Dr Rupy: Miguel, can what we eat improve ADHD?
Dr Miguel: Definitely. So that's the short answer. And now because I'm ADHD, I'm going to give you the very long answer. So basically, yes. Everybody's a little bit unique, so ADHD can be experienced by different people in in different ways, but definitely you want to be supporting your executive function in the brain. Largely that's based in the the front of the brain, the prefrontal cortex. And in ADHD there's a lot of emotional dysregulation, so people feel that their emotions are actually driving them more than their logic. So doing things in a sequential order or changing from task to task or even just the anticipation of a task can actually make you quite nervy and then you procrastinate and you don't do it and all this kind of stuff. So if you take anything that is going to give you a quick burst of energy, like a very starchy meal or a very sugary meal or loads of coffee, that might give you a really quick release of energy, but it's going to burn out really quickly as well. So I think the the basis on which people should be thinking about eating to I wouldn't say improve their ADHD, but to improve their ADHD symptoms or to improve how they experience their ADHD. A good balance of protein, complex carbohydrates, which carbs get a bit demonised as well, you know, all carbs are bad. Well, you need them. So good protein, whether it's plant-based or animal. Plant-based for me preferably, not because I'm a vegan, but because plant-based protein will also give you fibre, which is really important to then soften that spike of sugar that's going to keep you energised throughout the day. So in a way it's almost like a an ADHD adapted blood sugar control diet in a way. So your good protein, your fibre, minimise anything ultra-processed. Read the ingredients on labels, just use real food as much as possible. So those are broad strokes as to how you manage your ADHD naturally.
Dr Rupy: Are there particular elements of hyper-processed foods that litter most supermarkets that can exacerbate ADHD symptoms beyond the sugar and refined starches that can put you on a sugar rollercoaster?
Dr Miguel: Definitely. I'd say anything that's got names that you cannot pronounce and loads of E numbers. Some E numbers might be inoffensive, maybe just a little bit of colouring that may be based on curcumin for example, but some of them have been seen to have an effect on people who are neurodivergent, so ADHD, autistic, because they may actually block the way that you absorb other nutrients. So they may do things to the microbiome and there's now good science on how emulsifiers and things like that might actually have an impact on the diversity of your gut flora. And then because of the gut-brain axis that I think we're going to be talking about anyway, the connection between the gut and the brain, your gut microbes are not doing the best job that they can do for you. And that's going to have an impact on how your brain feels. So anything that when you look at labels, if it doesn't look like food, if it's a coconut, it's a coconut. If it's an apple, it's an apple. There's no mistaking. If it's something that you need to look at the label because it comes in a box, there are many variations of ultra-processed. So I, for example, did a clinical trial on comparing people who ate vegan sausages and meatballs and burgers. So fake meats basically. I don't like the terms, but that's how it was publicised when it came out. And it has attracted quite a lot of attention. It's been cited a lot of times now, every day I get a citation. It was a small clinical trial, 20 people in a group replacing their animal meats or animal protein, so fish, meat, eggs and so on with the plant-based protein, and then the other 20 just continued as they were, just eating their regular kind of like British diet. And it was really interesting to see the changes in the gut microbiome, which was the what we were trying to measure basically. The composition had actually changed favourably in people who ate the plant-based protein. And we saw something very interesting as well that a group of microbes that produce this thing called butyrate. It's a waxy molecule, a little bit like wax that you put on your hair or something like that. It's that kind of like consistency, a little bit like butter. It's called butyric acid. In fact, butter has got a lot of butyric acid. And and that is produced by a group of microbes. We'll probably talk about them later, but you know, Faecalibacterium, Roseburia, Coprococcus, you know, and so on. And we saw an increase in the abundance of those bugs and also we did some analysis on how they produce on their function. And there's this thing called metabolic pathways of those microbes and we saw a trend. It wasn't significant in in terms of like, you know, a proper statistician telling you this is a significant result, but there was a nice positive trend. So what this is telling you, and the hypothesis as well in the study, the way I wanted to formulate it is that not all ultra-processed foods are actually the same. So if you look at how the company that put the products together, how they put them together and you look at the list of ingredients, there was minimal things that you could think, oh that's actually nasty, it's going to do me some damage. It was pea protein. Okay, so from a pea to the pea protein, you need to process the pea and it ends up looking different to the pea, so you couldn't actually figure out from the protein that you see in a powder that is actually made of peas. But then the effect on the body was positive. So that bit of ultra-processing was actually beneficial to the body, if that makes sense. And they combined it with rice protein, with rice powder, with psyllium husks, with, you know, sesame seeds, whatever. There was a lot of wholesome ingredients in there, but processed in a way that if you actually went to the manufacturing plant, you wouldn't recognise them from the food. So we can be a little bit too purist as well. And we live lives that are complicated and people go, you know, it took me an hour and a half to come here. If I got hungry on the way and I got something from a shop on the high street, I don't want to be freaking out because there's been something ultra-processed in my day. There's always going to be something in your day that is not what you had planned. And I think that kind of focusing on controlling everything can actually be quite damaging for your mental health.
Dr Rupy: Absolutely. I think there is this puritanical streak in the conversations that we see online about removing all processing from your diet entirely and that, as you've just pointed out, is just not possible when you're living in an urbanised environment. Yes, it might be if you live on a farm, but not when you're living in a city environment or, you know, even a suburban environment. And it's interesting because my initial thoughts were potentially if you're having the meat product, that might be beneficial in some certain circumstances to some of the ultra-processed vegan products or plant-based products that we see on the shelves. But I guess the type of processed, and I'm saying that in quotation marks, processed product that was used in your study seemed to have like really good ingredients in pea protein, psyllium husk. These are all things that we know are uniquely beneficial for the microbes in our in our guts. Do you think there is, I know that was a small trial, are there other studies that have looked at the quite refined and very different sort of unwholesome vegan plant-based products out there?
