Microbiome Medics

Microbiome Science for the Future: A Discussion with Dr. Jack Gilbert

• Konijn Podcasts • Season 1 • Episode 24

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In this episode of Microbiome Medics, host Sheena welcomes microbiome science celebrity Dr. Jack Gilbert about his journey from butterfly ecologist to a leading figure in microbiome research. They explore the American Gut Project's goal of understanding microbiome diversity, the Nutrition Precision Health Program’s focus on linking nutrition to health outcomes, and the clinical implications of microbiome data in patient care. Jack highlights the potential of pharmacomicrobiomics and discusses advancements in linking the microbiome to mental health. He also introduces his co-authored book, “Dirt is Good,” aimed at helping parents support their children's microbiomes. This conversation offers a compelling look at the future of microbiome science and its impact on health.

This podcast is brought to you in collaboration with the British Society of Lifestyle Medicine.

Disclaimer:
The content in this podcast is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your doctor or qualified healthcare provider. Never disregard professional medical advice or delay in seeking it because of something you have heard on this podcast.

Sheena:

Right, hello and welcome to a Microbiomedics podcast. Today I am joined by Jack Gilbert. Now Jack Gilbert is a bit of a celebrity in the field of microbiome science. He has been involved in some of the biggest microbiome projects the world has seen, starting with the American Gut Project and the Earth Microbiome Project. And now he's moving on to translation of microbiome science into the clinical world. So welcome, Jack. Thanks for coming on the podcast.

Jack Gilbert:

My pleasure. Thanks, Sheena.

Sheena:

So, Jack, I just want to give the listeners a little idea of the scope of your work. So can you just give a little brief introduction as to where you started, what you started doing and where you've come to now, just so the listeners can understand a little bit more about your work?

Jack Gilbert:

Yeah, I mean, it's a complicated situation. I started out as a butterfly ecologist, working in the Natural History Museum in London. But I got tired of butterflies and wanted to work on something more complicated, so I became a microbiologist, and then I became a protein chemist. And then, I don't know what I do now, but a little bit of everything. So I guess I got into microbes about 20 years ago, 25 years ago, and I've followed them around the world, trying to understand how they work, how they talk to each other and how they communicate with the rest of the ecosystem around them. Microbes are amazing, right? They are the oldest form of life and they are the most adaptable, the most flexible. So it's given me, I guess, carte blanche to work in any environment, any ecosystem, whether it's human health or environmental health and to visit pretty much everywhere on earth as well which is um which is a fantastic privilege.

Sheena:

And you started off in the uk um you did your schooling and your university in the uk is that right.

Jack Gilbert:

Yeah so i got my undergraduate at king's um and then i went to i did a phd after i worked at natural history museum i did a phd at um at nottingham university working with the company unilever and yet she sent me down to antarctica to find bacteria that produce proteins that stop ice crystals from growing in food which was fun so it was there for like 18 months.

Sheena:

Okay. All right. And then you've moved to the States. So you're in San Diego now?

Jack Gilbert:

Yes. I was at University of Chicago for 10 years. And then in 2019, we moved here to UCSD.

Sheena:

Fantastic. Fantastic. So tell me, how did you get involved? Because I don't know if our listeners know about the American Gut Project. We've talked to them about the British Gut Project in the past. Um so how did you get involved in the american gut project.

Jack Gilbert:

Also myself and my colleague rob knight um we wanted to do something which would enable people to um well we had to do two thoughts about this the first thought was we wanted a really really big database so we can understand how the microbiome varied between people um so this is 2010 um i just moved over from the uk we just launched the earth microbiome project and we just basically wanted to do the earth microbiome project but for human beings and so we uh we started that out as a as a um on a fundraising website managed to raise close to three hundred thousand dollars or three hundred fifty thousand dollars quite a lot of money at the time to to get people their microbiome samples so we launched that and we expanded it we got australian gut and we started british gut um and you know in, because i am british and and uh and new zealand gut so because uh rob's uh kiwi and we basically went around the world saying you know who wants to help launch these programs and run these programs. So that was the idea the idea was to give people the opportunity to get some data but more importantly to build a database that we could use to contextualize all of our studies so if i did a analysis in you know 10 people looking at how the microbiome associates with colorectal cancer i can now compare that small study to a study with 20 or 30 000 people in it right and understand how the microbiome profiles i see in my small study relate to a much bigger population which is the reason we started british gut british gut was um we brought tim specter on um uh back in about 2012 and said you know let's let's work together to to launch this program and then he took it and uh took the data and weaponized it into zoe which is fantastic yeah.

