New gut science: 3 bacteria that keep your heart healthy with Prof. Tim Spector and Prof. Nicola Segata

Imagine an unseen world within you, teeming with trillions of tiny inhabitants – your gut microbiome. Just like any ecosystem, some bugs are beneficial, while others wreak havoc, quietly disrupting your health.

What if these disruptive "invasive species" are silently driving the rise of cardiometabolic diseases, the leading cause of illness and death in Western countries?

This episode reveals groundbreaking new ZOE research, soon to be published in Nature, that maps this hidden world.

Together, they reveal the top-ranked gut bacteria – both good and bad – that influence your health. Discover three powerful "good bugs" and how feeding them can suppress the "bad," transforming your gut ecosystem and paving the way for better health and potential therapeutic breakthroughs.

Learn actionable tips for boosting your beneficial bacteria, starving the detrimental ones, and why gut testing is forever changed.

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Transcript

Jonathan Wolf: Nicola, thank you so much for being here. 

Prof Nicola Segata: Thank you. It's a pleasure.

Jonathan Wolf: And Tim, thank you also. 

Prof Tim Spector: Looking forward to it. 

Jonathan Wolf: So Nicola, we have a tradition here at ZOE where we always start with a quick-fire round of questions from our listeners. We have very strict rules. You can say yes or no, or a one-sentence answer if you absolutely have to.

Are you willing to give it a go? 

Prof Nicola Segata: Let's try. 

Jonathan Wolf: Good. Alright. Are diseases like heart disease and diabetes on the rise? 

Prof Nicola Segata: Yes, they are. 

Jonathan Wolf: Could some gut bacteria protect us from these diseases? 

Prof Nicola Segata: Yes. Some protect us, some actually can actually be against us on this, yes. 

Jonathan Wolf: And could the wrong balance of gut bacteria push us towards disease?

Prof Nicola Segata: Yes, absolutely. It's not only about single bacteria, but the community of them. 

Jonathan Wolf: And Tim, can we change our gut microbiome composition in a matter of weeks? 

Prof Tim Spector: Absolutely. 

Jonathan Wolf: Can scientists now link individual bacteria to your likelihood of getting sick? 

Prof Tim Spector: We can now, yes. 

Jonathan Wolf: And lastly, what's the most common misconception about our gut health?

Prof Tim Spector: It's probably that we think it's so complicated, we can never really understand it properly. 

Our research, certainly over the last year, has really changed that, so that we can now really define what a healthy gut and an unhealthy gut looks like, and we can start to tease out the key players there like never before.

It's really exciting. 

Jonathan Wolf: It's amazing, and I'm very excited to have you both here. 

Now, just before the show, our team did some research, and apparently, around the world, heart disease, type 2 diabetes, and other cardiometabolic diseases are now the number one cause of illness and death. 

Now your new research reveals that gut bacteria may play a big part in our level of risk for these diseases.

There's nothing we like more than to discuss new science on this show, but it's even more exciting this week because these breakthroughs are actually a result of ZOE members who listen to this podcast and who have actually contributed to this research themselves. 

So I'd like to dive in, but maybe just to set the scene, Tim, what are these cardiometabolic diseases, and why are we seeing cases climb?

Prof Tim Spector: Well, it's a group of diseases that we used to think of as really being separate. So things like heart disease, stroke, high blood pressure, diabetes, obesity, central obesity, and resulting metabolic problems from them. 

We now know that there's a common causality. There are pathways that are all causing increased risk of all of these diseases together, that are coming from an interaction between microbes and the immune system, and producing inflammation, upsetting the way we handle glucose, upsetting the way we handle fats. It's all coming together that these things interact in a way we weren't aware of just a few years ago.

So it means that just by changing something as simple as our gut microbiome, we can actually impact all of these diseases and reduce our risk of all of them by interfering, in a way, with these pathways and reducing inflammation and impacting our immune system. 

Jonathan Wolf: And Nicola, can you help us to understand what are gut bacteria and what do we know today about their role in diseases like the ones that Tim's talking about?

Prof Nicola Segata: Yeah, so gut bacteria are trillions of single microorganisms present in our gut. Thousands of species, more or less in each of us. And they are part of an ecosystem that are an interface between the food we eat, our environment, and our health. 

So the diet, the food we eat, is broken down by gut bacteria that are in the host, producing molecules, small molecules that are then arriving in our blood and in our system. And so they are having an impact on us.

Prof Tim Spector: I call them mini pharmacies.

Prof Nicola Segata: Yeah, mini pharmacies. In addition, they also interact with our cells, with our immune system. So they're directly touching and interacting with us. 

And so if you have the good bacteria that are able to produce good little molecules, because metabolites are good, otherwise not. So it is like an amplifier of our diet. The good bugs are amplifying the good effect, the positive effect of a healthy diet, and vice versa; they can actually be detrimental for our health in other situations.

So we need to push, increase our gut ecosystem to be an ally for us. 

Prof Tim Spector: So you want to have more of these good pharmacies and you want to have less of the bad ones, doing the Breaking Bad-type home chemistry and producing these nasty chemicals. 

Jonathan Wolf: And is this real? Is there such a thing as a good bug and a bad bug?

Prof Nicola Segata: It is not so much black and white. And also, in our research, we see that there are bacteria that tend to be associated with better health and better diet. 

But we also need to consider that our gut microbes are very personalized to each of us. So it's only with big, big numbers that we can tell apart which tends to be good in which situation from those that are likely not to be there.

But as Tim was saying, it is also about the diversity of them, because the more we have, the more good function they can bring to us. There is no single bacteria that can do all the work that is supposed to be done in the gut. 

Prof Tim Spector: So some of them bad ones, for example, may be quite harmless in small numbers, but when the conditions are bad, they're fed the wrong foods, they have an in so-called inflammatory environment, maybe the acidity changes slightly, then they can grow to an extent that they produce chemicals that influence everything around them, and they become bad guys.

There is this transition, and so it's best to think of this as a bit of a war between the good guys and the bad guys.

The more good guys you've got, the more you can squeeze out the bad guys so that it doesn't matter if they're around because they're in small numbers, and they're just playing around, and really any chemicals they produce are just so diluted you don't really feel the consequences. 

But the real problems are when you lose your good bugs and suddenly the bad guys multiply, and then you're really in trouble because you're producing all kinds of chemicals that attract even more unhealthy microbes, and the whole thing starts to go downhill very fast.

