ZOE Science & Nutrition - Recap: How your gut fuels your brain and mood | Prof. John Cryan

Episode Date: July 29, 2025

Today, we’re exploring the connection between your gut and your brain. For years, the brain was seen as somewhat detached from other parts of our body, working in isolation above all else. However, emerging research is flipping our idea of the brain on its head. Scientists now know that the gut acts like a ‘second brain’, influencing everything from our mood and memory to our risk of neurological disease. So, have we been neglecting a vital piece of the brain health puzzle?  Joining me to unpack this topic is Professor John Cryan, a world-leading expert in the gut-brain axis. Unwrap the truth about your food 👉 ⁠Get the ZOE app 🌱 Try our new plant based wholefood supplement - Daily30+ *Naturally high in copper which contributes to normal energy yielding metabolism and the normal function of the immune system 📚 Books from our ZOE Scientists: The Food For Life Cookbook by Prof. Tim Spector Food For Life by Prof. Tim Spector Every Body Should Know This by Dr Federica Amati Free resources from ZOE: Live Healthier: Top 10 Tips From ZOE Science & Nutrition  Gut Guide - for a healthier microbiome in weeks Have feedback or a topic you'd like us to cover? Let us know here Listen to the full episode here

Hello and welcome to Zoe Recap, where each week we find the best bits from one of our podcast episodes to help you improve your health. Today we're exploring the connection between your gut and your brain. For years, the brain was seen as somewhat detached from other parts of our body, working in isolation above all else. However, emerging research is flipping our idea of the brain on its head. Scientists now know that the gut acts like a second brain, influencing everything from our mood. food and memory, to our risk of neurological disease. So have we been neglecting a vital piece of the brain health puzzle? Joining me to unpack this topic is Professor John Cryan, a world-leading expert in the gut-brain

axis. He's here to explain how the two communicate and what you can do to support that connection. Are there links between the gut and the brain? What we know now, and there's been an evolution over the last two decades, I would say, is that there is now concrete evidence that the composition of the microbes in your gut influences brain development, influences brain function, and can help steer the brain in specific ways. The evidence is coming largely from studies in animal models. And John, just to make sure everyone is an animal model, what does that mean?

Usually a mouse or a rat. So because we can get mice that can grow up without microbes, ever having a microbe, you know, if you want to find out if something is important in a problem. process. We know from engineering or other areas of biology that if you take it out and see what happens, it's probably one of the best ways to see if it's important. So mice that have grown up without bacteria, they allow us to answer the question, is the microbiome relevant yes or no? And studies from our lab and from other labs over the past decade or more have shown that in these mice that grow up without any bacteria in their gut, that their brains don't develop

normally. That's amazing. And do you find special mice that you found somewhere in the world that grew up without any gut microbiome? Is that how you compare this? No, this is an unusual lab-based situation. So these animals are kept in this ultra-sterell conditioned where they've never been exposed to microbes. And this concept goes back to Louis Pasteur. He's first tried to do these, work with these types of mice. And they are not really translatable to anything human. with maybe the exception being the boy in the bubble that Paul sang about in the 1980s. These mice in the bubble, they allow us to have this specific question, is the microbiome involved? Yes or no.

Got it. So it's quite unnatural, as what you're saying. You have to create this incredibly sterile situation because we're constantly surrounded by these bacteria who want to get into us and presumably these mice. So you create this incredibly sterile situation to discover what happens if a mammal grows up without any bacteria. and that's what you're comparing then with the normal situation for mice and I guess for us, right? Which is we're stuff full of trillions of them.

