How to feed the 50 gut bacteria that shrink body fat, calm inflammation and cut cholesterol | Prof Nicola Segata & Prof Sarah Berry

Welcome to Zoe, Science and Nutrition, where world-leading scientists explain how their research can improve your health. Inside your body, there is an entire civilization. It tells a story that's millions of years older than humanity itself. Trillions of microscopic organisms inhabit your gut, like a vast unseen city, working in darkness, negotiating, competing, surviving. They decide how efficiently you pull energy from food, how your immune system reacts to threats, and how close your body drifts towards health or disease. For a long time, this hidden world has remained largely out of reach. But now, in arguably the biggest breakthrough in microbiome science for a decade, so is scientists and collaborators have finally brought this hidden ecosystem into tight focus, and unravel the secret of what makes a gut microbiome healthy. They identified a stark divide. Certain microbes consistently appear in healthier bodies, while others are linked to obesity, inflammation, and cardiometabolic risk. The gut, it turns out, holds a mirror to health, a biological fingerprint written in bacteria. However, the good news is that this record is not permanent. But unlike your genetic code, your microbiome is not set in stone. You can be the author of your own microbial story. The gut microbiome is responsive. It shifts with diathetic environment and daily habits. When conditions change, some species flourish. Others fade. And over time, the balance of this internal ecosystem can move gradually in one direction or another. This research has just been published in Nature, the world's most influential scientific journal. And I'm delighted to have two of the senior authors with me today. Professor Nicholas Agata from the University of Trenton and Professor Sarah Berry. So is she a scientist and professor of nutrition at King's College London. After listening to this episode, you'll know how to improve this dizzyingly complex civilization within your gut and help add extra healthy years to your life. Nicola, thank you so much for joining me again today. Thank you Jonathan, you're going to be here. And Sarah, thank you also. Pleasure. I'm really excited to be here with Nicola. And that also means you're a bit experts on this. So you know I'm going to hit you with a rapid fire Q&A. Are you ready to go? Yep. Nicola, is there really a link between the species of bacteria in our gut and our long-term health? Absolutely. Yes. It contains lots of bad microbes, are we stuck with them? No, we can change it. Sarah, if we change the food that we eat, can we increase the number of good gut bugs? Absolutely, yes. We'll take in a fibosupplement guarantee a diverse gut microbiome. No. And Nicola, what's the most exciting thing that you discovered in this groundbreaking new research? I think it's exciting that now we have the panel of the top 50, the best bacteria we may want to have in our gut. I'm thrilled to discuss today what I think is the biggest breakthrough in microbiome science for a decade. So nature, like the world's most influential scientific journal, recently published a science paper by Zoe's scientist, and the two of you are lead authors on this paper, which established this sort of first reliable repeatable way to measure the health of an individual's gut microbiome. And I'm excited because it's sort of like the culmination of more than eight years of work at Zoe. And it's also only been possible, thanks to more than 34,000 Zoe members who took part in this research. And I think many of those members will be listening today, in which case I'd like to say thank you to all of you for being part of this. And I suspect Nicola and Sarah are absolutely right. Thank you so much. So today I'm really excited to share how a listener can use this groundbreaking research to improve their gut health and therefore their overall health and sort of show the link between something they can seem very abstract, right? Some sort of complicated science paper and something that's really actionable. Before we get into sort of what's uncovered in the paper, Nicola, why is publishing in nature like such a big deal if you're a scientist? Well, naturally the most respected and most read scientific journal in the world. So everyone wants to publish there because yours will then be amplified to all the audience of scientists, but also non-scientists. And also it's very difficult now because you have a very strict policy of your work being reviewed, you know, it's called a peer reviewing process. And so there were five in our case reviewers that really scrutinize our work from the first world to the last number in the supplement. And so it means that it's also very scrutinized that our work was extremely valuable and eye impact. And the peer review process that it goes through is tough in most journals, but the peer review process that this piece of work went through poor Nicola's team were working around the clock for many, many months, you know, responding to some of the peer review comments. And ultimately it makes the science even better than it already is. We improve, thanks to them. And Sarah, what makes this research so groundbreaking from your perspective? So I think firstly for me there's the community science element to it and you've already thanked the many people that have contributed their data to make this possible. And I think the beauty of it is the size of it. And while size isn't always important in science, actually when it comes to microbiome research, you know, there's so much noise surrounding the microbiome that it's very difficult often to disentangle what's noise versus what's we call a real signal, a real idea that there is that actual link between. In this case, for example, dire and a change in the microbes or a change in the microbiome and a change in health outcomes. Also, these numbers are not only because of noise, no, also because we are much more microbiologically different than genetically. So there is an intrinsic variability in the best of microbiome that you can only cope with that only if you are really, really big numbers. And 34,000 went to the papers. We have even more now. And it's also exciting to continue looking inside that. You're saying that you need huge numbers. And partly that's because of this noise and complexity, but it's partly because there's just such huge variation in our microbiome is much bigger than the difference between my genes and your genes. Correct. We are 99.9% identical on the genome level, the human genome level. But if you look at the microbial species we have in the gut, we are only around 33% identical. And if you look at the variance of these species in each of us, we are much less similar. So around 0.1 something similar. So you need to be numbers to interpret all these diversity. And I think this has been the problem with previous research that when it's on really small numbers, you just can't get a signal that's above that noise. So it's very difficult to then translate that into something that's actually meaningful. If I can add on these, it's not only the number, no, but also the diversity of the population because we have the American population, the English population and covered all cities, more or less, all regions. And this is very important because there can be other signals, other characteristics of the microbiome that are linked to aspects that are not really what we want to explore. Yeah. And even something so simplest, whether you live