Feel Better, Live More with Dr Rangan Chatterjee - #20 IBS, Stress and Gut Health with Professor John Cryan

Episode Date: May 30, 2018

Dr Chatterjee talks to Professor John Cryan, world-leading researcher on the gut-brain axis and Professor of Anatomy & Neuroscience about how the connection between our gut and our brains affects all aspects of our health, including stress, depression, anxiety and IBS. Show notes available at drchatterjee.com/johncryan Follow me on instagram.com/drchatterjee/ Follow me on facebook.com/DrChatterjee/ Follow me on twitter.com/drchatterjeeuk Hosted on Acast. See acast.com/privacy for more information.

Hi, my name is Dr. Rangan Chatterjee, medical doctor, author of The Four Pillar Plan and television presenter. I believe that all of us have the ability to feel better than we currently do, but getting healthy has become far too complicated. With this podcast, I aim to simplify it. I'm going to be having conversations with some of the most interesting and exciting people both within as well as outside the health space to hopefully inspire you as well as empower you with simple tips that you can put into practice immediately to transform the way that you feel. I believe that when we are healthier, we are happier because when we feel better, we live more. I'm incredibly excited to introduce today's guest for the podcast. It's someone who

is arguably one of the world's leading researchers into gut health and the microbiome with a particular interest into the guts, the brain and our stress levels. He's published over 400 articles and he's co-author of the book, The Psychobiotic Revolution, Mood, Food and the New Science of the Gut-Brain Connection. He's won numerous awards. He's done a couple of TED Talks. It's Professor John Quyen. John, welcome to the podcast. Thank you very much. It's my pleasure. So John, I have recently realised that a lot of the work I've been looking at with respect to the microbiome for the last sort of five or ten years and been lecturing on, actually you are behind, you and your lab are

behind a lot of that research. So it's an incredible pleasure for me to have you on the podcast. I thought I might start by asking you, John, you know, how did you come to being an expert and actually spending a lot of your research time studying the gut microbiome? Well, that's a really interesting question in many ways. So for my entire research career, I've been focused on trying to understand how stress affects the brain and affects the body. And I'm a neuroscientist, so it may seem very strange that as a neuroscientist, the body. And I'm a neuroscientist, so it may seem very strange that as a neuroscientist, I've really started to work heavily on what's going on in the gut. And when I moved back home to Ireland now 13 years ago, I started to collaborate with people here who were very interested in

stress-related gut disorders like irritable bowel syndrome. Now, irritable bowel syndrome or IBS is a very common and unloved disorder in many ways. But it's very clear that it's a disorder of the gut-brain axis and that it's very much flare up in it, can be driven by stress. And so understanding it mechanistically was very much driven around understanding how stress affects the body in a general way. And together with my colleague Ted Dinan, who's the head of psychiatry here, we developed a research program around irritable bowel syndrome. of IBS, which is where animals are separated from their mothers during early life, that when these animals grow up, we showed over a decade ago now that their microbiome was quite different. And that was one of the key experiments for us because it's telling us that stress is affecting the microbiome. We followed that up with studies in other animal models of stress

showing that there are clear ways that the microbiome is influenced by stress. But that could be epiphenomenological, it could be down to many things. And it was kind of one of these look-see experiments that we did at the time. But it got us thinking, well, what if it's more than that? What if it's really could be something that we could harness to manage or treat this stress related disorder? So then we started looking at other ways to really investigate, you know, could there be a clear mechanistic relationship between stress and the microbiome. And so we looked then in animals that lack the microbiome. So these are what we call germ-free animals. And because in biology and engineering in general, if you want to know if something is involved, one of the easiest ways

is to take it out and see what happens. And when we take out microbes from animals, basically these animals are much more stress sensitive. Their hormonal response to stress is exaggerated. So that data, and there was work coming from Japan that supported that, and our own data showing that stress affects the microbiome the story started to come together and then the final two parts of the puzzle were then we basically hypothesized that the brain areas that are regulating the stress response and important for emotional um um maturation and and neurodevelopment that they would be out of kilter in these germ-free mice. And so we started investigating that. I did groups in Sweden and Canada, and we all showed the same

things, that basically we need the microbes for normal brain development and for mounting the appropriate stress response. And the final part then was, could we target the microbiome by certain ways either by individual strains of bacteria or by diets that would support the development of beneficial microbes could we reverse the effects of stress either in early life or in adulthood and we've done quite a number of experiments to show that and by 2011 then we had shown that in a mouse model. And that helped us really to confirm that the microbiome is not just an epiphenomenon, but a really core part of how our body is programmed to deal with stress. And we're still working on the mechanisms involved. And

of course, on the translation into human studies. Wow, I mean, it's some story. So I think it's worth right at the start of this conversation, just clarifying for those listeners who are not familiar with the microbiome, we're talking about this collection of bugs, you know, bacteria, fungi, viruses, many more that actually live inside us and their collective genetic material. And so it's incredible for me that you say we need these microbes to mount the appropriate stress response. I don't think when people think of stress, and obviously you're a neuroscientist who wanted to study stress. And I suspect that when you started studying stress, you probably didn't think you'd end up in the gut. No, because as you know, in medicine, we love to compartmentalize disciplines.