Jonathan Wolf: The three of us sitting here will we all have roughly the same bugs inside our gut? 

Prof Nicola Segata: Not really. I think we have around 30%, 40% of species in common. 

Prof Tim Spector: And at the level, when you get even below the species level, the subspecies level, it's probably even less than that. We are only sharing 10% to 15%.

So, all of us have a unique set of some microbes that the others wouldn't have. And if, even if you took a thousand people, you'd find nearly everyone has something unique to them. 

So there's a broad pattern that might be similar, but the more fine detail you get, the harder it is to find things in common.

Even in, as we discovered, Nicola and I, when we looked into this, even in identical twins, who have identical genes in every cell in their body, but their microbes are really only slightly more similar than unrelated people. 

Prof Nicola Segata: And probably they're more similar because they live together, because we see that we are transmitting our gut microbes, you know, or all our microbes. It’s like pathogens. If we live together, we are going to share some of these specific strains or variants, like we know for infectious diseases. 

Jonathan Wolf: You are saying that between myself and Nicola and myself and Tim, at least 60% of the bugs that I have are different from the bugs that each of you have.

Prof Nicola Segata: On average, yes. 

Jonathan Wolf: We talk often about DNA. Right? I think everybody listening has become very familiar with that. How does our DNA compare? Is that also about 40% the same, 60% different? 

Prof Tim Spector: No, we'd be 90, over 99% similar in terms of our DNA.

Your human DNA really is very similar, and we're talking about tiny little differences between humans that, you know, get us very excited at the sort of human genetics level.

But when you start comparing it to the diversity of the genes in our microbes, it's night and day. I mean, we're talking, as you said, the difference between less than 1% and these 70%. 

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This is a real insight because up to this point, we've depended on genetics to say, Okay, we're all really quite similar. 99.5% the same. Therefore, you know, identical twins, et cetera, must be identical. 

But what this tells us is that huge amounts of our DNA that is actually producing chemicals and vitamins are very different between us. 

So there is this huge personalized aspect, which really wasn't apparent 10 years ago, and I think this is a real breakthrough in science.

Jonathan Wolf: So, firstly, just all the bugs inside me are really different from the bugs inside everybody else. 

But also, even when it seems like we might have the same bug, it's a bit like saying, well, we both have a dog, but you know, I might have an alsation and you might have a chihuahua. They're pretty different. 

Prof Nicola Segata: And they behave quite differently.

Prof Tim Spector: Yes, absolutely. That's right. 

Prof Nicola Segata: Yes, that's the point.

Prof Tim Spector: 

Jonathan Wolf: Always worry for the chihuahua, right? 

Prof Tim Spector: Even if you had two chihuahuas, one would be aggressive and the other would be nice and docile.

Jonathan Wolf: So, having listened to all of this, is this just because people aren't eating a very healthy diet, Tim?

So if someone is listening to this and saying, well, that's interesting, but I know I eat healthy, so therefore I will obviously have a healthy microbiome, a healthy set of bacteria inside my gut, and therefore it's going to be protecting me from heart disease and these other things.

Prof Tim Spector:  So if someone out there is eating as healthily as they think they can for their gut, generally following, say, my advice and ZOE's advice, on average, they will have a healthier gut score. On average, they will be living longer, et cetera.

But they can't be sure they don't have the microbes that are maybe predisposing them to certain risks of disease, or others they're lacking that could prevent them from having disease.

And the only way to be sure about that is to do a gut microbiome test using this sophisticated genetics that Nicola has been working on. 

Jonathan Wolf: Nicola, is it only food that affects the makeup of my microbiome? 

Prof Nicola Segata: It's not only food. The microbiome is a complex system that is modified by a number of things, like food, for sure.

But your lifestyle, the activity you do, the interaction that you have, that sleep that you have, and so on and so forth. But also, as we were saying before, the interaction. 

We have studies, for example, of babies at the daycare that they acquire from their peers at daycare, so much microbes that they are reprogramming completely their microbiome.

And this is also in adults. Two students that are starting to live together, after two, three years, they share quite a bit of their microbiome that they didn't share before. 

So yeah, there are a lot of effects on the microbiome. Also, you know, pollutants, the environment we live in. So, tons of effects on the microbiome.

Jonathan Wolf: Thank you for sharing this. I always think it's amazing hearing about this sort of ecosystem inside me, and it's a bit like this coral reef inside you with all of these different species. 

Prof Nicola Segata: It's not an ecosystem inside you, you are an ecosystem. You are part of the ecosystem. 

Prof Tim Spector: You are the coral reef.

They just happen to be, you know, one part of it. You've got the human part, you've got the microbial part, and they're interacting. And the coral reef is the human shell, really.

Prof Nicola Segata: You wouldn't work without your microbes, so you are your microbes. 

Jonathan Wolf: I love it. I am the coral reef. I feel more elegant already. 

Prof Tim Spector: But, it also shows that because of this interaction with others and how you acquire new microbes, you do need to pick your friends and partners very carefully.

You really want to have the healthiest ones around you, not the most unhealthy ones. 

Jonathan Wolf: So it's good I'm spending so much time hanging around with you, Tim.

Prof Tim Spector: Exactly, yes. I should charge for my time. 

Jonathan Wolf: So I think the thing that feels really new is understanding more that these sets of bugs really can either keep us healthier or actually push us towards disease.

You mentioned already, Nicola, there are trillions of bacteria. That's a lot of bacteria. That's very complicated, and I think it's part of why, Tim, you said, you know, historically people haven't been able to sort of decode this and really understand what's going on. 

So I'm incredibly excited about this new study that I think is providing really unique insights into some of these most influential bugs.

Nicola, could you tell us about what your research has been doing? 

Prof Nicola Segata: Yes. So, in our study, we look at 34,000 individuals for which we know their dietary habits, their microbiome, and their cardiometabolic health. 

So we identify the microbes, we identify the food, we identify their potential risk for disease, and we correlate everything. And so at the end of the day, because of these big numbers that had not been done, these scale so far, we can link which foods are pushing or favoring or decreasing which microbes, and in turn, which microbes are associated with favorable or unfavorable cardiometabolic markers.

So we did this map of interaction and this ranking of which are the species, the bacteria that are more or less associated with a favorable diet and favorable cardiometabolic health.

