ZOE Science & Nutrition - Gut microbiome testing: What can it reveal about your health?

Episode Date: September 21, 2023

Your gut microbiome, a bustling community of microorganisms, is a vital player in your overall health. It doesn’t just impact your digestive system — it has a profound influence on your brain health and well-being. However, the gut microbiome is a complex, long misunderstood realm, and figuring out how it affects daily life can leave even the most dedicated health enthusiasts scratching their heads.  Here at ZOE, we’ve transformed our understanding of this bustling microbial world, where both “good” and “bad” gut bacteria reside. In today’s episode, Jonathan speaks with Prof. Nicola Segata and Prof. Tim Spector to explore how ZOE's microbiome testing and unique microbiome health scores provide personalized insights into your gut health. Download our FREE guide — Top 10 Tips to Live Healthier: https://zoe.com/freeguide If you want to uncover the right foods for your body, head to joinzoe.com/podcast and get 10% off your personalized nutrition program. Nicola Segata is a professor and principal investigator at the Laboratory of Computational Metagenomics, at the CIBIO department of the University of Trento. His background is in metagenomics, machine learning, microbiome research, and microbial genomics. Tim Spector is ZOE's scientific co-founder and one of the world's top 100 most cited scientists. Timecodes: 00:00 Introduction 01:41 Quick fire questions 03:38 Why should we care about gut microbes? 07:00 How many different microbes do we have in our gut? 11:37 Why would we want to measure our microbiome? 13:15 Can we change our microbiome? 18:00 Is it possible to make a dramatic change in your microbiome over time? 20:21 What does the latest data tell us about improving our diet? 23:24 How does the ZOE micobiome gut test work? 27:07 What goes on in the lab to get these results? 30:54 Is there enough information in the gut microbiome to make a full health assessment? 34:20 What can our microbes tell us about diseases? 35:55 What useful information does the microbiome test show us? 36:51 Are we still making new discoveries in the microbiome? 41:03 Do different microbes prefer specific foods? 43:14 How do different lifestyles around the world change your microbiome? 47:44 5 simple tips to improve gut health 50:45 How rapidly can you damage your microbiome? 53:58 Can taking painkillers regularly negatively impact the microbiome? 56:10 Summary 60:03 Goodbyes/Outro Mentioned in today’s episode:  The person-to-person transmission landscape of the gut and oral microbiomes from Nature  Sharing of gut microbial strains between selected individual sets of twins cohabitating for decades from PLoS One A genetic gift for sushi eaters from Nature Find Nicola on ResearchGate and X. Episode transcripts are available here. Is there a nutrition topic you’d like us to explore? Email us at [e-mail], and we’ll do our best to cover it. 

Welcome to ZOE Science and Nutrition, where world-leading scientists explain how their research can improve your health. Gut bacteria are not a new discovery. Early in the 20th century, scientists knew that trillions of microbes lived inside us. Back then, these bacteria were considered an annoyance or even a potential source of illness. But in the last 20 years, we discovered these bacteria are actually crucial to our health. Leading scientists now believe the variety of microbes we have and the number of good

versus bad bugs in our gut may both play a huge part in our long-term health. These microbes can affect our cravings, causing us to put on excess weight. They're also linked to our risk of long-term diseases like heart disease and stroke, as well as to our mental health and even our energy levels. So how to find out how our microbiome is doing? Well, until recently, we couldn't. But now, using state-of-the-art technology developed right here at ZOE, we can test our gut microbes from the comfort of our toilet seat. And thousands of you now have. Today, I'm joined by Nicolas Agata. Nicholas is a professor at Trento University and a longtime scientific advisor here at

ZOE. He's widely regarded as the world's leading expert on microbiome analysis. Also joining is Tim Spector, my ZOE co-founder and one of the world's top 100 most cited scientists. In this episode, they share what they've learned from testing the microbiome of thousands of people and they discuss how this new technology can help all of us improve our long-term health. Nicola and Tim, thank you for joining me today. And I'm very excited that Nicola has flown over especially for this.

So why don't we start, as we always do, with our quick fire round of questions. And Nicola, we designed this especially to be really difficult for professors. So the rules are, you can say yes or no, or maybe, or if you have to, a one sentence answer, but no more. Are you okay with that? That's right. Yes. Fantastic.

All right. And we'll alternate. So starting with you, Tim, if I didn't have a gut microbiome, would I die? No, you'd have a pretty miserable life. Nicola, can I improve my gut microbiome? Yes, you can. There are several ways to do that, and we are going to learn them. Fantastic. Tim, could altering my gut microbes prevent or even treat disease? Absolutely.

Nicola, have you discovered gut bacteria that are linked to good health that weren't even known to science a year ago? Yes, many actually. It's amazing. We're definitely going to talk some more about that. So this is definitely a cutting edge podcast. Tim, do you see a future where everyone has their gut microbiome tested? Absolutely. All right. And then finally, for each of you, what's the biggest myth that you often

come across about the gut microbiome and sort of gut microbiome testing? I think that it's that you can diagnose specific diseases with it. And I think that's probably the commonest one. Most people think it's, they criticize it because it's not particularly good at diagnosing a particular type of disease, whether it's diabetes or heart disease or cancer or whatever. And that they're missing the point, really.

It's a much better tool at understanding your general health, your immune health. Fantastic. Yeah. For me, the myth is that the microbiome can tell you everything. It can tell you everything, but only when connected with the other health measures of your body. Got it. So it's, in both cases, you're saying it's giving you this really big insight, but it's not sufficient on its own. Yep. Yep. Brilliant. So look, let's start at the very beginning. And Tim, why should we care about the microbes in our gut at all? Hi, I'm Zoe's US Medical Director, Dr. Will Bolsowitz, and I'm excited to tell you about a free resource that's going to kickstart

your journey to better gut health. If you're a regular listener, you probably already know how a healthy gut microbiome is important for digestion, immune support, and mental well-being. And that a high-fiber diet is a great way to improve your gut health. But where to start? And what exactly does a high-fiber shopping list look like? With 95% of US adults deficient in fiber, clearly this is not common knowledge. Zoe's Gut Guide has the answers. To get yours for free, simply go to zoe.com slash gutguide and start feeling the benefits of a healthier gut today. Although it's not a question of life or death, they are pretty much crucial for so many processes in our body.