And I work in a medical school. So neuroscience is generally focused on what's going on from the neck upwards. generally focused on what's going on from the neck upwards. And the disciplines of microbiology and neuroscience, whether it's neurology or psychiatry, rarely have intersected. There's been some exceptions when we try and understand what syphilis was doing to the brain 100 years ago or what the HIV virus was doing more recently. But on the whole, these disciplines are very different. But the important thing about stress to remember is that stress doesn't just affect a few neurons within the hippocampus of the brain. It actually affects the entire body. And so I'm largely talking about chronic stress or traumatic stress.

But it creates a whole body syndrome that has implications for what's going on in our gut, in our cardiovascular system, in our metabolic health, as well as brain health. Yeah, I think it's a really, really good point, because when we think about stress, I think when, you know, a lot of doctors, but a lot of the lay public think about stress, we think about this, just the signals coming into our brain and how we perceive things. We're not thinking about how it can impact, you know, our guts, our hearts, but also, you know, type 2 diabetes. Type 2 diabetes is, you know, reaching epidemic proportions these days. It's just getting a bigger and bigger problem for society. And a lot of people are not aware that actually our stress levels and chronic stress can also impact our blood sugar levels, which is just incredible. Absolutely. And it's closely intertwined with our immune system and the inflammatory aspects, which are also out of kilter in type 2 diabetes.

Yeah. And I think something you said, John, really is something that I really resonate with, which is this whole idea that, you know, we are quite compartmentalized in the way we're trained at medical school, but also the way that we are conditioned to do research for many years. And I get, you know, I understand where that has come from. As a GP, the problem I find with that is that so many of the problems that are walking into my surgery door every day are multifactorial. And actually, it's very hard to put them in a neat little box. So you mentioned Irritable Bowel Syndrome, you know, IBS, which, you know, I think some studies have shown affect maybe 20% of the population.

You know, it's just incredible. One in five of us are going to get IBS at some point. I am finding more and more now I'm taking a multifactorial approach with these patients. I'm changing multiple things. Has your research backed that up? Because I guess a lot of your research probably has to look at one particular area, um, so that we can understand the mechanism of how something works, but then how do we translate that into real life patients?

Sure. And that's always a challenge. Some, some parts of it that we can do and we can control in a laboratory setting is looking at what is the driving factors underneath it. And so early life adversity is one of the key risk factors that we know is present in IBS patients, but also in depression, et cetera. And to understand what this stress in early life is doing to multi systems, it's really important that these systems all talk to each other. And so if we are only focusing on one readout, we sometimes could miss specific things. So we try and build that into our research program, both in our animal studies, but also now in our human studies, where we're looking at cognitive stress responsivity. We're looking at the immune system. We're looking at changes in the microbiome. So we're trying to have a

holistic view on what could be gone awry. But many of the driving factors could be single incidents or single events, could be an infection, it could be a specific stressor early in life. Yeah, absolutely. Okay, so I think it's probably worth going back and sort of looking at why do we have a stress response, you know, because you mentioned clearly it was chronic stress or traumatic stress. But I think it's probably important that we emphasize that actually stress and the stress response is absolutely necessary and served an important role for us in evolution. Absolutely. It's a clear way that our body has in dealing with a form of threat or a change in what we call homeostasis. We have a very well-wired system, both within our brain and how the brain talks to the body, to be able to alert us, to sharpen our cognition, to basically get us stopping doing things that are irrelevant at that time.

So that's why digestion is – there's no point having a meal if you're being chased by a tiger or something. So these are very closely wired together. But the problem is when we get chronic stress, these systems also go out of kilter. And so that's why it doesn't just affect the brain, but it affects the digestive tract. It affects the reproductive tract, hormones. It affects all aspects of the immune system because our immune system is sharpened during a stress to deal with any invasion of pathogens or anything else.

And so understanding that, I think, has been one of the key functions in stress research over the last two or three decades and that we we can have an alice what we call an allostatic load basically the more load we add on to our system the more it's going to be weighed down and be more vulnerable as we move forward and we're particularly interested in stress at key times across the lifespan so we're interested as, in early life, but also we feel that in adolescence and in old age, that stress can do different things as the brain is changing across the lifespan, as the gut is changing across the lifespan, and can interfere with this gut-brain axis in different ways.