Dr Miguel: This is growing, but obviously the politics of the industry. So it's not in the industry's best interest to actually put themselves out to scrutiny. So this was a little bit of a fluke study in the sense that, you know, they were looking specifically at the microbiome and and it just happened to turn out that way. Anytime that you have a product and you do a randomized control trial and you're actually going through the whole of the ethics process that it involves to go through a university and everything else, you just don't know what the science is going to say. And you it's a bit bad to actually then not publish it because the results are negative. So I think there's big money to be made in plant-based products. So what I was saying before, I most days I wake up and I get a citation basically. The study was published two years ago. It's got something like 70 citations already. And which is, you know, I've done other studies before, they get like three citations, you know, like three years later. This has raised a lot of interest. I think people are kind of like interested in the idea, but then they haven't got the guts for lack of a better word to to go to go ahead and explore that just in case it's negative.
Dr Rupy: Yeah, it's very interesting. I was chatting to Robert Lustig on the pod a few months ago and he did this big project in the Middle East where they looked at processed foods and tried to optimise them from an omega-3 point of view, increasing fibre, using more wholesome ingredients like, you know, psyllium husk for example that I've spoken about on the pod before. And there seems to be a middle ground whereby you can have sort of the taste, the texture, but also the price point that is acceptable to many people, which are the benefits, quote unquote, of the of the processed foods that we see today with some of the added advantages of of wholesome ingredients. Do you think that, and we're going a little bit left of field here, but do you think that is a potential middle ground or the way forward for for both food, the food industry and us as a as a population to improve health?
Dr Miguel: Yeah, I think people like convenience. So when I was looking at the literature before engaging in the study and formulating the the the trial, formulating the hypothesis, the hypothesis basically was a little bit different to what people may have been expecting because what I was saying is that not all ultra-processed foods are actually detrimental to the body. And and then of course we were we had an endpoint of the gut microbiome and we were looking at changes in composition and and metabolic pathways in in microbes, how they actually function. But when I was looking at studies, it was interesting for me to read that vegans, and again, my study was actually based on flexitarians, so actually people adopting a largely plant-based lifestyle, but not necessarily going vegan, which, you know, it's not for everybody. It's not the commitment is is big and there's a lot of politics involved and not everybody wants that kind of thing. Lovely if you want it, not everybody does. The flexitarian literature was telling me that people actually like products that look like the real product they are trying to replace. So they had done studies in several places. I cannot name one right now at the top of my head, but they had done studies comparing groups of people given something that looked like plant-based protein, but it didn't have a shape. And another group of people given the same, but it actually did look like chicken. It looked like a chicken fillet or it looked like a like a sirloin steak. So it actually did look like the like the product it was trying to replace. And the preference was much stronger for the product that it was trying to replace. So the texture, the smell, the look. So if you make a beef steak, the more it actually looks like beef, people were more attracted to it.
Dr Rupy: I've seen some of those as well. They look really realistic. They look incredible now. Like the the the speed at which this industry has has travelled over the last two years is phenomenal.
Dr Miguel: Yeah, yeah, exactly. So that tells you exactly what what people want. So to go from that to something that may be a little bit more wholesome, but may not look exactly what what you're trying like what you're trying to replace, it goes back towards the just use whole foods all the time, which is more of a commitment. I think people want the convenience when it comes to these foods because everybody really can cook from scratch to a certain extent. You know, even tinned foods or jarred foods are excellent sources of nutrients. You know, just because they are cheaper, they they are not necessarily worse for for your body. So everybody can get some black beans out of a tin and some corn and and something else and mix it up with a bit of olive oil and and make a wholesome salad. Do you want that and do you want to invest the time in doing that for you or do you want something that comes ready packed and it gives you the illusion that you're having something else? So there's a lot of psychology involved in this and and also like going deeper a little bit into the the psyche, are you worth it? Do you think you deserve that? So you're investing the time on creating something that is really wholesome or are you not that bothered and you think, oh no, I just rather have the five-minute burger that comes in a pack.
Dr Rupy: Yeah, yeah. It's a that's a huge point and I think that doesn't get enough attention because it's very easy and you could look at it through the lens of price and I would argue you can find healthy wholesome products at a similar price point. Time, you can, like you've just articulated, bung a few things in a bowl, mix it to go with some olive oil and then that's your lunch and that's cheaper and and easier than a sandwich. But it's the psyche, it's the psychology, am I worth this? Am I am I comfortable in my own skin? Do I feel like I deserve it? All those different elements that are a little bit harder to ascertain and a little bit harder to sort of bring out in a patient or someone that I'm consulting for example. But I feel that that's an underlying tone that I'm I'm I'm getting as to why people struggle to eat well every day. We're going to we're going to go into that a little bit later. I'd love to. I want to bring it back to foods to improve ADHD. I know that you were involved in a probiotic study, I believe, where you you gave people kefir, I think it was. Is there a role for probiotic foods and ADHD? Is there any improvement there or is it again just sort of improving the gut microbiota and improving sugar balance? What what are your thoughts on that?
