10 million deaths predicted but science is fighting back! The secret gut viruses that attack cancer, fight infection and slow aging | Prof Martha Clokie & Prof Tim Spector

Welcome to Zoe Science and Nutrition where world-leading scientists explain how their research can improve your health. Tom lies motionless on a hospital bed, sweating, hallucinating. His body riddled with bacteria is rapidly failing. Just days earlier he'd been enjoying a holiday in Egypt. Now he's close to death. An antibiotic-resistant superbug is coursing through his veins. Every antibiotic has failed. This bleak tail plays out every day as antibiotic-resistant bacteria become increasingly common. But what if science already has an answer to this deadly problem and it comes in an unusual form? A virus that is harmless to humans but deadly to bacteria. Thankfully Tom's wife was a scientist who had heard of these phages and with the help of laboratories around the world she managed to procure some of these magical bacteria killers. Three days after treatment he awoke from his coma and his recovery began. But if these viruses are truly the answer to such a deadly problem why aren't they widely available? And what does this mean for your gut health? Because right now the lining of your gut wall is stuffed with trillions of these viruses that your own immune system is coordinating. Today I'm joined by Martha Clokey, a professor of microbiology at Leicester University and one of the world's leading experts on the mysterious phage. For the last 20 years she's pioneered research on phage therapy as a revolutionary approach to treating infections without antibiotics. We'll explore how these overlooked viruses could end the use of untargeted antibiotics that can wreak havoc with our microbiome and replace them with targeted therapies to destroy only the specific bacteria that is making us sick. Martha thank you so much for joining me today. Thank you for having me. And Tim great to have you here too. Likewise. So Martha we have a tradition here at Zuri where we always start with a quick fire round of questions and I know you said you've listened quite a few times so this is your chance to do it and you know we have these very strict rules for scientists so you can say yes or no or a one sentence answer if you have to. Okay. Are most viruses harmful to humans? No. Is it healthy to have viruses in our gut? Yes very much so we need them. Do bacteria make up the majority of our gut microbiome? They make up the majority in terms of abundance but viruses are the most numerous. Could the viruses in our gut help keep our microbiome healthy? Yes absolutely. And finally what myth about viruses do you hear most often? I think that viruses are bad. Many viruses as we'll discuss are good and much needed. Most of us have heard of viruses but what are they and how are they different from bacteria? So the main difference between a virus and a bacteria is that a virus does not have its own metabolism so in order for it to be alive as it were it needs to infect another cell. So we're used to viruses that infect us, don't we know about flu and COVID but bacteria interestingly they have their own viruses that infect them so they're highly, highly specific but they only become alive as it were when they attached to an infecting bacteria. Are there a lot of viruses out there? Yes viruses are the most numerous biological entities on the planet. So for each bacteria is thought there's at least 10 bacteria of ages so that adds up to a very, very large number of 10 to the 31. So that's far more stars than there are in the visible universe for example. It's an extremely large number. If you lined up all the little bacteria of ages head to tail, head to tail, head to tail you'd make a path 200 million light years long. So 200 million light years long made up of little viruses that only actually attack bacteria. Yeah. I heard some statistic how many there are even in the sea. Yes. So we think of the sea as a sort of sterile place just with a bit of salt in it but it's absolutely full of these tiny viruses. Yeah that's right that's where I started my journey with bacteriophages actually more than 20 years ago. I was studying the bacteria in the oceans and there's a million bacteria in a teaspoon of seawater. They're mainly just fixing the light and making a living like that and each bacteria there has 10 bacteriophages that infect it. So they're really, really numerous in the oceans and actually it's studying the bacteria in the oceans that has then allowed us now to look at them in other environments closer to home such as the human gut. So you're saying there's 10 million viruses in a teaspoon of seawater? Absolutely. You've jumped straight into bacteriophages but this is one sort of virus. Could you maybe paint the overall like what a virus is for, how do they exist and then help to understand these particular bacteria, phage viruses? Yes of course. So a virus is a small parasite. It just consists of a genome, so an RNA or a DNA genome, sometimes a bit of a protein head surrounding it or some lipids. So they're the ultimate parasites. Now the phage virus is interestingly that in fact bacteria tend to be a bit more complicated. They're much larger. They have a more complicated structure, bigger genomes, although they infect very small things. They're a more complicated form of a virus. So all viruses are like predators really aren't they? Yes. And I think there's some debate about where the viruses came before bacteria. It's not quite resolved as I understand it but they're these killers really that can only win by gaining entry into some other organism cells and they might be trained against bacteria. In this case the ones we've discussed today or human cells or any animal cell. Yeah all plants and animals and fungi, we all have viruses. They're the ultimate predator. So they're just small chunks of a genome that replicate. They need something else to be able to replicate in so they don't have their own machinery. So even plants can get viruses? Yeah yeah plants get there. Anybody who gardens will often see that plants suddenly look terribly sad and often that's due to a viral infection. And they're on the leaves of most of the plants we're eating as well aren't they? So every time we're having a salad or something there'll be viruses on it as well as bacteria. Totally freaking me out now. It's fascinating. So the viruses are sort of like these attackers. They need to plug into some other sort of cell and you're saying it's not just an animal which I think is how I've always really thought about it but it could also be a plant or a bacteria. And I think you're also saying that going back to those quickfire questions like one virus can't plug into me and it could alternatively plug into a bacteria? No they're highly, highly specific. So even within bacteria a virus that infects one type of bacteria wouldn't infect another and even often within a species are very very specific within that. So there's no way that a virus that infects a bacteria