And then one of the other key exciting points of this whole stress field right now is why do certain people not get stress-related disorders? And this idea of resilience. So it's not just susceptibility, but resilience needs to be built in as well. And on resilience, would you say that having a healthy gut microbiome helps provide us with that resilience, that buffer against stresses? And as part of answering that, could you also maybe define what we currently think a healthy gut microbiome looks like? So the first is, can our microbiome help buffer resilience? Well, that's something we're really working on right now. My gut feeling is that it really can, but we need to develop more data to look at that.

And then we have experiments running right now, both in laboratory settings and in animals to really test that out. Working in an educational institution allows us to chronically stress our students all the time by putting them through exams. So we're looking at whether the exam stress period is having an effect on the microbiome and whether there's a resilience or a susceptibility to that can be built up. So we can't say for sure yet that a strong...

No, it's too early. I mean, we have to remember that until about five years ago, people in the stress field were ignoring anything to do with what was going on in the microbiome. So it's still very early days. microbiome um so it's still very early days but i think you know we're we're developing enough data now to really begin to think that this is a very logical and very important aspect of resilience what have you seen so far john if you don't mind me asking that makes you feel i mean you mentioned your gut feeling which is quite interesting how I think humans have intuitively known for many years how various things affect us. You know, the word gut feeling says it already.

It's already in our vernacular that we know that when, you know, that we know that we can feel things in our gut. That sort of is, I guess, a very non-scientific clue. But I wonder, what have you seen so far that actually makes you feel actually maybe a healthy gut is going to buffer us against stress? You know, what are some of those clues in the research so far? Right. So I guess some of the key things that we found is that when we look at how in animal studies, for example, when we look at how we stratify animals based on their microbiomes, different composition of their microbiome, we were able to correlate the changes that we see with specific stress-related responses.

So we were interested in how the respiratory system responds to a stressor, and we found that correlated very well with certain microbial species. We also were interested in how the cortisol response, the equivalent in animals, how that responds to a stressor. And we were able to make direct correlations there. But some of the best data is emerging now also in human studies, where we've, for example, given healthy volunteers a specific bifidobacterium, and we put them through a stressful laboratory testing scenario. And in the lab, we stress people very ethically, but we stress them in two ways.

One is subjecting them to what we call a cold presser test, where their arm is submerged in an ice-cold bucket of water. And then there's someone watching them, so to give a psychological component to it. And they feel pretty stressed, and they mount a stress response. And we have a variety of biological skin conductance and paper-based psychological profiling we can do. And the other way is we can make them do what's called a Trier social stress test, where they have to basically prepare for their dream job and give an interview in an interview style situation. And in both of these, we're able to mount a very nice acute stress response. But what we found was, and this is a study we published just over a year ago now, we showed that a bifidobacterium, if it was given beforehand, was able to blunt this stress response.

And this is in healthy volunteers. So that was quite a remarkable finding. And I think that's very exciting. And there's a number of studies now emerging with different strains of probiotics or combinations of probiotics that are showing this. And I think that that's very exciting. It's worth noting, though, that most strains will do nothing. And we need to do the science behind it because there's a lot of what I would say. It's easy to overhype this field.

It's very easy to assume that all probiotics are the same. But they're not. But we think it's a really exciting area. And we've coined this phrase psychobiotic and and that we feel is a targeted intervention of the microbiome usually a probiotic or or a prebiotic and a prebiotic by definition is basically a dietary uh substance that bolsters the the production of the beneficial microbes so it's kind of like a fertilizer could you give some examples for people who are listening what they might look like? From our diet, inulin would be a really good example from our diet or fibers. So a high fiber diet would be really good in that regard if you can tolerate it because there are certain situations where these are not tolerated such as in certain forms of IBS. Yeah, I think that's an important point.

When I was speaking about gut health in the past and we talk about the importance of fiber and a diverse you know range of fibers a lot of people also feedback saying yeah but I can't tolerate that and I want I wonder whether we should just touch on that briefly for those people listening who might be wondering yeah that all sounds great I've heard about fiber but I can't manage fiber what what would you say to those people? Yeah I know it's a really good point of, you know, tolerability is an issue. What we do know is, though, that in ancestral communities, their fiber intake was much, much more than what we, we take and was much more diverse. And I think people's view of what fiber is, it can be a little bit skewed, that it means it's some form of bran or whatever else. But there's

lots of really good green fibers in vegetables. And there's many sources of fiber than some of the traditional ones as well. But there are other ways to basically have to really bolster the microbiomes. A Mediterranean diet in particular has a lot of the components that will also allow for a beneficial microbiome to actually, I would say, prosper overall. And inulin and other inulin-like substances are really good and are found in lots of different vegetables. Yeah.