in a city versus if you live in a rural setting, so you live in a countryside, that has a huge impact on your microphone. So when you're trying to actually decipher what is due to diet, you've got to get rid of all of that other noise that's going on. And it's only by having this large amount of data thanks to all of the community scientists and all of the members that have taken part in Zoe that we can actually achieve that. And Sarah, you were telling me beforehand that you think about the paper as having almost two different parts? Yeah. So I think from a research point of view, there's two elements that are really interesting. One is that we've been able to collect a lot of data at one point in time that shows us these very, very clear links between what we eat and the composition of our microbiome, and also very clear links between the composition of our microbiome and a whole host of different health outcomes from inflammation, to blood cholesterol, to blood pressure, to body composition. But then where it gets really interesting as a researcher is that we've actually been able to look at what we call longitudinal or interventional data. And this is data where we have looked at how by changing the diet in clinical trials, does that bring about a change in the microbiome? And how is that then linked to a change in health outcomes? And this is really important because a lot of the microbiome research out there, just like a lot of diet and health research, doesn't show that causal link, doesn't show, okay, so that diet does actually lead to a change in this microbiome. A lot of it just shows that association. And so whilst these might seem like very boring technical terms, causality versus association, actually it's critical in human research. And it's really important that we can show that changing the diet changes the microbiome, and that's exactly what Nicholas' team within Alice's, they've done, has shown in this paper using our fantastic ZOE data. I can tell that you're both incredibly proud and excited about this paper and some I to have some association with it. So let's maybe jump into the first of those two things that you talked about Sarah, which is this idea that for the first time it establishes a way to know how healthy your microbiome is. Nicholas, can you explain this to us? If we say hormones, what's the first thing that comes to mind? your reproductive system. Or maybe you're thyroid? We're going to guess you're not thinking about your gut. Well, you should be. It's a hormone factory. It produces some of the most important hormones for our overall health, like ones that regulate our metabolism, appetite, and energy levels. All your hormones together function like an orchestra, each playing their own part to contribute to a symphony. When your gut health suffers and your microbiome is disrupted, it can throw the whole orchestra off. The good news is that tuning things up is helped by your diet. Fidio got the right variety of plants, fiber, and other kidney trins, and it'll be able to do its job producing and processing hormones much more effectively. At Zoey, we want to help you to listen to and understand your internal hormonal orchestra. Find out more about hormonal health with our free guide. We can download it now at Zoey.com/hurtility or click the link in the show notes. Back to the podcast. Yes, so we have hundreds of bacteria in our gut, and overall there are thousands in the population. And our question was, can we look at which of them are always or almost always associated with LT diets on one side and LT cardinumatorbocular markets on the other side? Because this gives us some sort of guilt by association. If in LT people that are eating well, we always find the same eye microbes, both present, but also eye-liabandant, it has to be meaningful. And so what is exactly what we did, there was ranking the abundance, so the abundance and the presence of bacteria in our gut with these set of markets on one side for the diet on the other side for cardinumatorbocular. And we have these ranking 661, if I remember well, total species that were enough abundant to be profiled and seen with statistics. And we have about top 50 and the bottom 50. The top 50 is like the most wanted bacteria that we would all love to have in our gut. If I ask you which micro should you have in your gut, you can look at this list and say, yeah, they were on the top, then a bit of the others and so on and so forth. It does not mean that we all have only the good bugs and not the bad bugs, of course. But we should all aim to have more of the top 50 than of the bottom 50. And I think what's really interesting here, Jonathan, is until now I don't believe there's ever been a good enough marker of what a healthy micro-bio-miss. And it's even something that we've had challenges with some of the research that we've been publishing as very far markly in our trials, is review as often say, well, how do we know what a healthy micro-bio-miss? And I think that's the most groundbreaking part of this research is that not just will it help us at Zoe with the dietary advice that we give, it will also help researchers be able to have a way of measuring whether an intervention, a food, a diet, a lifestyle change improves your micro-bio in a way that we believe is healthy. Yeah. And in fact, it is not the healthiness of the micro-bio-miss. It is the micro-bio-miss associated with the healthy human characteristics. And this is the way we define it because otherwise the concept of an healthy micro-bio-m is difficult if we don't bring into the picture also our body. So I think what you're saying is, for the first time, you can actually do this analysis of someone's microbiome, which means measuring all the different species that are in there. And then you can find, oh, you've got like these 27 ones which are from the good and these 13 from the bad. And then if we were actually able to give a measurement of the health of the microbiome and before, you know, you knew you had species in here, but you just weren't able to tell whether or not this was good or bad. Exactly. And which of them were more good than others or else associated as we prefer to say, actually. And so what makes a micro good or bad? That is actually much more difficult to define. And it's not what we did here, but we do think that the good microbes are those that are able to digest fibers and produce immunostimulatory metabolites, so for example, sugar and fatty acids, and that will add a series of metabolites. I say that we don't know very well also because inside our top 50 microbes, there are some microbes that no one saw before us. So we define them, we saw them, but no microbiologists before us was able to have them growing in vitro. So they never seen this bacteria, but we saw them directly using these techniques called metagenomics in the samples. And especially the good ones are a lot unknown. And I think that's really exciting again that we've now identified in simple terms these new bugs. And so again, Zuri, but also as researchers, we can now be on the lookout for these as well when we're thinking about how to improve health outcomes via microbiomemediated mechanism. I've heard you use this phrase, the dark matter of the microbiome, Nicola. Yes, there are the unknowns in the top 50. So these are bacteria that we see from our analysis, but again, they are not grown in the lab. They are not handled in the lab. We don't know the name. We named some of them. Actually, one of them was called segatella. So there is a segatella in your gut, Jonathan, which is