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

16:12Prof Nicola Segata: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 like grown them in a Petri dish. It's literally like in the past going into like the Amazon jungle for the first time and discovering all these animals that nobody knew about.

16:39Prof Sarah Berry:Correct. We recognize the elephants, for example, from the genome, but we never seen elephants. We don't have them in a zoo. And it's the same with the bacteria. So we see their 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 % of our gut microbiomes that are really unknown. So still to be discovered even by metagenomics.

17:07Prof Nicola Segata: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. oils. What about a bad micro? What's that doing?

17:17Prof Sarah Berry: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 some extent. There are exceptions, there are some that are bad in any situation, in any gut, others that are only bad under certain circumstances, certain diets, or certain conditions, diseases, and so on and so forth. But mostly they are inflammatory for the gut environment.

17:44Prof Nicola Segata:I think a really fascinating example is where you look at some of the detrimental effects of meat and there's 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 metabolized 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?

18:22Prof Sarah Berry:This chemical is called trimetham in this specific case. And I mention it also because there are many other chemicals that also in this case, we don't know, they are dark matter and they are influencing our gut. And we think that these are the link between the bad microbes and our health.

18:37Prof Nicola Segata:And Sarah, you and Tim convinced me that Zoe 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 of scientists. We are not here to sit and just make millions for Zoe. Otherwise, we wouldn't have published all the 40, 50 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.

19:23Prof Nicola Segata: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 Nicola, 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?

19:43Prof Sarah Berry:Correct. And it is what we do. And also looking at which of the top 50 and bottom 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 abundance, and we can kind of derive a score out of these to try to give a summary of how health-associated that the microbiome is.

20:09Prof Nicola Segata: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 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 micro bone because like Nicola's explained you know it's so complex you've got trillions of different bacteria you've got different types some associated with favourable health effects some associated with unfavourable health effects you've also as well as 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 favourable 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.

21:16Prof Nicola Segata: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 your gut microbiome is so 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 a cutting-edge journal like Nature and a new drug or something like that actually being available to consumers.

22:24Prof Nicola Segata:Is that right?

22:26Prof Sarah Berry:Well, I think in our case, it can be much, much faster, 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 in the right direction or not, for example.

22:59Prof Nicola Segata: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 published a paper only a couple of weeks ago to do with 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.

23:47Prof Nicola Segata: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 Zoe. 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 timeframes and then there's just the rest of the world timeframes. 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 being collected from our sample of poop, that you can actually apply this new analysis to microbiome samples that have been done in the past?

24:31Prof Sarah Berry:Absolutely, yes. The way we sequence the microbiome, the way we read the microbiome, didn't change in the last 10 years or so. It got maybe less expensive, if you like. So the information is the same, is that we learn how to mine that information better. And this was, again, due to the availability 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.

25:08Prof Nicola Segata:And 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 sampled 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?

25:32Prof Sarah Berry:Yes, it needs to be the whole metasomic sequencing, as we call it. So it's the sequencing of the whole 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, or 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.

26:16Prof Nicola Segata:And 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 a way of looking at those rankings that Nicola's been talking about, of those microbes that are most associated with certain health outcomes and putting them into meaningful groups from a health perspective.

27:03Prof Nicola Segata: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.

27:41Prof Nicola Segata: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 Nicola's team's 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, i.e. so particularly bad for inflammation, and 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.

28:30Prof Nicola Segata: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 Nicola, I've had a tendency just to think about, oh, well, 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 like harmful causes. Do we understand at all what's going on, why particular bugs could be linked to any of these things?

29:02Prof Sarah Berry:We know that there is a cross talk between our bacteria and our gut, especially. And this happens at the level of chemicals, as Sarah 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 fibers especially or polyphenols or other 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 molecules as input to our gut, so a diversity of bacteria can specialize on fermenting the single component, because every bacteria will produce something different.

29:51Prof Sarah Berry:So those usually starting from fibers are producing 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 high end of our ranking.

30:12Prof Nicola Segata:So I can't just have like one good bug. No. That helps, but actually these different good bugs are actually sort of creating different good chemicals. Exactly, correct.

30:20Prof Sarah Berry: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.

30:32Prof Nicola Segata:Different bugs eat different bits of food coming into our gut, as well as producing different chemicals. So you need that diversity of foods, fibres, 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.

30:52Prof Sarah Berry:And on the contrary, those 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.

31:09Prof Nicola Segata:So the bad guys like the sugar. The good guys like all of those wonderful fibers and polyphenols.