would infect a human. Probably most of us never thought about viruses very much until COVID and then obviously suddenly we all sort of got a bit of a crash course on understanding what they are. But I think we understood oh okay so there's viruses that maybe can infect other animals and at some point there's a mutation and then it can be a problem for humans and of course we then saw the way that that COVID virus sort of was mutating right and changing. Why is it that you're saying so confidently that these viruses for bacteria couldn't be harmful for me? So a virus has to gain entry to a cell in order to do damage. So COVID virus jumped from one species into humans and then became problematic when it could enter our human cells. So bacteriophages they can only enter bacteria because the surface of a bacterial cell is very different to the surface of a human cell. They might be able to go inside a human cell but even if they did they wouldn't be able to do anything when they got inside it because again they've evolved to work with the specific machinery inside a human cell. So they can't gain entrance and then even if they did somehow get in through some other means they wouldn't be able to do any damage because they can't exploit the human machinery. They need a bacterial machinery in order to be able to operate. I'm now showing my age and thinking about the world before everything was on the cloud and you know I've got my DVD or my VHS tape or whatever and I have to have the right machinery to play this on. Yeah. Is that the analogy that you're... That's a very nice analogy. That's really nice because first of all even within bacteria a lot of the whole of the battle between the bacteriophages and the bacteria is all about that surface. So that's where they're very, very specific within which bacteria they can actually enter in the first place and then if you think about the outside of a human cell it's just got this very composed of completely different material to a bacterial cell so it couldn't get in and I'd like your analogy that even if it did get in it's got the wrong equipment it would just be probably eaten by the human cell. So we're talking about these bacteria phages. That's a fancy word for viruses that work on bacteria. Yeah. So phage just means eat. It's Greek from the Greek to eat. So bacteria for you just a bacteria eater. So this is a virus that eats bacteria. Yes. Yeah. Now I think I'm starting to get a hint. What happens if this virus like gets into a bacteria? So what they do is they go in and they hijack that machinery with bacteria and they turn it into a virus factory or a phage factory. So they essentially make perhaps 10 or maybe 100 or more bacteria phages. So that poor old bacteria is just happily living doing what bacteria do. The virus comes along and all of its genetic machinery gets turned into making more viruses. So it copies the virus and then it turns that information into viral proteins and then eventually in a very timed way they all burst out. So you'll have 100 new bacteria phages. It's like your worst zombie nightmare Jonathan. So that basically they're taking over your body and then it's like there's suddenly hundreds and thousands of zombie Jonathan's will be running around. I think that might be your worst nightmare. Definitely. Definitely. Now I feel rather ill now. You've emphasised firstly that these viruses don't cause any harm to humans. We've also talked about them being like distinct to individual bacteria. It feels like it would be much more efficient if that virus could just stick on to every bacteria. It would find many more ways to go and create this plague of more viruses. There's a lot of misinformation when it comes to nutrition. From toxic diet culture to a broken food system. It's no wonder so many of us feel stuck, overwhelmed or misled and not as healthy as we want to be. If you feel like you've tried everything to improve your health and still don't know who's advised to follow, it's time to listen to your gut. After eight years spent measuring 300,000 gut profiles, Zoe has released a brand new app and gut health test to show you exactly what your body needs to thrive and to help you build healthy eating habits that actually stick. With AI food tracking, you simply snap a photo of your meal to get personalised insights into how your food will impact your body. You can even identify which processed foods in your fridge are high risk for your health and which aren't a worry. The app will help you eat more mindfully, allowing you to track progress with daily diet feedback from your in app AI nutrition coach. Along with the app, your gut health test can tell you how to improve your gut microbiome with personalised advice to help you support your gut function and help increase your abundance of good gut bugs. This isn't the latest quick fix, miracle plan or crash diet, likely to make you feel worse than when you started. This is a personalised nutrition app and gut health test backed by real clinical results and the world's largest nutrition study. Ready to join the gut health revolution? Go to Zoe.com. Yeah, I mean, it's interesting, isn't it? They it's just if you think about the fact that bacteria have been on earth for 3.9 billion years, we live in a sort of microbially dominated world. In general, we tend to just think about the ones very often that are associated with us, but bacteria have been evolving for a very, very long time. And with them, their own bacteria phages have been endlessly in a sort of almost like a dance and continuous evolution with them. So the bacteria phages are actually very useful for the bacteria in many ways, which seems a bit counterintuitive, doesn't it? Because they kill them, but they also are capable of interacting with them in different ways. So I largely study these ones that immediately they go in and kill. But some of them can go in and kind of hang out. And when they're hanging out, they can make the bacteria better as a bacteria. They can make the bacteria more toxic, perhaps, or it can make it better at surviving certain situations. Like, for example, in an anaerobic gut, they can have useful things in there that help the bacteria survive. Certain chemicals, can't they? The metabolites that could be helpful for us humans as well. Yeah, absolutely. It's like you can think about the bacteria phages as one they infect in that way. They have to pay their rent. OK, so it's a good strategy for a bacteria phage to be able to just make a partnership with a bacteria. So while it's in there, it has to do something useful for that bacteria to give it a bit of a selective advantage compared to all the other bacteria. So you have this whole world, really, where all bacteria are being shaped by their bacterial predators. And it's a sort of the phages are always trying to get in and the bacteria are kind of they want them there, but they don't want them to be too much there. So they're trying to block them. And then the phages counter evolve and then the bacteria counter evolve. So you