getting past sort of immediately next to the gut wall and into the other, you know, you're talking about your kidneys or your heart or whatever?

There's a lot of people studying this right now. People have found not just bacteria, but fungi associated with tumors in cancers such as pancreatic cancer. And it's still a very, I think, early days to start making claims about this. But there appears to be something there, whether it is a microbial byproduct that is influencing the tumor environment. Because

microbes in the gut, they produce a lot of chemicals that will spread into the systemic circulation. And so how those affect distant sites, it may not be directly the bacteria translocating itself.

It might not be that the bacteria themselves are traveling through my blood to somewhere else. It might be they're creating chemicals in my gut. Those chemicals are going elsewhere. And that might then be triggers for some of the diseases that you might be studying. Exactly, yeah. Yes, chemicals or it could be their cell walls, which might be dead cells.

the proteins in them can travel out and act as a sort of immune stimulant. That's the other thing. Because people are actually looking at this in the brain, where we thought previously there was no way the gut and the brain could connect. But just as we're seeing it leaking out of the gut, these mechanisms going to different organs, nothing's off limits now. I think everyone needs to look everywhere and see where

these microbial signals are going. Could we step back for a minute and just help to understand a bit more this sort of broader role between bacteria and the immune system? Because you've sort of been focusing in on this particular part with belly fat, but then saying actually that that's just part of your immune system. What do we know about how the immune system is influenced by the gut microbiome?

Hugely. Most of our immune system is around our gut, our intestines. So 70% to 80% of all the immune cells in our body are actually in the lower intestine where all our microbes are, and that's not chance. So they're interacting all the time along this gut barrier. And it's a two-way communication, so they're always talking to each other via chemicals.

And this means that the immune system is sensing what the microbes are telling them all the time, which is a sort of gauge to the outside world. So, you know, what you're eating and the general health of the host is coming in all the time, these signals, which means that the immune system can then respond properly and see off threats of infection. Hi, I have a small favor to ask.

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So what do we currently know about the relationship between the immune system and the bacteria in our gut? We know they're intimately connected, and one is crucial for the other one functioning. We can't have a proper immune system without gut microbes and vice versa. We need both to survive, and they need to be seen as part of the same system. Over 70% of all the immune cells in our body are

concentrated in the lower intestine where all our gut microbes are. And they're constantly talking to each other, usually through chemicals that are produced from the microbes and then chemicals that are produced from the immune cells that are lining the gut.

And this means that we have an immune system that is protecting us, is making sure we don't overreact to allergy, foreign, you know, we don't think every time we eat food that it's an invader, so we don't overreact. It stops us getting autoimmune disease. And yet when there's an infection, we can really deal with it. And so the immune system is also important for us, surveillance, monitoring,

to help us fight accelerated aging, clear up damage from cells, fight cancer, does everything. And probably also is really important even for mental health as well because it controls inflammation and the idea that everything needs to be nice and calm for us to function efficiently.

And if things are out of sync, if the immune system has been getting messages from the microbes that things aren't quite right, it just ramps everything up a notch like the thermostat going up. So it's constantly looking for a fight. And that's really why there's such a close connection between them. So we never really realized this until just a few years ago about how important it is then

having really healthy gut microbes means that your immune system is then functioning optimally and then can help us. And in a way, why it fails and you get these autoimmune diseases like Crohn's or ulcerative colitis or allergies or whatever is part of this process, that something breaks down in this connection. So really important for all of us to have a really well-functioning immune system that

And which means that everything is efficient and we deal with problems, but then everything goes down to a nice quiet level. Whereas unfortunately, at the moment, most of us have a slight increased, you know, we're at

DEFCON level that's not the right one. We think there's some emergency going on in our bodies, and this is the sort of Western diet, Western way of life. Everything's a bit too stressed. The education of our immune system by a microbe starts from the moment we're born.

Looking at the early life, you know, microbiome, the first year of life tells you a lot about the interactions with the immune system and the gut microbiome. There's...

A lot of research now on this really critical window where a baby is born essentially sterile, no microbes until they get the first bugs from their mother. And immune cells, as more bacteria start to colonize the gut, so do more immune cells start to develop in the intestines as well.

And what's really interesting is there's this weaning period, weaning meaning when you go from breast or formula onto your native diet or table foods or adult diet. And that introduction of food, you had this rapid expansion of immune cells in the infant. And a lot of that is attributed to the more diverse foods you eat, the more diverse microbes that colonize the gut. And so there's this beautiful evolutionary conserved interplay between

microbes colonizing immune cells growing, which you want. That's a good thing. You want diverse immune cells so that when you grow up and see different foods, as Tim said, and different life exposures, you don't react and auto-react.