Sheena:

And now the you were saying the american gut project has now become zoe in america as well.

Jack Gilbert:

No no no no or is it just in britain we didn't commercialize it it's now called the micro setter initiative as in the rosetta stone for microbiology micro setter and the micro setter initiative is run out of the Center for Microbiome Innovation here at University of California, San Diego, and it still is, it's a citizen science program, so people still chip in a small amount of money to get their microbiome sequenced and contribute to this ever-growing database that we have. But yeah, we weren't maybe as industry savvy as Tim was.

Sheena:

Tim, yeah, yeah, yeah.

Jack Gilbert:

Tim's great in the fact that he's still embedded in running clinical trials and supporting the evidence-based research for this. So I'm really proud of what he's been able to achieve.

Sheena:

Yeah, he has managed to achieve some amazing studies with his PREDICT studies and things. And what about the American Gut Project? so what were your main findings with it.

Jack Gilbert:

Well it's it's complicated every time you do a survey asking what the main findings are is always difficult right we said the same for the earth microbiome project what did you actually find you sequenced hundred thousand samples what did you figure out we figured out well the world's diverse you know it's complicated um but you know what was really important about the american gut project was it did create uh for the first time a large database of people, right? And that hadn't really been done. Obviously, Flemish gut came up shortly after that in the Netherlands. And there were other studies that were pushing it forward. But we had, you know, 20,000, 30,000 stool samples that had been sequenced. And we could compare that to patient-reported information or participant-reported information. So for us, it was an opportunity to see how the microbiome varied in a very large population. And we showed it varied. Geographically, based upon diet, based upon age, we could say things that were associated. But more importantly, it gave us a bit of a clue into how... The microbes and the metabolites they generate varied in these kind of scale populations and what association that might have with lifestyle and with health and disease. So, you know, nearly everybody was healthy, but people had conditions and reported those and we were able to associate those. And that led to a lot of clinical studies, including our Nutrition Precision Health Program that we run with the NIH which is a big effort to try and understand some of the associated trends with health and disease with nutrition that we saw in the American Gut Project and the British Gut Project and relay them in a much bigger population with more detail.

Sheena:

Okay and how long have you been doing the nutrition project for now?

Jack Gilbert:

We're at our just end of our third year entering into our fourth year now so it's a it's a 10,000 people being clinically recruited into a hospital. And then we keep them in the hospital, any of them, and put them through very, very prescribed diets and record everything that goes on in their lives over this period of time. So not just blood sugar and things like that, but we know everything about their muscle tissue, the chemical composition of the urine, of their blood, of their skin, of their saliva, of their hair you know and we know how they are physiologically and metabolically responding to the types of foods that we provide them and then we have the microbiome sprinkled on top of that to create some fun.

Sheena:

It's really interesting. And that's done in a hospital environment.

Jack Gilbert:

Yep. So we have people recruited. Majority of them are in the hospital providing the information. There is also a secondary cohort where they're doing this at home. So we can understand. They do the clinical practice, but they do it at home. So we can understand if where people are receiving their food has an impact upon their physiological response.

Sheena:

And that's good, because I remember reading a study once that was talking about how your microbiome changes when you enter a hospital environment. Of course, most people entering that hospital environment aren't very well. So, of course, you know, there's a whole lot of other variables like drugs and, you know, just the stress and all the rest of it when they're not well. But yeah, that's really interesting. So when are you going to publish results from this? Or are you already publishing?