end up with all of these different trajectories of huge, huge numbers of viruses. Can I make sure I understood that for a second? You're saying a lot of these bacteria phages that just go in and they immediately kill the bacteria. Yeah. But actually it's more complicated than that. There's a whole bunch of these viruses that inject themselves into the bacteria. They don't kill it. Yeah. And actually potentially giving it almost like superpowers that you wouldn't have otherwise. And we think about taking some medicine or some we talk often about particular food, right, which helps our health or indeed having bacteria inside us. And so you're saying that these viruses aren't always bad, which I'm finding very radical as a thought. They're not. They're sort of the viruses are doing lots of things to for the bacteria. So from from our perspective, they're just they're controlling the bacteria. They're determining which bacteria are actually there. So they're killing some, which means others can then grow up and then they're releasing stuff and then other bacteria can then come in and grow there. So we've got we've got bacteria phages just really controlling that biology. They're actually determining which bacteria are there. One analogy is like they're acting as gamekeepers. Part of the fact there are lots of them. Yeah. There are lots of instances, aren't there, when you get an overgrowth of some bacteria in your gut. And if they did overgrow, they would probably outlive their food supplies that will die off. So actually what these phages are doing is pruning them back a bit like, you know, a cowl. If there's too many deer in a forest, you introduce wolves. And that keeps them down so that they're actually healthy. And then that whole environment is much healthier. So that's another way to look at it, acting like you would in an environment that has this ecology that's evolved to be the most efficient. Yeah. So when when bacterial numbers get really high, that becomes advantageous for the bacteria. There's more likely that a bacteriophage will be able to infect them. So they will bring that abundant thing down. So they're really helpful in general for any ecological system because they're controlling the balance of what's already there. I think of them entirely as a bad thing. So this seems quite radical. Is it only bacteria that can benefit from viral infections? Yeah. Well, it was interesting. We don't really have a very good idea at the moment of whether bacteriophages are good or bad for for us. What we know is that within a healthy gut, we have a high diversity of bacteria and a high diversity of bacteriophages, which are starting to work out now. In particular diseases, this balance seems to change. So, for example, in Crohn's disease and inflammatory gut disease, we know that the amount of bacteriophages and the diversity, the types of bacteriophages reduces. And we also now know as well that in other diseases, there seems to be a correlation sometimes between both particular bacteria and phages. So in certain settings, they are driving disease. And in other settings, they are clearly playing a role in keeping the natural sort of diversity because it get when you see a disease state, we see the bacteriophages and the bacteria out of balance. Yeah, we've done some studies in twins and it does seem that the diversity of these viruses, so how many different species and types there are, correlates with the diversity of the normal gut bacteria, which we know correlates with health. So again, it seems to be the more different ones you've got, the healthier you are overall. I mean, these very early findings, but it seems to be behaving the same way as we're perceiving the gut bacteria. We want more of them, more different ones. We don't just want one strain that takes over. That would be very bad news, but this variety does seem to be beneficial. And I've read that there is evidence when viruses are in your mucus layer, so in your gums and things like this, they've shown to be definitely protective for, I can't remember, it's fighting infections particularly and they might also do the same in the gut. Is that? Yeah, no, that's absolutely right. It's thought that bacteriophages can sit in the gut and protect us from the invasion of bacteria that cause disease. So bacteriophages are covered in these little domains called IG domains, a bit like antibodies. So they sit in the mucus lining of our gut. And then if a bacteria comes along that would cause us an infection, bang, they'll protect us against it. So they're part of our sort of defense system to bacteria that would otherwise cause us some disease symptoms. Now, just as you described that, now you're talking about these viruses actually inside our gut. Can I just take a moment because I think you were just saying the evidence is the more variety of different phages is your shorthand, is it? Yes, yeah. These particular viruses, these phages, the more different viruses I have in my gut actually seems to be positive for my health. Is that right? It does seem to be that's the case. Yes. I have in my mind that whenever my body sees a virus, it just goes out and kills it. So what's going on that you're saying that my gut lining is like full of all of these viruses just resting there? Yeah. So from a very early age, as we become colonized by bacteria, we're also colonized by bacteriophages, by phages. So for every different bacteria cell that's there, there'll be 10 bacteriophages. Now, in both of these life cycles I told you about, so some of them are infecting and killing, others are infecting and hanging out. They're shaping what's there, they're changing the biology of what's there. And then they're also living within our gut. So just sitting. But our immune system is effectively trained to see them as friendly. Yes, that's right. We don't pick them up as like a gastroenteritis virus, which would trigger our immune system. These ones are your friends and foe. Most of them are friendly and from early age, babies, immune systems are being trained every time they eat food or take anything in. They're getting viruses and that just says, OK, relax. We're on your side. And so they don't you don't get a reaction against it. So our immune system knows that these viruses, these phages are actually safe and actually helpful. And so it says, I'm not going to attack you. Yes. I think we're all familiar with the idea that like there's unhealthy bacteria that I can eat and that's why we tend to wash our hands. What about viruses? Oh, yeah, you can easily get viruses that make us sick and terric viruses will make us sick or human viruses. So our body will definitely mountain immune system when they see them. But the phages are quite different in terms of their relationship with us. It's not that we can't see the viruses in our gut like our immune system absolutely can see them and then it's like, oh, I know you're safe. That's how the virus comes along that can make me sick and it's immediately pouncing and attacking. Yeah, exactly. So in the