Dr Miguel: So the study is is ongoing. We published a a pilot study a couple of years ago. We then just about to publish the study protocol, which is this is the politics of science and publishing. We're nearly done with the randomized control trial. We've seen a number of people and and put them through the trial. We're going to begin writing that and extracting the the data. It's looking good, but the protocol hasn't been published yet because it's going to be published in a high profile journal. And it's literally taken like a year and a half for it to be reviewed and you know, it's kind of, you know. So these are the kind of things that happen in between, you know, behind the scenes in science that people are not really exposed to. So it's it's cute that the actual protocol will probably be published like later than the actual RCT. So, cut a long story short, the pilot looked at children who were not on medication or on CBT. So they have been diagnosed with ADHD and we did require the diagnosis, even though we'll talk about being diagnosed and and just identifying or, you know, later. But in this case, we're looking at formally diagnosed by a clinician, children from I believe eight to 15. And we looked at a symptomatology, so severity of symptoms. And again, in ADHD, there are different symptoms that you can take into account. So you can look at hyperactivity, which in in children it can be quite noticeable. So like tapping, you know, and doing things like this or like tapping with your fingers and all of this kind of like nervous kind of stuff is a way to regulate your emotions when they are there's too much going on in your brain. So it's quite physical. It can get irritability. For parents, it can be difficult because they can be a handful and they are just struggling. They can also be inattentive. So you can just, you know, I can probably put this here, then forget where it is and I get into a panic just looking in the room and I go back to the tube station thinking I left it at the tube station. I'm convinced and it was there all along. That's happened to me like all my life. My mom used to laugh at me when I was, you know, living in the house because I used to leave my keys all the time. And I literally every single time I went three flights of stairs down to the ground floor and thought, oh my god, my keys. And I went back up and she was already at the door of my flat like, you know, with my keys there you go. And like things like that and books and all that kind of stuff. So that we looked at all of those and it's a multidisciplinary team. So it's led by Dr. Kate Lawrence at St. Mary's University. She's the principal investigator. There are people from Goldsmiths, there are nutrition people from St. Mary's. So it's psychology, neuroscience, microbiome. We have Professor Paul Cotter as well has joined in the later studies. So what we're looking at is changes in the gut microbiota. The pilot allowed us to see that we needed to look at function as well. So you can analyse changes in your gut in different ways. And you can also look at what the bacteria are actually doing, which goes a little bit deeper into the detail. So we basically looking at what the pilot churned out. I suggested that we needed to look at what the microbes were doing as well. So it's another way of looking at microbes called shotgun sequencing. It's a little bit more precise or it's different than 16S, which looks at composition. And we look at a number of psychological measures as well, self-reported, very important. And I'm a big proponent of self-reported because it goes into something we're going to be tapping into, lived experience. Everybody's experience is different and unless you ask them, you miss out on that. And it's great to have a number. The number is precise and statisticians love a number because it's like, you know, it's easy to process. If you ask me how I'm feeling and I just go on and on and on and you need to transcribe that, you need to then process the interview, you need to code it, you need to understand what are you looking for in what I've just told you in an hour. You just let me talk. So the bit in between are these things called patient reported outcomes. You basically have like a structure and you follow some structure. So it ends up being like a number, but you've taken the person into account. And then loads of other things that the psychologist know better than me because they are kind of, you know, sleep measures and a thing called actigraphy as well, which tells you about different functions of the brain and so on. So basically we put all of that together and the results look good. So drinking kefir is is more complex than taking a probiotic because kefir gives you is a whole food and it gives you apart from the probiotic bacteria, it gives you probiotic yeast as well. So this is a a booming field in the microbiome field because we talk about lactobacillus and bifidobacteria all the time. These are the kind of like stars of the show. But yeast are hugely important. We tend to think of yeast as bad, but we used to think of bacteria as bad years ago and now it's all the rage. So yeast have a very, if I had to summarise in a quick word how they how they function, they have two ways. One is they crowd out other microbes because they take up a lot of space in the gut. And the gut is a limited room. And if you invite 20 people into a room, you're going to be more crowded and you're hoping that the nasty people will leave the room. You invite nice people in, the boring people or the nasty people will go. We'll talk about that later. And then the the second way is that they stimulate the immune system. So they kind of gently touch the lining of the gut and the gut contains a lot of the immune system in the body. A lot of what happens with how your body reacts to infections stems from the gut. So if you gently stimulate how your gut cells are producing mucus, for example, that mucus feeds beneficial bacteria that they can chomp at it and and feed on on the actual mucus. The mucus is very rich in a mix of protein and carbohydrate and it contains a lot of nutrients. So then the beneficial microbes that you want to stay in your gut are thriving basically, especially the ones that like to live next to the mucus. And there's a whole section of them. And they happen to be bugs that produce this thing called butyrate again, we we go back to the same things. And butyrate kind of like lubricates the communication between the gut and the brain. So you have this weird thing going on between the gut and the brain and people say the gut is the second brain and all this kind of but nobody really understands. Even like, you know, I did my doctoral degree in that, gut microbiome and mental health. If I had to tell you in like two words how it works, it's very difficult because there's so many things going on. But it's almost like you have a an internet connection sending messages like a broadband connection between the gut and the brain. And you have loads of different actors and gut bacteria are almost like the protagonist in this in this thing. But the actual system itself is really important. So how healthy is the the actual gut lining? How healthy is your digestion from your mouth to the other end? If you're not chewing properly, you're not going to get the opportunity to extract nutrients that then may be needed further down in the small intestine or in the colon. If you're really stressed, and that's the the the the top to bottom branch in that communication, if you're really stressed, what your body is going to go into is this kind of like fight or flight response. And we're told, you know, fight or flight, there's going to be a lion coming to get you and all this kind of stuff. But there's no lion. It's just your bills, your Instagram notifications, your whatever, you know, anything that is just requiring your attention all the time. It's sending you into this mild state of panic. Your brain is thinking it's panic, but then you're saying, no, it's fine, it's not. So you're constantly using energy. And this for ADHD people is actually very exhausting because you you have a more difficult time actually switching from one thing to the next because you might be hyper focusing on something and it takes you away from that and then you get resentful and there's a lot going on in that brain that people who are not ADHD don't need to contend with. But there is that broadband communication system. And there's a wire, it's called the Vegas nerve. And again, you'll have heard about it. I'm sure you've had loads of people talking about the Vegas nerve here. And then there's the Wi-Fi, which is, you know, hormones, tiny bits of protein that are these things called peptides that are the basis for things like serotonin and dopamine and, you know, neurotransmitters that are again communicators in the brain. They do things differently outside of the brain. So there's this thing that people say serotonin is mostly produced in the gut. And to an extent it's true, but it doesn't mean that the serotonin in the gut then goes into the brain and then it makes you be happy all the time. It's a lot more complicated than that. And there's this butyrate and butyrate again, I refer to it as a lubricant because if you have all of those cables wiring and all of that communication going on, it's almost like getting an upgrade onto your Wi-Fi. So you go from like very poor Wi-Fi to, you know, to cable Wi-Fi, like one gig each way. And that's what butyrate is doing. It's promoting that really smooth communication between the gut and the brain both ways.
