Instant Genius - The surprising ways the microbiome affects our brain development, emotions, and sex lives

Episode Date: May 30, 2024

We humans are never truly alone. This is because our bodies are colonised by vast numbers of microscopic organisms that can be found living everywhere from the surface of our skin to deep within our guts. Collectively, this population of microbes is known as the human microbiome, and they play a key role in maintaining our health and wellbeing. In this episode we catch up with Dr James Kinross, a colorectal surgeon and researcher based and Imperial College London and author of the new book Dark Matter: The new science of the microbiome. He tells us about the fascinating ways that our microbiomes can impact our brain health, regulate our emotions and if we could ever use them to make an effective love potion. Learn more about your ad choices. Visit podcastchoices.com/adchoices

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Visit name audio.com to learn more. Hello and welcome to Instant Genius, a bite-sized masterclass in podcast form. Each week, you'll hear will-leading scientists and experts talking about the most fascinating ideas in science and technology today. I'm Jason Goodyear, commissioning editor, a BBC science focus. We humans are never truly alone. This is because our bodies are colonised by vast numbers

have microscopic organisms that can be found living everywhere from the surface of our skin to deep within our guts. Collectively, this population of microbes is known as the human microbiome, and they play a key role in maintaining our health and well-being. In this episode, we catch up with Dr James Kinross, a colorectal surgeon and researcher, based at Imperial College London, an author of the new book, Dark Matter, the new science of the microbiome. He tells us about the fascinating ways that our microbiomes can impact our brain health, regulate our emotions, and if we could ever use them to make an effective love

patient. So first off, welcome to the podcast and thanks very much for joining us. Oh, it's my pleasure to be here. Thank you for having me. So first of all, you wear quite a few different hats. So can you briefly sum up what you do, please? So I am a colorectal surgeon. So I'm a consultant surgeon. and I work at Imperial College, NHS Trust in London. But I'm also a clinical scientist, which means that I have a research group and we perform science to try and understand why people get disease, so in my case, bowel cancer.

And we try and apply novel technologies to the treatment of diseases like cancer. And in my spare time, I guess, I also write books. So that brings us on to the topic of today's discussion, talking all about the microbiome. So this is the colony of microbes that live on our bodies, and they're incredibly numerous, and we have sort of different sub-microbombs in different areas of our bodies.

So where are these found? So you're absolutely right. A microbiome is a collection of all microscopic life forms and all of the things that they need to sustain themselves within a niche, so a particular bit of the body in this case that they like to grow on. And they exist in lots of different niches. So the skin has a microbiome, your mouth has a microbiome,

and your gut has one. We have a urogenital microbiome that they exist across the body. And I think there's two really key importance when you're thinking about microbioms and asking what they do. The first is that they have an evolutionary basis. So that means that those microbes are not there by accident.

They're there because they've evolved to either live in those particular places or because they have a, what we call a symbiotic relationship with us, which means they help maintain our health. At the same time, they have a nice place to live. And the second thing to understand is that they also are dynamic. So they change depending on where you are in your life cycle.

So when you're born, we don't have many microbes at all. And then we're slowly colonised. And then as we get older, they change a little bit. And so depending on what time and where you're looking, those microbes may change a little bit. So when we're talking about microorganisms, what exactly are we talking about? Well, within the gut, which is where I do most of my work, we are talking about bacteria.

But we're also talking about all other microscopic kingdoms, if you like. So we're talking about RK, which are sort of ancient, different small microscopic organisms. They look a little bit by bacteria, but they're not really. And also we're talking about parasites that you might find in there. So worms and nematodes and these sorts of things. And then viruses. So viruses are not living, of course. They belong from a slightly different empire to living microbes because they can't self-replicate.

But they're all really, really important part of the microbiome. And then there's yeast and fungi. And all of these things interact in a complex and quite sophisticated network. So coming off the back of that, we're finding out more and more about the key role the microbiome plays in our health and well-being. I think by this point, most people will probably be aware that it's essential for a healthy digestive system and for fighting off infection, etc. But I thought today we could look at some of the less discussed effects that the microbiome can have that you mention it in your book. So first off, let's have a look at brain health. I thought this was really interesting.

is the brain and the microbiome have a really intimate link? Yeah, they really do. And I think the microbiome is so important in brain health for a couple of reasons. The first is that the microbiome and the brain seem to develop in a sort of partnership. So growing a brain is very hungry work. It requires a lot of energy. And a lot of that energy comes from microbes. And microbes produce a lot of small molecules, which are very important in shaping the brain.

brain. And of course, microbes influence how the immune system work. And the immune system plays quite a big part in shaping brain development. So it seems from a number of different studies now from across the world, that actually if the gut isn't very happy in early development, but actually the brain might not be happy as a result of that. Similarly, it's really important when the brain ages. So microbiome is very important in, for example, determining your risk of conditions like Alzheimer's or some forms of dementia. But it might also be important in influencing how we feel. So in terms of our moods.

