Is Your Gut Microbiome Preventing Weight Loss?

Belly fat is more than just stubborn weight – it plays a complex role in our health, interacting with the immune system and gut bacteria. But could microbes hold the key to understanding and managing belly fat?

Together, they share surprising ways our microbiome influences fat storage and share practical tips for supporting gut health. You’ll learn how small tweaks to eating habits can have a big impact on gut health, and even on belly fat.

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Transcript

Jonathan Wolf: Suzanne, thank you for joining me today. 

Dr. Suzanne Devkota: Thank you. 

Jonathan Wolf: And Tim, it’s always fantastic to have you with us. 

Prof. Tim Spector: Great to be here. 

Jonathan Wolf: 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?

Dr. Suzanne Devkota: Sure. 

Jonathan Wolf: 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? 

Dr. Suzanne Devkota: Yes. 

Jonathan Wolf: Does belly fat play a role in our immune system?

Dr. Suzanne Devkota: Yes. 

Jonathan Wolf: Tim, could too much belly fat increase our risk of disease? 

Prof. Tim Spector: Yes, even if you’re thin. 

Jonathan Wolf: And finally, Suzanne, what’s the most surprising thing that you found in your research on the gut microbiome and belly fat? 

Dr. Suzanne Devkota: That bacteria actually can live in fat tissue. 

Jonathan Wolf: Amazing. I know we’re going to get into that and 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 full of this anxiety. I’d love to just take a step back, and it sounds really obvious, but what is belly fat? 

Dr. Suzanne Devkota: 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 of the deeper layers.

We really are looking at the fat that’s attached to our internal organs. We call that visceral fat. That visceral fat that’s attached to the organs, expands with 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. 

Jonathan Wolf: If I understand right, you’re saying I could have fat just 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? 

Dr. Suzanne Devkota: When we chronically eat too much and we gain fat. We need those 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.

Prof. Tim Spector: 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.

Dr. Suzanne Devkota: 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. 

Jonathan Wolf: 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 put some weight on.

As part of the initial clinical trials that we were doing with ZOE in the early days, we had 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 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 really surprised and looking at it really carefully, and then passing on. Eventually,, I got the results back a little bit later, and I remember Tim explaining to me that basically, I’m thin on the outside and fat on the inside. And actually, I had a lot of fat layered into this visceral fat you’re talking about, which is the first time I’d ever heard that term. And this was very bad news. 

Prof. Tim Spector: You were a toffee. Thin on the outside, fat on the inside. Which a lot of people are in a way. They don’t realize that they have poor metabolic health because of that.

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. 

Jonathan Wolf: And it was a big shock to me, to be honest. It’s one of the things that really kick-started 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 eat this very classic Western diet, huge amounts of sort of refined carbohydrates. And I’d assumed that it was having no impact on me. So it was really amazing to realize that I was not as healthy on the inside as I had thought.

And that was the first time I’d experienced this. So, is that very unusual to only have this visceral fat and not have lots of visible fat everywhere else across your body? 

Dr. Suzanne Devkota: It’s not unusual. As Tim mentioned, there’s definitely subgroups of individuals and there’s some genetic association as well, of individuals who are very thin, you would never view them as having 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 overweight or obese, but they may be just as unhealthy on the inside. 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? I think we can learn a lot from comparing the two types.

Jonathan Wolf: So I’d love to go from this to your own research on belly fat because you’ve found this amazing way in which it might actually interact with our gut bacteria in a very surprising way. I know you specifically studied people with Crohn’s disease, and I’d love 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, why did you choose to study people with Crohn’s disease? What is it? 

Dr. Suzanne Devkota: In graduate school, I was in an inflammatory bowel diseases lab, but my background is actually in nutrition and metabolism. 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?

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 today and I have learned a lot about how no disease is one thing, there’s many different subtypes of disease and it’s true in obesity and diabetes and it’s true in IBD.

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.

Jonathan Wolf: And Suzanne, the GI tract is? 

Dr. Suzanne Devkota: Oh, the gastrointestinal tract. So, really, your GI tract is from your mouth to your anus. The whole two. 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.

Jonathan Wolf: And lots of people listening to this won’t be familiar with Crohn’s disease, so could you just help to understand very simply what is going on? Is it very common? 

Dr. Suzanne Devkota: The epidemiology of it is very interesting. How, where in the world, 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.

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, poor diet, and processed foods. 

There is a genetic component to it. So we say that with Crohn’s and colitis, 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. It could be any two or more combinations of those, of those items can trigger the disease.

Beyond that, we honestly don’t know. For every person who comes in to, with a new diagnosis, what caused it are usually very different, and so it’s really hard to say this causes IBD.

Jonathan Wolf: And could you give us a sense of what it’s like to be living with Crohn’s? 