Dr Rupy: I I really like that that that term you used, butyrate is lubricating the connection. And this Wi-Fi analogy is pretty up for me because I've had I've struggled to get Wi-Fi in this building. So I'm loving these analogies. You need a bit of you need to call your Wi-Fi butyrate. Yeah, yeah. I need some sort of lubrication to the Wi-Fi. I just wanted to double click on the serotonin point you made there because I think you're right. I hear this a lot about serotonin mainly produced in the gut. And whilst yes, it does have an impact on mood, you're probably going to tell me it's it's complicated and we don't have a clear answer. But what why does why is serotonin produced in such quantities in the gut if it doesn't have the impact on on mood directly?
Dr Miguel: Yeah, so serotonin is produced by cells in the gut called enterochromaffin cells. Long mouthful name. But the most important thing is that it's produced to allow you to go to the toilet because it helps with gut motility. So if you haven't got enough serotonin, you probably struggle having a regular poo. And that is one of the main things that it does. It's also a regulator of vasodilation, so basically how your arteries are expanding and contracting to the rhythm of the heart. And then that translates into the expansion and contraction of tiny capillaries that are kind of like bringing oxygen to tissues that, you know, in all parts of the body. So it has a role in that as well. So it's completely different roles to what it does in the brain. So this is called peripheral serotonin. It's mostly produced in the gut and then used peripherally. So not in the brain. And and then you have the serotonin in the brain that does regulate mood, it regulates to a certain extent appetite as well. It can make you feel connected in if you produce it at the same time as other hormones as well. So it's not just high serotonin means more bonding, more connection. But if you produce it in an environment that leads to connection and you're hugging somebody, you might feel that you love them. So it's kind of like the hormone of or the neurotransmitter of love and and bonding and connection. And for example, mothers and and children when they are looking at at each other's eyes or when you're looking at a dog in the eyes, they do that as well. We produce this thing called oxytocin, which is another peptide that makes you feel connected to that person. You're probably producing oxytocin because I'm looking into your eyes and I'm doing the same. It helps understand the situation. It also has a double edge, the oxytocin is, if you look at evolutionary medicine, is there to assess whether you, the person you're talking to or you're looking into their eyes is an enemy. So you need to be, you know, kind of like judging, do you trust them or not? So I think it's just been blown into is the hormone of love and you know, you want to hug everybody and kiss them. It's kind of like it's got a, you know. Yeah, exactly. And and then if you produce that with serotonin, then it's a lovely kind of like bonding experience and it's what you feel. If you had to kind of like talk about the chemistry of love and and attraction and so on, there's oxytocin, there's serotonin, and dopamine as well, because dopamine is about anticipation about what's going to happen. And again, another little bit of a myth about dopamine is that, oh, get your dopamine by completing tasks. Dopamine doesn't give a damn about completing. It's all about what's going to happen. And that's why it's really involved in the reward system and and when you look at the negative elements of dopamine, it's involved in gambling and sexual addiction and drug addiction and any substance kind of abuse. I worked in in mental health nutrition for a while, like six years in a multidisciplinary team led by a consultant psychiatrist working with people who lived with addiction issues. And you see the pattern psychologically in this kind of like profile of person is all about what's going to happen. And then once you've done it, it's a, you know, whatever. If you are really, it's the expectation of doing the drug and then you do the drug or the drinking and it doesn't satisfy you as to why we can talk about that later, you know, and and it resonates a lot with food as well and with trauma and with loads of things that might be going on in somebody's brain. But yes, I I find it cute that, you know, there's a lot of Instagram activity about like, oh, completing your task will give you a dopamine, a hit of dopamine. Dopamine is not produced by completing a task. It's produced by the anticipation of the task. And it's about preparing you for for the task. Maybe a little bit produced when you complete the task, but that in itself is not is not going to give you the.
Dr Rupy: Gotcha. Yeah, yeah. It's a it's a that's a huge point. And I think this is great because I I I hear these sort of like little nuggets across social media and to have it from from you to explain it in that way is just a lot clearer in my mind as well. And you know, we've basically been speaking about the gut-brain axis. If you were to articulate what the gut-brain axis is in a couple of sentences to a newbie without the sort of lengthy explanation and how complicated it is, how would you describe it?