And I think what we're realizing is just how crucial they are for our immune system. Because we've assumed that, okay, microbes are there to digest our food, which is true. They have thousands of chemicals that our body doesn't have itself in order to break down food and extract the nutrients. We know that from mouse experiments, if they take away the microbes, make them sterile, those mice have to eat like 30, 40% more every day just to stay alive because they don't have those careful processes. So life would be a struggle. But I think the new science is telling us that the immune system is the key to why we need a gut microbiome to be healthy. Because 70% of our immune system is in the lining of our guts. And that's interacting with our microbes.

So our microbes are essentially mini pharmacies pumping out chemicals that are interacting with all those cells, those immune cells, and that's priming them so they know whether to attack things or to defend things or just to get it right. And when it goes wrong, that's when you get food allergies. That's when you get autoimmune diseases. That's when you don't detect early cancers. And that's when you don't repair some of the processes of aging. So increasingly, we're expanding our view of what the microbiome does from a rather

limited idea of, oh, it helps break down food and it's quite useful for our energy balance and our metabolism to a much broader idea of what they all really do, which we're starting to see in some areas like cancer and immunotherapy, et cetera, et cetera. So I think that's why everyone needs to know about the gut microbiome. And everyone really needs to know that it's not just about how we break down food. It's absolutely crucial. And that explains a lot of the Western epidemics of chronic disease, that as we've lost our gut microbes over the last 50 years, we've also gained all these diseases, all these allergies, all these immune problems.

And we're facing this pandemic of ill health. So by understanding the gut microbes, we can get back on track and really start to get back to our set point of health. And to do that, we need a healthy set of gut microbes. And I will actually also add the brain, because there is the gut-brain axis. Microbes are connected with our brain through chemicals, through neurotransmitters that are produced. And so there is a connection between our gut and our brain. So even more functions.

Yes, they actually produce the neurochemicals to make these key differences between us being happy and sad, depressed or anxious. And we're only just discovering all those intricacies there. So yes, they're key to virtually all the bits of our body, and we ignore them at our peril. I always love hearing Tim and Nicola talk about this, because you come away just thinking how amazing it is and how important it is, and of course, how new it is as well. And I think we can explore a bit today, sort of the things that people are starting to understand. Before we do that, just can you help us to understand how many different bacteria and other microbes

are there in our gut? Well, Nicola might have a different number to me because everyone you ask can't really give you an exact figure for this. But in total numbers, there are hundreds of trillions of bacteria. But there are also another related species called archaea, which we don't talk about much all that lot, we've got fungi, we've got yeasts, and we've even got parasites, which we're starting to find are of great interest, and some of them are even healthy. So we've got this menagerie, if you like, it's like a jungle out there of lots of predators eating each other, controlling each other, struggling for survival, little ones, big ones, fat-eating ones, protein-eating ones, sugar-eating ones, fiber-eating ones. And they're all in these ecosystems struggling for survival. And as they eat the food, they're pumping out all these incredible chemicals that are used by our body,

our immune cells, and our health. So you've got to try and envisage this as this living community of microbes working together and totally dependent on the food that we give them. And I think that's really important, which sets their environment. And if we get that wrong, that environment shifts and those populations shift. Just like, you know, if there's no rainfall in a forest or you spray pesticide all over it, you're going to get a very different environment. Everything from the tiny insects to, you know, the lions and the big beasts, they're all inside our gut. And everyone has a very different community. We're all totally unique.

And Nicola's done this work on not only the species, but also the strains. So within each species, there are subtypes called strains, where just a little tweak of the DNA makes it quite different have a different function and so we're seeing even greater diversity than we imagined because of the new these new techniques yeah so there are probably thousands of different species in each of us no but not all are the same so me and you team may we may have only maybe 30, 40% of the species in common. And as you said, these strains that count is like COVID, no? We know there are many different variants.

And the COVID has been around three years, more or less. Our gut microbes are around since hundreds of thousands of years. And so they have spread a huge amount of different variants. And it's very likely that you and me, we don't have even one variant in common. So very, very diverse, very different. And we've all got, isn't it true that we've all got some variant of a bug that literally nobody else has? Exactly. In 10,000 people or something.

We know that our human genome is unique, but our human microbiome is even more unique. It is really personalized to each of us. It's amazing. So you're saying that, if I think of your jungle analogy, we might all have an orangutan inside us, but actually it's a completely different variety of orangutan. Like the one that might be in Indonesia and one that's, I don't think they have one in Africa. My analogy has broken down but you're saying that actually when you really go down to understand it really each of these is this is different even though at the high level description of it as a type of bacteria might they don't just look different they are different they eat different food they they produce different

chemicals so very diverse within the same species amazing So I think we're getting a picture of like this incredible complexity. And also, I love this jungle analogy and the idea that the food we're eating might be a bit like pouring pesticides or I'm thinking a bit about Brazil, you know, burning parts of it down or, you know, it's a slightly scary analogy you've also set up there, Tim. I do want to talk a bit about testing in this context because, you know, I think most people listening to this, they're used to this idea of maybe regularly testing their blood pressure when they go and see their doctor, or probably used to the idea of having things tested in their blood regularly, like their cholesterol, all these sorts of things. These have become completely normal for maybe like 100 years in the West. I think most people are not used to the idea of measuring their poo.