So, for example, we see that patients who have depression or patients who have anxiety have quite different microbiomes from those that don't, even when we adjust for things that you might assume would influence that. So what you eat, for example, or the medicines that you take. And what's most interesting about that is that you can do something about it. You can target the microbiome as a form of therapy to help common conditions that affect people's mental health. So another thing that you mentioned that is linked with this, that I thought was really interesting, was the idea of addiction. That's something I'd never heard of before.

Yeah. Much of the evidence from that comes from studies that have looked at both people who have addiction, but also in some animals and identified discrete types of microbes that seem to be either more abundant or more relevant. But we also see evidence from it in studies that have used a particular sort of experimental tool. which I'm sure we'll talk about in a bit more detail called fecal transplantation as a potential treatment for addiction. So for example, in alcohol addiction, where it seems, you know, from very early studies and very early data at least, to have some sort of promise. So, yeah, it is an important mechanism. It's not just that the microbiome affects how you feel when you take a medicine or a drug or how, when you drink alcohol, for example, or it's side effects that you might experience to the toxicity of these things, but also whether or not you might feel addicted to it. So that's absolutely correct. Yeah, so let's have a look at these possible treatments then.

They sound a bit icky, don't they on the surface? Yeah, they do a bit. And I'm afraid they are, if you're sitting down to have, you know, a bit of breakfast or a bit of dinner, depending on you're listening to this podcast, I can only apologise. But this is exactly that. It's the concept that sometimes it's quite hard to give just one strain of bacteria or one bug to try and treat condition. What you've got to do is you've got to transport an entire community. So not just the bugs, for all the small molecules that they make and all of the things that they need to survive. And if you like, reset an entire ecosystem within us. And that means taking quite often feces and transplanting it from someone who's well,

who doesn't have one of these conditions into someone who's not well, as a method for doing that. And we know that when we do that in very particular condition, so there's a particular type of infection that affects the gut called postridium difficile infection, that actually is incredibly effective. It completely treats it. But we also find that it works in a number of other conditions, particularly conditions where the immune system seems to be an important part in causing a disease state. So a really good

example of that would be a condition called inflammatory bowel disease, where the resetting the ecology of the gut seems to reset the immune system of the gut and therefore it has a beneficial effect. So the obvious question here then, I think next is, where does the donor fecal sample come from? Oh, good question. So I'm pleased to tell you, turning much more into a science than an art form. And historically, it has literally been a kind of a random event. Now, what we tend to do is to try and identify, obviously, people who are healthy. So like in any form of transplant, whether, for example, you were getting a kidney, we screen those donors to make sure that they don't have infections that could be transmitted from the donor to the recipient. But we also try and screen for

non-communicable disease. So diseases that we don't historically associate with infection. So for example, cancer or obesity or cardiovascular disease, because we know the microbiome is important in transmitting that risk. So we don't want to inadvertently change someone's risk profile. We also tend to try and identify usually family members because they are more likely to have a similar microbiome and therefore it's probably more likely those bugs will be grafted, or at least people who are similar. And we're getting much better at, if you like, matching donors to recipients based on an assessment of them actual microbes,

although at the moment that still is an emerging field. So what we really want to be able to do is to target that much more accurately. And then, of course, I think no one really needs to imagine, you know, what giving a sample is like. But what we then do is then we try and process that sample in as a controlled and safe way as possible. So that doesn't just mean screening for pathogens and bad bugs that might cause harm.

But actually increasingly we have to do that under what is called anaerobic conditions because most of the bugs that live within our gut die in oxygen. They live absolutely in conditions that have no oxygen at all. So we have to try and then reconstitute those samples in anaerobic conditions before we can transplant them. So once we've got the sample, how do we get it into the patient's body? Well, we've got some choices. We can choose depending on the clinical need.