Dr Miguel: Yeah, so it's the gut-brain communication system. So it's the gut talking to the brain and the brain talking to the gut. The brain talking to the gut is going to be more binary, it's going to be more kind of, you know, yes, no messages. Go to the toilet, do not go to the toilet. Um, you know, mostly it's about that, really, if you look at narrowing down what it's doing. Um, process food, do not process food because you're stressed. If you're stressed, you don't want to be using energy in your gut to be processing food because the stress response wants you to get away from that lion, imaginary lion that's going to come and get you. If the lion is going to come and get you, your brain is going to reduce the appetite response. It doesn't want you to have a sandwich and have a chat with the lion. It wants you to leg it from the lion. So it's uh, and it's also going to stop the juices being produced that are going to allow you to process that food. So people with IBS, for example, with problems that haven't got a label, so many people bloating, gas, um, irregular times they go to the toilet and all this kind of stuff, allergies, all of this, they are not processing food properly because their brain is hyperactive. It's saying to the stomach, do not produce stomach acid, slow down, do not churn the food into into a little baby food kind of a consistency so it can be processed. So I go back to the definition. So there is that, the going down from the from the brain to the gut. From the gut to the brain, you're basically getting again that lubrication in the system. You're getting kind of like signals from the environment, so butterflies in the stomach typically is this kind of like intuition, something's going to happen. There's a lot of neurotransmitters involved in that kind of thing as well. Um, and you're getting a better absorption of nutrients that are going to take a really play a really big role in in the brain. And the brain is a heavy machinery with loads of cogs. It gets it's easily inflamed. It can get inflamed because of the activity. It's a lot of what we call free radicals, basically from friction, from just the way that it works. It's a heavy supercomputer. So it's almost like getting heated and then it needs to cool down at night and kind of like process what's happened during the day. By having a healthy gut, you have a better chance to process what's happened in the day, to cool down the system, so in the morning it's actually working better again. Uh, and and in a way that would be a simplistic way to to talk about that. It can go into many different avenues when you look at a healthy person versus a person with a susceptibility to anxiety or depression or a neurodevelopmental condition like ADHD or autism, there are many different avenues that that the health of the gut microbiome can actually um have an impact on the brain. But in general is to calm down what might be happening in the brain that is mostly your immune system in the brain reacting to things. And your central nervous system reacting to things. So we as a species, humans, are very good at picking up signals from the environment and the brain just goes on one and starts kind of like, you know, and everybody, I'm sure can relate how you need very little input for your brain to start thinking about things that uses a lot of energy. When you're using energy, it's almost like if you imagine the brain as a supercomputer and it's processing a lot of information, it's heating up, there's almost like smoke coming out. There are immune cells in the brain that get heated, they turn into super active, I want to kill everything that may be a threat, and that produces some toxins in the body that the brain that needs to they need to be cleared out. It happens normally in the night when you're asleep, but then again, we don't sleep as much as we need to, or we break our sleep because of exposure to screens late at night or caffeine or alcohol or a diet that is not conducive to good sleep, stress and so on. So there's a lot of stuff that kind of like converges.
Dr Rupy: Yeah, yeah. And and it goes to show just how complicated this topic is because you can go down threads and that thread has an impact on lots of other threads and other threads have an impact on that as well. So you've just, you know, diet and sleep and etc. Um, a lot of people talk about neurotransmitters being produced, you know, one of them being serotonin. Um, you have those short chain fatty acids, your acetate, propionate, butyrate we were just talking about. Um, what what is the, just to zoom in in a second and we'll zoom back out because I I want to keep the sort of listener on a journey of what we're going. What is the mechanism by which these neurotransmitters actually uh have an effect on the brain? Do they actually cross the blood-brain barrier in certain circumstances? Because I think there was a suggestion that serotonin was doing that. Now you've articulated already that that's not necessarily the case. Are there other metabolites of digestion in the in the large intestine that that can cross the blood-brain barrier in certain circumstances?
Dr Miguel: So a lot of the neurotransmitters that are produced peripherally stay peripherally. Um, but you do have the precursors, so you have the building blocks. So what happens is that you have a meal that is rich in tryptophan, for example. Um, off the top of my head, like foods rich in tryptophan, um, beans, if you're looking at like plant-based, beans always have everything. They are amazing. But otherwise poultry is typically the thing that you know, if you look at like dietetics books is like, you know, it's top of the list in in tryptophan. So you'll produce some serotonin using that tryptophan. You'll change that tryptophan into more digestible versions of that tryptophan of that amino acid that can actually cross the blood-brain barrier. Depending on how you, if you're looking just at serotonin and without getting into a chemistry class, depending on how diverse your your gut biome is and depending on how many of the beneficial microbes you have versus potentially other microbes that are detrimental to the gut because they produce substances that damage the gut lining. Um, so depending on this balance, if the balance is on the good bugs, then you have a better chance to produce positive versions of this tryptophan serotonin compounds that can go into the brain and they can be converted into serotonin and they have anti-inflammatory activity and they feed into the right channels so you get the most out of that serotonin. If you don't have an an amazing balance in the gut, like most people will will fluctuate from day to day, but if your balance consistently is towards the bad um bad bugs or the the the bugs that are in the gut but you don't want too many of on a regular basis, then you are more likely to produce negative versions of that serotonin compound that will also end up in the brain and will be neurotoxic. So serotonin as a as a tablet, if you could have it, you know, have this serotonin tablet, if you took it in your gut, it's very difficult for it to actually make it to the brain in that current form. But versions of it can actually go through the blood-brain barrier.
Dr Rupy: I can tell the way you answered the question around serotonin, you were careful not to say bad bugs and good bugs because I think there is a bit of a binary explanation that we're used to when describing our our gut flora. And that oh, these are bad and these are good. When actually now we're finding out some of those bad guys were actually doing quite a lot of good stuff at the same time and it's really around balance. And so that leads me to my my next question, which is about gut testing more broadly. So you you mentioned shotgun sequencing, the 16S RNA that gives a different sort of fidelity to the investigations that we have. How useful do you think it is for people to understand or to to actually do gut testing on a regular basis if they are asymptomatic, i.e. they don't have any gut issues and they just want to know, versus if they do actually have, let's say IBS symptoms or a diagnosis of of IBS for example. Do you think it's useful for people to have this sort of knowledge or do you think there are things that we can do without the unnecessary the unnecessary detail?