same way that we don't mountain immune response to our commensal bacteria, we don't mountain immune response to our bacteria phages. They're just part of us. So a lot of the work in my lab is finding phages that we can use to treat bacterial disease. So for example, we've done a lot of work in Salmonella. Now, if I wanted to find Salmonella phages, I was originally going to sick animals and sick people. We didn't find any because at that point the bacteria is escaped. But if you just go to healthy animals, healthy pigs, healthy chickens, healthy sheep, you'll find in their feces really good viruses that kill Salmonella. So part of one of the reasons why we're healthy is that we have these phages that kill things that invade us. You have your defense system so nobody attacks you. And so you're saying if I've got all of these bacteria phages ready in my gut, I don't get the Salmonella. But if I didn't have those and I'm overrun with Salmonella, you're like, well, that's because there is none of these phages to protect me. Yeah, exactly. So the phages are just part of our natural defense that's keeping us healthy. But it can be overrun if there's too many of these Salmonella bacteria, which just overwhelm the system and then cause toxins and all the other kind of havoc they can wreck or the person is unwell for other reasons. And we know that general sickness can reduce the number of these normal healthy phages in your gut. And that's why older people and people who have other diseases are more prone to these bacteria you get in food. Could you help me to understand that a little bit more? Of course. If you look at the viral diversity of people as they age, we know that when you're born, you don't have bacteria phages and you've got that that gets colonized in the same way it gets colonized with bacteria. And we can see that that diversity goes, it starts to go up and then it stabilizes at the age of two. And then again, it goes up a little bit more through your teenage years. And as you get old, it's what Tim is saying, that the amount of phages, for some reason, it goes down so you lose your diversity with age. So we have a sort of a relatively static phageome in the same way we have a relatively static microbiome in general, that with age, the diversity drops. One of the things that's happening is I'm getting older and worrying about, obviously, maintaining my health. You're saying this like diversity of viruses that are protecting me is falling away and therefore I'm like more at risk from infections than I would have been when I'm younger. I don't think we know quite enough to know that yet, to be honest. But I think that certainly there's a lot of variety in terms of the component and what they're doing. And I mean, amazingly, really, there's so little known actually about what those viruses are encoding. So if you think we've got perhaps a billion bacteria in your each gram of gut material, there'll be 10 billion bacteria phages. Now, they're really unknown. So about 80% of them, we have no idea what they encode, how they act, what they're doing, how they're behaving. So there's in terms of discovery space, but there's so much to try to unpick. Yeah, I mean, if we compare it to what we knew about the microbiome, it's about 25 years behind. Yeah. So you've got to try and imagine what we knew about the microbiome 20, 25 years ago. And that's the sort of state of play of what we understand about these gut viruses, but we have the advantage of knowing all the things we know about the bacteria so that we can project a lot that we didn't know. So we're having to sort of guess a lot at the moment because they're really, really hard to study. I was told that I have to ask you about the healing waters of the River Ganges and why they might actually be healing waters. Yes, this is really fascinating. The Ganges, of course, are a long history of being a very spiritual place. And people is known that people go to the Ganges and get healed from things. But interestingly enough, the very, very first observation of what turned out to be bacteriophages was seen in the Ganges. So in the late 19th century, there was a British biologist. He was there, hankin and stankin, his name was. And he was looking at the water and he realized there was something in the water that killed bacteria and he didn't know what it was. But he knew that if he boiled the bacteria, he didn't get this effect anymore. So what's happened is I think that the Ganges is a really interesting place for bacteria. People is a lot of connection with humans. A lot of human bacteria in there from us. Also, it originates in the Himalayas, lots of natural bacteria washing in from the soil. So huge diversity of bacteria. So big diversity of bacteriophages. So if you have a bacterial ailment and you go into the Ganges, it could easily be that you'll find a natural vage that will then cure you. So could be that some of those healing properties. You have to be, I would say, quite brave. I did go to the Ganges for there was a big religious festival there. And people were jumping in and drinking the water. Yeah. Thousands of people going in there. And at the same time, I'd witnessed that morning burning bodies on the banks of the Ganges. And you had dogs, you know, still sniffing around these bodies. So there's human remains in there. There's all kinds of things that you don't want to really comprehend. So the idea of drinking Ganges water to be healthy. Yeah, it's a big leap of faith. But it is interesting that they keep doing it. So they can't really be getting that ill. So it's not on your 2026 habits to adopt Tim as drinking Ganges water? No, I'm sorry, Jonathan. I'm happy to sponsor your trip there and see if you're not willing to do it. Then it's definitely outside of like anything I'm going to try. I chickened out. I was offered some Ganges water, but I did turn it down. But maybe, you know, the science will support me next time and I'll be brave enough. Have you tried it, Martha? I have been to the Ganges. I was there last year. I was at a Fage meeting in Varanasi where my collaborators had actually purified pages from the Ganges and they were actually using them already to treat patients. So they were treating patients with really bad multi-drug resistant infections that could not be treated with other methods. So they were actually using Ganges fages. So I think purified Ganges fages are probably a different thing to drinking the actual water itself. I would love to talk about that. Can you start by helping me to understand what antibiotic resistance is? And I've definitely heard that somehow this is a really big potential danger for us. We use antibiotics for all aspects of medicine, don't we? If we have a bad chest infection or a skin infection, we will go to the GP and we'll get antibiotics. Antibiotics also underpin all surgeries, cancer treatments and so on. But what's happening is because they've been overused, bacteria are capable of becoming resistant to them. So they just evolve different ways of being able to exist