So the first studies were typically done with something called an enema, where either with a bended tube, you can put it into the patient's bottom and rectum, or we can do it with a colonoscopy, where you fiddle the tube all the way around the colon, and then we can inject it with a syringe. Sometimes we give something called a nasogastric tube, which is a tube which goes in the nose, and it goes all the way down to the stomach, and then when we're sure in the stomach, we can almost put up a drip of the infusion, and we can give it that way. But increasingly we choose to give them through something called a crats, which is effectively a freeze-dried section of the FMT, which goes into a small dissolvable capsule

which you swallow like a tablet. It's quite a big tablet. You'll be thrilled to hear it doesn't taste too bad. And actually, it's quite an easy way to take it. And at the moment, what we're doing is studies to try and work out what is the most effective way to dose patients based on the conditions that they have or the need that they have or the type of microbes that we're trying to give. You said this place was steps from the water. We just haven't found the steps yet. How much did we save? Enough. Enough to get lost.

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an unforgettable listening experiences at home. Try it for yourself at a focal powered by name boutique. Visit focal powered by name.com for more information. Okay, so let's shift gears a little bit here then. So one thing that really stood out in the book for me, was the role that the microbiome may play in selecting a mate. So what's going on there? Well, we have lots of really good examples from nature and from other species of animal,

where we know that microbes seem to be very important in influencing behaviour. And so what I was doing here was trying to draw analogies with human behavior to see whether or not that might be feasible. So of course, the first thing to say is that we know that social groups, So people that have big social groups have more diverse microbes within them than those that perhaps don't have quite such big social groups or perhaps you live alone. And we know that that is one way through which we can promote, if you like, our microbial diversity within us.

We know that microbes play a very important part in maintaining skin health or some aspects of the way that we look. So, for example, how our hair grows or general external markers of health that you might look for and a mate. And we also know that they influence how we smell, right? So, you know, of course, when you go out on a date, you want to, you want to smell great. And microbes might play a role in that subtle pheromone signaling that happens between individuals through mate selection. And it plays a really big role in determining how our hormones work, how our sex hormones work. And that's obviously super important in mate selection, but also in the process of reproduction.

And that's very variable between men and between women. So it's not necessarily that when you're, you know, swiping on a dating app that you should be looking for a good microbiome. Of course, modern dating is, you know, it's a complex process. But it is true to say that microbiome has a subtle but important role. So one sort of fun, slightly silly question coming off that then is, would it theoretically be possible to make like a love potion? Yeah. I don't think that's a silly thing at all. I think we should absolutely try and do that. I think there's a good question there, which is whether or not we would really want a love person. I think half the fun is that actually we can't formulate some of the emotions that we have for potential mates.

And maybe it's best that we don't. I think in a big data world where everyone's trying to commercialise every aspect of our dating lives, it's quite nice to have some mystery and some magic. And maybe it's better that we just don't know. But it's an interesting concept that actually, if you look at things like mating panda bears, that actually microbes have really important part to play in determining the pheromones that these animals secrete that really heavily influences their mating behaviour.

So your suggestion is not actually a silly one. It's one that is in fact plausible. The problem is, of course, is that humans are quite as sensitive to the pheromones as a panda bear. But nonetheless, it's something that we could definitely explore. So say that I'm married, I have a wife, we live together for 20 years. So during that time of our might as well, microbiomes become more and more similar?

Yeah, absolutely have. So they have for lots of different reasons. So for example, of course, when you are married or when you're with someone, anybody, you know, you're going to physically make contact and that means you'll physically share microbes. When you give someone a good old snog, you're probably sharing about 80 million bacteria per kiss. So there's a sort of physical sharing with microbes. But there's also an indirect one. So actually our homes, our houses, have their own microbiome.

But that's because of the dust that's in there, the animals that live in there, the things that you bring out of their home, the foods that you cook, they're all completely discreet to you and to your family. And so you can actually identify an individual based on the microbes that you find in your house. And in fact, when you move house, you take your house microbiome with you. And that might be super important, by the way, for understanding why people in urban populations have different sorts of, you know, health conditions to those that live outside of it.

And it's absolutely why when we're doing studies with faecal transplants, we try and identify people who perhaps live together because they are more likely to have similar microbiomes. But it's equally true that two people can be married and live in the same house and have quite discreet and different microbiomes, either because they share different sexes or genders, or maybe they take different medicines. So medicines like antibiotics can have a really big impact.

So it doesn't necessarily mean that you're going to be the same. In fact, there will be very distinct and important differences between you and your wife. So sort of maybe slightly tangentially from that. How about the role that the microbiome plays in the manufacture of hormones? Yeah, really interesting question. And a question that we are very interested in. So, of course, the gut manufactures and produces lots of hormones. And those hormones do things like regulate our appetite and how we feel about food.