And so there's a lot of studies saying, okay, what happens when we mess that up and we give babies a lot of antibiotics early in life or something like that? And studies show that their immune system doesn't develop as well as their microbes don't also. And the hypothesis being, could that be predisposing infants, children to autoimmune diseases?

airway allergies, food allergies, and so on. So I think we study a lot what happens in adults, the defects that happen in adults, but a lot of it starts very early in life. That's probably why we've got so many allergies now that we didn't have

40, 50 years ago because breastfeeding rates have gone down and diversity of baby foods has gone right down. They're now getting ultra-processed foods very early on in life. And you combine that with cesarean sections plus antibiotics, it's a recipe for all these allergies we're getting, isn't it? Because as you said, a badly trained immune system that our ancestors didn't have. They had the perfect system to train it.

I'm always conscious when we listen to this, you know, having two children of my own that it's really hard to, you know, go through pregnancy, have a baby, get through this. And that often this podcast always feel like, and here there's yet more ways in which as a parent and often particularly as a mother, you feel like you're failing. So I always want to feel like, I think this is a hard, you know, it can feel hard and lots of people are trying really hard to do their best.

One of the things that I'm really struck by is how much on this podcast in the last year we've been talking about ultra-processed food and much more so than when we first started Zoe eight years ago. And thinking about my own experience with my youngest one, the extent to which we're all sort of pushed towards these sort of pre-packaged foods that say they're super healthy and have all these organic ingredients. But basically, you're giving them mush out of a packet and there's only about four types of mush.

And I think, Suzanne, you're telling me you really want to be giving your children a lot of different foods because that's what's needed to give them a lot of different bacteria. And you want to do that because that's what's needed. I've never heard this before. That's what's needed to get a lot of different immune cells, which set you up well for life. Yeah.

There are certain things you can, you know, you have to slowly introduce diversity in, but there's a window where you make choices about what you can expose a baby to and training a diverse palate, right? And spices and flavors and trained diversity in food, you know, preferences early actually will...

a more diverse diet going forward and then a diverse microbiome as a result. And so, yeah, trying to create as much diversity for a baby as possible. But I think you made a point that I really agree with and I always want to, you know, make sure parents don't always feel like they're doing something wrong. All of this research actually says the opposite. It's like, take it easy. If something falls on, let your kid play in the dirt. Let your kid lick stuff. Let your kid do stuff that would make you like,

like, you know, go crazy because that actually is giving them the exposure that they probably need to educate their immune system.

It's really fascinating, I think, this link between the food we're eating, the fact that we know that the food we're eating is not as good as we had in the past, the impact on our gut bacteria. A lot of listeners to this show are Zoe members. They'll have had their gut microbiome tested as part of this, and many of them will have it also retested after going through the membership of this app and sort of guide you to what to eat. And what's striking is, you know,

how many people living in the West have very poor microbiomes. So like the variety of the microbes they have, the number of the ones that are correlated with better health is like strikingly low. And then you're describing this link here between sort of the immune system and what happens else. And so we've definitely got ourselves into a difficult place, haven't we, that we now need to sort of wind out of.

Before I switch to therefore, what are the things you could do? I just wanted to finish on visceral fat. We've talked a lot about this study with Sudan. Tim, is there anything else we know about relationship between gut bacteria and visceral fat? We've been studying this for over a decade now. We started with the twins. And we know that the amount of visceral fat you put on does have a genetic basis. So the fact that you have a tendency to put it on even when you're not

overweight generally. It's all my parents' fault, is it? It's not all your parents' fault. It's half your parents' fault. Half my parents' fault, all right. Okay, it's half your fault. Yes, there's a genetic basis, but we also found that lots of microbe associations were associated with visceral fat as well. So of all the associations we found in the twins, and we looked at hundreds of different

what we call phenotypes, sort of everything ranging from depression to food allergies. And visceral fat came out as the strongest link

to gut microbes. So every study done has shown this. And it's stronger than your overall obesity level or adiposity, as we call it. So there's something very specific about visceral fat that is linked to the gut microbes. Over the last 10 years, we thought we had the answer. We knew exactly what the microbes were. And we put some of those microbes in mice and replicated those results.

But it turns out that as the microbiome sequencing gets better, we're finding more and more different species involved in this. So there isn't just one culprit. There's a whole series of them that seem to be associated with

this deposit of visceral fat that we don't really understand yet. And so I used to be quite certain, oh yes, we can get a magic bullet based on these microbes that could cure everybody. 10 years ago, we found some microbes that prevented visceral fat.

in mice. And so several companies started up trying to put this in your cereal and then, you know, every morning. Unfortunately, they've gone bust because it wasn't as simple as that, as usually is the case.