31:15Prof Sarah Berry:Correct.

31:15Prof Nicola Segata:I feel somehow everyone listening is not surprised to hear that.

31:18Prof Sarah Berry:There is more than that, I think, because it is something we're still investigating, but the microbiome 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 health-associated bacteria, a diversity of them, are building something, a network of interacting chemicals that are adding more than what each single microbe can do.

31:43Prof Nicola Segata:I'd like to move on now to the sort of second part, Sarah, of what you described in this paper, because, you know, it's really cool to be able to measure that your gut microbiome is healthy or not. But I think what everybody's really interested in is, can I improve my score, right? Can I increase the number of good gut bacteria? Or is it like so many things in my life, well, you know, I would have liked to have been a bit taller, but, you know, 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 this, Sarah?

32:14Prof Nicola Segata: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 what we call cross-sectionally at one point in time, we also took data from two randomized control 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.

32:58Prof Nicola Segata:This is called the MyPlate guidance or follow the Zoe personalized nutrition program, which is leveraging all of this research from Nicola's group around the best food for your gut 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.

33:38Prof Sarah Berry:Nicola, what did you find? So we found actually that the top 50 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.

34:00Prof Nicola Segata:And when you say number and abundance, could you just help me to understand what that means?

34:04Prof Sarah Berry: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 bacterial cells in your gut or 90%. So when you say increase in 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.

34:35Prof Nicola Segata: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.

34:57Prof Sarah Berry:And the statistical methods that we use to quantify them, strictly speaking, is a little bit more complex, but we arrive 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.

35:13Prof Nicola Segata:And that's really important 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 Nicola's group does, 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.

35:49Prof Nicola Segata: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 one of these good microbes. I need to have lots of them.

36:07Prof Sarah Berry:We have several examples of bacteria moving from being barely detectable, so traces, to be a part of the community. These are the positive bacteria that are increasing and this is a strong signal.

36:19Prof Nicola Segata: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 and a lot of human biological research, randomized control trials are the gold standard. 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 cause a link.

37:02Prof Nicola Segata: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 diet is causing this change in our microbiome, which we believe is associated or will be associated with an improvement in these various health outcomes.

37:25Prof Sarah Berry:A question that maybe can arise here is, can we take health-associated bacteria and give it to people to increase it? Well, this is something very difficult to do. It's 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 the final causality, if that is the bacterium changing. But the diet, we don't need to wait 20 years to make sure that these microbes, we have the technology to give you those new microbes.

38:08Prof Sarah Berry:So again, it's important for us to act on diet and it's actually what we are trying to do.

38:15Prof Nicola Segata: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 CTs. 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.

38:54Prof Nicola Segata:And in this case, it was like red 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, their mood, their energy, their hunger, their sleep.

39:27Prof Nicola Segata: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, didn't we, change, which was the bug that was from the probiotic. And we saw almost no change or very little change from the control, these bread croutons.

40:13Prof Nicola Segata:Lots of people have said, oh, why did you use bread 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. And 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? And so 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 had these bread croutons.

40:48Prof Nicola Segata:And Nicola, I'd love to understand what happened to the microbiome for people who were taking this supplement, because I know that that's a big part of what was in the paper.

40:58Prof Sarah Berry:Yes. Again, the top 50 bacteria increased in their presence and in their amounts. This was really, really strong. And not only in the top 50, also, you know, still the top 100 or so, we see huge increases, especially something called Lachnospiraceae again. On the other side, instead, we saw disappearing enterocluster or other bacteria like Ruminococcus that we know they are pro-inflammatory. And this made a lot of sense to us now, because we know in the prebiotic world food supplement there are thousands of different chemicals associated with healthy plant foods now and so this is exactly what we are discussing before different healthy 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.

42:04Prof Nicola Segata:And 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, our upbringing, our social settings, and our taste preferences. And 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. And 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 are associated with very healthy outcomes.

42:41Prof Nicola Segata:I think it's safe to say that those results were a lot stronger than actually either of 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-plant supplement.

42:56Prof Sarah Berry:Correct. So as scientists, we frequently have an hypothesis. So when we see that hypothesis confirmed, it's nice. But in this case, it not only was proved, but was proved a strength that was much higher than what we were hoping for. So we were surprised ourselves and positive surprise, of course.

43:14Prof Nicola Segata:And is this a sign that the plant diversity in our diets today is just incredibly low compared to sort of what we would have had historically to support our microbiome?