But also the body makes hormones that predominantly from cholesterol that's made in the liver, but also our sexual organs manufacture androgens, which are kind of hormones like testosterone. in men, we also have low levels of, you know, estrogen progester, but women, it's obviously predominantly estrogen progesterine. And microbes co-metabolize these hormones, which means that they can create small molecules that bind to these hormones and influence how active or inactive they are. Bacteria also break down bits of our food to release hormones in some of the foods that we consume. So a really good example of that would be phytoestrogens.

that are actually quite well are known from some sort of various fermenting processes that are kind of vary between different populations. So it turns out they're really, really quite important. And in fact, they are very underrepresented in our understanding of the importance of hormones for human health. And so many women, for example, when they're having their menstrual cycle, if they have IVS, they will notice at the time of their menstrual cycle that their IVS gets worse. And we think that's not just because the gut has receptors for these particular hormones,

but also that actually the microbes are responding to different kind of menstrual state, if you like, the different hormones that are going up and down at that particular moment through ovulation, and they are therefore changing their relationship with the gut as well. So if you like, there's a sort of gut microbiome hormone axis, which is really important a missing part of our understanding of how they work. So it can also have an impact on fertility rates. Well, it might do. And of course we have an alarming decline in global fertility rate.

and infertility, of course, happens to both men and to women. And some of the reason that the microbiome might be really important in influencing fertility might be through the gut, because it allows us to create lots of vitamins that we need for spermatogenesis, for example, vitamin A, but also it might have a more direct effect. So, for example, in women, the vaginal microbiome seems to be extremely important determinant of infertility. And the reason that's so important to understand is that if you know that, you can do something about it. So we're also starting to see now the first vaginal microbiota transplants being done

as a treatment for infertility. And it works because very often infertile women have a kind of very low abundance of particular types of bacteria in the vagina. We can replace them. That has the second impact, of course, on the immune system. And then we think, therefore, it has a beneficial effect. So that's very exciting to me because it's an important way of reversing a worrying global trend. So we've sort of discussed that all of our microbiomes are unique to us. But you said earlier that babies are born, you know, with a very limited number. So how does it develop? How do our microbiomes develop over our lifetime?

That is such an interesting and important question because I think that if we can understand that, then I think we can really prevent quite a lot of very common chronic diseases. So the general theory, or if you like conventional medical wisdom, is that we are born sterile. We are born without any microbes at all, and that we are first colonized when we are born, so either through the delivery of the vaginal canal, or when we were born by cesarean section,

when we come into contact with our mother's skin or our father's skin. And then when we begin to explore the world, so we start to feed, we start initially breastfeed, you then get these big blooms of microbes, and then the microbiome starts to develop. But it might just be that the microbeam plays in a role before all that. So what we know is that the maternal microbiome, and in fact actually also the

paternal microbiome, it turns out, but the maternal microbiome in particular seems to be able to produce lots of very important molecules which can cross the placenta and can influence the development of the baby and the development of actually their long-term risk of disease. So a really good example of that would be bugs in the mum's gut, breaking down fibre to produce a molecule, particularly molecular called butyrate, which is a form of short chain fatty acid, but they also produce acetate and propronin. And these cross into the baby, and if they're not in the right abundance, it affects organ development, it affects your risk of obesity. It might also be that actually our theory of the sterile birth hypothesis is not quite right, that there could be very low abundances of these microbes

that can in fact get into the developing gut in the second trimester of birth and that, in fact, they might have an important role to play in programming the immune system of these developing babies. Now, this is really controversial. It's really controversial because, A, it's really difficult to study. B, there's lots of technical challenges when trying to look at very low abundances of bacteria because the way that we do the science means it's very prone to contamination and quite tricky. But what we absolutely know is that these babies do have particular cells with an immune system called memory T cells, which have been taught something by a micro at some point. So they know a good bug and they know a bad bug and they can select it out. And we know that we can absolutely reproduce that

in the laboratory, and there's been some pretty good studies that have done that work. So the microbiome is, if you like, it's challenging some of our deepest held beliefs about how we're colonised and the role that these microbes have in our health from the minute we're conceived through certainly birth and into early life. Sort of sticking with health then, another thing that I found very surprising was our microbiomes can affect how we respond to exercise. Yeah. So it's really, really true. And in fact, actually, we've had some quite interesting science just published this year suggesting actually the microbiome seems to play a very important role in determining our, if you like, health benefits from exercise. So we know that certainly from studies in both humans