But I think there's a suite of them. There might be 100 of these microbes that are working together. But it's possibly what the chemicals they're producing that might be the key factor. We simply don't know. But we do know they're heavily involved in this whole process. And it's fascinating to work out why that might be. But if they are associated, it does mean we can do something about it because it means we can manipulate those microbes. Mm-hmm.

Tim, I think you have a big new paper that's coming soon looking at the latest data of associations between bacteria and the source of health outcomes. Can you tell us a little bit about that and sort of sneak peek? Yes.

Now, the ZOE database of all the members who've given their microbiome is over hundreds of thousands of individuals. And many of these we've linked to their diet and these other factors. And so we've put a lot of this together to work out new ways of scoring what is good and bad bugs. Because up to now, we've just used this, what's called diversity, which is the number of different microbes, which I think Susanna agrees is a rather crude tool that doesn't really sort of

help in a number of situations because you get good and bad ones lumped together. And what we've found is by getting all these outcomes, including things like visceral fat and body mass index and heart problems and blood cholesterol and blood pressure and

Everything bad about you, link that to foods that are associated with that and link to microbes that are also associated. We've come up with this cool way of finding what are the good and bad microbes that predict these outcomes. So this is a paper that's coming. But that first paper is mainly to give us a new way of looking at gut health.

through these really big, massive samples that finally are going to tell people how they can assess their own gut health compared to others in a way that doesn't get messed up like it used to in the past by

You can have lots of inflammatory microbes and you have a good diversity, but that doesn't mean you're healthy. So this sorts that out. And in that, we've found some associations between microbes and fat again. But again, it's not like one microbe we need to deal with. It's dealing with the whole system holistically that I think is really important.

It feels like the longer we've gone on, the larger the number of bugs that we're identifying that are both associated with health and poor health. And therefore, the way that we're scoring this as you go through and do this test is like sort of taking into account more and more of these bacteria. So it's not as simple as there's like this one bad bug and there's like these two good bugs. It's like there's a lot of complexity here. It's looking a bit like the genetics. People have been following the genetics revolution for...

And 20 years ago, we thought, oh, it's just one gene per disease. We just thought in Crohn's or ulcerative colitis, you just got one gene and then you measure everyone.

Again, human biology is much more complex. And so we also know that unlike genetics, all of us are much more unique in our gut microbes. So we need very big databases to work out how you would commonly assess, say, even the three of us to say who's healthier in terms of gut microbes because we've got to have the same group that are common between us in order to compare them. No point you and I comparing if we only share...

on average, you know, 20% of them. So yeah, it's really complicated, but the good news is we're making progress really fast because now, thanks to all the Zoe members, we're getting this vast database that is doing things that no one else can. It's really valuable information. And I think the...

Inter-individual differences in the microbiome are sort of the big wrench in all of our studies. Any person you encounter, you have a different microbiome, and that makes it difficult to—that's why one size doesn't fit all for anything, really. But you're your best comparison, ultimately. So—

Being able, if you have the opportunity to sample yourself over time, you can see what's changing within yourself. We often use this word dysbiosis in the microbiome field, which means

essentially a weird microbiome that's not normal. But what is that for every, there's no normal for everyone and there's no abnormal for everyone. And so I always press, define dysbiosis compared to what is it to your own starting point is really had the best way to define it.

And then you can start to understand, just like you see many individuals with diabetes who walk around with a blood glucose of 200 and they're not passing out, they're just fine. Their set point is a little bit different than everyone else's. The same is true for your microbiome.

And so you really sort of just pay attention to yourself, pay attention to what works, what doesn't, what foods work and what don't. Your microbiome is yours. And maybe you can compare to individuals within your household. You're more likely to share microbes with them versus others.

But I think frequent sampling within an individual is very valuable. I love to hear you say that because I do that a lot. It's one of the benefits of being the co-founder here. So I've been taking my microbiome frequently and there's a podcast that I recorded with

Tim and with Will Bolsovich talking about sort of what to do when taking antibiotics because having sampled this regularly, I had to take some pretty heavy-duty antibiotics at the beginning of last year and it basically smashed my microbiome and took a very long time to start to come back. And I think only with that comparison do I also sort of know I've still got further to go, which I find quite motivating.

Now, all of that said, I'm going to be in a lot of trouble if I don't switch to actionable advice. So I think people are listening to this. They're saying, wow, there's this link between the microbiome, my belly fat. That's important. I want to do something about it. I'd love to talk about what we can eat that might be able to make a difference. And we had Tim talk about this a lot. So actually, Suzanne, I'd love to start with you. And I think also you've done a review around this recently.