with them. So normally an antibiotic will kill the bacteria and they have many different ways that they can just actually become resistant to them so they can survive in the presence of it. So that means that the antibiotics are not working anymore. So there is more and more bacterial diseases that are literally resistant to every single antibiotic that we have available to us. So it's an incredibly worrying situation. It's estimated more than a million people dying every year from an infection that can't be treated and also several million more associated with these infections. Did you say more than a million people are dying every year from infections that can't be treated by antibiotics? Because there's lots of different types of bacteria and lots of different diseases. It's somehow not given the attention that it should, but it's incredibly serious already. We need to do something now because it's estimated that if we don't do anything, we'll perhaps have 10 million people dying every year. So it'll exceed the number of people that are dying from cancers. And it's not just the overuse of antibiotics in the public for colds and viruses. It's also in our food supply. It's used in low levels in a lot of food production. For example, chickens grow faster and cut out infections in animals and it's used preventively. In Europe, they've managed to cut this down a lot, but a lot of the world, it's still very prevalent and fish farms still use it. So it's a real global problem. So can I just clarify, you're allowed to give antibiotics to animals, even if they're not actively sick? In Europe now, for about 10 years, they've changed the rules. So you can't give it totally preventively. But if you just say that one of my animals is sick out of 10,000, you can then give it to the rest of them. So it's not completely black and white. But it's pretty different from what we do with people. I can't be like I met Tim this morning, like I told me he had an infection, so I'm going to pop antibiotics. And everyone you know, yes, everyone I know. Yeah, that's the equivalent. So it's still lax and many countries haven't signed up for this. So it's a global problem. Yeah. So about 70 percent of antibiotics that you use, you use actually in agriculture. They're used in the production, particularly of poultry, swine and fish farming. Yeah. So we literally put it into the water. Yeah. I should say that I've done a lot of work with a poultry in the UK and our UK poultry farmers, they actually stopped using them for this purpose before it was banned. So there are community led initiatives within the industry. So stop this happening. But in many countries, it's a major problem. So we have to really think about our antibiotic resistance, where it's coming from and how we can stop it. So you can see we really need to understand a one health approach. It's not just the antibiotics we get into humans. If we give antibiotics to the animals that we eat, we will then get these resistant organisms. And we have a lot of listeners in the US. What's the usage of antibiotics in animals there? I think the extent of the problem in that area is still not fully known, but it's known that there are transmission risks. And the thing is, once it's present, bacteria are super good at swapping and telling another bacteria, this is how you do it. They're really good at spreading resistance amongst them. So once you've evolved that resistance, it can spread really rapidly. I think anywhere where there's mass agriculture, where you're putting thousands of animals together, whether it's in fish farms or these cattle lots, you're going to get problems of antibiotic overuse. And this is a problem for everybody. So even if we stop now, we're still in a quite perilous state of having not enough antibiotics to treat these common conditions. And so things that we thought impossible, you know, people are looking at if we fell over in the street in 10 years time, cut our leg, there might be no antibiotic that would stop us getting sepsis and dying from a simple cut. And I think the thing is it's happening now, even in the UK, it's estimated there's more than 7000 people a year are dying of an infection. When I never solicit this information, because we're doing the research on bacteriophages to make sure we develop the correct ones. But I get emails all the time from doctors who write to tell me that they can't treat their patient because their patients have got an infection. That is resistant to everything. So it's a problem now, a major problem now. We need to do something sooner rather than later. So could we now come back to this magic Ganges water and the phages in it? I think you've described this rather terrifying idea that we're handing this out like candy, not just to humans, but to like animals to make them grow faster. How might this magic Ganges water help us? Well, it's not just the Ganges water. I mean, that was just where they happened to be seen, first of all. But anywhere where we have high numbers of bacteria, we will have high numbers of phages and phages can be developed as a treatment against antibiotic resistant bacteria. So actually, it might surprise you that they were developed before antibiotics. So more than 100 years ago, phages were actually isolated in 1915 by a British person, Frederick Ford, and a couple years later by a young French Canadian called Felix de Raell. So phages were isolated and Felix de Raell actually started to use phages to treat people in the 20s and 30s and 40s. So they were actually used for a fair chunk of time before antibiotics were discovered. And then antibiotics, because they're simpler and easier to develop, they sort of overtook in terms of a treatment. They, they, they're marvellous and they became a cornerstone of modern medicine. And then this whole area of bacteriophage science as a medicine in most parts of the world was terminated. And so why was the antibiotics better than the phages? Well, antibiotic is a simple compound and that can kill lots of different types of bacteria. So for a start, it's much less specific. You don't really need to know what you're killing. You just need to do something making your gut sick. And then you can give the antibiotic roughly. So they're much broader in terms of their specificity than the bacteriophages are. So you're going to need to know what the target is really for, for your phages to work. So this is sort of like, I'm stretching my analogies a bit here, but the antibody is sort of like a nuclear bomb and like blows all of this up. That's right. Whereas you're saying the phages, it literally has like the photo of the exact bacteria that it's looking for. And it lets everything else go until it finds that one. Within that analogy, it's like a sharpshooter. So if you want to use a phage, you need to have one that is perfectly matched to the bacteria that you need to try and treat. Yes, that's right. So actually what the country that is most developed in this whole area is Georgia. So the former Soviet Union was really big on phages