Dr Miguel: So it is useful, but and I've worked in microbiome testing for a long time, so obviously I I love the information you get from it. But equally it can get obsessive and that's the risk. So what people need to take into account is that the microbiome is like, imagine trying to take a snapshot of London today. So you take a photo of London where you see, you know, how many people with like different faces, physiognomies, races, you know, whatever are in London at that particular time. And then you start making plans as to, I'm going to build this housing here and I'm going to make three new parks and blah blah because there are so many people who are young and they need schools. So okay, let's knock up another, you know, 10 schools and three more hospitals. You take a photo of London three months later and it's completely different. So the risk is that if you're going to make changes that are wholesome, all encompassing, take into account your psychology, take into account you, why do you want to make those changes? What are you what are you chasing with those changes? Then I'd say if you're happy that the right reason is coming from within, go ahead and do all the explorations. If you're going to go into the small detail and you get freaked out because your Faecalibacterium was, you know, 11% of your microbiome last time you tested and now it's 7% and you go into a complete frenzy of like, you know, I wanted to increase and oh my Akkermansia is so low and surely that's bad for me because I'm trying to lose weight and Akkermansia is the skinny microbe and you know, and like, you know, whatever, then that is completely the don't do it because that's going to send you down a downward spiral. So and I want people to actually learn about things and and again, if you look at it from the point of view of testing, if you go to your doctor regularly to get your cholesterol checked or your iron or whatever, it makes sense to keep an eye on that if you've had a hint that your cholesterol may be on the, you know, on the border of not being good or whatever. You wouldn't just do that and then just not have another cholesterol test for 10 years. So it makes sense to kind of like keep an eye on it within within reason. Like in Spain, people freak out about cholesterol quite a lot. So it's very rare that anybody's got less than maybe like three blood tests in a year.
Dr Rupy: Oh, really?
Dr Miguel: Yeah, yeah, yeah, yeah. In the Spanish NHS is like full of people like, you know, freaking out about their cholesterol. My dad has been, yeah, it's it's like a, you know, like Brits talk about the weather. Like Spanish people talk about cholesterol. It's like, how are you? How is your cholesterol? My triglycerides are really good. You know, they there's a lot of prevention in Spain as well. So that's good. The system is slightly different. So that that is a a good element, but people are very um they've got a hypochondriac kind of like streak to their personality. I think it's the culture is like, you know, and
Dr Rupy: Has that translated into better cardiovascular outcomes? Do we know?
Dr Miguel: Yeah, yeah, yeah, definitely. There's uh, you know, the and there's lots of studies done on cardiovascular prevention and cardiovascular health and the Predimed study was done in Spain as well and you know, and there was a whole branch of of that. The Predimed study was a study done, it was one of the iconic studies initially done on the microbiome and different um health outcomes basically and cardiovascular health is one of them because it was done by people in the University of Navarra, which is one of the best places in the world to have cardiac care. So there's a university hospital in there and uh, yeah, so definitely it's um it's it it I think it's the context as well, like the Mediterranean eating and all of that kind of stuff. But yeah, so going back to testing, why would you want to test? So you learn a lot about composition if you do a 16S test. So it's not better or worse than shotgun, it's just different. So a blue jacket is blue, a green jacket is green, it's not better or it's just different. So 16S is telling you about how the microbiome, it's almost like building a catalogue. So and it goes through a lot of processes, but then the person gets um percentages. So it's abundance of microbes like lactobacillus, Roseburia, Ruminococcus, whatever. Now, to interpret this, sometimes you need to bring it down to a simplistic level and you were talking about good bugs and bad bugs. And some bugs get a bad report for, I don't know, for some years, and then suddenly there's one study that looks at how Ruminococcus, a type of Ruminococcus may not be bad, may actually be the next probiotic. And then people start thinking, okay, so all Ruminococcus are good. And then there's an understanding of biology that maybe the person on the street doesn't care about, which is you go into levels of how those bacteria are classified. And Ruminococcus is this thing called a genus, it's a big group. And then you have some nasty Ruminococcus that can cause some damage and they have been seen to be detrimental to the body. And they are the species and you have some species that may be detrimental, some species that may be beneficial, and maybe groundbreakingly beneficial. So Ruminococcus bromii, for example, is supposed to be an amazing thing and there are loads of studies being done on it. Ruminococcus gnavus with a G is supposed to be detrimental and there's lots of studies reporting how you could have infections from it and you know, whatever. So you have the two. Now, 16S is really good at looking at things very accurately to that level that doesn't go into the species. When you go into the species, it kind of like loses fidelity. So it gives you an understanding roughly of how your gut is doing because your gut changes a lot and you even have below the species, you have strains, which are even more specific, which you could have the Rupy strain, I have the Miguel strain of the same microbe because it's learned to behave differently in in our bodies. So and now what we are learning is that strains have their own characteristics and they can actually give you either a benefit or a detriment. So it all gets a little bit tricky when you're looking at it from a high level. It does give you an understanding, are your lactobacillus low? Are your bifidobacterium low? Because mostly they are beneficial and you can hardly go wrong by supplementing lactobacillus by drinking kefir, for example, or eating more yogurt or feeding your bifido with fibre-rich foods. Like bifido has an affinity with this thing called inulin, which is in chicory, is in Jerusalem artichokes. Uh, you know, it it can feed from other um fatty acids that are made in the gut by other microbes as well. So it's difficult to get it wrong when you target specific microbes. Butyrate producers that I love, I think they are the next frontier on how we need to be tackling the microbiome. Faecalibacterium, there's a microbe called Faecalibacterium prausnitzii that's quite famous. It it makes a lot of butyrate. And there's a lot of it. So when you measure somebody's gut, it's difficult not to see probably like 10% of a person's microbiome is going to be Faecalibacterium. Roseburia might be like 4, 5, 7%. So they are substantial compared to tiny lactobacillus might be a 0.05. So, you know, in comparison, they are really active, but they are tiny, tiny. You could if you're really, really active in your lactobacillus, you could have a 0.5 or something, but it's not a substantial amount of the microbiome. When you're looking at shotgun, you're looking at specific things. So again, 16S is like you're casting a net, you're picking everything up and then you're classifying it. This is lactobacillus, this is blah, blah, blah, this is, you know, and you create this kind of like like a library system. And in fact, when you're talking to the bioinformaticians, the people behind the scenes doing the the clever things, there are different libraries that you can actually tally up what you're picking up from your poo against. So you're comparing that what is in there is actually that. Now, with the shotgun, it's literally just like fishing for one particular fish. So it's almost like a shopping assistant that only goes to Gucci. So you say, darling, I only want Gucci. You know, if you go Bond Street, don't get me anything from any other brand. I only want Gucci. And you basically use that assistant to go to Gucci and it only comes back with Gucci goods. You know, you're getting your Gucci bag and your scarf and whatever. And then you send them out again and they go Louis Vuitton or they you know, or Primark, you know, but you're getting you know exactly what you're getting. And with 16S, you haven't got that fidelity. But then shotgun doesn't tell you about everything because you haven't you haven't got to Bond Street and just like, you know, got information from all the shops. You've just gone specifically to one of the shops. So it's just basically you need to program the software in a way that yes, it will be very precise that what you have got is particularly lactobacillus longum, substrain, blah, blah, blah. And and you know exactly that is that. But you're missing out on the whole community. So in an ideal world, you'd have like a bit of both as opposed to just basically assuming that X, Y and Z bugs are good bugs, X, Y and Z bugs are bad bugs and then give them that reputation because science is fluid and you need to sit on the fence a little bit because if you go too far onto saying something is whatever and you're going to have a harder time later saying, actually, you know, I was wrong and this is now good.