not in the top 50. What do we need to do to get one named after us? Well, I didn't name my bacteria, not because it's only other scientists that can name after you. Yes, we're really nice to necklace, Sarah. I've just taken them out for lunch, Jonathan. And there'll be a bury, yes, for sure. But there are some bacteria to be named into in the top 50. There are a lot of bacteria in the family of the lactobacteria, lactospiria, actually, which are bacteria told to be able to degrade fibres, complex fibres and produce short fatty acids. And those are all names or bugs that you can name after whoever you want, Sarah. You need a bit of more characterization, but it's doable. So you're saying that you found these 50 good bugs. And these are like the best bugs you want to have them inside you. And amazingly, lots of them have never been discovered by science before. And you've identified them sort of from their DNA in the way you analyze this. But no one has ever grown them in a petri dish. It's literally like in the past going into the Amazon jungle for the first time and discovering all these animals that nobody knew about. Correct. We recognize the elephants, for example, from the genome, but we've never seen elephants. We don't have them in it, and it's the same with bacteria. So we see the genome. We characterize the genome. We know they exist. We know whether you and I have genomes from the same species. But we don't know the biological features of these bacteria. There is still 5, 10, 15 percent of our gut microbiomes that are really unknown. So still to be discovered even by metagenomics. Now, you helped to explain, I think, the good bugs. We don't understand completely, but you're saying they break down these fibers and they make these sort of positive chemicals. What about a bad micro? What's that doing? They are more inflammatory, associated with simple sugars that are present in many foods. So they are not specialists, they are generalists, and they are inducing inflammation to do some extent. There are exceptions. There are some that are bad in any situation, in any gut, others that are only a bad under certain sequestances, certain diets or certain conditions, diseases and so on and so forth. But mostly they are inflammatory for the gut environment. I think a really fascinating example is where you look at some of the detrimental effects of meat. And there are certain bugs that live in our gut that are able to convert certain compounds from red meat into a particular chemical that can be further metabolised to be quite harmful for us. And that's a great example of where you can see the complexity of, okay, it's partly dependent on what you eat. So are you even eating red meat in the first place? It's partly dependent on what species you've got in there. Is it then converting some of those compounds in that red meat to that harmful chemical, which then goes on to impact your health? This is our chemical is called trimetermin in the specific case and I mentioned it also because there are many other chemicals that also in this case we don't know they are dark butter and they are influencing our gut. And we think that these are the link between the bad microbes and our health. And Sarah, you and Tim convinced me that so we should publish this list of bugs rather than keep it a secret. Can you tell us why? Well, first and foremost we're academic researchers and therefore it is inherent in us as academic researchers to get our science out there to publish our research so that other scientists can benefit. We're a community as scientists. We are not here to sit and just make millions for Zoe. Otherwise we wouldn't have published all the 4050 manuscripts that we've already published. And we want to benefit from all of these amazing community scientists that are enabling us to create this new research. It's important it's out there in the scientific community and it can advance as we've already said other people's research by developing this kind of signature of this health associated microbiome. And Nikola, I understand that therefore this can be used as a way that is better than just thinking about this gut diversity we've been talking about for the last decade. Correct. And it is what we do now. So looking at which of the top 50 and what of 50 you have and also the others to be honest and we can also report overall what are the amount of top 50 in a gut of someone. We also can look at their bodies. And we can kind of derive a score out of the user to try to give a summary of how else associated are certain microbiamies. You know, when I think about going to the doctor, there's a sort of simple score and they'll say something like, "Oh, well, this is good, but you know, your cholesterol level is a bit too high." And then sometimes I give you this sort of little readout. How can this information that's been presented in the paper actually be used to create a sort of measurable score for my microbiome? So it's actually been very difficult to give a single score for the microbiome because, like Nicholas, explained, you know, it's so complex. You've got trillions of different bacteria, you've got different types, some associated with favorable health effects, some associated with unfavorable health effects. You've also, as well, it's got the different types. You've got different amounts of each one, so it's not like simply saying, "Oh, your cholesterol's high or your blood pressure's high or low." And again, I think this is what's really exciting about this research is that by very clearly ranking those most closely associated with favorable health outcomes, and those most closely associated with unfavorable health outcomes, we can take that information and we can actually create a score that has some meaning in terms of health. And so with the score that we've created, which is out of a thousand, it considers the different types of bugs, how many of the good ones do you have, how many of the bad ones do you have, but it also considers the abundance, so the amount of each of ones that you have. It then goes into this black box again where the amazing data scientists at Zoe have created all of these algorithms that are very complicated, that are further tweaked to maximize their relationship with the different health outcomes. And that gives a score out of a thousand where the higher your score is, the healthier you've got microbiomes. So in really simple kind of summary terms, it means you've kind of got more of the good bugs, and less of the bad bugs, with a bit of complex data science mixed in there. So one of the things I know I've heard you both talk about is that normally there's something like a 20 year gap between a research paper being published in like a cutting edge journal like nature, and like a new drug or like something like that actually being available to consumers. Is that right? Well, I think in our case is it can be much, much faster, not because we can act on diet to change the microbiome. I think the most exciting thing about the microbiome from my viewpoint is that we can change the microbiome. Your body is difficult to change it, almost impossible. Our microbiome can be changed. The challenge is to understand how of course. And the rankings are very important to me because by improving the diet, we can see whether our microbiome improves as a response to that. So it's also for us to understand whether we are going the right direction or not, for example. But this has been quite rapid, I think, in the typical timeline of scientific research, particularly nutrition and dietary research. And so you talk about a 20 year lag between maybe a new drug being developed and out on the market. Yes, because there's lots of safety stuff. But even the kind of studies that I do at King's College London, which are quite safe, randomized controlled trials, looking at how a particular fat might impact a particular health outcome. That's often a massive time to let I publish a paper only a couple of weeks ago to do a particular type of fat from a randomized controlled trial. That I first had the idea back in 2012, I actually got the funding in 2014. I started the trial about two years later because of all the bureaucracy and red tape at the university. And then you've got to run the trial, do the analysis, write the paper. 