in general. That's because this first person that found the French Canadian, he trained the young Georgian scientist. And whilst most of the world stopped using phages therapeutically, the Georgians carried on. So I think one of the things that I know from personal experience is that if you take like sort of big, I think they call them broad spectrum antibiotics, it can sort of wreak havoc in your microbiome. And if I was to take these phages, would it have the same effect of knocking out my whole microbiome? No, not at all. When we've looked at the additional phages in our different largely done in animal studies, we can see that they don't, the phages just will take out that one species. They don't and they protect the rest of the microbiome is left intact. So they have a much less detrimental effect on the whole of the command, all the good bacteria are maintained basically. Are there any examples of this phage therapy actually working in humans? Because in a way, this sounds really exciting. But I think one of the things I've slowly learned over almost 10 years now at Zoe is sometimes there's a very long way from speaking to a scientist doing like research in their lab or talking about something in animals to like this thing is actually like real and works in human beings. Yeah. So they're used, as I say, they're used routinely in places like Georgia, where they have they treat thousands of patients every year. They're largely used at the moment in worst case scenarios where there's nothing else has worked, so therefore phages are allowed to be used. So there was a very nice paper published last year where from Belgium and the military hospital there where they just treated 100 patients and they wrote a paper of how they'd use the phages and how they'd combine them with antibiotics. So there are those types of cases where they used. There was one very interesting case with a man called Tom Patterson. So he was a psychiatrist. He is from San Diego and he was on holiday in Egypt and he managed to get himself infected by a multidrug resistant bacteria. So they couldn't treat him, infected his kidneys. He tried to get treated in Egypt. They couldn't treat him there. He went to Germany. They couldn't treat him. And he ended up in a coma and very, very ill in San Diego. Now, Tom was lucky enough to be married to a woman called Stephanie Stratady. Her background was in epidemiology and viruses. So she knew a lot about microbiology in general. And she managed to get hold of bacteria phages from various places. And they were able to find some different phages that were able to treat his infection. So he was basically dying and given chance, very, very low chances of survival. And they managed to find some phages that they used to treat him. Did he recover? Yeah, he's perfectly fine now. Back to, you know, so he's completely better. And he was the doctors have basically given up because the infection he'd picked up in Egypt was resistant to all the different like literally every antibiotic that exists. Yeah, exactly. So it was resistant to everything. He was he was very, very ill. And Stephanie, she told I met Stephanie several times. She's great. And she told me that she's basically said to him, if you want to live, squeeze my hand. And he did. And she managed to get phages from the American Navy, from there's an institute in the States where she also got them from one of the big phage centers there and then from one of the private companies. She got hold of all the phages she could, different types. And they gave him the phages and he lived. So that was one of the first sort of high profile cases in the States. Were bacteria phages were used? Do you think we should all be going to Georgia to stock up on our supplies in case we get ill? I think there's a lot we can learn from Georgia for sure. I think what we need to do is understand bacteria phage biology to the point where we can make it mainstream in this country and where it's not just used as a as a last resort. It needs to be brought much earlier into the intervention. Ideally, you'd like your GP to be able to access both phages and antibiotics. It used to be possible to buy bacteria phages and boots the chemist in the UK until about the 1960s. And then they stopped stocking them. But you can see in boots records, they'd used to sell them here. Wow, that's really interesting. Yeah, so it's a traditional medicine here. We just forgot about it like fermentation and other things. Yeah. What are your thoughts as we're talking about this, Tim? Is this like really niche science is going to be very hard to translate into something real or is this a real way forward to avoid this sort of broad spectrum antibiotic usage? I think it's pretty much the only approach to counteract the fact that we're running out of antibiotics and the millions of people that are going to be dying every year is going to increase. We are realizing that this antibiotic resistance is real. And this is the number one treatment that we that we've just heard has been used quite widely. It's pretty safe. That's the other thing. It sounds really scary to drink a vial of viruses. Right? You don't look very comfortable. We may be getting to try it afterwards with your tea. But, you know, it is pretty safe because they're so specific. You know, they're only going to go after the specific bacteria that are in you and they're not going to attack anything else. So I think once we go over the psychological barrier of using viruses or drinking viruses as treatment, then we can make big progress. But we can see how it's really hard to get these sort of medicines into our very conservative system. And that really needs to change. But I think as well as the antibiotic resistance, I was talking to some colleagues about cancer treatment that the very nature of these phages is that you can target these phages to attack essentially cancer cells. Yeah, you can you can actually you can change the specificity and use them as delivery vehicles so they can recognize the outside of a cancer cell and recognize differentiate that from a healthy cell and deliver a drug. So that's one way that we're looking at sort of even taking them into a different area, the outside of the bacteriophage is very specific and finds the right bacteria. So what we can do is we can modify that so it doesn't recognize a bacteria anymore. But instead it recognizes cancer cell when a cell becomes cancerous in the human body. Again, the outside of it changes within the whole mass of a human body. You can get the phage to go to that cancerous cell. And then you can previously have engineered it to have what we call a payload. So instead of injecting a bacterial genome, it will inject a cancer treatment. So it's one of the ways that we can use phages when we understand them better. We can use them both to manipulate the microbiome, but potentially also to deliver things to these specific assassins. They're so targeted that they make it really safe. And so you could drink a whole bucket of them and they'll only