Jonathan Wolf: How did we get these samples, these 34,000 people, in the first place, and why haven't we done this 10 years ago? 

Prof Tim Spector: Up to now, most of the microbiome research has been done in universities or hospitals where they've collected 50 or maybe a hundred people with a disease and looked at a hundred people who are controls. They’ve either been paid volunteers or part of a university grant or project.

But what's different about this one is that we've used ZOE data. So these are people who have had a gut test done by ZOE in order to get their own information. And at the same time, we've asked them to complete dietary questionnaires and questions about their health and their health risk. 

This is what's unique about what we are doing because we're using a more commercial model to do the science, which allows us to do it a hundred, a thousand fold, the scale that you could do with the old-fashioned academic model.

And it's much faster and it's much more efficient. And we know that we need these big numbers; tens of thousands, hundreds of thousands of individuals. 

We've now collected samples on, you know, nearly a quarter of a million people that we will be analyzing in the coming months. 

Jonathan Wolf: So you're saying that basically people who are getting their microbiome tested as customers of ZOE are actually able to participate in the scientific research?

Prof Tim Spector: Absolutely. So, everyone who gets a ZOE test kit is asked if they want to take part in research as well, and a vast majority of people are giving their approval for this, which means that we can use the data to publish papers and make this data publicly available. 

So it's a real overlap between the normal commercial model and the scientific academic model, which means that we can use the speed and agility of commercial companies to really move science forward at a much faster pace.

Jonathan Wolf: And how much bigger is this than whatever has been previously published, Nicola? 

Prof Nicola Segata: This is extremely exciting. I remember a couple of years ago, we were here talking about the first study with 1000 individuals, which was the largest at that time. 

Jonathan Wolf: A couple of years ago, 1000 individuals was the biggest study?

Prof Nicola Segata: The PREDICT-1 study. Exactly. 

Jonathan Wolf: And can you remind us how big this is? 

Prof Nicola Segata: This is 34,000, and we are already working on a much larger sample size, as Tim was mentioning, 250,000 more or less.

So in a year from now, probably we are here even more excited with this larger number. 

So it's important because we are not just doubling the number of individuals each year here, we are doing 10 times more. It means a leap forward in the science we can do with these numbers.

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Jonathan Wolf: I love how excited you both are about the idea of 34,000 poop samples. Yeah. 

Prof Tim Spector: They're not all in my room. 

Jonathan Wolf: So what does this enable us to do, Tim? 

I think you're helping to explain a bit about why that's different to get at this scale. Because I think a lot of people listening might be like, Why does it matter? Why wasn't a thousand people already enough? 

Prof Tim Spector: Well, we have to learn this through trial and error. That's how science generally works, because to be a scientist, you've got to be an optimist; otherwise, you wouldn't be in that job. 

So you always think that whatever experiment is going to give you those answers. And when it doesn't, there's lots of reasons why not. 

But I'm lucky that I went through the genetics revolution first, which sort of preceded the microbiome one by 10 or 20 years. And I'm seeing exactly the same patterns. 

So in genetics, we got very excited when we could do the most basic genetic test on a hundred people. And would publish papers on this, showing that some gene area was related to a disease. 

It turned out that for 10 years we were publishing results that turned out not to be true, that were later completely shown to be false once you'd got 10 times the number. 

This took a long time for people to realize that they needed these very big populations to do the job, in order to tease out all the individual genes in the human genome, and they're associated with disease. 

That's sort of where we've been in the past. In the early days of the microbiome, many of the studies that people relied on were based on too small a group of people to be actually useful. 

So it's only now, we're in this new phase where we know the results are robust and they're going to be replicated by others. And that's really one reason why we're putting this out there in the public, because we want everyone to share in this new science, this new way of looking at the gut microbiome. 

Prof Nicola Segata: It's not only about the size. No, it's also about the representation. So studies done in the past were done with a specific population, you know, the London population around a hospital, and this is not representative.

So what Tim was saying was that what we see and we put in the paper is what came out to be reproducible in the U.K., in the U.S., in different age categories. 

Prof Tim Spector: Yeah. Age, sex, pre-, post- menopause, different ethnicities, different diets, people with all kinds of conditions. 

So it's much more useful data than these very limited ones in very narrow studies, which we've been relying on in the past.

It is exciting, and it's certainly not the end. This is really, I think, just the start of the new era.

Jonathan Wolf:  And you just mentioned a paper, so this has just been published. I know that's important to scientists. Where's it been published, and what does that mean? 

Prof Tim Spector: It's been published in Nature, which is the top journal in the world. And this gets scientists very excited because for us it's like winning the Oscars, and it's not hard to get a paper published. 

The analogy would be like you film yourself and put it on Instagram and get it into a minor journal, and there might be a hundred thousand minor journals, but is that film likely to win you an Oscar? No. 

And so that gives you an idea, you know, between an Instagram flick and winning the Top award. So that's why we're so excited about this, and that's why our peer scientists are excited about it. 

Because not only is it showing us this link between foods and microbes in great detail for the first time, but it's also telling us a new way of looking at gut health.

Jonathan Wolf: I love that. And I remember when I first started at ZOE eight years ago, I had no idea that there were all of these different scientific journals, that it was really important. 

I've come to learn that this is really directly like your Oscar's analogy, right? Because it sort of proves that the science is really high quality. It's very, very hard; it's reviewed by other people. The bar is very high.

Prof Nicola Segata: The work is checked by other scientists before being allowed to be published in those journals. 

Jonathan Wolf: So, how pleased are you feeling, Nicola? 

Prof Nicola Segata: Ah, it is great. You know, it has been a lot of work, a lot of discussion, with all the other people involved, but also with the reviewers, that, of course, ask question and we answer question. We strengthen the work. 

And it is great to see now, the public and everyone can read, can also expand on it. 

Jonathan Wolf: We will, of course, have the link to the paper in the show notes. But for people who don't want to dig through the paper, and the paper is quite hard going, I have to admit, because I did look at it.

Tim, could you summarize what the breakthrough from this paper is, and what it tells us about, impacting our health? 

Prof Tim Spector: Yeah, I think there are two major themes in this paper. 

The first is that we've uncovered certain microbes that are associated with increased risk of disease, and also are modified by diet, and also the opposite. So there are good and bad bugs. 

So you've got 50 good bugs ranked and 50 bad bugs that we know are correlated with diet and disease. So this is a really good starting point, and we talk about some of those bugs in detail. 