So, you know, without going into dietary situations per se, but I think what we're going to have is in the whole field of nutritional psychiatry moving forward is that we will be able to target individuals with specific diets that will, A, suit their symptoms, B, suit their microbiomes, and hopefully relieve some of their underlying pathologies. Yeah, thanks, John. I mean, I think as a clinician myself, I think what I have seen is that, you know, you mentioned these ancestral diets. We know that, you know, communities like the Hadza tribe in Tanzania, for example, you know, I've read maybe have 100 to 150 grams of fiber per day.

And the average Westerner probably maybe 15 or 20 grams or certainly a lot less than what these communities were having and what they could actually tolerate. no doubt explore this as part of this conversation such that the resilience there that the you know the composition of our gut microbiome is has been significantly affected so some of us can no longer tolerate those fibers because we've we've in some ways got a less robust gut and you know i did speak to a dietician a few podcasts ago who specializes in IBS. And she spoke a bit about the low FODMAP diet, which is something that often people do with nutritional professionals when they take out some of these fibers or these foods that actually they can't tolerate. But that really isn't meant to be a long term thing. It's just a short term thing, you know, as a tool to relieve symptoms. short-term thing, you know, as a tool to relieve symptoms. But ultimately, we want to sort of improve the health of the gut so that long-term people might be able to tolerate those

fibres. I mean, certainly that's my take on it so far. Absolutely. Yeah. So it's, you know, we've got to recognise that our guts just aren't what they used to be. And, you know, I remember reading Martin Blaze's book, Missing Microbes, a few years ago, just being fascinated by how much of that diversity that we have lost. I'm not sure if we, I keep probably moving you off track, John, but I wonder if we could maybe just very clearly state, what does the research tell us so far about a healthy gut microbiome? Yeah, no, it's a great point i mean the conundrum we have in the microbiome field is is is really defining what a normal microbiome is we all think we're normal so it's obviously our own microbiome but my microbiome is going to be different to yours it's going to be different to all of the listeners.

And we haven't really worked out what are the essential components of that microbiome. We know that in adulthood that diversity is key. So a diverse microbiome, which is generally driven by a diverse diet, is seen to be a good thing. driven by a diverse diet is seen to be a good thing. However, that's not the case in infancy, where in infancy, we see that breastfed, vaginally born infants have actually a less diverse microbiome. So that only happens in adulthood when things have stabilized. And so we know that the diversity of our microbiomes generally in the Western world is significantly less than that of these hunter-gatherer type populations. That we have extinguished many of the microbiome components that our ancestors would have had. would have had. And it's intriguing to think about this from an inflammation point of view, because chronic inflammatory diseases that are so ripe in today's society are absent in these ancestral communities. And we think that could be due to the microbiome. Indeed, people are associating this more and more. But we don't know yet what we need to get to be the ideal.

If I map my microbiome today, I don't know how that will be, whether that's a normal or not. What we do know is in certain disease states, such as in inflammatory bowel diseases or in metabolic disease or obesity, etc., we know the microbiome is quite different. And so that's all we can say. It's different. And we probably don't want to have a microbiome that looks like that. But where I see this moving is that it's going to be a very key area in precision and personalized medicine, whereas as an individual, my microbiome might be different to yours but but in terms of i can track it as we as i age and as i go through different diseases or and i

hopefully be able to see whether there are signs or changes in the microbiome that might uh predict or at least help monitor how um i'm going to respond to certain treatments or whatever as I age. And then that's my prediction with the microbiome more than anything else. Do you mean a bit like we all have blood tests now? Do you think there will be a point in the future where we all might have our microbiome tested as a sort of baseline to see what we need to improve on? I really think so. I really think so. And as a GP, I think this will be part of your reality within the next five or so years, because the costs are coming down. The knowledge about what it means is going up. And so we're able to use large data sets like the American Gut Project,

which published a huge paper last week, outlining what the American microbiome looks like. And if you have enough metadata, so information at a population level, you can start to ascribe changes. And there they were able to look at specific bacteria that were implicated in certain mental diseases, and particularly in relation to depression. So we're beginning to see more and more of those. I want to move on to mental health in just a second. But I tell you the thing that's fascinated me the most over probably the last five or 10 years of really, you know, trying to read up as much as I can in this area

is the microbiome appears to sit at the intersection of so many different disease states that it's, you know, I know we don't want to sort of over-agate, we don't want, you know, we're waiting for research to confirm a lot of the suspicions. But, you know, even in something like type 2 diabetes, for example, which, you know, a lot of people are, you know, everyone's talking about sugar, and of course, sugar is a significant component of that. You know, I've read a lot of animal data. I've seen studies, I think, from 2007, 2013, where, you know, when they introduced lipopolysaccharide, which is a substance we all have in our guts on the, you know, on the coat of our gram-negative bacteria,

when that then, but when it enters our body and our bloodstream, that can have a negative impact on mental health. It can have a negative impact on the way blood sugar is sort of controlled in the body. It can cause insulin resistance, all kinds of things. It's very hard not to feel that once we understand the gut microbiome more and more, we'll see that that is really the intersection point for many different conditions. Absolutely. But, you know, you could have a cynical view on that too. And people have often addressed this to me, like, is there anything that the microbiome is not involved in? Because, you know, it becomes an issue there.