Absolutely. And our group and the group of Rushdala Heights in Karlinska and Jane Foster in McMaster well over a decade ago all showed roughly around the same time that these mice have messed up brains in different ways. In terms of their behavior, they respond differently to stress. We show that they don't have proper social behavior,

that they don't have proper fear learning, and their pain processing is different. So they've given us a real entry point into convincing us that there's something about microbes and brain function that we need to pay more attention to. And that's taken us on this journey that my lab has been on for well over a decade. And John, one of the words that I think we often hear is like gut brain access, which is a great sort of phrase, which I don't really understand what it is, but I'm hoping you're about to explain. Is that this or is that something different? Well, yeah. So the gut brain axis has been long known. It's basically how

signals from your gut go to your brain to change your behavior. Now, that's been very well studied in the context of food intake because we take food into our bodies, but the reason we do that is in response to hunger signals that come from our brain. And then we take it in and then we stop eating based on signals that are telling us we're full. And they are also brain-derived. And so the gut brain access has been around for a long time, mainly in that context. Then people started being more understanding that disorders like irritable bowel syndrome, which is a very common unloved disorder associated with abdominal pain and bloating and various other functional side effects, that this is really a disorder of how our gut and our brains talk to each other.

What we now think of is a microbiome gut brain access. So the microbes are the new players, so it makes things even more complex. And what we're trying to figure out is how do the microbes in the gut talk to the aspects of gut brain signaling to change brain and behavior? So it's a new dimension, a new player, if you will. We have to think that the microbes were there first. And so that's an important aspect of all of this in our learnings. From an evolutionary perspective, microbes were there. And so there's never been a time where our brain or our gut existed without microbial signals.

So we kind of have to contextualize that. And we're very human focused in our primacy of what's the most important. But we have to remember also that the mitochondria, the powerhouses of cells, are actually microbes that got lost into the cells. And so there's such a close relationship between our microbes and everything through evolution. And so once you start contextualizing it in that way, it's probably not surprising that the microbiome could play such a key role in so many aspects of our physiology and our behavior. So just to make sure I got that, what you're saying is, hey, the microbes were there before there were any human beings. In fact, before there were any mammals. And so, you know, even from the very beginning of building this gut, there would have been microbes there.

So it's hardly surprising that they are a sort of built-in feature, if you're. like of our body rather than how, you know, I think we obviously all thought about them until a few years ago as a sort of an irrelevance. Yeah, absolutely. So I think lots of listeners have asked this question about, well, how does that work? Because I think they can understand that your microbes affect the way you digest your food. They're in the same place. That makes sense.

But, you know, my gut and my brain are in two different places. Bacteria are really small. How do these bacteria affect what's going on in my brain? I know this is something that you study. Yeah, and it's a large part of what our lab is focused on is really trying to delineate the mechanisms and pathways as far as it's communication. And there are a number of ways.

First of all, it's worth noting that within our gut, we have a second brain. This is called the enteric nervous system. And this second brain has more nerve cells than our spinal cord. Enteric nervous system is very important for digestion, motility, various aspects of gut function, but it's also a really good conduit. for signaling directly to the brain. So that's an important first pass on it.

The second thing is we have a nerve. It's one of the major cranial nerves, which sends signals from the brain to all the organs, and from organs back up to the brain. It's called the vagus nerve. Now, Vegas comes from the Latin for wandering. It's the same derivation as vagabond or vagrant. And this nerve is really well-poised

to be an important highway of communication between the gut and the brain, and between the microbes and the brain. And so over a decade ago, we showed, together with the late John Bean and Stocks Lab, that when you cut the vagus nerve in a mouse model, we severed all of the effects of a specific lactobacillus bacteria on brain and behavior were gone. So as I like to remind people, this tells us that what happens in Vegas doesn't just stay in Vegas, but will actually affect our emotions in certain ways.