and in animals, that exercise changes the microbiome. And we also know that you can influence someone's ability to exercise by changing the microbiome through, again, fecal transplant models, which we've done in mice. So if you take a mouse and you get it to spin on a wheel, lots and lots of and it loses weight. You can take that microbiome, put it into a mouse that's a bit lazy, doesn't really want to get on the wheel, and the mouse will then get on the wheel and it will start exercising. Similarly, we know that if you look at athletes, so if we look at athletes like endurance runners, so particularly there was a study that looked at the Boston Marathon, it was looking at people who did very well in the Boston Marathon, they sequenced out their microbiomes,

then actually they have an overabundance of a particular type of microbe, which is quite good at co-metabolizing a metabolite called lactate. So lactate is one of these metabolites. that you get too much of when your muscles, when you exercise and it causes your muscles to ache. And what they were able to do is then again do a nice transplant study where they could take the individual strain of bacteria that they identified, put that in an animal model and improve their exercise tolerance. But we know, again, that particularly in studies of humans who are perhaps overweight or perhaps suffering from other health side effects, that when you exercise, you change the microbiome, it's the microbiome that seems to be an important part explaining why we get

so many health benefits from exercise. So the moral of the story is here. Exercise is good. It's almost good for all health indexes. So do as much of it as you can. So we've covered quite a lot there, and it's fairly obvious that our microbiomes are incredibly important, but they're under threat. So how's that happening? It's happening because of the same reasons that we have a sort of planetary global climate crisis. And you have to think about your microbiomes, like an ecosystem that's as fragile as any other, that's dependent on its biodeficism. for its health. So, of course, our global addiction to a westernized diet, so high fat, high protein, low fibre diets, are addiction to antibiotics and drugs. And the change in lifestyle that comes from urbanized living and the pollutants that we experience through urbanized living, whether that's microplastics in our gut or whether that's, you know, pollutants that we

inhale is causing this tremendous environmental pressure on the microbiome. And what we're seeing is that that pressure has been applied over an incredibly short period of time. Basically, since the end of the Second World War, when antibiotics started to be mass produced and started to be used, you know, in farming in very, very large numbers. Now, in any kind of, you know, state of crisis, if you like, there are winners and there are losers. So what that means is, is that we are losing, or some of our microbiome is becoming extinct. And we know that because we can track it over time. But also what we're seeing is that because microbes have this fabulous ability to adapt and to share genes and to grow very quickly, that they're also winners. And so you're

getting these blooms of microbes that are just not so good for us. And that's a big problem because we think that if you look at the changes in the microbiome that have happened over the last 70 years, you can map them onto the growth rates of immune mediated diseases. And you can look at allergies and you can look at asthma and immune mediated diseases like rheumatoid arthritis or conditions of the bowel, like inflammatory bowel disease. But we think it's also an important part of the explanation as to why younger people are now more likely to get conditions like bowel cancer. So because we are losing this very important relationship that is transgenerational through the maternal microbiome, and because the microbiome is so important in the development of our immune systems and setting up how our guts work, that actually we simply have microbeams that cannot cope with a kind of urbanised post-industrial

environment. And that is really worrying. The good news, because I think it's important that we are a little bit positive about it, is that you can change it, you can do something about it. And we've shown that in the studies that we've done that when you meaningfully change your diet, when you delete your food delivery app and you start exercising, actually you can make really big changes to your microbiome, and it's really important. But it also means that if we want to, if you like, rescue the microbiome, not only do we have to make individual choices about how we eat, for example, the medicines that we take or how we socialise, but also we have to make societal changes, right? And that means being much more proactive in how we use and regulate antibiotic consumption.

It means that we need to invest in innovation and technologies that give us the precision that we need in killing pathogens, because we've got to kill pathogens because they cause a lot of harm to everybody, right? And we need innovation. And that's the value of the market. And that's the value of the microbiome. The most important thing about the microbiome is it's a way to prevent disease and to treat this really big growing burden of disease that we've got. So I'm really optimistic about the future in that sense. Thank you for listening to this episode of Instant Genius, brought to you from the team behind BBC Science Focus. That was Dr James Kinross. To discover more about the topics we've just discussed, check out his latest book, Dark Matter, the new science

of the microbiome. If you enjoyed what you just, heard, please consider subscribing to Instant Genius on your preferred podcast platform. The current issue of BBC Science Focus magazine is out now. Pick up a copy wherever you buy your favourite magazines or download us on your app store of choice. You can also find us online at sciencefocus.com. This podcast is sponsored by Name, Audio and Focal. The texture and emotional depth of music can be lost through digital sources or poor signal. Name Audio believes you can have digital.

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