Jack Gilbert:

No, no, no, nowhere near it yet. We're still in recruiting. We'll probably get a few papers out in 2025 on some of the preliminary data. It's a very complicated date. It's associated with the All of Us program, which is one million human genomes in the United States that's been going for about the last eight years. So we'll see. You know, like what Zoe's done with the PREDICT studies, which are individual people providing information. We're more driven now towards trying to do this in a clinical setting and drive clinical translational practice. So it takes longer to do that. It's not just a citizen science study that we can publish like we did with American gut and British gut. It's more of an opportunity to drive precision health in a translational setting like a hospital which takes a lot longer to get done properly.

Sheena:

Wow okay all right that's fantastic so I mean you've been involved in a whole lot of different areas of research with with your microbiome research because you've got the nutritional side obviously the earth ecology and and just mapping the the American gut what other projects have you been involved in because I remember when we met we were at a meeting a royal society meeting and And you were talking about your involvement in the testing of microbiomes and looking at the actual devices that people are using to test their microbiomes in a home environment and things. You're still involved in that?

Jack Gilbert:

Well, so yeah, so I've launched companies in order to solve problems that I have in clinical settings. Um what you're referring to is something called the gut lab um and the gut lab is a device which sits in a patient's or a participant's or a human's bathroom and um allows them to uh collect a stool sample and hand process it immediately there on site so it's it's an entire molecular laboratory in a in a box that sits in your bathroom battery operated cleans itself and so you can you can collect stool samples from a participant going through a clinical trial in a very very easy way it's very very reproducible it's incredibly significantly cheaper and is a lot easier for the patient to to do um because they don't have to poop into a hat and scoop their poop out into a tube and and do all the kind of gross stuff that most people don't want to interact with so it's um it's a it's a it's a i wanted that tool so i formed a company to make that tool um and i think that's that kind of translational impact has been really important for us, you know i work in so many different we have 53 ongoing research programs at the moment across the multiple labs that are run wow everything from depression and mental health to women's health to understanding cancer risk and trying to suppress cancer recurrence and metastasis to skin health and everywhere in between.

Sheena:

Wow, that's impressive stuff. Okay, all right. So we're not going to be able to go into all of these areas. Obviously, that's too big a podcast. I think we were going to talk a little bit more about precision microbiomes and how we translate all of this science into the sort of clinical setting. As a GP that's really interesting to me because I feel like we know enough now that we should be acting on some of this knowledge in the clinical setting but I feel like so few of my colleagues know anything about microbiomes and how to use that information so tell me more about what you see as precision microbiome.

Jack Gilbert:

Yeah so there's two pieces here if I took your stool sample right now, there's a very limited number of things that I could clean from just that one stool sample, right? I might be able to predict based upon the data we have from American Gut, British Gut, and you know, companies like Zoe and Day2, that the, that you have a microbiome that may be associated with say your blood glucose or lipid levels. And we might be able to predict a meal plan that would reduce the variation in your blood glucose levels and potentially help to reduce bad triglyceride signatures and that kind of thing right that's pretty much where we're at and there's only the other examples are usually the pre-clinical or early clinical phase trial area, right? There's only two FDA, Food and Drug Administration over here in the United States, FDA-approved clinical therapeutics using microbiome. They're both for recurrent clostridial disease difficile infection. So we're still at an early stage. We've only been doing this for 15 years, right? Maybe 20 on the outside, it takes a long time. You think about genetic diseases and genetic treatments, that's taken 50 to 60 years, right? So we are a young scientific field. So getting into clinics is hard, but it's not impossible. So what we've been trying to focus on are strategies that would allow a GP like yourself to be able to interact with the data that's generated from a patient in the whole data ecosystem for that person. So imagine, you know, a chat GPT or a large language model kind of interaction that you could then ask simple questions of. If you have a total data ecosystem, you know everything about that patient's health history, you know their current blood work, you know their heart rate, you know their BMI, you know their weight gain and loss over time, and you know about their microbiome, you could ask a very simple question. Should I prescribe this type of medication based upon this individual's history, this individual's social construct, this individual's ethnicity? How can I use the information that's being provided in an effective way to help GPs make more effective decisions and faster decisions that are more accurate? So that's where we're driving this precision healthcare system to. The gut microbiome is a piece of that story, but it's not the holy grail. If I sequence your gut microbiome I'm not going to be able to tell you everything about you it's just one extra piece of information that could empower a GP or a person an individual to make more effective decisions about their health journey.