14 years ago, I had that idea. 12 years ago, I got the funding for it. Back then, no one had heard of Zerry. I hadn't had the pleasure of meeting you and then look where we are now. So we are talking quite different timescales. And I do remember meeting you Jonathan. I did say, well, there's Zoe time frames and then there's just the rest of the world time phase. That's lovely. I think the other thing that you said to me, Nicola, is that because this is sort of all this new information is being applied to this sort of genetic information that's been collected from our sample of poop. You can actually apply this new analysis to microbiome samples that have been done in the past. Absolutely. Yes. The way we sequenced the microbiome, the way we read the microbiome, didn't change the last 10 years or so. It got maybe less expensive if you like, but so the information is the same. Is that we learn how to mine that information better. And this was again due to the validity of large data sets data to discover these new unknowns. So we can go back in samples even of 10 years ago. And now we can see those bacteria that were not known at that time. So yeah, I think this is a huge potential of the science that is building upon data from the past. That's why it's really important that we are publishing this, that we are identifying the names of all of these different species that they are there for scientists to be able to then go back and look in their own data sets as well. And just for clarity, in case anyone's listening to this that has had their microbiome sample in the past, because you're saying it could be any test in the last 10 years. But I think it needs to be done in a particular way. Yes, it needs to be the whole metasome sequencing as we call it. So is the sequencing of the wall genetic material inside the sample. There were other techniques, especially in the past that were looking at some fraction of the bacterial genome and that are not accurate enough for what we did. And I also want to expand a little bit because our list of microbes is also important for other researchers because someone else may find that some of these bacteria are associated with another disease, a disease that we are not looking inside of the risk for another disease. And so it will be very important for us to take back that information because we may know how to act on diet to increase or decrease that specific bacteria that someone else found to be associated with a disease. Now we're continually scientists learning from each other within our own discipline and from other disciplines. So again, sharing this kind of information really enables us as a science community internationally to advance science in a way that wasn't possible before. So I understand that there's also some further research that is not captured in this nature paper where you found what you call clusters of gut microbes linked to specific health conditions. Can you give us a little sneak peek into that? Yeah, so the cluster work that we've been doing at Zoe is the way of looking at those rankings, the Nicholas been talking about of those microbes that are most associated with certain health outcomes and putting them into meaningful groups from a health perspective. So the clusters are kind of how we're packaging this information and feeding it back to individuals. And what we've done is we've developed four clusters. We've developed a cluster related to inflammation. We have a cluster for blood sugar control. So that's considering how we respond to carbohydrates, but also what our baseline sugar levels are. We have a cluster related to heart health and cholesterol. So that's considering lots of different fat measures, not just simple measures of cholesterol, but we have lots of different ways that we look at what we call blood lipids, which are different types of cholesterol. And then we have one to do with body composition, so whether it's a healthy distribution of fat in our body. And what we've done is we've taken the work that Nicholas teams been working on. And we've looked at which of those species are most closely associated, for example, with inflammation, which are the ones most positively associated. So particularly bad for inflammation, which are most negatively associated as in particularly good potentially for inflammation. Same we've done for some of the other clusters. So for cholesterol and for blood sugar. And then when we test people's microbiome, we can tell them if they have more of an inflammatory microbiome cluster or less of an inflammatory microbiome cluster, whether they have more of a blood cholesterol heart health cluster and so forth. So it's kind of a nice way of packaging up these results in a way that a user, I think, can understand what's very complex science. And Nicholas, I've had the tendency just to think about, oh, there's like good bugs and bad bugs, but it seems like this is saying that these bugs are more specifically linked to particular either like health supporting or potentially harmful causes. Do we understand at all what's going on? Why particular bugs could be linked to any of these things? We know that there is a cross talk between our bacteria and our gut, especially. And these are upends at the level of chemicals, as Sara mentioned, and also other molecules that are interacting with our immune system, our cardiometabolic system, and so on and so forth. So usually the basic mechanism is that some healthy foods, they contain a diversity of five versus special year or polyphenols rather chemicals that are stimulating several bacteria, some bacteria that are fermenting these molecules. And that's why it's also very important to have a diversity of these molecule as input to our gut, so diversity of bacteria can specialize on fermenting the single components because every bacteria will produce something different. Now, so those usually starting from fibers are producing in modulatory and positive chemicals, and the more variety we have of that. the better. That's why it's also important not only to have the best bug of our list, of our ranking, but also a diversity of bugs toward the eye end of our ranking. So I can't just have one good bug that helps, but actually these different good bugs are actually sort of creating different good cases. Exactly. So one bacterium cannot do thousands of different main functions. Also, you need thousands of different microbes to do thousands of positive actions in your gut. Different bugs eat different bits of food coming into our gut, as well as producing different chemicals. So you need that diversity of foods, fibers, bioactives like polyphenols, as well as the diversity of the bugs that might preferentially choose one food over the other and also produce different chemicals. And on the contrary, not sugars can metabolize by all bacteria. Those that are less