Dr. Suzanne Devkota: Yeah, it’s pretty awful. So chronic inflammation, you will, 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 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, and people are not often very comfortable talking about bathroom habits. So it adds that added layer of social discomfort to that as well.

Then you’re on constant medication. 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 creates a lot of frustration for patients.

Prof. Tim Spector: Yeah. And I used to see, I mean, when I was a rheumatologist, obviously it’s an auto immune 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.

You also get skin changes, you can attack your own skin, and arthritis is quite common. So about 10% or something like that of these people get quite bad, what we call seronegative arthritis. 

So 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 over excited and working hard all the time, which makes me gives you everyone fatigue as well as these specific gut problems. 

Dr. Suzanne Devkota: 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. 

Jonathan Wolf: So first, 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 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?

Dr. Suzanne Devkota: 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 like blood infections of bacteria. People have reported recovering bacteria from the liver and other places.

And so when I joined Cedar 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 it 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 intestines. 

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, you know.

And I said, well, that’s really interesting, but where would I get these patients and these samples? And he said, well, I can get them for you. I see them every week. 

That started probably an eight-year collaboration with Phil Fleshner, 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.

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 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. 

Jonathan Wolf: Normally, should any bacteria be coming out of my gut and going into the rest of my body? 

Dr. Suzanne Devkota: 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. 

Jonathan Wolf: You’re saying in a normal healthy person, actually some of the bacteria is sneaking through the gut and into the surrounds of my gut all the time, but it’s just that my immune system is zapping it before it goes off and causes some horrible infection or something. Is that correct? 

Dr. Suzanne Devkota: Yes. And it’s very different types of bacteria in 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 a 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.

Jonathan Wolf: So tell me what you found at the end of these eight years and all of these samples, what was the discovery? 

Dr. Suzanne Devkota: So the big mystery was how does fat tissue on the outside of the intestine 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. 

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. 

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. 

We were absolutely stunned to find the sheer numbers and diversity of different bacteria living in the fat tissue. 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. 

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. 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 they’re presented with an environment that’s rich in fat. 

Jonathan Wolf: 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 happily there, munching on, well if this was me, me, effectively, is that what you’re saying? 

Dr. Suzanne Devkota: Yes. 

Prof. Tim Spector: Your fat. 

Jonathan Wolf: And when you said they’re lipid-optimized, that’s science speak for they eat fat particularly.

Dr. Suzanne Devkota: They can use fat for fuel. Yeah. 

Jonathan Wolf: 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 that’s not where you want it, or in the right way, before anyone is suddenly thinking this is…

Dr. Suzanne Devkota: 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. 

Prof. Tim Spector: Don’t worry, Jonathan, it’s not all going to disappear. 

Jonathan Wolf: I wasn’t worried about that. I was just thinking that you’re blowing my mind here. So I just want to make sure I understand. 

Dr. Suzanne Devkota: 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 stem cells in the fat and so on, when they see the bacteria there, and this is what we’ve been working on 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, 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. 

Jonathan Wolf: So Suzanne, you’re basically saying that I’m actually going to grow more fat to  wrap around this bacteria that’s where it shouldn’t be, almost like sort of encase it. 

Dr. Suzanne Devkota: 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.

Fat is this very dynamic, responsive, active tissue that’s doing more in our bodies. One of the other things that it may be doing is responding to bacteria to protect the body. 

Prof. Tim Spector: So it’s part of the immune system, really?

Dr. Suzanne Devkota: Yeah, you could view it that way. 

Prof. Tim Spector: 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, 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. 

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 to threats of infection or autoimmunity. So, that’s really, really fascinating. 

Dr. Suzanne Devkota: 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 like these sentinel sites for mobilization against further bacterial stimulation. A lot of really interesting adaptive immune cells that typically are not there. 

Prof. Tim Spector: Are these microbes ones that as well as liking fat, do they like the inflammation because generally, fat cells produce these inflammatory chemicals, don’t they? 

Dr. Suzanne Devkota: 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. 

Jonathan Wolf: 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? 

Dr. Suzanne Devkota: 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. 

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 asked, what does the fat look like around these other organs? 

We get from docs who do the kidney transplants, they always say, the kidneys that have more fat wrapped around, those individuals always do worse with their transplant. 

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. 

So we are trying to collect samples from individuals so we can better understand the microbial component of this. 

Jonathan Wolf: And we did a podcast on colon cancer and gut cancer, And one of the things that was mentioned, it’s a podcast we did a while ago with some suggestion that potentially there might be bacteria being implicated in cancers that were not directly in the gut but elsewhere. 

I’m just listening to you talk about this translocation that I’ve never heard of before, which is a very cool name. Is there any reason to believe that these bacteria might ever be getting past immediately next to the gut wall and into the the other, you know, you’re talking about your kidneys or your heart or whatever. 