That seems quite radical. Why would we want to measure our microbiome? Well, there are a number of reasons. I mean, the first is that if I get a sample of, say, your microbiome and a sample of your DNA, and I do sequencing on both, I can tell much more about your current state of health from your microbiome than I can tell much more about your current state of health from your microbiome than I can from your DNA. And this came from me as an ex-geneticist. So I've totally changed my views on that. So the microbiome really says, what's your current state? It doesn't necessarily

predict 50 years time like DNA might, but it gives you a much better idea of your current health and also an idea of the state of your diet, whether your diet is appropriate for your microbes and whether it's pro-inflammatory or anti-inflammatory. I think one question though that I think I immediately had when we first started talking about this probably six years ago, I think many people have, is around whether this can change. Because there's one thing which is, hey, I've got this measure like my DNA, it tells me some things, which often feel a bit depressing, right? Like it's saying, hey, I've got this high risk for getting breast cancer, for example. And that's actually sort of is a bit depressing if you feel you can't do anything about it. And

one of the things that was exciting, I think, about the idea of the gut microbiome is the idea that it might actually be able to change. And we actually did a, we actually asked our community on social media, a question in preparation for this podcast about how quickly they thought somebody can change their gut microbiome. And we had many thousands of responses. And interestingly, 50% said they thought that you could change the gut microbiome within a week, 31% within a month, and 18% would take six months. So to what extent can we change our microbiome? And what does the latest science tell us about how quickly you can start to see a change? I think they are all

right actually okay well done everybody there are multiple scales now so uh what i eat today will change my microbiome tomorrow for sure but it's also what i ate for the last 10 years that are changing in a more radical way the microbiome they have today so it's a combination of the short-term diet and the long-term diet and also the lifestyle. And that is what is really exciting, though, because it's the fact that we can change our microbiome at multiple levels. And the challenge here is to understand in which direction we need to move it, which microbes we need to improve, and which food we need to improve certain microbes.

This is the real challenge today, and it's only with big data, actually, a lot of information from a lot of microbiomes, a lot of people, and health information, and diet information, that we can study everything together and pinpoint which are the reproducible changes that we see, and we can then tell people to do.

And the other point I think is that if your gut is in a bad way, then actually by radical change to say you're on a junk food meat diet and you change to a vegan diet, you see dramatic changes within five days. And the opposite is also true. So I think there are these extremes that if you have a very poor diet or a very good diet and you swap to the extremes, you will definitely see effects within a few days. And that's been proven with some very carefully done studies. It's harder to change someone who's on a really good diet to improve them than it is to improve someone who has a very poor, very non-diverse inflammatory diet. So I think there is this variation, these timescales we've talked about, but there's

definitely a large proportion of the gut microbiome that is very changeable, very amenable, and very unlike your genes which you know you really can't do much about at the moment apart from just blame your parents and i blame them for a lot already so and i think there are two levels here no because one thing is that with our food we can increase or decrease microbes that we already have but we can also acquire new microbes and the microbes then can colonize ourselves, depends on what we eat. But, you know, if I change my diet today, I cannot immediately acquire new microbes. I need both acquiring microbes and finding the right food for them.

So, again, it's a combination of two and not to always say the same thing, but it's more complex than what we currently appreciate also. And only with the big data, we can really understand it more. I think one of the things I've discovered over the last six years is always these things are more complicated as you get deeper into them than they appear on the outside. And Tim's smiling here because I think that's the history of his career. I actually have my own personal experience here, which is quite fun. So I first had my microbiome tested in 2019. So four years ago, as part of the very first Zoe predicts study. And at that point, I hadn't made any changes to my diet. I thought I'd been eating

pretty healthily. I subsequently discovered it really wasn't that healthily, but I thought so. And I scored 52 out of 100 in terms of the Zoe gut microbiome score, which is basically completely average in the UK. So sort of 50 is sort of the ZOE gut microbiome score, which is basically completely average in the UK. So sort of 50 is sort of the average score. I've had it tested repeatedly since then. At the end of last year, I scored 78, which put me in the top quarter of people. Thank you.

So I'm very proud about that. But I think what's interesting is I was able to make a really dramatic change in my microbiome over those four and a half years, And it clearly took time to achieve this. And so, you know, in my own particular example, it wasn't a sort of transformation that happened in a week. I wasn't eating a sort of an all junk food diet, but I clearly also was not eating, you know, I've made very big changes with Zoe. I know we have very little data of people's microbiome over time because actually almost nobody was having their microbiome tested properly with this thing we'll talk about in a minute, the shotgun sequencing.

But we've got two of the world's experts on the microbiome in the room right now. Do you think that might be typical? What would you guess? You really need to change the environment in your gut to make new strains, finding the new home. So, yes. Also because I think we need to think about the microbiome as an average, because we can't really measure every minute of our microbiome for a lot of reasons.

So it's the average of what you ate in the last year. And I think that's really the timeframe we need to test ourselves on. Every six months or so, we should see the improvement if we are changing our diet. If we change today, we see the difference tomorrow, but then we change again and again. So it's really probably over a few months that we can see the improvements. And yeah, you did great. And I think you did some substantial change in your diet then. Yeah. So I think you're a bit slow in your diet then. Yeah.

So I think you're a bit slow, Jonathan. You should have sped it up a bit. Four years, come on, you can do better than that. So I think- I may not have been the perfect student. If you'd followed my advice, you'd have definitely improved in six months. And I think that's what really we should be seeing. For everyone who isn't sort of really high, I think that goes back to the point, the better your microbiome is, the more stable it is, the harder it is

to make it better or worse, because it's such a really tight-knit community. It's working so well together, it fights off other guys and doesn't like to change. Whereas if you've got an unstable one, it's not very diverse, it's inflammatory, those are the people that can really improve dramatically and probably in less than six months. So I think we're going to see an interesting picture here. And of course, you know, coming back to this is, you know, unlike everything else in the body, we're all so unique that just because it hasn't changed doesn't mean there's anything wrong. You might be someone that needs a longer time frame. Some people will change faster.

Some people change slower. Just like we react to drugs in our microbiome at much different speeds as well. And to be clear, it wasn't that nothing happened for four years. I want to be clear. There was a sort of steady improvement through this period. I've been testing more frequently, more recently, as the costs have come down a lot. It seemed quite expensive to start with, but now it's got much cheaper, which is fantastic. So there was a sort of steady improvement through this.