specialized in good fibers are those that are growing probably if you eat only simple sugars. And those usually, unfortunately you may say are the bad microbes in our gut. So the bad guys like the sugar, the good guys like all of those wonderful fibers and polyphenols. Correct. I feel so bad. Everyone listening is not surprised to hear that. There is more than that, I think, because it is something we still investigate. But the microgram is a community, a complex community in which the community is working more than the sum of each single bacteria. So there is the layer in which a delta-society bacteria, a diversity of them, are building something, a network of interacting chemicals that are adding more than what each single microgram can do. I'd like to move on now to the second part, Sarah, of what you described in this paper, because it's really cool to be able to measure that your gut microbiome is healthy or not. But I think what everybody is really interested in is can I improve my score? Can I increase the number of good gut bacteria? Or is it like so many things in my life? Well, I would have liked to be in a bit taller, but your height is fixed. And I understand that this is something that is really novel that's been addressed in this paper. Can you tell me about the Sarah? Yeah, so one thing that we have always known is that the microbiome is very malleable. So we know it changes through diet, but we haven't known which specific foods change which specific bugs, except in a few rare cases. And so what we did with this research is as well as looking at what we call cross-sectional at one point in time. We also took data from two randomized controlled trials that we've run at Zoe together with Nicola. The first of one of these trials was called our method study. And this was a study that we conducted a couple of years ago where we randomly allocated over 350 people to either follow the US dietary guidance. This is called the my plate guidance or follow the Zoe personalizing nutrition programme, which is leveraging all of this research from Nicola's group around the best food for you've got microbiome. We followed them over 12 to 18 week period. We took various samples at the beginning of the study. We took various samples. At the end of the study, we measured lots of health metrics as well as taking microbiome samples. And as part of this new paper, what Nicola's team did is they went back and they had a look at what dietary changes occurred but also what microbiome changes occurred during the 18 week period. Nicola, what did you find? So we found actually that the toughest bacteria in the gut environment after the intervention increased in number and abundance. So exactly what we were hoping for. And the opposite thing for the bottom 50 bacteria that decreased both in abundance and so in their amounts and also in their presence, some of them were not detectable anymore. And when you say number and abundance, could you just help me to understand what that means? Yes, so one thing is counting how many of those 50 top or bottom 50 bacteria you have. But then each bacteria in your gut will be part of a community and you can quantify it. So you may have a bacterium at 1% of the total amount of bacteria cells in your gut or 90%. So when you say increasing abundance, maybe they move from being at 5% to being 7 or 8% is an increase, meaning that that positive or negative bacteria is counting more inside the microbial community in the gut. So what this research showed is that by following this healthy dietary program, then you're increasing the number of what we call these good bugs. You're decreasing the number of these bad bugs, but you're also increasing how much they're dominating the good bugs. Your overall amount of bacteria that are in your gut. And the statistical methods that we use to quantify them strictly speaking is a little bit more complex, but we arrived to what is called statistical significance. So we proved in the paper that it cannot be by chance. It's really associated with the change of the diet. And that's really important is because when you're dealing with large numbers, also a large diversity of different outcomes, which is what we're dealing with when you've got so many hundreds of different species that they're more than 600. Quite often, you can find things by chance. And so that's why scientists or in the analysis that Nicholas grouped as there's lots of ways that you can make sure that when you do the analysis, it's not just a chance finding. So it really gives us great confidence that what we're seeing is relevant, is significant, and also is due to the changes in the diet that have come about through our intervention. So what you're saying is in a relatively short period of time, then you're saying like sort of 12 to 18 weeks, your microbiome can really change in a way that means that it is healthier afterwards than it was at the beginning. It's not just that I want to have one of these good microbes. I need to have lots of. We have several examples of bacteria moving from being barely detectable. So traces to be apart of the community. These are the positive bacteria that are increasing and these are strong signals. And you often talk about this being the gold standard Sarah. Can you explain to us why this is such a big deal? So in nutrition research, a lot of human biological research randomized control trials are the gold standards. So these are the trials where you will randomly allocate people to a control or an intervention. And so instead of just looking at association, you can start to see a causal link. So what this enables us to do is to say, okay, the diet is causing the change that we're seeing in the microbiome. Just because something's associated doesn't mean that it's actually going to bring about a change in a given health outcome, but this shows that causal link. What we know then is that this change or these microbes that are increasing, we know from our other research is associated with all of these favorable health outcomes. So it gives us some confidence to say, okay, the change that we're making in our diets causing this change in our microbiome, which we believe is associated or will be associated with an improvement in these various health outcomes. A question that maybe can arise here is can we take elder associated bacteria and give it to people to increase it? Well, this is something very difficult to do. It is incredibly difficult to grow this bacteria in the lab. It's even more difficult to put it in a pill or something arriving to our gut. And it's something we cannot do right now also for regulatory reasons. We need to make sure this is safe from many different viewpoints. So yes, this will also validate that the final causality, you know, if that is the bacterium changing. But the diet, you know, we don't need to wait 20 years to make sure that these microbes we have the technology to give you those new microbes. So again, it's important for us to act on diet and it is actually what we are trying to do. Now I understand that because this was nature, you didn't just do one of these gold standard trials. You have to do a second one as well that's in here. Of course we're greedy. I'm greedy. I love our cities. So we actually also conducted another randomized control trial. This was called our biome study. And the biome study was a randomized control trial where we randomly allocated people to either of three interventions. And we had about 130 people in each intervention. And they were allocated to either consume our daily 30, which is our whole