But my response is always this, is that we have to remember that the microbes were there first. remember that the microbes were there first and there has never been a time where our brain or our body has existed without signals coming from microbes so if we understand and can step back and and not be so human cell centric and try and think of it from an evolutionary perspective we have co-evolved with these microbial friends and they have helped us benefit from many, many things. Wow, they came first. If we take what, you know, Mark Blazer talks about missing microbes and your research is showing, if the microbes came first and then we evolved with those microbes, I guess in the last 50 years, because of modern living and a lot of modern practices, we're starting to decimate the populations of those microbes. So arguably, we're now entering a time where maybe for the first time in our evolutionary history, we might be living without the presence of certain microbes. Wow, that's an incredible thought, John.

Yes, it is. Yeah. You mentioned right at the start about the gut-brain axis. I'd love to delve into that a little bit. What is the gut-brain axis? I think many of us know that when we're stressed, that can have an impact on our gut. I've got many patients who tell me that when work stress gets too much, even if they don't have a diagnosis of irritable bowel syndrome, they find that their stool is often a bit looser, which is just incredible. I've heard that many times in my practice.

But I think we're also finding out now that actually what we do with our guts can also send signals back up to our brain. So I just wonder if you could clarify what is the gut-brain axis? Yeah, so the gut-brain axis is not a new concept at all. We've known about it for hundreds of years, but it's only in the last, probably since the advent of brain imaging, that we began to really see that stimulation of the guts could actually directly influence what was going on in the brain. And we're working out all the time the main pathways of communication

and how important they are for maintaining this homeostasis, this sense of equilibrium, if you want, that the body needs to be in all the time. sense of equilibrium, if you want, that the body needs to be in all the time. And most studies in gut-brain axis are actually focused around food intake, because food intake is actually quite a complex behavior. We take it for granted, but it's driven by signals from our gut to our brain to basically say, eat now. And there's lots of different hormones involved in that regulation. But also, and so that's well known and that's been studied for a long time.

And then we have what's called the enteric nervous system, which is often referred to as the second brain. And we have more neurons in our enteric nervous system than we do in our spinal cord and this is this really second brain has a lot of power it controls you know fundamental processes like motility and permeability and how the digestive digestion works but we're beginning to see more and more that it's also involved in signaling directly to the brain and how the brain responds to different stimuli in general. And also the protocol between the microbes, which are in the lumen of the gut, they often are able to send signals that can activate the enteric nervous

system, which in turn can activate other nerves that can communicate with the brain. So understanding gut-brain access is really important for a variety of different diseases, ranging from GI disturbances like irritable bowel syndrome, but even other disorders involved in complex emotional processing. Wow. I mean, that really ties in with a lot of the research that's coming out now about how our food can affect our mental health. And, you know, there was that trial from February 2017, I believe, the SMILES trial, where they showed the positive benefits of the modified Mediterranean diet.

I wonder if you could expand on that at all, John. Yeah, so this is a really fascinating study from Felice Jacquez group in Deakin University in Australia. And Felice has been a long term proponent of the relationship between nutrition and mental health and has done some really classical epidemiology studies showing that people who have generally bad diets with processed food, that they're more likely to have changes in their mental health, negative changes, as well as even changes in the structure of the hippocampus in the brain. So the SMILES trial was her taking what she had known from this epidemiology way and turning it upside down and seeing can we intervene with a good diet and boost what's going on. It's still a relatively small trial,

and it's important to note that all of the patients on it were maintained on their medication or their psychotherapy. So it wasn't a replacement trial. It was an additive trial. But it was very exciting for the field because it really reinforced that nutritional interventions can support a good mood. And, you know, I think it'll be a landmark study, even though it's quite small, for the field and moving forward. But the big question that remains and one that we are actually collaborating with Felice on a little bit is in relation to what is driving this positive effect of diet on mood. How is this happening? And we really think that the microbiome is a key conduit in this signaling because not only do we have a gut-brain axis, we really now have a microbiome gut-brain axis.

And you can add diet as the fourth part of that. So it's a diet, microbiome, gut-brain axis. And so we can, you know, through the modified Mediterranean diet, you're increasing the intake of essential components that are supporting beneficial microbes. These include the omega-3 fatty acids, the polyphenols, which are very heavily present in this diet. And so studies need to prove this, but we know the Mediterranean diet does positively affect the microbiome.