And the other point is that we've shown that the ratio of the good to bad bugs in everybody, because we picked the hundred that are generally present in most people in the U.K., and the U.S., is a much better correlation of gut health than anything we've had before.

So this allows people to take a snapshot of their gut microbiome and say, You have a moderately healthy gut microbiome, less healthy, poor, terrible, really good. 

It also allows us better than ever before to really track it over time. So, in the past, we haven't had a really good measure that works well in clinical trials.

It's a bit like blood pressure. If we didn't know how to measure blood pressure, it'd be very hard to know what tablets we should be taking to prevent stroke. 

Now we've got this great new score, and we're hoping that the rest of the world will also adopt this, so we can move forward and really get some amazing advances, new treatments in sight, and everything else.

For me, that's the really exciting part that we can do something that really advances the field dramatically. 

Jonathan Wolf: Now, I understand that within this, you've also discovered some brand new gut bugs that nobody knew about before. 

I think today, Nicola, you're going to share three of these newly discovered gut bugs that could help to reduce our risk of diseases like heart disease.

Prof Nicola Segata: Correct. So, let's start with the bacteria that nobody else saw before. So you cannot grow it in the plate. Microbiologists never saw them under the microscope. 

So, this guy, let me read it because I never remember, but it's called Sgb15249.

Jonathan Wolf: That's very catchy. It's currently called 15249. 

Prof Nicola Segata: Exactly. We need to find a better name. It is part of the family of bacteria called Ruminococcus, which is not telling you much more, actually. But there are some good and some bad bugs in these. 

So these specific species in the family is the best one, is the one that is most associated with healthy diet and also with favorable cardiometabolic outcomes.

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Jonathan Wolf: This is the number one bug that I would have in my gut to help look after me. 

Prof Nicola Segata: Correct. 

Jonathan Wolf: I think a lot of people listening and say, well, hang on a minute, how can you have found it? But you also said nobody's ever found it. 

Prof Nicola Segata: Correct. 

Jonathan Wolf: Could you help us to understand that now? 

Prof Nicola Segata: That is the power of shotgun metagenomics. And this is the idea of reconstructing the puzzles of each genome, of each the genetic content of each bacteria.

Each bacteria has a different genetic code. We read the genetic code, and if we find a code, a book, the genome, that no one else saw before and is different enough from everything else that is known to scientists, that is a new species. 

And, this bug was found thousands of times in different rivers. So it cannot be judged by chance that we messed up the puzzles. And this is a new species, then. 

Prof Tim Spector: So it's like we found a totally new color in a jigsaw puzzle that wasn't there before. And I think that's a decent analogy.

And Nicola's team are really the best puzzle solvers at the moment in the world. 

Jonathan Wolf: That's amazing. So it's a bit like people hunting dinosaurs, and you find this little bone of a dinosaur, and because you're an expert, you figure out there's this whole new species of dinosaur that no one had ever seen before. And this is what it looks like. 

But you are doing this with the DNA. So even though it hasn't been grown outside, you actually have found the DNA of this bacteria over and over, and you've been able to see that it's linked to people being healthier because you just have so many samples to look at.

Prof Nicola Segata: Exactly. And you correctly said, you know, analyzing this data is a lot of computer science, is a lot of statistics, there's a lot of artificial intelligence, which is 90% of what we do.

Because it seems that we are looking at the Microsoft…, we are not; we are analyzing DNA, which means just staying on the computer and analyzing big data, like how it is done in other fields. That is the secret here. 

Jonathan Wolf: So as soon as I heard you explain that this was the top bug, I obviously went back and asked the team whether or not I have it.

And I think as many people listening to this show will know I broke my toes, two years ago, and ended up having these very intense antibiotics, and it wiped out almost all the bacteria, good and bad, inside my gut. 

And since then, I've been testing very regularly. So I've tested about 18 times, and sure enough, straight after the antibiotics, I didn't have this. In fact, I only had six of the 50 good bugs. 

And a year ago, I still didn't have this bug either. But it turns out that on my last two tests, I have had exactly this bug. 

Prof Nicola Segata: Congratulations.

Jonathan Wolf: So, I'm excited. I still only have about 23 of the 50, which is still quite a bit less. I had 38 before I took the antibiotics, which was the result of quite a few years of it going up. But I do have this one, and now I feel much better about my score than I did yesterday.

So thank you, Mr. 15249, for helping look after me. 

Prof Nicola Segata: And I will bet you also have the third microbes in this ranking because that is the microbe that is also more changing when you improve your diet. So do you have SGB 4964? 

Jonathan Wolf: I'm going to have to come back... I haven't got the list in front of me. They need some catchier names, Nicola, for me to remember.

But I do know that there's a second one that you wanted to talk about today that you are also really excited. Could you tell us about that? 

Prof Nicola Segata: Yeah. The one I asked you about is called the ‘nuts and seeds’ microbe because is the microbe that is changing the most when you increase the amount of nuts and seeds that you're eating.

After the bacteria that grows only with coffee, it is the second bacterium that is mostly impacted by the diet, and is impacted specifically, we think, by nuts and seeds, and maybe some particular nuts and seeds. We still need to find out.

Jonathan Wolf: Is that new, to understand this link between individual foods and individual bacteria?

Prof Tim Spector: Absolutely, yes. Before that, we'd just had groups. 

So we could see changes in thousands of microbes together as a group. But only because we've got to this number, this scale of this project, that we can now identify an individual microbial species that is strongly correlated with a particular food.

So that's why we're making this link. This is why when we saw the coffee microbe, it was a one-to-one relationship. 

Here we're also seeing this microbe, just like me, loves nuts and seeds, and it really doesn't need anything else to thrive. And that's what we're seeing, it's just this level of detail that wasn't possible before.

This is so much more important than seeing thousands of them, that some of them going in one direction, some of them going in other direction. It doesn't allow you to have that same precision about the advice you can give people, and the personalized advice. 

Jonathan Wolf: Some people listening will be saying, Why is there any particular link between the food that I eat and the bugs that I have inside my gut?

Prof Nicola Segata: Well, because the food is feeding also your bacteria. The bacteria are growing; they need food themselves. Specific components of the food are feeding specific bacteria. 

So, fibers are an example that is very well studied; different fibers are the food for different kinds of bacteria. We do think that things inside the nuts and seeds are the substrate, the food, for these microbes. 