be going after that that cancer cell, they would leave all your other cells alone. And so very little collateral damage, unlike antibiotics. And I think that's what's so exciting about them. And so is this entirely theoretical or in labs are they actually able to create these sorts of phages that can actually go after a cancer in a human being? Yes, so phage engineering is again quite in its infancy. But what we've done, for example, in our lab is make phages that can attach to human gut epithelial cells. So therefore you could use them potentially to deliver something to the gut. There aren't products at the moment. This is still very much in the research phase. And regard to cancer, another really interesting thing is one of my colleagues, he's a surgeon treating lung cancers, and he's shown that he can predict whether or not patients will respond to his cancer treatment based on the micro human microbiome. So he can tell from the fecal, the gut microbiome, if that patient will or will not respond to cancer treatments. So you can imagine that a use of phages in the future isn't going to be just the uses we've been talking about just taking out one bacteria, but it's potentially modifying that gut to a to a state that's appropriate and receptive to another treatment. So we can use phages as a kind of if we understand how they're manipulating the gut, we can then influence them and push the gut microbiome in to a sort of composition that makes it amenable to other treatments. So like how the gut microbiome is really important for these immune modulating drugs in cancer, so that these new treatments for melanoma, kidney cancer, lung cancer. So what you're saying is that these phages could be in addition to that. Yeah. So they're rather than just giving people fiber and probiotics and prebiotics. You could also give them phages, which was sort of help the immune system fight the cancer. Exactly. They'd be part of that mixture. And that might happen faster because you could be more general. You could be we could try the Georgian mixture, for example, in some of these cancer cases. Yeah. Amazing. If you know someone who's working hard to improve their gut health and microbiome, why not share this episode with them right now? So they can start thinking about getting those healthy viruses into their gut too. I'm sure they'll thank you. What do we know if anything about how these viruses might be influencing our gut bacteria today if you're listening to this show? So we know that we have a lot of viruses in our guts. And what those viruses will be doing is they'll be killing certain bacteria. And that means that when those bacteria die, they'll be burst open and food will be provided for other bacteria to grow in. So the viruses are actually already determining that composition. So we're eating food, the bacteria eating the food that we eat. And then the viruses are then eating them and then sort of shaping them. So we know that that's what the viruses are doing naturally. Now, if we eat a nice, diverse set of food, we'll have bacteria that will be growing in a particular way, which makes it more likely for the phages to then come in and then burst them open. So really, we've got the sort of diet affecting the bacteria and the state of the bacteria affecting the way that the bacteria phages are then interacting with them. So that's sort of what's going on amongst us the whole time. It's not just a static microbiome. Yes, the way I see it, viruses are mirroring the state of our gut health. So the healthier our gut are, the more diverse they are, the more diverse our diet is, the more diverse set of phages you have that are then able to really sort of do the forestry and husbandry correctly so that our immune system is is working really well and everything's in in nice balance. Because I don't think there's any particular foods or anything that affect viruses and not bacteria that I'm aware of. It means not a very researched area. There has been a little bit. There was an interesting paper that subjected hundreds of bacteria in our guts, lots of different types of food. And they could see some quite interesting things like there seems to be a positive correlation between phage types and coffee, which I thought was interesting. We could see that people that drank coffee regularly, they were particularly high on a set of phages within their gut. People who are drinking coffee tend to have more of these phages than people who don't. Yeah, we don't we don't know. They're probably they're probably good phages. They're certainly not bad phages. They're just it's very, very hard to turn correlation and to causation when it comes to many aspects of the gut microbiome, including the phages. So what people have done is they did there was this one particularly nice study and they they they showed that some foods seem to make the viruses pop out of the bacteria. Actually, one of the most potent things was Stevia. I think you've discussed discussed that in some of your other podcasts. So listen, it's a sweetener that comes from a plant. And that seemed to those viruses I talked about that were hanging out with a bacteria just in there, they popped out. They didn't like the Stevia. So what about if I wanted to get more of these phages into me? And I think one of you is saying something about potentially they're living in, like the plants that I might eat. Could you explain that to me? Yeah, well, we know that if we if we eat vegetables that are grown just in in have me packaged in artificial atmospheres, they're covered in bacteria and they're covered in phages. And so if we just buy by parts of a normal healthy diet, where we're eating plant material, the pesticides and herbicides affect. They will affect it. Yeah, yeah, they will reduce numbers in a significant way. The same way that they reduce the bacteria, they will reduce the number of the diversity of bacteria and the diversity of phages. Alongside that, yeah, there was a study that showed that if you eat lettuces that are just grown in your own garden or small market gardens, they had a much higher number of probiotic bacteria and phages associated with that compared to bagged salad. So we will get phages from our diet from the natural plants that we eat. So I think what we know is that if we have a large diversity of plants and starting material, we will have a larger diversity of bacteria. And with that, we'll have a large diversity of phages. I don't think we have really the concept of what makes a healthy phage that and and really which phages are going to drive our guts in the right direction. I think it's just part of a natural Mediterranean or a naturally non-artificially based diet appears to be good at promoting that phage diversity as well as the bacterial diversity. I think we can say that we're realising that as well as this diversity of bacteria, we've got this whole extra sort of layer of the phages sort of directing all aspects of that bacterial biology. And as we unpick that more and understand it more, we'll be able to know