But what's interesting is like it's continued and it's been step by step and probably has followed behind some of the impact I felt in terms of energy and things like this were very fast, sort of losing some of these slumps. So it's interesting that there's definitely something here that's taking quite some period terms of energy and things like this, we're very fast, sort of losing some of these slumps. So it's interesting that there's definitely something here that's taking quite some period of time and other things we were seeing sooner. And I think this matches up to some of the latest data that the two of you have been looking at, right? There's some unpublished data that will be coming out in a paper soon, I'm sure, looking for the first time at what happens with repeat measures of people

who are following, in this case, the ZOE advice. Can you share a little sneak peek for the listeners about what that's showing? Yeah, I can start off and Nicola can add the details, but essentially, we took people who'd adhered to an improved diet. So they were eating towards gut-healthy foods, more fiber, more polyphenols, more fermented foods, less junk foods, et cetera. And we got improvements after about between three and six months. About over 80% of those people improved their global scores. And of course, lots of changes in individual microbes, which may or might not be significant, but Nicola's team got together this score that summarized these changes. And so really for the first time, we're now confident we've got a

scoring system that works to monitor people's change over time. And no one's managed to do this yet. It's very interesting in the literature. There's a whole dearth of these problems because it is so difficult to summarize not only the complexity of the microbiome, but also this incredible interperson individuality. But I think Nicola and his team have finally cracked this. And by looking at the 50 healthy bugs, 50 bad bugs, that ratio, that is proving really consistent for us. And I think we've suddenly got these exciting results, which mean we can start testing. We know what success now looks like. So therefore, we can start to work out what works best for which people and how we can tweak our advice because until that point we were floating a bit in the dark yeah yeah and as you were saying people with a bad starting score improve the

best so over 90 percent of those with a not great score improved it and more than those that were already high in the score yes and that in a way 90 is like a minimum because there's a bit of error in those in those results so it's probably we were capturing virtually everybody who started with a low score and then adhered to a gut-friendly diet. So I think that's fantastic news for the whole field, really, because we just haven't had that sort of clarity before, which means that we've now got a way of monitoring how our gut is doing over time. The show you're listening to right now that's providing you the latest evidence-based health and nutrition information from the world's top scientists, well, making it takes a lot of time. We think it's well worth it,

all in the name of improving your health. All we ask in return is this. Send a link to this podcast to someone you think would benefit. And if you haven't already, click follow this podcast wherever you're listening right now. Okay, let's get back to the show. I think it's safe to say we were quite excited as the first data started to come back about whether these personalized advice is really starting to work. So we will definitely talk more about that at the point that the paper is ready. I'd love to talk a little bit more about the test because there'll be lots of people

listening to this who either haven't done it or even they have really, they have no idea what's really going on behind the scenes. Could you maybe start, I mean, maybe Tim start with like what you do as just, you know, as it were a patient, a customer in terms of the gut testing. Then Nicola, I'd love for you to sort of explain the magic behind behind the curtain after that but let's say i've got this box i'm sitting at home to him probably there are a few people thinking oh this sounds a bit scary what happens next yeah so you get this you get this box with some instructions and it has pictures of toilets in it and various other bits that all sound a bit icky but basically all these tests and the zoe test in particular gives a way of collecting your stool sample so there's a little sheet that comes out

that you put over your toilet you do your normal business and leave a bit of this in this sort of paper that's covering the the toilet which allows you to scoop out a little bit like there's a little spatula and you put that into and how much because people might be thinking minute amounts so we're talking yeah less than a sort of fingernail you hardly need any because there's so many billions of microbes in a in a in a millimeter of this stuff you just say you don't don't have to to fill the tube or anything. It's just a minute amount, forensic type amounts you put in. And you basically put into this tube, which has a medium in it, which preserves the DNA so that when it goes to the lab, it doesn't matter

if it's wasted a few days or not before it, say, goes to Nicola's lab. And then that's when the sequencing starts. Now, what we've noticed is we've been doing this for over a decade. And we started with our volunteers, the UK Twins, who are always the guinea pigs for all these things. I can tell you, when they first heard they had to collect their own poo samples, they were pretty shocked. And they said, this sounds very icky. And you ask people,

oh, I never look at my poo. I never turn back. I always just flush and go. And so this is a new thing for many of them. But as each year has gone on, the acceptability has gone up from about 40% to about 95%. So I think people are now used to this idea in this country. And in other countries, probably in Italy, this is quite normal. I remember when I was working in France and Belgium, patients were always showing me their poo. I didn't want to see it, but it's very cultural. That's interesting. Whereas in Britain and the USA, I think we have a bit of a problem, but we're overcoming it. We realize it is just like a urine sample, a blood sample, saliva sample. I mean, I would just say at a personal level, it is definitely a lot easier than changing

a nappy or a diaper. So anyone who's ever had to do this, that is so much worse. Or picking up your dog's poo, as well. Exactly. So I think, but it's interesting, you know, I think it does tie into something, you know, we're all brought up, I think, as as small children that sort of poo is a bit is something that you're sort of like it's a bit all a bit icky as you say tim and so i think there is something that one has to get over and then i think um you know that fits into a lot of this

but this is going to be talk about something that's actually very important this is going to be commonplace and i think everyone knows if they're i think it's over 60 they get a standard colon cancer test now from the nh, where you do the same thing on the stool test, really to look for blood in the stool. It's a very crude measure compared to the microbiome, but it's a similar thing. And I think people are now realizing this is part of normal health prevention. So I'm not worried that we're going to continue that aversion to it. So that's where we are. You close the pot, put it in an envelope,

and then it goes off to Nicola's lab, and he's going to tell us. Tell us what happens next, Nicola. We have to do a simple thing, which is not simple. It is reconstructing the jungle, so having a picture of the jungle. And there are several ways you could do that. In the past, they were trying to isolate, grow single microbes. But this is inefficient and it's not giving you the jungle. It's giving you the single animals and in a cage.

So it doesn't really work. Yeah, so in the past, we only got 1%, 1% or less of all the microbes in us. We thought because we could see them grow, we ignored all the other ones. Exactly. The other 99, you know, 5%. But they isolated, they were also in a cage. we thought because we could see them grow. We ignored all the other ones. The other 99, you know, 5%. But they're isolated. They were also in a cage. So they were not representing what they were doing in the jungle. So the revolution was DNA sequencing.

