Revisited: Secrets of the gut microbiome
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Microbes. Every moment of every day we're surrounded by them.

They're around us, on us, in us. There's about 100 trillion bacteria in your colon, which is about the same total number of cells that make up the human body. They're such a fundamental part of us that in some sense they are us. Our genome is dwarfed by the microbiome. About 23,000 genes code you, but you probably have around 30 plus million microbial genes in your colon alone.

We've evolved together with these bugs over millions of years to form a relationship so close and miraculous that it continues to bewilder and surprise. It's your kind of sixth sense, literally your sixth sense. It interacts with everything in your environment.

And as we delve deeper into what's there, where they've come from and what they're up to, we're discovering how microbes shape us and how modern Western lifestyles are changing them in return. If we take the hypothesis that our health is determined by the biodiversity of these microbial ecosystems at critical moments in our life and that that biodiversity is being lost, then it's an internal climate crisis.

So, as scientists race to understand the worlds within us, we're taking a look at what we know about our microbiomes so far and how we can better look after them. Over three episodes, we'll be exploring three different ecosystems, the gut, the vagina and the skin. Today, it's the biggest of them all, the gut microbiome.

To me, it's the key to everything. It's the key to absolutely everything. I'm The Guardian's science editor, Ian Sample, and this is Science Weekly. Dr. James Kinross, you're a colorectal surgeon and senior lecturer at Imperial College London, where one of your big research areas is how our gut microbes affect our health.

And you're the author of the book, Dark Matter, The New Science of the Microbiome. So there's a lot I want to ask you about, but first we'd better get our house in order. What do we mean by the gut? At its simplest level, the gut is just a long tube that starts at your mouth and ends at your bottom.

When we talk about the microbiome in particular, though, quite often we really think about the colon. So your colon is what you might call your large bowel. It's basically a giant fermenting engine. The microbiome is pretty massive and the majority of the microbes are located there. And is that microbiome all bacteria or are there other microorganisms in there that we need to be thinking about?

So a microbiome refers to all of the microscopic life forms and all of the environmental things that they need to maintain their health within a niche. It's definitely not all bacteria. And bacteria kind of get the limelight because they're the most studied component of it. But it also contains archae, so an ancient kingdom separate from bacteria, but single kind of prokaryotes. It also contains yeasts.

and kind of worms and wriggly parasites that 2 billion people around the world carry within them, but then also viruses. So viruses, of course, are not living. They're intracellular parasites and they live within their own empire, if you like. But the virome is increasingly understood to be a very important player in the microbiome, and we have almost no working knowledge of it whatsoever. To

To give you a sense of scale of what I mean by that, the average person probably has about 500 species of bacteria in their gut, but there's probably about 150,000 species of viruses within our gut. And none of them are in our databases, and we have no idea what they're doing, how they're regulating bacterial populations, how they're interacting with our immune system, and how they're defining our health. So it is a literal black hole. And where do all these gut microbes come from?

from? As far as we know, and this is kind of controversial, when you're in utero, when you're gestating in the womb of your mother, you're sterile. And then as you're born and you're delivered into the world, you come into contact with your first group of microbes through the birth canal and then through breastfeeding, the things that you touch. And slowly, your gut and your skin and your lung is colonized. And it changes with us at key moments in our development and our aging process. And that has very, very important implications for our health.

So your maternal microbiome, or the maternal microbiome, I should say, has a very important role in defining the health of the gestating infant. Then the second phase is from the minute you're born, because the microbiome then changes very dramatically into about the age of three to five, because it's so vulnerable to nutrition, dietary, drug, environmental changes. And it also, therefore, has a very important role in helping our organs grow and our organs develop, most importantly, the brain.

It then stabilises. There's argument as to what happens around puberty. It probably goes through another subtle change around the time of puberty. But then in adulthood, it's pretty robust and very stable, actually. It takes quite a lot to really change it until the age of around...

70-ish, and then it starts to become slightly more vulnerable to change, slightly more fragile, and you see changes at kind of broad levels in the microbiome. And are people's microbiomes completely different, or are there sort of common microbes that we all have, you know, strains of bacteria that dominate, if you like? So there is a sort of, if you like, a common genetic microbiome that we share that allow our guts to function healthily, but individual variance is massive.