food prebiotic supplement or to consume a functional control. And in this case, it was like bread croutons or to consume a probiotic. And in this case, this was one of the most commonly consumed over the counter probiotics that you get in many health stores. Which means it had some live bacteria in it? Yes, it had some live bacteria. And we had to prove that it had some live bacteria in order for us to actually get ethical approval to conduct this study because we had to make sure what we were doing was correct. We took measurements before they started. We took measurements six weeks later. We took measurements for how people were feeling. They moved the energy, the hunger, their sleep. We took measurements of their gut microbiome as well as some blood measures. So you had these three different arms Sarah. And I think what you were looking at is like, does this really shift the microbiome? What were the results? So what we found is for those taking the prebiotic whole food supplement, we saw a huge shift in the gut microbiome. We saw a large increase in our good bugs. And we saw also a decrease in our bad bugs. And this was really quite. pronounced compared to those taking the probiotic. We saw only one bug and didn't we change, which was the bug that was from the probiotic and we saw almost no change, or a little change from the control these red croutons. Lots of people have said, "Oh, why did you use red croutons as the control?" In nutrition research, it's really important you try and use a functional equivalent, because most of the time it's not like a drug trial where you can have an active pill and then a placebo pill. This is why dietary studies are so difficult, because when you add something in, you're taking something out, or what are you going to use as the comparator? Because the whole food prebiotic supplement is intended to be added onto food as a kind of salad, topper, sprinkler, we wanted to use something that would be used in the same way, which is why we have these red croutons. Nicola, I'd love to understand what happened to the microbiome for people who were taking the supplements, because I know that that's a big part of what was in the paper. Yes, again, the top 50 bacteria increased in their presence and their amounts. This was really, really strong, and not only in the top 50, also still the top 100, also we see huge increases, especially something called lachnospiracia again. On the other side, instead, we saw disappearing enterocloster or other bacteria like ruminocaucus that we know they are pro-inflammatory. These made a lot of sense to us, because we know in the prebiotic world food supplement, there are thousands of different chemicals associated with LD-planned foods. This is exactly what we were discussing before. Different, LD input chemicals stimulating many of the top 50 and top 100 species in our gut. They were increasing, and we really measured it and saw it again with statistical significance, which means that it cannot be by chance, but it's something that we saw strongly and reproducibly. I think what's really exciting as well from a nutritional perspective is we know it's really difficult to change your diet. We know our diet is so ingrained in us from our culture, upbringing, our social settings and our taste preferences. That's the biggest challenge that many of us know what we should be eating, but we're not doing it because of various other barriers. The beauty I think with this supplement is it's something so simple. It's a single, simple dietary strategy that's actually brought around such profound changes in the gut microbiome that our data shows associated with their healthy outcomes. I think it's safe to say that those results are a lot stronger than actually either you had originally expected, given that on these two examples, one is sort of like trying to get a full dietary change, and the other one is just this sort of 30-planned supplement. Correct. As scientists, we frequently have an hypothesis. When we see that hypothesis confirmed is nice, but in this case, it's not only was proved, but was proved as strength that was much higher than what we were hoping for. We were surprised at ourselves and the positive surprise, of course. Is this a sign that the plant diversity in our diets today is just incredibly low compared to what we would have had historically to support our diet? Yes, I think this is the point. Our microbiome evolved with us over hundreds of thousands of years. We told the plant based chemicals we were in contact with. We still have the signature, but if we remove the diversity of plants going in, we can lose these diversity in a second. This is actually why we think that these prebiotic product works. Well, also in the comments, not just the food. I know this is something you've spent quite a bit of time researching as well. There's so many other factors in our environment that impact our microbiome, whether it's the kind of more sterile environment we live in. We know that soil microbes play a really important role. We have another paper actually in nature talking about how we gain microbes by interacting with the people we are in contact with. This is also very important. Haven't you done something looking at petonies? Petonies, yes, it was with the kids. We enrolled six classes of daycare babies and we also have their parents, siblings, educators at the daycare and also the pets at home. We tracked a very complex network of transmission. There are some strains or some specific variants of some bacteria jumping from the pet, the baby, the baby, the other baby at home. We also, one mother transmitted to the baby, the baby to another baby at the daycare and this other baby to another father, to to his father. There can be stories about our mother for certain kid who can donate the strains to a father of another kid. We don't do gossip, so it has to be through the transmission at the daycare. I think you might be suggesting something that I'm not going to talk about like that. This is why the uniform of a fingerprint, I think. Yes, yes, yes, yes. We can match perfectly the babies that were in the same room. No different rooms, they don't share bacteria. Two kids that were for two, three months in the same room, they shared up to 10, 12, 15% of their gut microbiome. So surround yourself by healthy people. I need to spend more time with you and Tim, Jonathan. I would love that. So, next up, before I move on to like, okay, what's the really practical advice? I had one question listening to this, which is you've talked about all of these microbes improving and that's great because you want to have these 50 good bugs. Is it possible to change the level of all of the gut bugs I have or are some sort of essentially stuck? So it doesn't really matter whether I eat more healthy food, like I just can't shift it. Yeah, so in our intervention, we saw that not all the 50 bacteria were changing in the same proportions. No, so definitely there are some that are more active in changing the change of diet. This can be due to the specific foods that we eat or the specific prebiotics that we eat that are stimulating some in the not others. It can also be that some bacteria are more stuck for certain reasons. There are some associations that we don't understand. There are some bacteria that are depending on other bacteria and also it's complex. But yes, I think one of the next challenges is to understand this. Why some are more able to change than others as the diet changes? Do you know someone who cares about their gut health? But isn't sure of exactly