Okay, I love that. So I've got a Vegas nerve inside me, which a bit like Vegas, all sorts of bad things can happen and come back to haunt me afterwards. How would you think about what people should be doing either for themselves or is they're thinking about their children or relatives? The important thing is to realize that your microbiome changes as you navigate life naturally. There's a natural change overall. In the early life, it takes about two years for stability to start to come in and it's really primed to maximize what it can get from milk. overall. And then into adolescence, there's less studies, but we're beginning to see more and more relationships between the microbiome, and then we get a stable microbiome unless we shift

our environment. And then as we age, then we see it to the serious effect of aging on the microbiome, which we've been showing, for example, that that affects brain health. So we've been able to take the microbes from young animals and reverse the effects of aging on brain health. And that's been quite remarkable. So we know that we need to mind our microbes for optimal brain health. some of the practical things that I would tell people to do, that has some evidence, although we could do it more. So there are certain things to enrich in your diet, which is increasing the levels of prebiotics, fibres in particular, would be really, really important. Fermented foods, the 3Ks of kimchi, kfirr and kombucha, but there's loads of other fermented

foods, and throughout the world we have a rich cultural history of fermented foods, and not so much in Ireland, I would say, but in other places. But studies like from Justin Sondonberg's group and now more recently from our own has shown that there's a science, a biology, how these fermented foods are interacting with the host to have positive effects. So really, really doing that. We know colour is great. Polyphenols give lots of foods colour and polyphenols are broken down by microbes, but they

also act on microbes and they can be broken down to chemicals that are really important. So heavily present in things like onions and grey. and nuts and also in green tea, and people often talk about it in the context of red wine, of course, but it's also in grape juice. But polyphenols are really good. There's been an increasing interest in polyunsaturated fatty acids. So these are the poofas that are very good for how membranes and cells work, but they also can have effects directly on the microbiome. And so maybe some of the positive effects of these polyunsaturated fatty acids may be really good. And then there are things we should avoid in our diet or as much as we can. And that's the processed food, artificial

sweeteners in particular have been shown to have consistently negative effects on the microbiome overall. We know that certain lifestyle other factors can influence the microbiome. So our sleep and our circadian rhythms and jet lag all has effects. So we need to be careful on that. Exercise, in particular aerobic exercise has been shown to have really good effects on the microbiome and potentially then onto brain function overall. Mode of delivery at births that we should, as a public health, should be really encouraging more people to, if they can, give births naturally as opposed to by C-section

because there's enduring effects of C-section on the microbiome that can potentially translate to behavior in later life. And then finally, there's great data now accumulating from population-wide studies that having a pet, and particularly a dog, is good for your microbiome and probably maybe some of the beneficial effects of companion dogs on behavior may be related to their effects on the microbiome and gut brain signaling. That needs to be figured out, but I think it's a really intriguing area overall. I just want to pick up on this sort of older age thing.

So if you're listening to this and you want to maintain your brain health, which I think has become an increasing focus for many people, right, as we age and we see all of these problems, is there anything specifically within that or on top of that that you need to do? Should they all be immediately going out and getting a pet? Is that the key additional activity? Well, it's interesting. A lot of the pet work is coming from early life studies. So there hasn't been much data that I'm aware of in older people right now.

And we know the social interactions themselves. By living with someone else your microbiome starts to shift and change. The best study on old age then have shown that things like the diversity in the diet is what gives the best health outcomes in the context of frailty. and other medical outcomes. There's been no reasonably good data yet on brain function as we age in humans. But the studies like the new age study and the Al Jermat studies, which would really support this increase in diversity of foods and Mediterranean-style diets are really good for your microbes.

So therefore, they should be also good for your brain. That makes sense. And what about adolescence? I think you talked about like a big shift going on in the brain at this point. So the adolescent brain is really a brain that's still under construction. We often forget that. Our brain goes through quite remarkable changes during this period. And basically, it's a period where the brain has to decide what to keep for the rest of the life.

So there's a lot of what we call pruning. So synaptic pruning where basically our immune cellar are saying, okay, keep or not keep what's going to be essential for what you need to keep you going. I'll end this recap with something I think you'll like, a free gut health guide. created by our team of scientists here at Zoe. Many of us aren't sure how to best support our gut, so we developed an easy-to-follow guide, complete with tips, recipes and shopping lists,

designed to help you look after your gut. The guide is delivered straight to your inbox, along with ongoing nutrition insights from Zoe, the Science and Nutrition Company on a mission to transform the health of millions. To get your free gut health guide, just visit zoe.com slash gut guide. Thanks for listening.

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