Dr. Suzanne Devkota: 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.

Jonathan Wolf: 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.

Dr. Suzanne Devkota: Exactly. Yeah. 

Prof. Tim Spector: Yes, chemicals or it could be their cell walls, which might be dead, 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, are going.

Jonathan Wolf: Could we step back for a minute and just help to understand a bit more this broader role between bacteria and the immune system. Because you’ve 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? 

Prof. Tim Spector: 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 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. 

Jonathan Wolf: So what do we currently know about like the relationship between the immune system and the bacteria in our gut?

Prof. Tim Spector: 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. 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.

This means that we have an immune system that is protecting us, is making sure we don’t overreact to allergy, foreign… 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.

So the immune system is also important for us, surveillance to help us fight accelerated aging, clear up damage from cells, fight cancer, it 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.

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 a really healthy gut microbes means that your immune system is then functioning optimally and then can help us. 

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 in this connection.

So it is really important for all of us to have a really well-functioning immune system, 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, we’re at a 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. 

Dr. Suzanne Devkota: The education of our immune system by a microbe starts from the moment we’re born. Looking at the early life 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.

What’s really interesting is there’s this weaning period. Weaning means when you go from breast or formula onto your native diet table foods or adult diet. At that introduction of food, you have 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.

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.

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. The hypothesis being, could that be predisposing infants and children to autoimmune conditions, 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. 

Prof. Tim Spector: 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.

Jonathan Wolf: I’m always conscious of, listening to this, you know, having two children of my own, that’s really hard to go through pregnancy, have a baby, get through this. And that often these podcasts 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 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 sort of 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 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. You want to do that because that’s what’s, I’ve never heard this before, but that’s what’s needed to get a lot of different immune cells, which set you up well for life. 

Dr. Suzanne Devkota: Yeah. There are certain things you can, 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 train diversity in food preferences early, actually will help.

Encourage a more diverse diet going forward and then a diverse microbiome as a result. 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 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. Let your kid play in the dirt. Let your kid lick stuff. Let your kid do stuff that would make you go crazy because that actually is giving them the exposures that they probably need to educate their immune system.

Jonathan Wolf: 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, to what to eat. 

What’s striking is how many people living in the West, will have very poor microbiomes. So the variety of the microbes they have, the number of the ones that are correlated with better health is strikingly low.

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 Suzanne. Tim, is there anything else we know about the relationship between gut bacteria and visceral fat?

Prof. Tim Spector: 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. 

Jonathan Wolf: It’s all my parent’s fault, is it? 

Prof. Tim Spector: It’s not all your parent’s fault, it’s half your parent’s fault. 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, everything ranging from depression to food allergies and things, 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, we put some of those microbes in mice and replicated those results. 

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.

So I used to be quite certain, oh yes, we can get a magic bullet based on these microbes that could cure everybody. Ten 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 every morning. Unfortunately, they’ve gone bust because it wasn’t as simple as that, as is usually the case.

But I think there’d be a suite of them. There might be a hundred of these microbes that are working together. It’s possibly 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.  

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

Prof. Tim Spector:  Yes. Well, 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. 

So we’ve put a lot of this together to work out new ways of scoring what are good and bad bugs. Because up to now we’ve just used this, what’s called diversity. This is the number of different microbes, which I think Susanne would agree 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.

What we’ve found is we’ve managed, by getting all these outcomes, including things like visceral fat and body mass index and heart problems and blood cholesterol and blood pressure, 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 it’s 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.

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, but 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. 

Jonathan Wolf: 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 taking into account more and more of these bacteria. 

So it’s not as simple as there’s this one bad bug and there’s these two good bugs. There’s a lot of complexity here. 

Prof. Tim Spector: It’s looking a bit like the genetics, people have been following the genetics revolution. 20 years ago, we thought there was 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 what you would commonly assess, say that 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. There’s no point in you and I comparing if we only share on average 20% of them. 

So yeah, it’s really complicated. 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. 

Dr. Suzanne Devkota: 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’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 the word dysbiosis in the microbiome field, which means, essentially, a weird microbiome that’s not normal. But there’s no normal for everyone, and there’s no abnormal for everyone, and so I always define dysbiosis compared to what? Is it to your own starting point, is really the best way to define it.

And then you can start to understand just with, 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 pay attention to yourself, pay attention to what works, what doesn’t, what foods work, and what doesn’t.

Your microbiome is yours and maybe you can compare it 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. 

Jonathan Wolf: I’d 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 Bulsiewicz talking about 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.

I think only with that comparison do I also know I’ve still got further to go, which I find quite, quite motivating. 

Now all of that said, I’m gonna 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 hear 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.