43:27Prof Sarah Berry: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 this diversity in a second. And this is actually why we think that this prebiotic product works.

43:50Prof Nicola Segata:Also, Nicola, it's not just the food, is it? 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 gut microbiome. Whether it's the kind of more sterile environment we live in, we know that soil microbes play a really important role.

44:07Prof Sarah Berry: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.

44:17Prof Nicola Segata:Haven't you done something looking at pet owners?

44:20Prof Sarah Berry:Petonus, yes, it was with the kids. So we enrolled six classes of daycare babies. And we also have their parents, siblings, educators at the daycare, and also the pets at home. And we tracked a very complex network of transmission. There are some strains or some specific variants of some bacteria jumping from the pet to the baby, to the baby, to another baby at home. We also saw, you know, one mother transmitted to the baby, the baby to another baby at the daycare. and this other baby to another father, to his father. So, you know, there can be stories about how a mother of a certain kid can donate strains to a father of another kid.

45:00Prof Sarah Berry:We don't do gossip, so it has to be through the transmission. I think you might be suggesting something that I'm not going to follow up on right now.

45:08Prof Nicola Segata:This is like the new form of a fingerprint, I think. Yes, yes, yes.

45:11Prof Sarah Berry:Yeah, you know, we can match perfectly the babies that were in the same room. Now, 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.

45:27Prof Nicola Segata:So surround yourself by healthy people. I need to spend more time with you and Tim, Jonathan. I would love that. So Nicola, 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

45:57Prof Sarah Berry: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 due to 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 and 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.

46:39Prof Nicola Segata: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 like a big fiber supplement to solve all of this?

47:12Prof Sarah Berry: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 whole food supplement is what you really want for your microbiome. Again, diversity of chemical, positive, healthy chemical as input means higher diversity of microbes able to digest it. which means in turn more positive chemicals produced by these bacteria, starting from the input chemicals, that are impacting positively our health.

47:43Prof Nicola Segata:I've already heard you mention 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 bitter taste, but also what gives the plant the colour. 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 our large intestine, where they are metabolised, so eaten by our gut microbiome, to produce certain chemicals.

48:27Prof Nicola Segata:and it's those certain chemicals that the gut microbiome is producing as it eats or metabolizes these polyphenols that have their beneficial effects. For example, acting on inflammatory pathways in a favorable way, acting on lots of health-related pathways again in a favorable way. And what we know is different gut bugs eat or metabolize 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 Nicola's explained with the fibres, it's really important to have a diversity of those different types of polyphenols because there's lots of different types of polyphenols, just like there's lots of different types of fibres.

49:09Prof Nicola Segata:So you're maximising the different types of chemicals that are produced that 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 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.

49:50Prof Nicola Segata: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 and postmenopausal women that if you take soy isoflavones, 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 that it's hugely variable between people. Some people take soy isoflavones and they have a huge benefit.

50:23Prof Nicola Segata:Some people say, oh, well, I've almost had no benefit. We now understand why. And that's because the soy isoflavones, this type of polyphenol, can be metabolized by your gut microbiome. And some people have species, so they have bugs, that enable them to convert the soy isoflavone into a very active type of chemical that binds really strongly to your estrogen receptors because the reason you get your symptoms when you're peri or post-menopausal is because you have a reduction in estrogen so it binds really really strongly more strongly than the original isoflavone and so if you have these gut bugs what we know is from randomized controlled trials you will experience on average a 75 percent greater reduction in your menopause symptoms compared to someone that doesn't have these bugs or isn't able to convert the soy isoflavones into this very active substance and this is another reason I think as particularly as a perian post-menopausal woman myself is you know everyone's at that life stage where they're like you know what did you try what worked for you and you've got to be quite cautious that again you know you see an influencer saying oh my god I took this wonder drug I took isoflavones that's it I'm this a new woman, I feel 30 again and my whole life is better.

51:39Well, great.

51:40Prof Nicola Segata:They might have the species that are able to convert to this very active form, but it might not work for you. And so I think that's a really great example of showing just how much of an impact something so simple as just those gut bugs being able to convert that isoflavin to 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 soybeans because it needs that microbe to convert it to have this super duper 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 enable you to convert it to that more active form.

52:21Prof Nicola Segata:And Sarah, 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 Nicola's 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.

53:27Prof Nicola Segata:Amazing. I was thinking about my own experiences. And one of the things 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. And I was quite worried. So they're all gone. And what I've seen is they're slowly returning. So my first question, Nicola, is where are they coming from?