We now need to make sure to join all the dots in this together to show that it is them changes that are going to have beneficial effects on mood. We've done other studies that have helped reinforce this conviction that we think that the microbes could be very key in depression. For example, we've shown that in a group of depressed patients, they have a much narrower diversity of the microbiome than healthy controls. And then we took that microbiome from both populations, depressed individuals and healthy individuals, and transplanted it into an animal, into a rat. And we were able to basically transfer the blues. The animal had lost interest in pleasure in things it normally finds pleasurable, like sugar.

It was much more anxious. It had a pro-inflammatory phenotype, increases in tryptophan metabolism was changed. So this was quite remarkable for us that, you know, there's something within the microbiome that's driving behavioral changes so relevant to depression. Well, that's key that you're taking, you know, that shows cause and effect, really, doesn't it? That you're taking that gut microbiome from someone else. You're putting it into someone who doesn't have mental health issues and they are getting mental health issues on the back of it. This was in animals, right?

This is in animals. This is in animals. We haven't done it in humans yet, but it really helps us go towards a causative nature of what's in the microbiome. And then other groups have done this for irritable bowel syndrome. The Canadian group of Chemek Bercek has done this in IBS, very elegantly shown that they could recapitulate an IBS phenotype in animals by taking the microbes from patients so we're seeing this more and more yeah it's incredible and you know just to expand it out there are some studies out there which are suggesting that this could also work for things like obesity potentially where

they've taken the microbiome from you know someone I think it was an animal studies you know an obese animal and transplants it into a lean one and i think that's changed their weight changed you know whether that person that animal was obese or not and so i think one of the things is so useful is that they help to show cause and effect potentially because i think a lot of people for years have been saying well yes there is an association between you know a a certain microbiome and a disease state but we don't know that that's the cause. Absolutely. And we need a lot of caution in this field because the correlation does not mean causation. And we can have a lot of correlative studies, but we need to actually get back to almost to Cox-Fostulates type of an approach. John, I can tell you, when I see a patient with you know, my practice over the last 17 years has evolved substantially to the point now where I will very rarely, if ever, just change one thing.

So if I've got a patient with IBS and let's say they don't want to go down the medication route or they want to try something different, even if they make some changes to their diet, I find that that can often be limited unless they're also addressing their stress levels. And I guess if we think of the gut brain, that's the same. There's messages going from the gut to the brain, but also from the brain to the gut. That would sort of make sense, wouldn't it, that you kind of have to tackle it both ways. If you just tackle one half of that, you're not going to get a result. Absolutely. And we're understanding that all of the systems in the body are so intertwined. And that gives the huge power in the microbiome because unlike your genome, which you can't do much about

except blame your parents and your grandparents, your microbiome is something you have the potential to modify. And so that gives you as an individual or as a patient, some level of empowerment in a way. We just have to learn how to do that in an appropriate way. And that's in a way why we wrote that the book that we wrote this year was really to kind of give people a sense that they have the power themselves to modify your microbiome, to change what's going on in relation to your brain and how you deal with stress. John, look, you know, you mentioned your book, The Psychobiotic Revolution. Can you sort of let the listeners know what sort of

information might they get from reading that book? You know, is it going to be a walk through the science? Are there going to be a walk through the science? Are there going to be some practical take-home points for them as well? What exactly is in the book? Yeah, so the book is one that Ted, Diana and I wrote with a science journalist, Scott Anderson. So it's written totally for the lay person and hopefully doesn't have too much jargon in it. We wanted it to be as practical as possible for an individual who's starting on their own journey and trying to figure out about their own gut health. And we wanted it to be informative,

but we also wanted to offer some practical solutions. So we devised like a new dietary psychobiotic pyramid, which could help people to, you know, what foods that are good for supporting beneficial microbes and others. We also talk about how to read a label of a specific probiotic, which would be more relevant maybe to U.S. readers, but it was important for us to give practical advice and to talk about certain foods that would be beneficial. But all of it needs to be taken with the cautionary words that I always want to give is that we need to do a lot more research. We need to figure out – we would never be launching drugs onto the market without having clear clinical evidence that they're going to do things.