Dr Rupy: And if we were to sort of step back and the listener and the viewer is like, okay, great, I get it. Gut testing is complicated. Unless I'm really doing it with a a clear reason and being I'm taking a targeted approach. What are the general things that I can do beyond sleeping well, eating enough fibre, lots of diversity in my diet. You mentioned kefir that you're particularly excited about because of the yeast content. What are the yeast that you're specifically, what are the yeasts that you're excited about? And are there other probiotics in food that would be better than a targeted probiotic excluding the sort of specific circumstances where you might use a probiotic supplement?
Dr Miguel: Yeah, so I'm excited about kefir because not only because of the yeast that there are a few and it depends on whether it's real kefir or whether it is um kefir cultures. So you can make kefir with this thing called kefir grains. They look like weird like little creatures, like little sponges or something. And they are a combination of yeast and bacteria or like a scoby, like people are more familiar with a scoby for a kombucha. It's technically it's the same thing but with different a different community of microbes. And what they are doing, they are metabolising, they are digesting the lactose in the in the milk and even some of the proteins and they're just making this thing called kefir. So if you make it that way, then you have the full whack of microbes. Or if you buy it from somebody that has that kind of thing, if you don't want to make it at home. If you're just buying the kefir from the shop, what you're getting is a yogurt with added kefir cultures, which is typically lactobacillus kefiri, another couple of, you know, similar bugs. And so you're just getting, if you in your regular yogurt, you might get, you know, two or three different microbes. In your kefir, you might get, you know, 10, 15 according to what powder has been added to the process. It doesn't make it necessarily bad. I'd still have the one from the shop because if you compare it with yogurt, you're getting more for your buck. So for me, kefir is a winner always. The only thing is that I also like yogurt and I don't like to say, oh, just because it's good for me. I like the creaminess of a Greek yogurt. It's completely different experience to the kefir. To make a kefir like that, it's difficult and then you need like added stuff to the yogurt industrially and then you get into the processing. You want a kefir that's thick set like Greek yogurt is likely to have something added to it, typically starch or something and I don't want to be messing around with that. So just keep an open mind. But kefir is nice because it's got like things called postbiotics as well, which are quite trendy, which literally are dead cells, uh fragments of the membranes of the cells, they still have the ability to stimulate your immune system. Uh, it's also the the fatty acids that are being produced within the product while it's still live. So there's still butyrate being produced and acetate and so on. And that's still, that's also called a postbiotic. So it's got a nice mix. It's a whole living ecosystem. And I like that a lot. Uh people who are um sensitive to lactose, they can have this thing called water kefir, which in some studies it has been seen to contain up to 52 different microbes. Um so it also depends on how you do it. You put sugar into the fermentation, so some people freak out. Most of the sugar is eaten by the microbes, but you know, it's a bit like kombucha. You know, you need to put the sugar in for it to get the kick. So it's the same kind of like principle. Um so I would say yes, my favourite, but if you look at studies that have been done recently, like people from um University College Cork, um John Cryan, Ted Dinan, they did a really interesting study that was published last year, uh combining looking at the microbiome of people who participated and also self-reported measures. So again, prompts, this patient reported measure is looking at partly of the lived experience of the person, but in a more controlled way. So they're looking at um stress. There's this thing called perceived stress that is a a well validated questionnaire. It's 11 questions, very simple to answer. And from different angles, you're basically answering to the researcher how stress is affecting you. And uh and literally by combining a number of different fermented foods as opposed to just focusing on one and uh looking at they were students stressed by exams. So this is a typical environment because it's quite ethical because you're not putting somebody through a stress per se. You're looking at somebody who's going to have the stress anyway. It's a natural experiment. It's very nicely done. I love these guys. They're so elegant. They just produce so many studies. Like you, you know, literally you can have a new study every day. And um and literally the results were that those in the group that had the typical Irish diet, which is very very similar to the British diet, following the eat well guidelines kind of so to speak, healthy enough, but without fermented foods. The addition of fermented foods added a a layer of wholesomeness to to their gut-brain connection and it reduced the perceived stress basically. So there was a reduction in perceived stress in how so perceived stress is about how you react to a potential stressful, potentially stressful situation. They managed, it's almost like um if you want to make it into something that is not, but you know, you could make it into improve resilience. You become more whatever to stress. So that's brilliant.