how we can drive things in one direction or the other. But I think for now, it's mainly just knowing that we've got lots of good friendly viruses and our guts as well as good useful bacteria. I mean, one thing I'm really struck by, Martha, and I always think this is a sign of like speaking to the real scientists who do the research rather than, you know, some sort of social media influencer is that there are so many things about our human body where we just don't understand yet what's going on and we don't have all the answers. And I think phages are particularly new. The fact that we just don't know 80% of the content in our guts when we can send men to the moon, but we don't know what's in us. But I think what is exciting is even a decade ago, we wouldn't have had the tools to be able to get that genetic information and make sense of it. So we've been developing new bioinformatic tools to make sense and to understand this novel diversity. So phages are so, so diverse, I can still find them, look at them and not recognize anything. But now I can go into what we call structural space. We can predict how they might fold and how they might look. That can help us understand how they work. So I think it should be a really exciting time now in this area, because for the first time, we've actually got the techniques and the tools to be able to, first of all, understand it and then make use of it. I mean, these phages have been they're the perfect bacterial predators. We sort of ignore understanding them at our own peril, really. If I was going to ask you, like, what's the one thing that you're most excited about in terms of like the future for phages and human health? What would it be? I think being able to actually go from knowing that they're there in huge abundance and they're playing roles, actually being able to use them in ways that are useful to us, that is really exciting. We'll be able to use them to stop infection, to prevent infections and in a multitude of other ways to control our microbiome. So I think we're on the cusp of that, actually being able to do something useful with this knowledge. It's incredibly exciting. I love your analogy, Tymar's Martha. You know, we can go to the moon and all these things and we don't understand so much of what's inside our bodies. Yeah, no, it's we've always gone outwards and instead of inwards. And that's generally the human fallacy, really, that by looking at the stars and not looking inside us, I think I have enormous potential to get us out of this terrible mess that overuse of antibiotics is less to us with. And I think that's, to me, the really big hope. And that's why we need to be putting more funds and money behind this field, which actually we've been very slow on. You know, I don't think we've really grasped this and it's been very hard to get grants and things like, you know, I failed a few times to get some grants in this area. Yeah, I think you're right. It's sort of seen as being niche and sort of Grinjia. Yeah, which is ridiculous, really. And also it's seen as being risky, but we actually need to do the work to show how they want to be able to do the risk. Amazing. I would like to do a quick summary. And I'm just starting with the things that I've been most struck by. The first is there are like trillions of viruses in my gut. And apparently that's good for me, which I think is the exact opposite of like everything I've been taught my entire life, that maybe drinking Ganges water might be good for me because it's full of all of these amazing bacteria, phages, these phages you talked about, these viruses that attack bacteria. So actually, if I was really sick, perhaps drinking the Ganges would make me better. But if even Tim isn't willing to do it, I'm probably not going to experiment there. I think you also shared this this thing that in like one teaspoon of sea water, there's a million bacteria and 10 million of these phages, these viruses. Yes. Makes you realize how much we're coexisting with all of this life. And we have done throughout like our evolutionary history and we just don't realize this area of science is new. But we do know that actually when you look at a healthy gut, it has a lot more diversity of these phages and unhealthy gut. So just like we talk about with the microbiome and wanting to have a lot of these different good bugs, like similarly, we want to have a lot of these these phages and that interestingly, our own immune system is like trained to keep these. So you're saying that like in my gut right now, there'll be trillions of like these phages that my body is aware of and keeping there because actually it might attack if I get Salmonella or something like that. So actually part of my own immune system almost is to keep these phages ready to attack these bacteria. Just as we talked about like the bacteria has almost been part of our body and part of our system, you can actually even extend that to the viruses of the bacteria to help sort of protect us is wild. And then I think we talked about this amazing story about Tom Patterson, like getting so sick in Egypt with something that couldn't be treated with antibiotics, he was going to die and he was healed by taking these phages. So this is real. It can be transformative. And that's important because a million people die a year from antibiotic resistance bacteria, but it could be 10 million or 100 million could be a billion we need to have a solution here. And perhaps we can even be using this in cancer in the future, Tim was saying. So that's incredibly exciting. Now, in terms of actionable advice, it's early. So it's hard to like give lots of detailed advice. But what I heard is very much the advice you're following to get a sort of diverse, healthy microbiome is probably the same advice to get sort of this diverse and healthy set of phages. So it's the same thing of like eating plants and variety. And then I heard specifically maybe a couple of things, which is we can measure whether there are phages around on the food that we eat. So if you're eating food that hasn't been packed in like an atmosphere, you know, if it's more organic, so less pesticide, you're going to get more microbes on it and you're going to get more of these phages with it. And finally, Tim's going to be really happy because apparently coffee drinkers have more phages and Tim is on a campaign always to tell me that I should drink more coffee and so there's just yet another argument for how coffee is actually good for us rather than bad. That's brilliant, sorry. I love it. At Zoe, we never stop in curious about how people respond to food. So we recently asked thousands of people about their breakfast, what they eat and how they feel about it. Their answers may surprise you. Over 70 percent told us that their breakfast is balanced, yet only 6 percent get enough fiber. If you've been listening to this podcast, you know, that's not enough to be balanced. And it's no wonder that only 16 percent felt energetic after eating. 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