So we need to continue our skepticism about what's available because there's a lot of snake oil available out there without any scientific data behind it. And so why is it that certain bacteria or prebiotics are going to have beneficial effects and others not? And that's a big part of what we're trying to get people to understand. And once they find something that works for them, to try and dig into seeing find something that works for them to try and dig into seeing that that why that's working for them but it may not work for their partner it may not work for

someone else because of the individual nature of the microbiome yeah yeah that's i think it's a really really important point that you raise there just for the listeners you know i've been getting a lot of feedback since i launched this podcast at the start of the year but people want show notes and there are now show notes on every episode. And on this one, it will be at my website, drchastity.com forward slash John Cryan. And, you know, I will link to everything we speak about. You know, some of the papers John went through,

I'll try and put a link to some of those papers, a link to John's book and all these kinds of things that he's speaking about. So do check this out after the episode, if you're interested in, you know, delving a bit deeper into those papers. John, you say we need to do more research, and clearly we do need to do more research, but a lot of the recommendations that we can make to the lay public

to improve the health of their gut actually comes with no downsides. And I guess as a clinician, for me, there's a lot we can do with our diets or just teaching people how to manage stress a little bit better, which we know is going to have a positive impact on their gut health. So as a clinician, I feel very comfortable making recommendations that I feel are, you know, at the very least, they're going to do no harm. some of those top tips you know maybe three or four top tips for people that what can they do immediately after listening to this uh to go and start improving their gut health absolutely and i totally agree with you and many of these there is no downside so there are certain things we can do actively um and then there are things we should maybe don't which is is avoid. So on the do list would be to try and increase the diversity of the diet,

try and increase fermented foods. And they can be quite exotic things like kimchi and kefir and kombucha, but also yogurts and sauerkraut and various things like that. We know that they're going to have beneficial effects on the bacteria that we want to see thriving in the gut. We know that increasing the prebiotic, the fibers we talked about, the inulins, the green vegetables, that's very clear, positive things we can do to our microbiome. Then the don'ts was we should try and avoid processed food because we know a lot of the components of processed food

like emulsifiers, sweeteners, et cetera, are really bad on the microbiome. We know that antibiotics need to be minimized as much as possible. There's a huge increase in the amount of people born by C-section, many of it for non-medically indicated reasons. And so C-section automatically changes the trajectory of the microbiome and area life. Supporting breastfeeding is really important,

especially in the UK and Ireland where we have relatively low breastfeeding rates. And then having a pet has been shown in a large number of studies now to increase the diversity of the microbiome. And that's quite good. We should also try and have good sleep. Sleep, microbiome, circadian rhythm, microbiome interactions are, the field is now beginning to wake up to this. And exercise has been shown, especially aerobic exercise has been shown to have beneficial effects on the diversity of the microbiome.

So they're the kind of the things that people can look at themselves and try and look at, you know, especially, you know, if they're going to go through some stressful situations, whether it's having exams or doing interviews or traveling a lot, you know, there are things there that might be of use. Yeah, John, it's just incredible for me to hear, you know, yourself, one of the top researchers, probably in the world in this field um talking about the importance of

all these various lifestyle factors that you know i've been trying to talk about for years put in my my book the four pillar plan which is the importance of food movement sleep and relaxation and i sort of do in the book sort of weave together how those things all can actually impact our microbiome it's not just the food that we eat. Exactly. And I really think your four pillars could be very much underpinned by a foundation of what the microbiome is doing to the body as well. I think it's really a good way of linking all of them together. Yeah. You mentioned processed food, John, and some of the emulsifiers. So I wonder if we could just briefly touch on you know something

that a lot of people often put on my social media channels you know how bad is sugar for the guts per se and then a follow-up question would be how bad do we think sweeteners and artificial sweeteners such as those found in diet drinks might be so a lot of the data still is only in animal studies so so we know that artificial sweeteners are quite perniciously bad for the microbes uh there's been a number of studies from the u.s showing that uh even worse than sugar per se and sugar has its own downsides on things but but sweeteners seem to be pretty bad so that's one thing. And the emulsifiers really have been shown to be not good as well. And then there's a lot of components in processed food that have never been tested to see what they're doing to the microbiome in general. And we have a lot of

environmental factors that are also negatively influencing the microbiome. And so it's important that we understand that our microbiomes exist within us, but they exist within us in an ecosystem like any ecosystem that can have basically insults to us at any time that will upset it and allow it to go out of kilter. Do we know yet whether sugar per se, just sugar in itself, not in the context of a fizzy drink, but whether sugar per se has sugar in itself not in the context of a fizzy drink but whether sugar per se has a negative impact on our on our gut health see i i don't think the studies have been properly done in humans yet there are some studies in animals um but the question in animals is always about dose so um and a lot of the sugar doesn't get to the ax before it gets to in contact with microbes. So it's chemically used by the body in different ways. But what we do know, and you alluded to this earlier, is there is a very tight relationship between microbes and glucose homeostasis within the body in general.