So at a strain level, you and I probably only share about 10% of the same strains of microbes in our gut. And that's very, very important for a couple of key reasons. Number one, it makes microbiome science very hard to do because you've got to understand and have a measure of that variance when you're designing your experiments. But it's also a fundamental in explaining why so many of us experience disease so differently and in explaining how we're going to develop therapies for the future. ♪

James, although each of our microbiomes is unique to us, there are broad functions they all share. So are there external factors we know affect our gut microbes? So the answer is yes. Diet and nutrition in early life is the most important because that sets, if you like, the ecosystem for the rest of your life. And we know that breastfed infants have a different microbiome to those that are formula fed.

Clearly, a kind of globalized, ultra-processed diet has an impact on it. But probably, well, in my view, what is far more important is our addiction to antibiotics and also our addiction to pharma and to drugs. So antibiotic consumption, it's clearly a double-edged sword. I couldn't do my job as a surgeon without them, and they're a very precious and important drug.

But they have absolutely transformed not just the human microbiome, but the planetary microbiome, the global microbiome. And we consume just vast quantities of them. And the majority of antibiotic consumption is actually happening in low and middle income countries. It's happening in economies that are rapidly or have rapidly grown. So China and India, for example.

We take about 4 trillion doses of medication per year globally, which means that everywhere in the world, every day, about half the globe's population is taking a drug or a medicine. And many medicines that we don't typically think about as antibiotics actually have an antibiotic effect. All right. So about a quarter of them in one study.

And collectively, these things over a very short period of time have had a very dramatic impact on our microbiome. And because our microbiome is passed to us through our parents and it has a generational shift, that is, if you like,

eroding our microbiome. If we take the hypothesis that our health is determined by the biodiversity of these microbial ecosystems at critical moments in our life, and that that biodiversity is being lost or certainly changing, then it's an internal climate crisis.

And because our microbiome links us to the global environment, I mean, literally through the microbes that transition through us, we're, of course, connected to the broader global climate crisis that's happening. Okay, so drugs are a big factor. But I'd like to go back to diet because we hear a lot about that, particularly at this time of year. And it's an area where we potentially have a lot of choice as adults to

So how does diet determine our microbiome? And then how does that impact our health? First of all, you know, 80% of the world's antibiotics are made in food production. So the production of food and the manufacture of food is changing our microbiome through that process. And of course, not all food is sterile, right? So you can track things like sushi consumption with the rise in pinworm infections in the gut.

But generally, you have to think about your bugs as being pretty similar to you, right? Which means they're sat in your gut, pretty hungry, waiting for the next meal to come through. And they can only respond and react to the nutritional or dietary stress that you put them under.

Now, what we've done in our studies is that we have compared like a Western diet to an Africanized diet. So I'm a colorectal surgeon. I'm interested in bowel cancer. And if you are a rural South African, so if you live literally a rural life, your risk of bowel cancer is dramatically lower than someone living in the West. You don't get inflammatory bowel disease. You don't get...

diverticulosis. You don't get allergies. You don't get asthma. You get lots of other diseases of deprivation and they have higher rates of infection. I'm not saying that they have a perfect life by any stretch, but the disease is very, very different. And rural Africans eat a lot of fiber, tons of it, up to 50 grams a day. The average Londoner probably has about 10 to 15 grams. So if you were to have an African's diet, you'd blow up like a zeppelin. You'd be pretty unhappy and you'd fart a lot and your colleagues would hate you.

So what we did was we crossed over those diets between African-American men who have very high rates of bowel cancer and rural South Africans who have very low rates and have these very, very different diets. And when we did that, what we found was actually the microbiome doesn't change very much. If you're an African, you moan a lot about a high-fat, high-protein diet, but actually microbiome doesn't change. But the

the function of these microbes changes dramatically. So they start pouring out bile acids, short chain fatty acid metabolism dramatically changes. And the consequences of that are inflammation. So you can think about your microbiome like an engine. It's going to respond differently to the type of fuel that you put in it. And the efficiency of that engine is going to have a very, very big impact on the health of your car. Right. Well, as soon as this interview is done, I'm off to eat some fibre.