what to do to improve it? If so, why not share this episode with them right now and show them how to improve their gut health according to the very latest science? I'm sure they'll thank you. So we talked a lot about science and a lot about studies. What does that mean about what I can do to improve my gut health? I know that fiber is important for my gut health. So can I just take a big fiber supplement to solve all of this? A one fiber supplement will be one fiber. So it can stimulate maybe one, two, three bacteria, but you need the diversity of it. So that's why the prebiotics in a wolf food supplement is what you really want for your microbiome. Again, diversity of chemical, positive, healthy chemical as input means higher diversity of microbes is able to digest it and which means in turn more positive chemicals produced by this bacteria starting from the input chemicals that are impacting positively our health. I've already heard you mentioned as well as fiber polyphenols. What is that? So polyphenols are a type of chemical that are found in many plant-based foods, particularly heavily pigmented, so quite colorful foods. They're often what gives the plants a bit of taste, but also what gives their plant the color. And they have what we call bioactive like properties. So they act on lots of different areas in our body related to health. But we know that on average about 80% of polyphenols reach a large intestine where they are metabolised. So eaten by our microbiome to produce certain chemicals and it's those certain chemicals that the gut microbiome is producing acid eats or metabolises these polyphenols that have their beneficial effects. For example, acting on inflammatory pathways in a favourable way, acting on lots of health related pathways again in a favourable way. And what we know is different gut bugs eat or metabolise different types of polyphenols. So you need to have both the diversity of your gut bugs as well as the diversity of polyphenols. And just like Nicholas explained with the fibers, it's really important to have a diversity of those different types of polyphenols. There's lots of different types of polyphenols, just like there's lots of different types of fibers. So you're maximising the different types of chemicals that produce the act on all different types of health outcomes. And so how does this tie into this sort of 30 plants that I've heard you talk about often? So we know that it's really important to get that diversity of plants because you want that diversity in your fibers. So different types of fibers that are going to feed different gut bugs in polyphenols are going to again feed different gut bugs. So we know that by increasing the diversity, you're more likely to get a greater diversity of the different types of polyphenols, of which there's many and of the different types of fibers. And you said to me that there's some really interesting evidence that's related to perimenopause that's somehow linked into this whole story. Can you tell me about that? There's evidence to show in peri-imposed menopause or women that if you take soy-is-of-lavones, which are a type of polyphenol found in soy products, or you can actually get them over the counter as a supplement, that on average you'll get an improvement in your menopause symptoms, you'll get a reduction in hot flushes. But what we know is it's hugely variable between people. Some people take soy-is-of-lavones and they have a huge benefit. Some people say, "Oh, I've almost had no benefit." We now understand why, and that's because the soy-is-of-lavones, this type of polyphenol, can be metabolised by your gut microbiome. Some people have species, so they have bugs, that enable them to convert the soy-is-of-lavones into a very active type of chemical that binds really strongly to your estrogen receptors, because the reason you get your symptoms when your peri-imposed menopause was because you have a reduction in estrogen, so it binds really, really strongly. More strongly than the original isoflavone. If you have these gut bugs, what we know is from randomized control trials, you will experience on average a 75% greater reduction in your menopause symptoms compared to someone that doesn't have these bugs, or isn't able to convert the soy-is-of-lavones into this very active substance. This is another reason I think, particularly as a peri-imposed menopause or woman myself, everyone is at that lie stage with their lie. What did you try and what worked for you? You've got to be quite cautious that again, you see an influencer say, "Oh my god, I took this one drug, I took guys of flavones, that's it, I'm this new woman, I feel 30 again, and my whole life is better." Well, great, they might have the species that are able to convert to this very active form, but it might not work for you. I think that's a really great example of showing just how much of an impact something so simplest just those gut bugs being able to convert that way as a flavoured, the active form or not does have on your overall health. So basically, unless I have that microbe inside me, it doesn't matter if I'm eating those soy-beans because it needs that microbe to convert it to have this superduper 75% higher impact. So you will still get a benefit, but you will get an even greater benefit by about 75% if you have the species that are able you could have converted to that more active form. So I think that's sort of an example of a link between individual foods and individual bugs. We often talk about that concept as a gut booster. Can you explain simply what that is? So this will be where we have identified a food that is very strongly associated with a particular bug. So when we're taking our 50 good bugs, they're the ones that we want to promote in individuals and at an individual level, we might say, "Oh, Jonathan, apples are really, really closely associated with one of those top 50 bugs. We really recommend that you continue consuming or you consume even more of those apples because we believe that it will increase that good bug." And that's what a lot of our advice is based on and that's why it also makes so exciting some of the research that Nicholas added in as part of this nature paper where we've looked at how people's bugs have changed on the advice that we've given because often we've asked them to increase specific boosters as we call them specific foods linked to specific bugs. Amazing. I was thinking about my own experiences and one of the things that I've mentioned on the show a few times is that I broke my toe now a couple of years ago and I took these very intense antibiotics and I was measuring my gut microbiome and it basically wiped out almost everything. I was quite worried. They're all gone and what I've seen is they're slowly returning. So my first question, Nicholas, where are they coming from? I think most of them were not really wiped out. They were only incredibly low abandones, not really few traces. It is true that probably antibiotics are acting more on the health of the bacteria than the others because the others learn how to defend themselves from antibiotics. They are more generalists. So the take home I think for me is that an LT diet is even more important after antibiotics to try to rebuild it. But some of these bacteria may actually have been completely lost inside your gut and so that's where the social interaction again comes to mind because 99, probably percent of the microbes in our gut are coming from the gut of other people. You may feel a bit gross but it is what it is. But we build that over decades of life. We