We still need to find which one. Like the same with the bacteria that grow with coffee, we don't know whether it is caffeine, whether it is another component of coffee, also here, since these are still complex foods. 

So we need to tease apart which are the components, but still we know for sure that if you increase the amount of nuts, seeds, then this bacterium, on average, will grow. And this is a good thing. 

Prof Tim Spector: You've got to try and remember, any plant has hundreds of chemicals in it, and our microbes might be super specialized. 

So of those 800 chemicals, they might only be interested in about 10 of them, and they're the ones that really drive their production and their growth. 

But the other interesting finding is that there have been some researchers who have worked out that of the total amount of food we eat, our microbes are perhaps consuming something between 5% and 10% of it. 

I used to get told, Always leave some food on your plate for Mr.Good manners. You know, that was what my Jewish grandmother used to say. Well, actually, have an extra 5% for your microbes. And that's really important because you're not just eating for yourself. I think that's the other thing. 

Prof Nicola Segata: And this specialization also means that we need to eat a lot of diverse food.

So it's not about healthy food, but a diversity of healthy food. Because these different chemicals in each food are pushing or improving different microbes. And so the more healthy chemicals you eat, the more good bugs you are probably pushing. 

Jonathan Wolf: And to make sure I've got it, what you're saying is, you've discovered in this paper, these 50 good bugs that are supporting your health. They don't all just want the same food. 

So it's a bit like being in the zoo, and like all the animals are very picky about the different things they want. You might think, Why can't they all just eat grass? But that's not how it works.

And you're saying it's the same for these bugs. You need to be feeding them different sorts of food if you want to have not just one or two. 

I guess the question I might have is, why wouldn't I just want to have lots and lots of your 15249? That's number one. Why wouldn't that be the best thing to do?

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Prof Nicola Segata: Because this bug it is healthy, yes. But it is going to do one operation, one activity, and this is not enough. 

So you need a lot of activities, but different bacteria, different short-chain fatty acid, different anti-inflammatory molecules, and so on and so forth. So it's much better to have a little bit of all these 50 or 70 good bugs than having one of them or two of them that are most of what you have in the gut.

Prof Tim Spector: Yeah. And that's why people who say they only eat kale aren't as healthy as they think they might have been based on the old science. 

The old science would've said, Okay, they're getting enough fiber, it's all green, they're getting all the nutrients they need, but they're not. 

So it's the people with diverse diets have the diverse microbes, and they get more of our top contenders, and they're the healthy ones.

Jonathan Wolf: So, coming back to my latest gut health results, I was feeling really smug that I had number one, but I only have 23 of the 50 good bugs. So what you're saying is if I can push that up to 30, 35, 40, then that's going to be even better in terms of supporting my health. 

Prof Nicola Segata: Yes. Did you come back to the number you had before the antibiotics or…?

Jonathan Wolf: I haven't yet. I had 38 good bugs before the antibiotics, but when I started ZOE, I actually had about 20 good bugs, so I slowly increased. 

Prof Nicola Segata: Well done. 

Jonathan Wolf: When I first met Tim, I had about 20; I got it up to 38. Then the antibiotics wiped all that good work out in seven days, which is really depressing. 

But I think what is really exciting, I've been following this; I went all the way down to six good bugs straight after the antibiotics. It's been steadily going up. I've gone to 23, that's about double the number it was a year ago. 

But also interestingly, I've been looking at the bad bugs, and I know we're going to come to that in a minute, so I'll save that. 

I would say I have just been looking at the results since now you've told me this other number is really good, and since I do eat a lot of nuts and seeds, it turns out that I do have this bug within my 23.

And you're saying that you sort of predicted that because you knew that I was going to be eating lots of nuts and seeds. 

Prof Nicola Segata: Correct. You are confirming our science. 

Jonathan Wolf: I love it. I think you have one more newly discovered gut bug you wanted to tell us about. 

Prof Nicola Segata: Yes, I can tell you a little bit more about that guy because I can present it. It’s this guy here, it is called Catenibacterium.  

Jonathan Wolf: So Nicola, you're actually holding up a little stuffed animal. Do you want to describe what you've got in your hand? 

Alright, well, I've been passed it, so it's quite cute, isn't it, Tim? It's got little hairy stuff off the top, two little eyes, I guess that's probably not real. And it's made in sort of three segments. 

Prof Nicola Segata: It is kind of a chain shape, and that's why it is called Catenibacteria because in Latin ‘chain’ is ‘cateni’. 

We can show this because we saw this bug under the microscope. This is one exception, because we saw it with what I told you, metagenomics, but then we targeted it, and we were able to grow it in vitro, and then we are able to study it.

So this is not one of the 50 good bugs for a reason: because it's very rare in our populations in the U.K. or in the U.S. 

But there are a lot of these microbes in what we call non-Westernized populations. So populations that are unable to have antibiotics even when they need it. They don't have a high-fat diet and stuff like that.

And there's also the microbiome that was in our gut 5,000 years ago in our population. 

Prof Tim Spector: Our ancestors' microbes really. So we probably all had this bug, originally. Usually they're good ones, aren't they? 

Prof Nicola Segata: Exactly. We saw it in mummies, ancient mummies have these bacterium, and guess what? 

This was first isolated from my gut microbiome. So I had a very little amount, but they were still detectable in myself, and this was coming out of my gut. 

Jonathan Wolf: That's amazing. So, basically, you're saying we found this bacteria in mummies that are thousands of years old. We find it now in people who are still living non-Western lifestyles.

But that anyone listening to this in the U.S. or Australia is very unlikely to have it because of our modern diet and lifestyle. 

Prof Nicola Segata: Exactly. So that's why it's not in the top 50, but you know, this is more long-term science, I would say. Because we are trying to study this and try to study whether it is safe to think to reintroduce it in our populations, and whether we can then feed them the right food to keep it in our population.

This is sort of a new generation of probiotic intervention potential in the future. This is a very early stage. I just wanted to give you an example of where we can go with our science.

Prof Tim Spector: Seeing this chain bacteria in our yogurt in 10 years' time. 

Jonathan Wolf: Tim, can you just help us on what is a probiotic, and you know, we see them on the supermarket shelves all the time. Are you telling me that they aren't like really good stuff like Catenibacterium?

Prof Tim Spector: The probiotics we have in our shops are really the same that we've had for about a hundred years. They really haven't changed much. 