From our work in studying translocation, it really starts in the gut and healing the gut and maintaining a healthy gut barrier. And so foods that help support the integrity of the gut is really where it's at. And so then how do you do that? Yeah.

In my view, it is having... You need a lot of functional redundancy. What that means is you need a lot of diversity, which is a crude measure, but many different kinds of bacteria, their presence means that you have a lot of functions that can be carried out. And if you...

do something inadvertently to your microbiome and one drops out, you have others there to carry out those functions. And so how do you create diversity? We kind of touched on it earlier, but that is really a diversity of your diet.

There's been some interesting research from the Microseta Initiative where they looked at microbiomes around the world and really looked at metrics of diversity and associations with disease. And what they found is the diversity of plants in your diet is

relate to the more diverse microbiome. And they found that individuals who consume 40 or more different plant sources within their diet in a given week had a more diverse, robust microbiome. And plant sources come in all forms. And so what does that do to us? Probably the fiber content of the diet.

And fiber is really the key. It's not sexy. It sounds boring, but it is critically important. And there's a lot of deep research on what fiber does to certain microbes, what those microbes do with the fiber. And they relate to everything from educating the immune system, which we talked about earlier, to

to maintaining an anaerobic environment, a low oxygen environment in the gut, which is key for maintaining a gut barrier. So it's all cyclical, but it really starts with the diet. And feeding your good microbes through fiber, in my opinion, is you can't get around that. What would you add, Tim?

Two things. I think fermented food has been shown, thanks to a study from Stanford, to have anti-inflammatory effects, which means we get this boost of extra microbes that are in food and the probiotics in food if you have them regularly. And we're talking at least probably three probiotics.

times a day, you're getting a sample of it, can dampen down inflammation, keep your immune system in much better shape, less likely to cause these problems, which that visceral fat we think thrives off. So I think the idea is to keep that inflammation down. And the other

The other thing in addition to what Suzanne said is avoiding ultra-processed foods as much as possible. It's probably impossible to cut them out completely, but get it down to less than 10% of your diet so that you're getting many whole foods because we know that there's a pro-inflammatory reaction when you're having a lot of these foods and that

causes problems for your gut microbes, as well as depriving them of fiber and normal nutrients. So that's what everybody should be aiming at, is to shift more towards real food, less fake foods in their diet, plus getting more different fermented foods in their diet. And just to add to that, I'm a big fan of fermented foods. Thank you for adding that in.

The additional benefit to the fermented foods that we don't talk as much about is not just microbes in them, but all the postbiotic, the chemicals that the microbes are producing. Fermented foods are like a living food. And so you're getting not just live bacteria, but you're getting this...

sort of soup of all these beneficial products that microbes are making. And then when you consume it, you get the benefit of those chemicals as well. So there's multiple benefits to- Immune soup. Immune soup, yeah. I love that. I absolutely love that. For anyone listening to this, do you have any easy fermented recipes that they could get started with having solved on the benefit of the immune soup?

They don't get any easier than some of these. So everyone should be able to make sauerkraut is the one I go for, which is you take a cabbage, you slice it up, you weigh it, you mix it with 2% salt and stuff it in a jar and wait for a week. I mean, what's easier than that?

Anything easier than that might be to get some milk kefir or kefir and you buy a good one from a store. When you're running out, you keep the last inch of it and you add that to a bottle of fresh milk.

And then you keep that out on the counter for over 24 hours until it changes and goes solid. And then you've got some more kefir to last you. So you've literally just taken the previous kefir and made a new kefir. Without having to the expense of going to the store. Yeah. So that's called back slopping.

I did not know that. Very cool. Yeah, the name needs a bit of working on, but that's the technical term. So they're my two tips. Have you any other favorite ferments? If I'm honest, I buy mine. But you mentioned the Stanford study that's looked at the benefits of fermented foods. And when they looked at different fermented foods on a scale of the ones that had the most benefit, it was fermented dairy and vegetable brine, which you can actually buy for those of

you who don't have the ability to make your own, you can buy vegetable brine at the store as well. It's a certain...

acquire taste, but you can, you can get these things. Um, and it may vary depending on where in the world you live. Um, but the dairy and the fermented vegetables seem to have the greatest benefit. Um, and so kefir is great and certain Greek yogurts and, um, kimchi, sauerkraut, all of those are really fantastic, but be, be wary of pickles. Not all pickles are fermented. And so you want to kind of pay attention to, um,

usually they'll be labeled a little bit differently if they are truly fermented. I've heard people say that it doesn't guarantee it, but the fact that it's in like the fridge or something, it's definitely a suggestion that there's something alive, but people cheat now. And so they put the dead thing in the fridge to make you think about it. So you still have to read the label. Right, exactly. Got to watch out for big food.