Dr. Suzanne Devkota: From our work, you know in studying translocation it really starts in the gut, and healing the gut and maintaining a healthy gut barrier. 

So foods that help support the integrity of the gut is really where it’s at. And so then how do you how do you do that? In my view, 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. 

If you do something inadvertently to your microbiome and one drops out, you have others there to carry out those functions. 

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 Microsetta 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 relates to the more diverse microbiome. They said 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. 

Plant sources come in all forms. And so what that is due to was 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.

There’s a lot of deep research on what fiber does to certain microbes, and what those microbes do with the fiber, and they relate to everything from educating the immune system, which we talked about earlier, 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, you can’t get around that. 

Jonathan Wolf: What would you add, Tim? 

Prof. Tim Spector: 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 through, that are in food and the probiotics in food. If you have them regularly, and we’re talking at least probably three times a day, you’re getting a sample of it. 

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.

The other thing in addition to what Suzanne said is, avoiding ultra-processed foods as much as possible. It’s pretty 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 to real food, less fake foods in their diet plus getting more different fermented foods in their diet. 

Dr. Suzanne Devkota: 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, there’s not just microbes in them, but all the postbiotic, the chemicals that the microbes are producing are there. 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 the microbes are making. Then when you consume it, you get the benefit of those chemicals as well. So, there’s multiple benefits to fermented food. 

Prof. Tim Spector: Immune soup. 

Dr. Suzanne Devkota: Immune soup, yeah. I love that.

Jonathan Wolf: I absolutely love that. For anyone listening to this, do you have any easy fermented recipes that they could get started with having been sold on the benefit of the immune soup? 

Prof. Tim Spector: They don’t get any easier than some of these. So everyone should be able to make sauerkraut. The one I go for, which is you take a cabbage, you slice it up, you weigh it, you mix it with 2% salt, 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, 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 got some more kefir to last you. 

Jonathan Wolf: So you’ve literally just taken the previous kefir and made a new kefir. 

Prof. Tim Spector: Without having the expense of going to the store, yeah. So that’s called back-slopping. 

Dr. Suzanne Devkota: I did not know that. 

Prof. Tim Spector: 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? 

Dr. Suzanne Devkota: If I’m honest, I buy mine. But you mentioned the Stanford study and 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 acquired taste, but you can get these things and it may vary depending on where in the world you live. 

But the dairy and the fermented vegetables seem to have the greatest benefit. So kefir is great and certain Greek yogurts and kimchi, sauerkraut, all of those are really fantastic.

But be wary of pickles. Not all pickles are fermented. And so you want to kind of pay attention to usually they’ll be labeled a little bit differently if they are truly fermented. 

Jonathan Wolf: I’ve heard people say that it doesn’t guarantee it, but the fact that it’s in 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. 

Dr. Suzanne Devkota: Right, exactly. 

Jonathan Wolf: 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 they 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? 

Dr. Suzanne Devkota: 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, this is going to sound like a broken record, but by 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.

Generally, diverse could be spam and a lot of processed candy and things like that. I don’t necessarily mean diversity in that sense, but diverse common sense. We know what a healthy diet looks like. And really expanding within that concept is a diverse diet.

And so after a course of antibiotics, I would try to bring back, really focus on your salads and your different proteins and different carbs, grains, and things like that in your diet, maybe more so than you would normally in that window of repopulation. 

Jonathan Wolf: 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.

Dr. Suzanne Devkota: There have been some studies suggesting that taking a probiotic after antibiotics can actually delay normal recolonization of your gut. 

Then there’s the very specific disease conditions where a probiotic can actually be 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 normal recolonization compared to just diet alone.

Jonathan Wolf: Amazing. 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, either you have one of these autoimmune diseases or just your inflammation hasn’t got a handle on these things, it can be worse. 

Then amazingly, your fat can jump in and 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 it’s clearly not where you want to be. And so just another explanation for how important it is to have this 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 an aesthetic question, it really impacts your health and is linked to lots of diseases. That there’s this very deep link, therefore, between the visceral fat, your bacteria, and the food that you eat.

We talked quite a bit about the way that has actually been shaped from when you’re a small child, and 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 going to get more variety of immune cells and that’s going to 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 is 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 further better understanding of sort of a host of good bacteria that are linked to health.

Suzanne, you talked a lot about how 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 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, 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 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. 

Dr. Suzanne Devkota: Great. 

Prof. Tim Spector: Yeah, you cracked it. 

Jonathan Wolf: 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.

Dr. Suzanne Devkota: Thank you for having me. 

Jonathan Wolf: 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. 

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As always, I’m your host, Jonathan Wolf. ZOE Science & Nutrition is produced by Julie Pinero, Sam Durham, and Richard Willan. The ZOE Science & Nutrition podcast is not medical advice, and if you have any medical concerns, please consult your doctor.

See you next time.