Probiotic just means a live microbe that's been shown to be good for your health. And the ones that we're allowed to sell are those that exist naturally in foods.

So we've pretty much discovered all the ones we're ever going to find in food, and there are several thousand of them, but we tend to really use the same 10 or 20 over and over again. 

What we're seeing here is that with these new discoveries, we can suddenly go to much more important, much more advantageous microbes. And if we find they're safe to put into foods and into the human body, then that's going to be a massive advance because the probiotic field really hasn't changed much at all. 

We do know they're helpful, but they're not helpful for everybody, and they're not helpful in prevention; they're helpful for specific conditions.

But we think we can do so much more with these new bugs that Nick and the team are finding.

Jonathan Wolf: So Nicola, in this paper, you now have listed the 50 top bugs. Can I buy a probiotic from my supermarket for any of these 50 today? 

Prof Nicola Segata: Not yet. Absolutely not. But we are trying to cultivate it. Our science here is trying to target these microbes to culture them and think about having a new way of having probiotics.

So this is one of the goals is much more long-term goal than what we are talking about today. But it's something we are really working on. 

Jonathan Wolf: I feel like a lot of people will be quite shocked because I think a lot of people have been taught that if you want to improve your gut health, you go and buy a probiotic and you eat it.

And now every product in the supermarket has probiotics on it, and you can get probiotic soda and whatever you want. 

But I think what you're saying is that none of those probiotics actually are the good bugs that are going to support your health.

Prof Nicola Segata: None of the available, commercially available probiotics have any of those 50 good bugs.

Prof Tim Spector: So in a way it's a different mechanism. 

I think what we're talking about is the probiotics you see classically in foods and yogurts and kefirs and things been discovered historically a long time ago, and they're not normally part of our gut. So they would come in, and they would pass through, and they might stimulate our immune system, but they're not going to stay there and multiply.

Whereas what we're talking about with these ones are these are can naturally inhabit and live in our gut for a long time. Therefore, if we can get them into you, then they could have much more profound effects. 

Jonathan Wolf: And Tim, if you're listening to this and you're suddenly saying, Oh, I would like to have more good gut bugs and a bit like, you know, my own personal story, which is it went down to 6 and you get it up to 24. 

If you can't get it up to 24 by eating a probiotic, what can you do? 

Prof Tim Spector: Well, prebiotic is the other answer, and some people have heard of this term, that really means a fertilizer for your microbes. And it's a broader approach than a probiotic, which is just targeting one particular microbe and hoping that it has other effects.

So, prebiotic is scattering lots of fertilizer in the soil of your gut so that the good microbes will grow and they will push out the bad microbes. 

So we think that the way to improve your good microbes is definitely through fertilizers from the tools that we have at the moment. So we think this diversity of plants on a regular basis is really the key currently that's available. 

It's actually easier to give people these prebiotics than probiotics because there aren't any real health risks associated with it. 

Prof Nicola Segata: Absolutely. We have also to say that they are not enough. Probiotics alone or prebiotics alone are not enough because probiotics are living bacteria that are getting to your gut, even next-generation ones.

But then you have to feed them the right food; otherwise, they will not stay there. And the same with prebiotics. 

So, it is not that you can think of taking pre and probiotics and then eat just junk food all the day. 

It has to be a system approach. You need to get the right environment for your microbes. Then maybe you need the specific microbes to be given to you. 

But this does not mean that, you know, diet is not important. The first thing is diet. Then some supplements can really push an improvement. 

Prof Tim Spector: And I think in the future we might be looking at personalized fertilizers, personalized prebiotics, really to tease apart these different ones.

At the moment, we're going for generic. They work really well, but you know, I think we can do even better in the future. 

Jonathan Wolf: Now, we talked a lot about the good bugs, but I'd love to touch at least briefly on the bad bugs, the sort of the villains of this story. 

How are they impacting our health? 

Prof Tim Spector: The bad bugs are, as we've discussed, only bad when they get too numerous, and when they're too numerous, they seem to interact together and they produce a nasty environment.

They produce chemicals that irritate the immune system. They cause inflammation. They might cause slight swelling of the gut lining, making it leaky. They might change the acidity of the local environment. They can mess up your fat transport, interfere with the way your body gets rid of fat, so it's hanging around and causing even more inflammation.

Many of them seem to like sugar. They're like spoiled kids who only want to eat in the sweet shop. 

Jonathan Wolf: Tim, I can tell it's a long time since you've had kids.

Prof Tim Spector: Alright. So yes, they're like childish nuisances that are in your gut, and once they proliferate, it's very hard for your good bugs to make a comeback.

Because they're school bullies. They're elbowing out the other guys, they're pumping out all these chemicals, and the more nasty chemicals they pump out, the harder it is for the good guys to survive and flourish. 

It also attracts more bad guys. And there's even some evidence that if you've got lots of these bad guys, they even could send signals to your brain to say, Give me more junk food.

They've only done this in mice and rodents, and other lower insects. But it's a kind of cool idea that, yeah, I like this inflammatory environment; it suits my microbes. 

What do my microbes like to eat? Lots of fat, lots of sugar, lots of nasty stuff. 

Prof Nicola Segata: And what is most dangerous about this is that you don't feel the bad bugs because they are there, they're doing the inflammation, but it's not like they are not as bad as pathogens that they cause infectious diseases. Pathogens that are even worse than the bad bugs that we are talking about are making you sick. So you need to be treated. 

These microbes, you don't feel that you have them. Yes, you may have lower energy, lower more inflammation, things like that, but it is difficult for you to associate with that.

That's again, why it is important to test, to know that you have them, and be aware about that. 

Jonathan Wolf: And Nicola, I'd love to share again. I'm listening to you, and I have opened a set of results for my own microbiome test over time. 

Just before I smashed my toe to smithereens, I had six bad bugs in my gut. And immediately after the antibiotics, actually, that fell to three because it almost everything was wiped out. 

But I was looking at, interestingly, by the end of that year, my number of bad bugs had gone all the way up to 13. So I had twice as many bad bugs. And today that's slowly come down, and now it's back down to four.

How does that tie into the story that you're describing? 

Prof Nicola Segata: Your main focus should be improving your good bugs. Then, by growing, they will decrease the bad bugs. 

Jonathan Wolf: I like gardening. So this is a bit like weeds. The way I'm hearing this, like I've got a garden, there's only so much room in the garden, so if it's full of weeds, there's not room for a lot of flowers.