53:53Prof Sarah Berry:I think most of them were not really wiped out. They were only incredibly low abundance, not really a few traces. It is true that probably antibiotics are acting more on the health of the bacteria than the others. Just 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 healthy 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 it may feel a bit gross but it is what it is now but we build up over decades of life now 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 you know after the antibiotic treatment that you had that um the process kind of restarted at least partially and and probably yeah you needed time to reacquire the micro that you lost and probably you are quite slightly different micro because maybe you didn't do the same you know interaction with the same people that you did uh you know over the decade

55:09Prof Nicola Segata:before the antibiotics so nicola we recently did a podcast on the blue zones uh which are areas in the world you're probably familiar with where people live very long healthy lives and one of the features that's common amongst all of the blue zones is that social interaction as well as the diet and a few other factors but it's the social interactions most common do you think that the microbiome is underpinning much of that as well as the psychological side absolutely i don't think

55:37Prof Sarah Berry:we have specific studies in adults for that but for babies yes at the daycare we saw it you know babies at the daycare interacting all the day were increasing four months their 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 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

56:07Prof Nicola Segata: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.

56:17Prof Sarah Berry:But only with people that have a good microbiome. We can start renting these people out. So we screen people and we do the party only with those having a lot of top 50 bacteria.

56:27Prof Nicola Segata:Okay, we can start asking who of our zoantists 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.

56:39Prof Sarah Berry:Partner matching me on the microbiome. Cool.

56:42Prof Nicola Segata:We're at time, but just before we wrap up, I feel like we 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.

57:00Prof Sarah Berry: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 as 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 a certain viewpoint, if you improve the good ones, you're decreasing the bad ones as a consequence.

57:29Prof Nicola Segata:And that fits in really nicely with the approach we've always taken, 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. But 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, focusing on adding in a diversity of whole plants. So what else can we do to increase our fiber? So as well as increasing the amount of fiber, we can increase the diversity.

58:04Prof Nicola Segata:do 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 i think we don't often think about so for example there's a type of fiber called resistant starch and this has quite a big impact on feeding our microbes and our good microbes and resistant starch basically comes from starchy food that's been heated and cooled because upon cooling it causes resistant starch so what foods do i mean by this potato pasta rice and it stays in that resistant starch form even when you reheat it and so that's a really simple hack that if you like your potato your 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 resistant starch and it's really good for your gut microbiome.

58:59Prof Nicola Segata:Amazing. So when I think back 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.

59:36Prof Nicola Segata: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. And really interestingly, you know, when you took a probiotic, you moved just one of those microbes. Whereas with these 30 plants, you actually increased many, many of these good bugs. And so I think Nicola, what you said is it just shows, you know, how low our plant diversity is today in the normal diets that we're eating.

1:00:15Prof Nicola Segata: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're 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 bucks because the bad bugs will decrease on their own. So if you focus on 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 these good ones.

1:01:00Prof Nicola Segata:And then they just sort of squeeze out the bad ones naturally as a result. Love that. Fantastic. I know that we have now passed 300 ,000 microbiomes that have been tested here. So I assume, Nicola, that there is some exciting new science we'll be able to talk about in the future.

1:01:14Prof Sarah Berry:There's a lot of work to do though, because there's a huge amount of data. So what we call big data, but we are excited to look inside that, yes.

1:01:22Prof Nicola Segata:As you can imagine, hosting this podcast, running Zoe, juggling family life, it all keeps me pretty busy. So I try as best I can to stay energized and show up well in all those parts of my life by fueling my body with the right food, by exercising, and by adding a scoop of Daily 30 to my meals every day. If you haven't heard of Daily 30 yet, it's the gut supplement designed by our gut health scientists here at Zoe. It's made of over 30 high-quality, hand-picked plants, including seaweed, fungi, and different types of fiber. Better yet, it contains ingredients that support gut health, digestion, and energy, which is ideal for packed calendars and busy lives.

1:02:05Prof Nicola Segata:Simply add one scoop a day to any meal for an extra boost of fiber and plant diversity. And because it tastes delicious on just about anything and adds a satisfying crunch, it quite quickly slots into your life, becoming a daily healthy habit you'll always have time for. By the way, whenever we talk about Daily 30 as a good source of fiber, we're required to say that it contains four grams of total fat per serving. Obviously, that's all amazing healthy fats from plants. So, order yours today at zoe.com slash daily30. Thanks for listening and see you next time.

1:02:46you