And what we do on the sample is to free the genetic material of all these animals, all these bugs in the sample. And then we try to read it. But these machines, next-generation sequencing they are called, they can read only little pieces of the genetic code, so not the full genome of the microbes. So the machine will give us a lot of very small readings of the DNA, and at that point we have a big computational, computer issue,

which is reconstructing the puzzle of each single animal. So the genome of an animal, of a microbe, is the solution of the puzzle, and we have little pieces. It was called shotgun sequencing. Shotgun sequencing, yes. So you used to basically explode it, explode it all up into tiny pieces, and then someone has got to put this massive jigsaw puzzle back together. Exactly. But it's more difficult than that, actually, because all the pieces of the puzzle are scrambled together. So we first need to understand which pieces, which little pieces of DNA are coming from one microbe and the other microbe, and then we need to reconstruct

the genome. This is a really hard data science problem, right? That is what kept busy my lab for the last 10 years. Yeah. And it was nice because at the beginning we were only able to say, you know, big division of microbes like animals. We have mammalians in this sample. And now we can say, you know,

we have this specific animal, actually this subtype or strain of animal. And this was only done by improving the methods we can develop to look at that with a computer. So 10 years ago, this would cost at least 5,000 pounds a sample to do. Okay. So, and a bit like the genetic revolution in humans, which, you know, the first one cost a billion or something. The cost has come down sort of halved every year. So it's a few hundred pounds now.

Even less. And we're getting so much more than we were. And still most people who are offering microbiome testing are using a very crude method, which is called 16S, which Nicola can explain. Which is looking only at one gene. Microbes have 5,000 genes, more or less, each of the microbes. And this initial testing that we were also using about 10 years ago, it was looking at only one gene and looking at the differences in this gene that are characterized in different microbes. But this will not tell you anything about what is the machinery of each microbe to degrade a specific nutrient or something.

So it's giving a bit of diversity analysis, so an idea about how many microbes are there. But as you were saying, it's more important to understand which microbes, which subtypes of microbes you have, rather than how many. So it is amazing. And it continues to be computationally, definitely by far the most complicated thing that we're doing at Zoe and that I think that I've really seen actually in this whole sort of medicine, sort of human biology space in terms of data. It's extraordinary.

Now, having said all of that, Tim, some people claim that with a microbiome sample alone, you could deliver high quality personalized advice. And I know that, you know, you said you don't believe that's currently possible. You know, part of the reason that at Zoe, we don't just do a microbiome sample, but we also get all this other information like sugar and blood fat. Can you explain why that is? Because listening to it sounds like this is

so important. Why isn't it enough? Well, certainly 10 years ago, I thought it would be the case that by now we would have enough information that we'd be able to say, yes, you're going to get Alzheimer's disease. You're going to have heart disease. You need to avoid this food, you need to do this. And it's turning out to be a different tool to the one we envisaged. So as I said earlier, it's not really a useful diagnostic because in a way it's so complicated. There's lots of different ways for those microbes to work. So we just don't understand all of this yet. Correct. Yes, there's this jungle, but many of the animals are able to produce, say, the same chemicals. So you might have a different balance of microbes that are producing the same sets of chemicals. And in one person,

a different set of microbes producing exactly the same, so serotonin or whatever it is, or another one that might predispose you to cancer. So we haven't yet sorted anything out like level of detail we'd need to predict individual disease. So that's why at the moment, it's a much better test of the overall function of, say, the immune system or our metabolism than it is predicting individual disease. Now, I think that we're going to see, as we move from identifying the microbes to identifying their functions, that could be a step change. So once we perhaps use artificial intelligence or other sort of major computing factors to work out this combination of microbes, what chemicals could they produce? And are some of those maybe carcinogenic?

Then I think we're going to be in a position where we could do that in the future. But absolutely now, for the next couple of years, we're not going to be in a position that on its own, it's going to be that useful. So that's why we've found that, yes, we know what a healthy one looks like, an unhealthy one looks like. We want to improve that. tests like we do at Zoe, like with your blood sugar response to individual foods and your lipid testing are better predictors, say, of cardiovascular. And so we put all of these things, each components is, I guess, what you're saying. We're still going to take a holistic approach. I think it's going to be some time before the microbiome on its own could ever do that

job. We need to understand much more about all the chemicals that they're producing and how we manipulate them, if you like. But there are some areas like cancer and things where, and I know Nicola's been doing some work on that, that we're getting sort of close to be able to say. So people, their response to drugs and things like this, knowing what their microbes look like

can you tell us anything about that nicola yeah i think for certain diseases specific diseases for example colorectal cancer then our microbiome can tell us something directly but something more you know complex like cardiometabolic health we need to contextualize the microbiome. So it can be the same microbiome, can be a very good microbiome compared to what you eat, or a bad microbiome compared to what you eat. So we need still to contextualize the microbiome with respect to what you eat, with respect to your cardiometabolic readouts, and we need to take these into account. Our microbiome is an ecosystem, but is inside a bigger ecosystem, which is provided by our body and by also the environment we are all in. And it's complicated by the fact that it's also the reflection of the environment. So,

if you're eating badly, you might have a pro-inflammatory microbes because you're eating badly. Or if you have an inflammatory disease, they might be responding to that. And so there's a mixture of cause and consequence in our microbes that needs more sorting out before we can just say, oh yes, you're going to get that disease. So having made this big disclaimer that you can't just rely on your microbiome to give all your results. And I think, Tim, you've often said to me, as a doctor, there's actually very few tests where you would say that's the only test you use to paint a picture.

Is that fair? Yes, hardly any, yes. So it's part of the story. I think people listening are like, okay, enough with the disclaimer. Tell me what I can expect. So what's the information that I could expect to get back?

And how can I make sense of it so this is actually something that's useful for me? Well, what we can say is whether you have the right microbes. So when we did our first study with Zoe, it was 2019, we had at that time the biggest study, more than 1,000 individuals, and we identified 15 bacteria that were strongly associated with good outcomes and with good diet. And at the same time, 15 instead of the opposite side.

So they were bad bugs, let's say. But now we expanded everything. And just before we move on, that was the paper that you then published in 2021 in Nature Medicine, right? Exactly. We'll put the links in the show notes if people want to see that.

And that was, I remember you saying, Nicola, that actually the biggest study in the world of gut microbiome and these sorts of health markers that had ever been done. Which to me seemed extraordinary. It was like, well, there's only a thousand people. And again, I think we talk about this a lot on the show. It gives you a sense of sort of how small historically most of these studies are because they're very expensive and there hasn't really been the funding. So that was sort of 2021.