I'd like to dig into the role the microbiome plays in health a little bit more though. As you've said, it obviously impacts our risk of bowel cancer, inflammatory bowel disease and so on. But it's much bigger than that, isn't it? I mean, what do we know about how our microbiome is interacting with and influencing our immune system? So I think...

The immune system, if you like, you're born with a kind of literal antiviral software, right, which is pre-programmed. And that's called your innate immune system. And that has cells that are just going to attack whatever comes into that system that it's unfamiliar with. But then you have a learning immune system, which we call your adaptive immune system.

And it seems that the microbiome has a very important role in teaching both of these systems, actually, but particularly the adaptive system, what is friend and what is foe. So the microbiome, if you like, sits right in between the environment and your immune system. And it's there communicating constantly with your immune system through quite a sophisticated series of molecular languages.

And so from my research, what we're very interested in is what happens when that relationship goes wrong in very early life and what does that mean for your risk of things like allergy, asthma, eczema? And we think it's very significant. In fact, I think it's so significant that actually you should really think of the maternal microbiome, which I think is a really key part of that process, almost as a basic human right. Because if it's not set up properly in early life...

you might be exposing children to a lifetime of chronic disease from which there is no escape. And of course, the people that are most likely to experience that are the most vulnerable. So your engine is set very early by your mother's microbiome and in your first few years. And the more diversity you get in that, the better.

And as you say, we're beginning to understand how that impacts our health throughout the rest of our life. And then on top of that, what you're feeding the engine also has this huge role in our disease risk.

James, this growing knowledge of the gut microbiome is also changing how we practice medicine. In your book, you give an example of a retired London bus driver called Ray, who had been really unwell. He had been in hospital and was treated with antibiotics. He was discharged. And then as a result of all of that, Ray found himself with yet another very dangerous illness, Thalassiosis.

Tell me about that. Well, I mean, first of all, thank you to Ray and to his family. Ray sadly passed away, actually. So Ray was interesting because he had what you might call a superbug. He had a bug called Clostridium difficile, was what we used to call it. And he was very, very sick with it. And Ray had failed treatment with antibiotic therapy, and he was given...

Something called a fecal microbiota transplantation and that was because he was so unwell He was probably going to die if we didn't change tack very quickly that the only solution was to Completely reset his guts ecosystem and the only way that we can really do that at the moment Effectively is through this process of fecal microbiota transplantation, which is as gross as it sounds. It's a poo transplant. It's a poo transplant Yeah, and so what happened?

He was enrolled into a trial. And what happened is that a donor was found and that donor was screamed and mapped and a fecal sample was provided and then that was prepared. And when we prepare it, we screen out pathogens and bad bugs that we really don't want to give that we know are bad. And I think it is important to say that because this is not something you should be doing at home. And then that was put into like if you like a fecal milkshake. We mix it with a bit of saline. So it's a liquid form.

And then we place a tube in the nose, down into the stomach, and then we pass that fluid down the tube. What that microbiome transplant then does is it then, if you like, creates a more diverse ecosystem. It resets the ecosystem and it creates competition for this superbug, which can no longer survive. But it also changes the way that the gut works. And we think actually that is one of the important mechanisms through which the fecal transplantation is able to kill Clostridium difficile.

And in Ray's case, it was transformative. This man was incredibly frail. He was really very, very sick. And he was able to leave hospital just a few days later absolutely well. That's quite amazing that it had such a transformative effect, that a change in your microbiome can literally be life-saving. But so far we've been talking about physical illnesses like cancer and infections.

What about the microbiome's impact on mental health? There's a lot of research on how the gut influences the brain and vice versa, for example. How are these two talking to each other? You can't understand the engine of mental health without the microbiome because it has such a big cog in that machine.