acquired microbes from many different individuals. Some of them got adapted to us. Some of them choose us because of some reason that we don't really understand. So after the antibiotic titum that we had, that process kind of restarted at least partially. And probably you need that time to reacquire the microbes that you lost. And probably you are quite slightly different microbes because maybe you didn't do the same interaction with the same people that you did over the decade before antibiotics. Nikola, we recently did a podcast on the blue zones which are areas in the world. You are probably familiar with where people live very long healthy lives. And one of the features that is common amongst all of the blue zones is that social interaction. As well as the diet and a few other factors. But it is the social interaction that is common. Do you think that the microbiome is underpinning much of that as well as the psychological stuff? Absolutely. I don't think we have specific studies in adults for that. But for babies, yes, the daycare we saw it. Babies at the daycare interacting all the day were increasing in four months. They microbiome diversity by a lot. And you know what? The kids that had their microbiome less enriched by the environment at the daycare were those that they had a sibling at home, probably because the sibling already donated them a lot of bacteria. Okay. So what we need to do then, Jonathan, is any of us, when we go on antibiotics or anyone listening, you've got to throw a huge party about two weeks after where you're all in a really close environment and you're all giving each other lots of kisses. But only with people that have good microbiome. We can start with these people out. So we screen people and we do the party only with those having a lot of top 50 bacteria. Okay. We can start asking who our zoon-tists have the best microbiome score and we can start hiring them out for parties. I love this idea. It's brilliant. I love it. This could be the new business. Yeah. But after they've mentioned these on the microbiome, cool. We're at time. But just before we wrap it up, I feel like we've talked a lot about what we can do to increase the number of good gut microbes. But I'm guessing that there are things that we might eat that might actually reduce the number of good gut microbes. I think it's more difficult to directly reduce the negative gut microbes. But you can indirectly decrease them by increasing the good ones. Because we think about, again, the microbiome has an ecological entity. If you increase the amount of, again, elephants or lions in an environment, the others in percentage will decrease as a consequence. So given that there is limited space in our gut from certain viewpoint, if you improve the good ones, you're decreasing the bad ones as a consequence. And that fits in really nicely with the approach we've always taken at Zoe, that it's all about what you add into your diet rather than necessarily what you take away. Obviously, a natural part of adding in healthy plant diverse whole foods is that you will often take away some of these unhealthy foods. And I think the way you've explained how it then impacts the microbiome is a really nice way of reinforcing the kind of advice we give. Focus on adding in a diverse to your whole plant. So what else can we do to increase our fiber? So as well as increasing the amount of fiber, we can increase the diversity. So again, it just goes back to that really simple thing of having lots of diverse plant-based foods. But there's also some things that I think we don't often think about. So for example, there's a type of fiber called resistance starch and this has quite a big impact on feeding microbes and our good microbes. Resistance starch basically comes from starchy food that's been heated and cooled because upon cooling it causes resistance starch. So what foods do I mean by this? Potato, pasta, rice. And it stays in that resistance starch form even when you reheat it. So that's a really simple hack that if you like your potato, your white rice and your white pasta, which I know we do say to people to try and avoid having too much of it. But actually if it's been cooled down and then reheated, it can be a great source of resistance starch and it's really good for your gut microbiome. Amazing. So when I think about through all of this, firstly, it's really clear what a big deal the paper is and congratulations. There's this dark matter in here. We've discovered that so many of the bugs that are really good for us don't even have names. They've never been identified outside of this sort of big data approach and it just shows how much more there is to understand. But for the first time, you've been able to say we can identify and create a score for the health of your microbiome, identify within this long list of microbes, these top 50 and this bottom 50, the good and the bad. But I think much more importantly, you've shown that we can actually improve our microbiome and that through these two different trials that you did, that it's possible to really increase the score of your gut health afterwards, whether it be through like changing your diet or whether it's through this 30 plant supplement that you tested. really interestingly when you took a probiotic. you move just one of those microbes, whereas with these 30 plants, you actually increased many, many of these good bugs. And so I think, Nickler, what you said is it just shows, you know, how low our plant diversity is today in the normal diet's authority. Sarah, you gave this amazing example about soybeans on your perimenopause symptoms, and that basically whether or not you have a specific microbe has a huge impact on how effective these soybeans are because they are able to convert the soybeans into something that like locks in more like estrogen. If you haven't got enough microbes, then, you know, get your babies into daycare as soon as possible to swap them around and then pass them to you. And if that isn't the right solution, then focus on increasing the good bugs because the bad bugs will decrease on their rights. So if you focus on like adding the good things into your diet, and that is really, that's the 30 plants, it's the plant diversity, then you will increase its good ones, and then they just sort of squeeze out the bad ones naturally as a result. Love it. Fantastic. I know that we have now passed 300,000 microbiomes that are being tested here. So I assume, Nickler, that there is some exciting new science we'll be able to talk about in the future. There's a lot of work to do, though, because it's a huge amount of data, so what we call big data, but we're excited to look inside at this. I'll end this episode with something I think you'll like, a free Zoe gut health guide. If you're a regular listener, you know, just how important it is to take care of your gut. Your gut microbiome is gateway to better health, better sleep, energy and mood, the list just goes on. But many of us aren't sure how to best support our gut. I wasn't sure before doing Zoe, which is why we've developed an easy to follow gut health guide. It's completely free and offers five simple steps to improve your gut health. You'll get tips from Professor Tim's Spectre, Zoe's scientific co-founder and one of the world's most cited scientists, plus recipes and shoppings, straight to your inbox. We'll also send you ongoing gut health and nutrition insights, including how Zoe can help. To get your free Zoe gut health guide, head on over to Zoe.com/ gut guide. Thanks for tuning in and see you next time.