Are we in the same place today? Well, in a couple of years, I think we made giant steps forward because it's at least 50,000 now tests and way more diverse from all viewpoints. And also in the meantime, thanks to this data and other data, we discovered many new microbes. Microbes that don't have a name because microbiologists never really cultivated them in the lab. So we have identifiers. We have some nicknames, let's say, that are not official

microbiological names because they don't exist. So just to make sure I've understood that, you are finding through your data these microbes that no one ever knew existed. They've never been grown outside of the human gut. They haven't got names on there. It's amazing. It's sort of like being an astronomer and suddenly discovering

that there are all these planets. Exactly. Instead of a new star, we discover a new genome, a genome of a bacterium which is so different from all the other bacteria that needs to have

a new species, needs to be a new species. And could have totally amazing new functions that we don't know about. So, you know, stars, you know, roughly what you know roughly what they do,

but this is actually more exciting because it's like discovering some totally new unknown factory that is producing a chemical. You've got no clue what it does. And the nuclear team are finding hundreds of these that weren't previously discovered. I love this idea that, you know, because I think sometimes you feel like

all the explorations got really hard, right? You know, my children are like, oh, I'd like to discover something new. And you're like, well, you know, people have been all over the world. They've been able to see everything. And here you're saying, well, actually inside your gut, you're literally just carrying around with you is this huge amount of undiscovered species. Indeed, two years ago, we were seeing only 50% of the microbiome because for 50% of our data,

we couldn't make any sense of. Amazing. So half the microbes, you had no idea. And now we are around 80% that we know. So only 20% of what we still call the microbial dark matter with a big name. So that's huge. The unknown has fallen from 50% to 20%. Yeah, exactly.

That's an enormous reduction. Exactly. And let's not forget that we haven't even discussed looking at the viruses and fungi, which are harder to look at. Viruses are fine. We're picking up a few parasites, which we'll probably talk about in another podcast, which are really exciting. But there's this whole world there that we're just uncovering.

And so just in a few years, we've managed to find another 30% of what previously unknown microbes. So incredibly exciting from a scientific perspective. If I'm listening to this, you know, somebody think about doing a test, you know, what does that mean for me? So at the end, it means that we move from 15 good bugs to 50 at least good bugs. 15 to 50? 15 to 50, yes. So we enlarge much more a number of bacteria that we really think are great for us and are associated with good food and good cardiometabolic health.

So this is the key. And have we done the same for the bad bugs as well? Exactly, 50 bad bugs there. Of course, we could have chosen 55 or 50, but more or less these represent. So a huge expansion in the number of specific types of bacteria that we can say, like these are actually associated with good health and these are associated with bad health. There is the one associated with coffee, for example. Coffee drinker, they always have much higher abundances of a certain bacterium. And is that bacterium associated with good health as

well? Partially, yes. So it's that within our 50 good bugs because it's not particularly good but is to pinpoint one single association and you may say you know coffee is a simple food well it still have a lot of it still has a lot of different fibers and there is one micro particularly good in in and so this is this example coming back to the, I just want to make sure that I've understood it, so coming back to the jungle, we all know, I think sort of from thinking a bit, you know, like the zoo or something, right? That all the different animals have to have different food. You can't feed the lion and the gorilla on the same food.

And so this is the same analogy here where you're saying this bacteria really loves the particular fibers that come from coffee and it sort of does a better job of eating them so you don't see it if you're not a coffee drinker you don't see it yeah it's like you know that's it so that's like if i'm not getting bananas like i can't even live i can't live off anything else so it only likes this fermented coffee bean that some people eat and others don't. So I think that's a really brilliant example of how specific our foods are and how important our food choices are to our health and are to us getting a diverse set of gut microbes that are really beneficial.

And this is why it's so interesting to understand which bacteria you have and the associations with food, because you should be able to end up therefore giving really specific advice to somebody saying, you know, here are the 15 gut booster foods specifically for you right now for the ones, you know, the good bugs are the low because you can really believe that over time we can get that tighter link. to link and that it's no good just eating one generically healthy food because it's a bit like your jungle example that you're, you're not never going to get that bacteria for the coffee. If you're not having any coffee, we're not saying everyone has to drink coffee. We're not changing the coffee habits here, but if you connect it with, uh, nuts and seeds or specific vegetables, for example, that is much more relevant. No.

And you believe this is real. So you believe that these individual bacteria are really linked to individual foods? Or groups of bacteria associated with groups of foods. And we are seeing that. And some of the changes that we also observe when we, as we were saying before, we retest someone in six months. So we see that there is association with eating more of a vegetable and increasing the bacterium that we

thought should have increased. And that's why there is this level of personalization in the diet that is aware of the composition of the microbiome, particularly regarding the 50 good and 50 bad bugs. So in the future, we're going to get really good at telling people exactly what they need to eat to improve these particular sets of microbes. We're doing, you know, an okay job at the moment, but it's going to be so much better as we get more and more data. who are still living sort of a traditional lifestyle, so not eating all of our processed food, not with modern sanitation. How does their gut microbiome score look? Yeah, we studied it quite a lot, and it's very different. It's very different. They have much more fiber-degrading bacteria,

complex fiber-degrading bacteria, and a microbiome that is really more unknown, the dark matter, the part that we cannot explain is bigger because it is less studied. And this is very interesting because we can see the differences with our microbiome. But another intriguing thing is that we went back in time also. So with some studies and some collaborators, we look at the microbiome of people of 5,000 years ago from mummies, actually. We sample the gut microbiome of mummies, these fossilized poisons that are called coprolites, and we can get microbiome profiles out of there.

And guess what? They are very similar to the current, what we call non-Westernized populations. And are these healthier microbiomes, these non-Westernized populations, Nicola? I would say generally, yes. But also in this case, we need to contextualize. So we need to understand why these differences are there, because it's not only diet, it's sanitation, for example. So we have to be careful with pathogens, of course. And how many different, just to get a sense, because I think Nicola is a good scientist.