So the answer is that at its most basic level, we're beginning to understand some of the pathways through which the microbiome interacts with our brain on a day-to-day level, right? So the microbiome produces a series of precursors for neurotransmitters that can cross the blood-brain barrier. It can influence brain development and brain function. It influences the way hormones influence the way we think and that we feel.

And the brain, of course, is constantly communicating with the microbiome through the vagus nerve and through the enteric nervous system. So it's kind of almost hardwired into the gut and the microbiome communicates with it very directly.

And increasingly, it's understood that the evolution of the microbiome and the growth of the brain in early life are very closely mapped. And therefore, when the microbiome is not able to evolve correctly, there might be consequences for brain development. But then similarly, at the end of life...

neuroinflammation plays a very big part in explaining why we get neurodegenerative diseases that affect the brain, like Alzheimer's and dementia. So I would argue you can't have a healthy brain, you can't have a healthy mind without having a healthy microbiome. But similarly, if you want to have a healthy microbiome, you've got to have a healthy brain. You've got a hardware problem, you've got a software problem, you've got to sort the two out together.

Another thing that I really had to ask you about was the impact the gut microbiome might have on our hormones and specifically our sex hormones. And I love this idea that you mentioned that our microbiomes could potentially be affecting our dating lives. I mean, tell me more about that. What's going on there? What we know is that microbes infect lots of the things that we classically associate with beauty or attractiveness, right? So whether or not we develop acne or how we smell because they influence our pheromones.

and social cues of our attractiveness. But also, they play a very, very important part in defining

how our androgens work so how our sex hormones work it might have a much more literal impact by the way in your sex life sex is an evolutionary way through which we transfer the microbiome between people and by which we maintain and optimize our microbiome so our oral microbiome is a good example of that like when you kiss you transfer about 80 million bacteria per smooch right so quite a lot of bugs and actually that's kind of important if you're trying to share genes are important in um

in how you digest your food, for example, or in how you might protect yourself against an oral pathogen. And we know by looking at the dental records of ancient humans that that definitely was an evolutionary vehicle through which we shared microbes. So kissing is good. You should do that for your microbiome.

James, beyond kissing more, what's your advice to people for developing and maintaining a healthy gut microbiome? Number one is don't take antibiotics unless you really, really need them. I'm not saying don't take antibiotics. I'm not an anti-antibioticist, but...

They are just a precious resource anyway in terms of antimicrobial resistance and you shouldn't be abusing them anyway. But if you're going to take an antibiotic, ask your doctor, am I taking the right one for the right reason? Is this as targeted as it can be? And ask them to prove that it really is a microbial infection that's driving it. Again, try and reduce your reliance on polypharmacy. So what that means is taking lots of medicine. So antacids would be a very, very good example of that.

Are you really doing everything that you can to try and reduce those things and their impact on your life? If you can minimize those unnecessary medicines in your life, your microbiome will be infinitely happier. Number two, get vaccinated. Because if you're vaccinated, you're much less likely to need antibiotics, right? Number three, obviously what you eat is very important. Delete your food delivery app.

and eat socially right so your food if you're sharing it with people you're sharing your microbiome and it's also good for your mental health it's good for everything right so share your food don't eat powder that comes out of a packet and think your gut is healthy it just isn't it's just terrible don't do it like your food needs a food matrix it needs substance because that's what microbes need right to properly absorb it and just avoid anything that's pre-packaged and ultra processed that's really your microbiome just does not like that and it's really not not not good for you

And if you take one thing away from this podcast, take this, which is that if you just put seven grams more fiber in your diet per day, your risk of stroke will fall. And the more you put, the lower your stroke risk will come. Part of that is because fiber is just a good thing. But part of it is because bugs are responsible for many of the anti-inflammatory properties of fiber, such as stroke prevention. James, thanks for coming on. Totally my pleasure. Thank you for having me.

My thanks again to Dr James Kinross. We've put a link to his book, Dark Matter, The New Science of the Microbiome, on the podcast webpage at theguardian.com. That's it for today. This episode was produced by Madeline Finlay, sound design by Jill Cox. The executive producer is Ellie Burey. This is The Guardian. We all have dreams. Dream home renovations...

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