Dr Rupy: How would you remember the dose of fermented?
Dr Miguel: Yeah, so literally three, I think they're recommending three at least three portions um and it doesn't need to be a huge amount, but the in a nutshell is a variety of different fermented foods. So they recommended um kefir, but they also um kimchi or sauerkraut. Okay. Um sourdough. And again, sourdough is a funny one because you don't get the live microbes. The microbes by the time you bake them, you fry them basically. But you get the dead microbes, so you get postbiotics. So the actual starter is rich in lactobacillus and so on and some yeast and then you kill them. So it's got that kind of like um priming the immunity of the gut gently by by the dead microbes. And but yeah, so literally what they are saying is combining a fibre rich diet with extra um probiotic foods, fermented foods, you know, you can get very purist as well. Some people say they are fermented, they are not probiotic. Okay, probiotic means pro-life. Fermented have been fermented by microbes that are typically beneficial. I'm not going to get too funny about it. I think it's just easier. It sounds nice, fermented foods. So fermented foods, if you have a range of them, I think that's my philosophy anyway in life, just a little bit of everything that you think is good for you and that makes you feel good is likely to be better than just focusing on something like really massively and going, oh, I'm just only going to have mushroom powders. You were telling me about mushroom coffee. I'm only going to have that and I'm going to
Dr Rupy: I'm definitely not mushroom coffee. I think the mushroom coffees out there taste horrible. I haven't tried a decent one yet. Yeah. But I'm trying to like add a little bit of mushrooms into my drinks just to see what the effect is. I'm just experimenting. Non-psychedelic mushrooms. Yeah, yeah, yeah. For now. Yeah, especially at the start of the day before this podcast. Yeah. You know, and on that note about how people can get quite sort of fixated on, you know, whether something is fermented or probiotic or postbiotic. The other thing I think many listeners will have experienced when they go to a health food store is when they peruse the probiotic aisle or even, you know, the fermented food aisle, it will say it's got X number of strains, it's got, you know, 5 billion CFUs, colony forming units, or ours has got 15 colony forming units, so this is, you know, people make the assumption in their head that this is better or stronger than the other. How if you if you had to educate someone navigating the sort of complicated health food aisle in a supermarket or a health food store, what kind of things would you advise them beyond, you know, just go for the fermented foods, get diversity in, ensure you've got high fibre. Are there any sort of extra um trinkets of information that you would give them when when trying to decide between which probiotic?
Dr Miguel: Yeah, so in general, if you have if you haven't got a concern, if you just want to make your life easier and benefit from better digestion and so on, the evidence points towards multi-strain. So anything that has got more microbes is going to be is a wide spectrum. So in a way, there may be fewer studies on some of the um ingredients than on some of the others, but by combining everything, you're kind of like spreading the hedging your bets in a way. I think you're like, okay, well, if I'm because it's all depending on on the person's lifestyle and genetics and everything else, um then you're kind of like thinking, I've got a little bit of most things that are likely to be good for me. And I think that's that's the best bet. If you're looking at, you know, particular situations of like mental health, you know, anxiety, depression, the studies are still very embryonic. So there are some some probiotics that, you know, like bifidobacterium longum, for example, there's a couple of strains that have been used in anxiety, depression with with good effects. But my only issue with that is that most studies are done for a month. They are really expensive to do studies. Yeah. Uh especially when you're taking loads of measures as well. So it's not just like I feel better. It's not just a questionnaire. When you're taking bloods and poo samples and everything, it goes into hundreds of thousands of pounds to do a study that is anything to write home about. So I would just say have expectations that are realistic because I'll mention another another study that was just published um earlier this year, uh researchers at the University of Santiago de Chile is it's on a Chilean study. They looked at um people taking probiotics and they looked at their lifestyle and they looked at different health measures. And they basically concluded that the reason why the group that took the probiotics versus the group that didn't take the probiotics felt better was not because the probiotics themselves, but because of the lifestyle factors that they engaged in. So, you know, they they created subgroups basically when they analysed the whole study. But they looked at people who were less stressed, for example, or who had they call them more positive life um yeah, lifestyle behaviours. So basically they went out in nature more or they talked to friends more often and they met socially. So all of those things, we are complex beings. So if you just try to reduce it to I'm just going to continue with my life as it is, maybe in an unhealthy relationship, maybe with myself, with my partner, with work, which is massive, you know, toxic environments at work are massive. I'm going to take this, you know, bifidobacterium blah blah and it's going to sort me out. It's going to a little angle. But if you put all of those other things in place, then that's guaranteed to have a a much better rate of success than if you just add those things and then you continue to have toxicity in your life, you continue to ignore the cues that the environment is giving you. So I think that's that's the kind of a ideal situation when you're combining the two.
Dr Rupy: Absolutely. Yeah. Um, Miguel, I I could talk to you for so much longer about not just this subject, but other subjects as well. Like we haven't even touched about on, you know, the differences between quote unquote normal and neurodivergence and like how one might go about even thinking about diagnosis or therapy for it. I think we're going to have to do that on another pod if if you'd come back. But um, I just want to thank you for your vulnerability, your analogies, they're brilliant. The way you communicate science is phenomenal. You know, the the amount of work that you've done is is brilliant and people can look it up uh in the show notes that we'll put down as well, your studies. Um, and for, you know, just the the shared experience. I I really hope this is going to help a lot of people think and rethink their life if they they might find that there are some patterns that they haven't addressed before. So I really appreciate your time.
Dr Miguel: No, thank you so much. It's been wonderful. Thank you so much for having me.
Dr Rupy: I really appreciate it. That was great, man. I appreciate you. Honestly.