And these are tightly linked. And so, you you know it's not surprising that sugar will have an effect salt is the other thing people have looked at salt and the impact of salt has it on the microbiome and there's lots of data on that and perhaps one of the most surprising things that i didn't mention about the microbiome but it's also really important that at least a quarter of all of the drugs that you prescribe um in your practice uh a quarter of them will have negative effects on the microbiome wow so 25 of the drugs that i might prescribe will have a negative impact on the microbiome and we're probably not even talking about that. Also there's really exciting work in the oncology

field but also in the metabolic field showing that the efficacy of certain drugs depends on an individual's microbiome for example checkpoint inhibitors in cancer therapy that if you had a certain microbiome you were more likely to respond to this type of drug. Yeah that's incredible I mean I guess that the flip side to a quarter of the drugs having a negative impact on the microbiome is that I think I read some research where, you know, one of the most commonly prescribed type 2 diabetic drugs, which is called metformin. Metformin, I believe, appears to have a positive effect on the microbiome and increases the growth of a bug called Acomansium mucinophilia, which we know helps with blood sugar regulation.

Is that the case? Are there any other drugs that you know of? That is exactly the case. And the Metformin data is really exciting because it's telling us that we need to understand how drugs are interacting with not just their main targets in the body, but also in the microbiome. We've shown, for example, that antipsychotic medications, also in the microbiome. We've shown, for example, that antipsychotic medications, as well as some antidepressants, can have direct effects on the microbiome and that some of the side effects of these drugs could be driven by their changes in the microbiome. So perhaps in the future, when you're giving a drug that is really beneficial for the patient, that there might be a probiotic or a psychobiotic drink to go with it to prevent some of the side effects. John, it's just so fascinating. I know we've only got a few minutes

left on this call before your next meeting. So I'll try and just quickfire a few more things. There's so much more we could talk about. But one thing that often comes up is we talk about the negative things in the modern world that can damage our microbiomes, whether it's highly processed foods, sweeteners, emulsifiers, having too many antibiotics, particularly in childhoods, being born by cesarean section. You know, a lot of these things, people might be listening and thinking, well, okay, I can change my diet, but you know, I was born by C-section. I can't do anything about that. I was given a ton of antibiotics when I was a kid because I kept having ear infections.

And often people can get quite down when they hear that. You know, do we know, you know, as the research stands, you know, yes, the early years are very important. And, you know, yes, going forward, we'd like to change society's approach to various things, you know, like using C-sections when they're only absolutely necessary rather than, you know, when they're not, for example. But, you know, for people who have had, let's say, a rough roll of the dice with their microbiomes,

are you optimistic that there are plenty of things that they can still do to optimize their gut health? Oh, absolutely. I think this is not a, you know, a fait accompli that something happens in early life, and then you're driven on this trajectory. It's just one of the key factors. It's all about relative risks and relative situations. We're very confident that by targeting the microbiome, we could actually override some of the miswiring that may have occurred in terms of the circuits underpinning our stress response, for example. And that's where we think the whole field of psychobiotics could come into play. We don't need to know what's causing the changes in brain function to actually target it with potential bacteria. So I'm very confident that by improving your individual gut health and whatever that means for you,

because it's going to be the individual aspect to that, you have the potential then to actually improve your brain health. Wow. Incredible, John, to lead people with that thought. And just to reiterate, John was saying that on the do list, he was talking a lot about diversity, about the different fibres, the different foods that you can have that you would typically get in a diverse Mediterranean diet. Guys, you've heard me talk about eat the rainbow before.

All these different colours have got lots of different polyphenols, lots of different components that are going to help you improve your gut health. But you also mentioned fermented foods. John, final question then. In all your years of research on the gut microbiome, have you, given what you have learned, changed things to do with your own personal health based upon your research? I'm often asked that question, Rangan. So it's interesting. I think I have more subconsciously than consciously so i do try and increase my uh fiber intake and definitely increase the diversity of the diet that i have

i'm more aware it's more about an awareness um and uh i think that's probably you know one of the things but i'm not the most stress sensitive person, so I can deal with stress pretty okay, generally. But I think that as I get older, I think I will be putting much more focus on it. And I think, you know, we have a lot of sense of, as I mentioned, empowerment within ourselves, that we can actually make changes in our lifestyle that we know will positively affect our microbiome and our gut health and that that could have positive effects on how our brain is john i've got to say it's been it's been such a huge pleasure for me to spend nearly an hour chatting to you um you know huge fan of the research you're doing i i you know i hope your lab continues to do such great research because it helps guide you know in the trenches clinicians like me it helps us understand how we can help our patients so i just want to from the bottom of my heart

thank you because the research you do really really matters and it helps the lives of thousands of people so you know a huge thank you to you but also to your team as well john thanks for your time today guys i really encourage you to check out john's book the psychobiotic revolution and john there's so much more we could speak about. So maybe we'll get you back for another episode in the next few months. But thank you so much for joining me. No, my pleasure, Rangan. Thank you. And it was a really enjoyable chat. And it's always good to talk to someone so informed. That concludes the latest conversation on my Feel Better Live More podcast. I hope you enjoyed it. If you did, please do take a screenshot of this page on your phone right now and post it on social

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