Suzanne, before we run out of time, we talked about antibiotics a little bit across the conversation and the way that it can destroy a lot of the good bacteria in our gut. As we think about actionable advice, and I know this comes up a lot through your work, what's your advice for repopulating?

I used to be in the camp that actively recommended probiotics, especially after a course of antibiotics. I don't recommend that anymore, mainly because most people haven't tested their microbiome and know what they might be missing. If you have tested it and you have an obvious depletion of a certain beneficial microbe, then a probiotic could be helpful.

But in the absence of that, I advise people, again, it's going to sound like a broken record, but eating a diversity of foods. Your microbes will repopulate. They will come back, largely similar to where you were. There's been studies showing that if you take antibiotics, you might go to a new normal. It may not necessarily be bad, but it might be different than where you started.

But really the key is repopulating. And bugs, their function is carried out by what you give them, essentially. And so if you eat a lot of diverse foods, you will support many diverse bacteria in your gut. And generally, if you are eating, you know, diverse could be spam and a lot of processed, you know, candy and things like that. I don't necessarily mean diversity in that sense.

but diverse common sense. You know, we know what a healthy diet looks like and really expanding within that concept is a diverse diet. And so after, of course, antibiotics, I would try to bring back, really focus on, you know, your salads and your, you know, different proteins and different carb grains and things like that in your diet, maybe more so than you would normally in that window of repopulation. And that's because you have a concern that potentially the probiotics,

Not just that they're neutral, they might actually potentially be harmful in the process you're describing? There has been some studies suggesting that taking a probiotic after antibiotics can actually delay normal recolonization of your gut. And there's the very specific disease conditions where a probiotic can actually be harmful.

not good for your immune system. But those are rare cases. But it's really just going off of some papers that have come out suggesting that it may delay the normal recolonization compared to just diet alone. Thank you, everybody. I would like to do a quick summing up, and I hope you'll keep me honest.

So we started with this amazing thing that bacteria can actually leave your gut and end up sort of floating around in the rest of your body, which has this wonderful term, bacteria translocation. And my takeaway is you don't want any bacteria translocation. It's not good. Normally, this does happen apparently all the time, but our immune system is zapping it. But if stuff is going wrong, you know, either you have...

have you know one of these autoimmune diseases or just your sort of inflammation is really honey these things it can be worse and then amazingly like your fat can sort of jump in and sort of try and sit around it act as a band-aid which sounds good but on the other hand you end up with these bacteria that eat your fat and there's like it's clearly not where you want to be and so just like another explanation for how important it is to have this sort of

healthy microbiome, healthy gut barrier because of eating the right food and keeping that inflammation low. We explained that this visceral fat is really important. So it's not just sort of an aesthetic question. It really impacts your health and is linked to lots of diseases.

and that there's this very deep link, therefore, sort of between the visceral fat, your bacteria, and the food that you eat. And that we talk quite a bit about the way that that has actually been shaped from when you're a small child. And so I heard, which I'd never heard before, that if you train your children with a whole variety of foods, particularly when they're very young, they're actually gonna get more variety of immune cells, and that's gonna sort of set themselves up for life.

so once again i can blame my parents for everything that isn't right for me because they didn't look after me properly when i was a small child tim was shaking his head we heard some exciting news from tim that there's a big new paper coming based upon now hundreds of thousands of zoe members who've tested their gut microbiome with sort of further better understanding of sort of a host of

you know, good bacteria that are linked to health. And Suzanne, you talked a lot about the way in which sort of knowing your own state of your microbiome is the best place to then know in the future whether it's healthy and why, interestingly, you no longer sort of tell people to take probiotics after antibiotics because they're not going to get the right things for them, but actually the fermented food and fiber and plants.

And I would say finally, you know, what's interesting is how strongly both of you have talked about fermented food today, not just because it's got live bacteria in it, but also, and I never heard this before, the immune soup of beneficial nutrients. So that it's not just the bacteria, it's everything they've sort of created out of this food. And if you think it's too hard, Tim says that there is nothing easier than making sauerkraut at home. So don't be scared. Great.

You know, you cracked it. Thank you both so much. Really enjoyed it very much. And Suzanne, as the studies continue, I hope we can get you back in the future. Thank you for having me. It's been a pleasure. Now, if you listen to the show regularly, you already believe that changing how you eat can transform your health. But you can only do so much with general advice from a weekly podcast. If you want to feel much better now and be on the path to live many more healthy years, you need something more.

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