I know it's always hard to pull you on this, but I think when you look at this on a slide, it's slightly terrifying and makes you feel like what you have is incredibly stunted compared to sort of what nature intended. We've lost a lot of microbes, haven't we? Yeah, we lost microbes. So people say up to a half, is that right? Probably, yes. So whatever differences you can see in our population, people eating completely different, vegans, let's say, and non-vegans, this difference is smaller than our difference with the non-Westernized populations. So I like to think like Tim is very proud of his microbiome, you know, it's really good. But, you know, that's comparing to people like me. And it's a bit, I think, I mean,

my analogy is a bit like, you know, you're really good at running because you're in your like your little village and you run around really fast. And then you arrive at the Olympics and you realize that these people are not 10 faster like twice as fast as you is this is sort of the analogy that i've understood is that yeah i think there are things that uh team cannot digest and uh other people in those population can probably do that i definitely wouldn't In a race with the hunter-gatherer tribes, I think my gut would lose. But I think for practical purposes, we're building a database for generally the Western world so that people know, importantly, they can judge what is the health of

their gut on a scale 0 to 10. Where do they sit? What is the room for improvement? And they can see the effect of illnesses, of changes in diet, of medications. All these things are going to be really important as we realize they're all interrelated. And so people have just ignored their gut health because we haven't had a good test of it. But it's a bit like having tests when you take drugs, for example. Many of the medications people take, like proton pump inhibitors for acid reflux or even things like antidepressants or painkillers, can have effect on your gut microbes that could be adverse. So having a check every six months of how that particular bit of your body is like having a blood test to see what your liver is doing in response to these drugs.

So I think we're going to see this much more as a routine test that everyone's going to want and gives them a goal to aim at to say, okay, like you did, like, you know, I'm going to, you started at five out of 10. I want to, I want to get up towards seven or eight out of 10 over the next couple of years. It's like trying to control blood pressure that you couldn't measure it. You just roughly say, okay, hopefully no one will die of a stroke. But suddenly, we've got this intermediate measure, which I think everyone can start to use. And as more people do it, the price will come down and it will become commonplace. We'll realize it's actually much better than doing a blood test

just for your baseline cholesterol or these things that we routinely do in our health service that actually have rather little use compared to these major insights. So some people will be listening to this and saying, you know, that's really great, but, you know, I can't get this for free from my health service today. I can't afford to buy this product today. And so therefore I'm obviously not going to get sort of this personalized advice, but I think the good news is we don't have to say, well, there's nothing you can do. Could we talk about like, what's the actionable advice you would give to somebody listening to this saying, I'd really love to improve my good bugs. I'd really love to shrink my bad bugs. You know, what's the key advice that you would give both of you?

Well, I've got five simple rules really to improve your gut health, which I've talked about before, but it's good just to remember them. First, try and eat a diverse range of whole plants. And we think at the moment, the optimum is around 30 plants. We're doing some other studies to see if that's still true now with these new tests. But 30 different plants a week is what people should aim for. Not a problem if you don't always make it,

but aim to get it right up. Currently, people have about five on average, right? So there's a long way to go. Second is eat the rainbow, try and eat colorful plants because of the polyphenols, these defense chemicals in them, which our microbes eat and is a source of energy, which we didn't know that before. And that includes all kinds of bitter foods as well. Extra virgin olive oil, for example, nuts, seeds, dark chocolate, and our coffee we mentioned.

Then fermented foods. We haven't really talked about that. That's another podcast, I think, but having regular small amounts regularly of fermented foods has been shown to improve your gut microbes and improve your immune function. So it dampens down those inflammatory microbes. And fourthly, give your gut a break. We've talked about time-restricted eating. If you can eat within a 10-hour window or if you can't do that, a 12-hour window at least, you give your microbes a rest overnight. That helps them. They make them more efficient.

And finally, don't poison them with too many chemicals from ultra-processed foods, because ultra-processed foods have a negative impact on your gut microbe in ways we're still understanding, but things like sweeteners, emulsifiers, preservatives, etc., etc. So, they're my five rules. And, of course, there are other ways, you know, the't there of course yeah these are the great general rules no but i think in addition the challenge is to understand what it personalizes to you and that that is what we are trying to get from the data because maybe for you the best is 30 for some 30 different uh you know vegetables for others maybe 20 or 40. So that is the personalized part of it that can add a big added value to that. And can I wrap up with a couple? We had a lot of questions from the community. I think we've managed to answer some of them. I want to pick a couple that we haven't

hit here that were specific. So I've got both of you, which is rather special to have you physically in the room here. So one question was like, how rapidly can I damage my microbiome? And we had a lot of questions saying like, I've gone on holiday. I've eaten really terrible food for a week. Lots of all the things that Tim tells me I shouldn't done. You know, have I wrecked my microbiome? Will my bad microbes have doubled during this period in a week? Like how worried should people be?

Well, I think you should be very worried if you go on holiday and then you get sick and you have to take antibiotics, for example. That will ruin, you know, the most of it. Otherwise, I think, you know, we all go on holidays and we need to eat differently. So it's not a huge problem if it is for a week or so because there is these

dynamics of the microbiome you can then go back and i think in general if you travel on holidays and you have a diversity of food wherever you are it's also going to improve so i think there is this memory of the microbiome that unless you continue with antibiotics or very bad food for a long time, it's unlikely you will disrupt it completely. The caveat might be if you go on a junk food holiday and you only eat junk food for, say, like 10 days, and you have zero fiber, no diversity, having the same meal. And this is the experiment I put my son through a few years back when he was a student.

So for 10 days, he had only chicken nuggets or a Big Mac and Coca-Cola, and he lost 30 or 40% of his diversity in that time. And I'm afraid to say still hasn't regained it. So the caveat is, don't go on a purely junk food, zero fiber holiday because your micros may take much longer to recover. And my takeaway from this is, and it's one of the things I think that you and Sarah and other people talk a lot about at Zoe is like, it's fine to have treats. It's fine to add some stuff on top. So in the sense in the holiday, by all means, have your pizza and your ice cream, but you'd like to make sure you're still having some food through this that's going to sort of

support your microbiome. Because it sort of makes sense, right? If you starve them for 10 days and they all, they like reproduce very fast, right? Nicola, it's like once an hour or something like this, right? You can see that's a lot of generations with no food, which I guess I sort of think of as, well, that's quite different, right? Than saying, okay, I'm going to give a lot of stuff that's maybe good for my bad microbes, but I am still providing some food for the good guys and we'll get them back after the holiday. Is that a sort of practical way to, that's like be my practical approach to holiday now? Yeah. Give them a minimum diet. But in a way for people should be relaxed. If you've got

a healthy gut microbiome, you can afford more leeway than someone who's got a really sick microbiome. And I think that's the key. If you've built up your gut microbes well, you can have the odd excursion with junk food and you'll bounce back. But if you've got a really poor one and you go overboard, then you're really in trouble. And I think the funny thing is that I also found my tastes have changed a lot. I still definitely want gelato. That comes up quite often on these podcasts. But there's a lot of junk food that I used to eat that actually now sort of seems quite disgusting. Having switched away from it for a prolonged period, you realize you sort of got addicted to this stuff.