If I have lots of flowers, actually, it's hard for the weeds to grow, right? Because they're sort of shaded underneath. But equally well, if I have lots of weeds, it's really hard for the flowers to show. And so if one grows, the other shrinks. 

Prof Nicola Segata: It's a balance. It’s an equilibrium. Yes, there is only so much ecological space, it is called, in the gut. And if you have enough of good bugs, there is no space for the bad ones. Yes. 

Jonathan Wolf: And so when I took the antibiotics, it sort of wiped out the garden, and then suddenly I have all these weeds shoot up. I'd worked hard on my diet, I mean, this is sitting next to Tim for a long time. He's very smug about how healthy is. 

And I'm like, no, I want to be on this path and feeling better. And then also took very intense antibiotics, and it sort of wiped it out… 

Prof Nicola Segata: You reset your microbiome. And that's why it is even more important, the diet just after antibiotics, because it is when you are regrowing your garden.

Jonathan Wolf: The food that you're eating after antibiotics is really important. After an antibiotic course, you want to sort of feed the good bugs, the flowers, and starve the bad ones. 

Prof Nicola Segata: Exactly

Jonathan Wolf: And what is the diet that the bad bugs really want? 

Prof Tim Spector: They love junk food. They love what we call pro-inflammatory foods that are high in saturated fats. They're high in sugars, and they're low in most of the traditional fibers that are hard to digest. 

Prof Nicola Segata: It's easy to be bad; instead, the good bugs are much more specialized in some operations, that is why you need to put effort in to diversify your diet. 

Jonathan Wolf: So the bad bugs basically love all the junk food, and the good bugs are like picky and you have to give them particular sorts of plants and things. Is that the sort of rather depressing message that you're, you're sharing here?

Prof Tim Spector: Sadly, yes. And we used to have the perfect diet, but, you know, suddenly the Western or the SAD diet, the standard American diet, has taken over the Western world, and that really suits the bad microbes and doesn't suit the good guys.

Jonathan Wolf: I'd love now to switch to really actionable advice, and I think we've talked about a lot of things that you can do, but I'd like to try and make it really specific. 

Maybe starting actually with what you can learn if you've actually done a gut test and got the results. Because I know a lot of people listening are ZOE members, quite a lot of them will have participated in their science, and they'll have been given a list of foods that are called gut boosters associated with their microbes.

What makes a food gut-boosting? Is it simply like it's a fermented food like we've been talking about today, or something else? 

Prof Tim Spector: It's something different. These are foods that we are associating with microbes. So when we're suggesting a gut booster, it is in the belief that if you increase that particular type of food, you're going to increase some of your good microbes and reduce some of your bad ones that are specific to you. 

Each time we evolve these scores, this advice is going to get better and better and more specific. And so hopefully this will be really very targeted advice, you know, within a few years’ time.

And so everyone could be pinning down, Okay, oh, microbiome number four is really low, what combination of foods do I need to get this guy up and going, because it has this very specific job that I want it to deal with. 

So this is really the start of this journey as we get these huge numbers, and we can really nail this down. But it's the era of personalized nutrition, very much, and personalized microbiome analysis, which is where we're all heading here.

Because yes, there is general advice, but that only gets you so far. 

When we find a new association between a food and a microbe, we will tell our members that this is what they need to eat without necessarily waiting for that paper to go through this rather lengthy process of peer review. 

So it's constantly evolving, it's constantly improving, and I think this is the whole name of the game in what we're doing.

And that's what makes it so exciting is our, as our data from all our members allows us to do better and better every time

Prof Nicola Segata: Almost real-time. 

Jonathan Wolf: One of my gut boosters was tofu. I never ate tofu in my life, but because it's supposed to be good for my microbes, I started eating it. And what do you know? After a while, I quite like this. It's an interesting example of something I've added to my diet now, thinking about it.

Now, a lot of people listen to this. Won't have ever had their microbiome tested. So what should everyone be thinking about eating more of if they want to support these sort of fussy good bugs that we've been talking about?

Prof Tim Spector: Well, the general principles are still the same. And, you know, our researchers are just confirming that having a rich diversity of plants in your diet is good. 

We still believe that hitting a target of 30 is achievable and seems to be a reasonable one to go for. 30 different plants, including different types of nuts and seeds, herbs, and spices. 

Trying to eat the rainbow so you're getting all the different chemicals from these polyphenols, these defense chemicals, into your diet. 

Having regular fermented foods which gives your gut microbiome a bit of a boost in ways we don't totally understand yet. And you probably need to have three little portions a day of ideally different ones, to really optimize it.

Jonathan Wolf: And Tim, you said before that none of the probiotics that we buy in the supermarket actually match up to any of the good foods. And then you're talking about fermented foods that have these live bugs in. Are they going to be some of the 50 good bugs, or is there something different? 

Prof Tim Spector: No, they're not, because there's a difference between the microbes that live normally in food and the microbes that live normally in our gut.

There's only a very small overlap of a few percent of these that you find food microbes inside your gut, and in general, they're not the ones that are in most of these fermented foods. 

I think I'm right, Nicola, on that?

Prof Nicola Segata: Yes

Prof Tim Spector: So it's a different type of microbe and we think they might have an effect on our gut through, say, stimulating our immune system, rather different mechanism to our normal gut microbes. And they might be working higher up, we don't know yet.

But we do know from our studies that we've done our own ZOE fermented food study and other more detailed ones that having at least three portions a day can, in just a few weeks, really improve your immune system, and that's going to help your gut microbes as well. So, everyone should try and do that and experiment with new fermented foods. 

The other thing I think people should do is what we call pivot their protein. Try and have less meat and get your protein from things like legumes and beans because you get pretty much the same quality protein, but you also get lots of fiber, which our microbes love.

So a lot of people aren't really used to, in the U.S. and the U.K., having a whole range of these beans and lentils. And I think that's something we can all do. 

And then finally, thinking about the quality of the food you're eating, which means you want to go for whole foods, you want to go for real food, and you want to really reduce your high-risk processed foods, or what's called ultra-processed foods.

Jonathan Wolf: And actually, Nicola, I was going to ask, because that's a lot about feeding the good bugs. 

What do I want to eat less of to try and push down those weeds, you know, the bad bugs that we've been talking about? 