And I know we'll talk about that on another podcast. Final question, because this came up interesting. It was like the top question. Is there any data about whether taking painkillers regularly can negatively impact the gut microbiome? Well, we know, as Tim mentioned, probably the two main worse medications are proton pipe inhibitors and antibiotics. But all the others are not positive for the microbiome for sure. So I don't think we have a lot of data from Zoe on painkillers, but also from other studies we see they are not good for sure. Not at the level of antibiotics and proton pipe inhibitors,

but definitely something to keep an eye on. For painkillers, we know that they've studied paracetamol quite well, and we know that the reason they don't work in some people is just because they don't have the right microbes. So it's quite possible that some of these side effects people might get might also be related to the gut microbes. We simply don't know enough, but we do know that at least 50% of all the drugs people take are interacting with your gut microbes in some way, and we have to be a bit cautious that all of them could be doing damage or interacting in some way. So it's an area we need to do much more research on.

But the example I did was just because there are very few examples that are documented. So with the variety of drugs that we can take and the rest of our microbiome, it's another line of research that should keep us busy. I think, Nicola, you feel like your career is set for the rest of your years, I feel. I still have a bit of work to do, yes. Yeah, absolutely. And, you know, we did some work on cancer therapies and immunotherapy. And certainly the state of your gut microbes is probably the number one factor that determines whether you're going to respond to immunotherapy and cancer.

And so increasingly, I think this, you know, when people are put on drugs, physicians are going to have to learn more about the gut microbiome and take that into account as we start to balance these things up. Because it really, in some cases, is a matter of life and death. Yeah. Tim and Nicola, I could keep going for hours, but I know I need to wrap up. Thank you very much. I'm going to try and do a quick summary of what we covered. So then we started with this wonderful analogy that the gut microbiome is like a jungle and you've got all of these different species that are interacting with each other. And then this latest information that our microbiomes are even more different than we had realized a few years ago, because it's not just that they look really different at the species, but when you get down to the exact strains, so the exact type of animal,

almost everybody is completely unique. We then talked a bit about how the microbiome changes. And I think the consensus was you can see these very swift changes in just a few days. But in general, if you're trying to make a sort of long-term improvement in health, so making it much better, probably you'd expect to see that in four to six months. But the data is still quite early. And there's going to be some exciting new stuff published. And then hopefully continuing to get it better steadily then over years.

We talked a bit about how microbiome testing actually works and why the latest science and what Zoe's doing is with this shotgun sequencing, the incredible complexity of trying to piece together what's going on and the way that just in the last couple of years, we've gone from only understanding 50% of the microbes to, I think you said, about 80% of the microbes today, which still means there's another 20% that we have no idea what they are. And as a result of this and the scale of the data, and this is, I think, where Zoe's research has really been able to be at the forefront of scientific research, which is really fun, that with now sort of 50,000 of these test results, you've been able to move to now discovering sort of 50 of these good bugs linked to good health, 50 of these bad bugs linked to poor health, and able to create a sort of score that allows you to understand that in the same way that we might get a blood sugar

score or a cholesterol score, that we're starting to understand the links with individual foods. And you gave this brilliant analogy that you can tell whether or not I drink coffee just by looking at my poop. And it's not because you're looking for coffee grains, it's because you're looking for a microbe that you will only find if you're eating coffee. And the belief is that there are these sets of microbes that are linked to all sorts of specific foods. So over time, you know, you'll really understand that, you know, you're not eating particular sorts of beans or cabbages or whatever it is. And that could really help you to get back towards the healthier gut, which it sounds like the really healthy gut is these people living a non-Western lifestyle.

But for normal people, I think we all aim to have Tim's gut. That's like my ambitious level. And, you know, I think we all aim to have Tim's gut. That's like my ambitious level and what are the things you need to do. And then I think we wrapped up with some key advice if you're listening about what you could do. And Tim sort of pushed this down to this really simple rules of eat 30 diverse whole plants, try and eat the rainbows, lots of different colors and bitterness, fermented foods, which is something I think we will definitely come back to in the future, restricting the amount of time you're eating. So at least 12 hours where you're not eating. And lastly, avoiding these ultra processed foods. And I think we had this rather terrifying story

from Tim about how he, for some reason, got his son rather than himself to eat Kentucky fried chicken for 10 days. And apparently that wiped out 30% of his micro- McDonald's. We don't know. McDonald's, I'm sorry. I don't want to be sued by Kentucky fried chicken. McDonald's, I'm sorry. Because that's obviously much better to be sued by McDonald's. For 10 days and lost 30% of that diversity. And I think you said that was 10 years ago? Getting on for that nearly, yeah. And it still hasn't all come back.

Yeah. So slightly scary there. But the good news is you can enjoy yourself on holiday. Just make sure you're still providing that core nutrition to all of these microbes and think about the ice cream on top rather than just swapping it all out. And so it's not that you can never eat any of these things, but you've got to make sure you're supporting the microbes. You got it. Nailed it all out. And, you know, so it's not that you can never eat any of these things, but you've got to make sure you're supporting the microbes. You got it. Nailed it. Amazing. Thank you both. And I think we are definitely going to come back to a bunch of

these topics. And I think we're also going to record some more in-depth material for some of the Zoe members to go in and talk in more detail about some of these new discoveries and how we can deliver them. Thank you. Great. Fantastic job, Jonathan, as always. He's being very cynical now. Thanks, both of you. Bye-bye. Thank you, Nicola and Tim, for joining me on Zoe Science and Nutrition today.

If you want to understand the health of your gut microbiome and access tools to improve your gut health, then why not try Zoe's personalized nutrition program? You can learn more and get 10% off by going to zoe.com slash podcast. As always, I'm your host, Jonathan Wall. Zoe Science and Nutrition is produced by Yela Hewins-Martin, Richard Willen, and Tilly Fulford. See you next time.