Prof Nicola Segata: But again, I don't think there is one single food that is bad for you a priori. Unless you eat too much of that bad food. So, you know, little amounts of bad foods here and there is not a big problem. 

I think it is much more the advantage of eating a lot of healthy foods and diversity, healthy food, and pushing down the bad bugs. So this is the first thing.

Of course, too much red meat of course is a problem, clearly. But we shouldn't feel bad in eating every now and then the food we love.

Prof Tim Spector: You can have the occasional pizza, can you? 

Prof Nicola Segata: Absolutely. I have to. 

Jonathan Wolf: And Tim, you mentioned about fermented foods. I think this is something that still for a lot of us is not very familiar. What fermented foods are in your fridge?

Prof Tim Spector: My wife says too many.

Prof Nicola Segata: You can smell them, probably. 

Prof Tim Spector: She can smell them from a long way away, especially if I've been home for a while and been doing a bit of my own fermenting. 

So I've got, always got yogurt, and I've always got kefir, which is fermented milk. I've just made a batch of water kefir, which is also called tibicos, which is sort of like a fizzy drink.

Prof Nicola Segata: No kombucha?

Prof Tim Spector: I haven't made any kombucha at the moment. I've got my blobs in the fridge, which looks disgusting to anyone who's not an aficionado like myself. 

I've got kimchi. I've got some kraut in there. I've got some miso paste. I've even got some garlic in honey. It's fermented in honey, which I use in salad dressings.

I've got usually a whole range of smelly cheeses, lots of different ones. And I also got my sourdough mother, and I've just made some sourdough yesterday actually. 

So that's on the go. So I've got a full range. And so I'm never short of fermented food. I always try and get my three portions in.

Jonathan Wolf: Amazing. Might you have a new fermented recipe, a simple one that someone listening to this could follow? 

Prof Tim Spector: Oh, it depends what you've got, but it's a very practical one. So often I find I have to go away on trips. I've left my fridge with vegetables in the bottom shelf that are probably going to go off if I don't do something with them.

So I call this my fridge-raid ferment. And whatever's in that lower compartment except aubergines, which go horribly soggy. So things, whether it's carrots, sweet potato, cauliflower, broccoli, onions, tomatoes, garlic, it doesn't really matter, a bit of cabbage, even it's a quarter of it. 

You chop it up into small chunks, half an inch thick. Try and get it fairly even. Stick them in a bowl, weigh them. Then do some maths and calculate 2% of that weight. 

And you put that as salt, and you throw salt on it, massage it in a bit until it's really worked into the veg stuff. Put it in a jar, which has a lid and ideally a little valve. So you've either got to burp it every day or the valve will do the trick for you and leave it for five days while you're away.

You leave it out in room temperature, and that will be bubbling away and fermenting, and you should, when you come back, have beautifully preserved, fermented, fridge veg. And, that's an easy way to start and very good for the planet. 

Jonathan Wolf: That sounds great. Tim, and I think that is actually a recipe that is coming from your brand new book.

Prof Tim Spector: That's right, yeah. This is a sneak preview, which you can pre-order, and there are many other recipes that are really useful and practical in this book if you want to learn more about your ferments. 

Jonathan Wolf: Well, we will share the recipe in the show notes, and we'll also share a link to your new book.

Tim, I know that you like to spend months and months hiding in your room writing these books, so I always think it's an immense amount of work, but I appreciate the amount of effort you go into to then allow us to understand the latest science and how that ties into our health. 

Prof Tim Spector: You are very welcome, Jonathan.

Jonathan Wolf: Thank you both. Thank you so much, Nicola, for flying in to take us through this amazing new paper. 

I'm going to try and do a quick summary. I think I'm going to start with the thing that is brand new for me and I love, which is I am a coral reef, which is a brilliant idea that somehow I have all these bacteria living in me and I'm coexisting with them.

On a more serious note, you're both clearly very excited. You feel like this is a really major breakthrough. Tim, you gave this great analogy that being published in Nature is sort of like winning the Oscars for scientists. 

The key point I think I've taken away is this is like 34 times bigger than the previous biggest study. And that scale is allowing scientists to unlock really the links between food and bacteria and the links between individual bacteria and health in a way that hasn't been possible before.

I would definitely like to thank everyone listening to this who's actually contributed to the research, which I know is a lot of the listeners who have, which is amazing.

I know you're very excited because you're already working on the next stage of this, with hundreds of thousands of samples. So thank you, everybody. 

The key thing that this enables us to do is to really take a snapshot of our gut microbiome today and understand its health. Not in some vague way, but really literally, yes, there are specifically good bugs and bad bugs, and you can look at the amount between them, and that then you can track it over time in the way that I've been able to do since my antibiotics and really see that you're making progress, which I find incredibly reassuring.

A big part of my motivation to continue is to see the progress, while also maybe a little frustrated that I haven't got all the way that I want to. Because I can be a perfectionist, but that's my own issue. 

I think the other big thing I took away is that the good bugs are pickier than the bad bugs. The bad bugs they love junk food, and they're really, you know, they then create all these chemicals that are damaging your gut and causing inflammation, but they're very happy with just eating whatever the junk is that surrounds you.

The good bugs are pickier. It's not all right to just feed like one good bug; actually you really want to have all 50 of these good bugs. So you need to be trying to feed them all of these different things. 

We know they like plants, but they like different plants, and so that is really where, you know, Tim, you often talk about this idea of diversity, and I think it sounds like the science is helping to understand more of this, which is, they actually respond differently.

And Nicola, you predicted that I had this particular bug, and you were right, which I wrote down 4964 needs a better name because we now know it really likes nuts and seeds. And if you feed it, then you are going to have that.

I think the final thing that I took away is the food that we eat and the sort of prebiotic, as you describe it, is the most important thing because we've all been told about these probiotics with living bugs that you can take, but actually we now know that none of those are actually the same as these 50 good bugs that you want. 

Even fermented food that you're talking about, which has really great positive impact, isn't going to replace the 50 good bugs. So I can't just say, Oh, I'm getting fermented food and then eat my junk food.

The most important thing is these foods that actually are going to feed my bugs. And if I can do that right, a bit like in my garden, I have more of these flowers, less of the weeds, and that brings us right back to the beginning of saying, genuinely, this is linked to better health and reducing my risk of heart disease and diabetes, and all of these things.

Jonathan Wolf: You got it. 

Prof Nicola Segata: Fantastic summary.