Sheena:

And I suppose you're looking for specific markers of diseases so things like you know specific microorganisms that are associated with certain diseases or ones that actually might be beneficial if you have a certain disease. So is that the sort of thing that you're trying to find at the moment?

Jack Gilbert:

Yeah, so 95% of it will be, you have signatures of your gut microbiome which are not necessarily healthy, might be producing too much hydrogen sulfide or too much LPS, lipopolysaccharides. These gut bacteria are potentially causing inflammation. and then 90% of it's going to be eat healthier, right? Here's a diet and it has more fiber, it has more polyphenols, more fermented foods. Eat it and everything will get better, right? We're finding it to be a lot more complex than that, but that's essentially where we're at still. Where we want to be is, for example, we've identified a microbial enzyme. An enzyme is a protein that does something in the side of the body, we found a microbial enzyme that when it's present will increase your chances of having a recurrence of colorectal cancer after we've surgically removed your tumor by almost two to three orders of magnitude. So that's what we want, because now I can say to, I can screen a patient and say, if we perform this colorectomy to remove your tumor, you have a very, very high likelihood of having a recurrence. Great. What can we do about that? Beautiful thing about the microbiome is it's modifiable. So once we've got a biomarker that tells us that person is at risk, then we can modify it. And the way we modify it best is through diet or antibiotics. So we can either try and kill that bug off. Turns out that doesn't work in this particular example because it's an ecosystem and other organisms have this same enzyme and they continuously replenish the problem. Or you can modify it with food. So I can give you a high fiber diet for a week before surgery, prescribed and paid for by the government or the health care plan. And your chances of getting recurrence will drop by three orders of magnitude, which is exactly what you want. You want people to be cancer-free after that surgery. So that's a great example of what we're trying to do. We're trying to identify the mechanism of action. We're trying to identify the biomarker so we can predict health risks or treatment outcomes. And we are desperately trying to figure out a way of modifying that problem so that the issue goes away.

Sheena:

Which is fascinating for all those scientists and all those consultants out there that need to have those markers. But having you know managed a patient um in the last few years who was um who had had two primary bowel cancers um and she was post chemotherapy for her second primary bowel cancer she um changed her diet quite radically um with my help um and she moved from her relatively high red meat kind of high um i think she used to barbecue a lot she's from south africa um and and she had a lot of processed food in her diet and not very much whole food and managed to get her to change her diet um start cooking from scratch really upping her plants in her diet um and a year later from this diet change she had her follow-up colonoscopy and she'd had hundreds of polyps in her gut prior to this colonoscopy and this colonoscopy showed that there were no polyps left. So they'd all gone with the high-fibre diet. Now, that was over five years ago, and she's still free from cancer and free from polyps. So she's managed to maintain that diet. I wonder whether we have enough knowledge now, as you say, most of the solutions are, in fact, diet-based, to say to people, well, do you know what? We know that diet is probably going to be part of the solution here. So why don't we just get in now with diet change for a lot of people's diseases while we're waiting for these biomarkers and all this other expertise to come? Can't we be moving now? What do you think?

Jack Gilbert:

We are. I mean, food is medicine is the primary driver behind 90% of our responses, both commercially and clinically, to microbiome solutions. Um you know as i said at the beginning our primary response if you see a negative microbiome signature is to say eat more fiber and more polyphenols and and consume more fermented food so that's that's an adage that's this is an easy thing to do right and people should be doing that now you should be eating healthier but there's a problem with that the issue is that your particular person is obviously highly motivated to do that but i like to tell the story um uh people get peripheral limb ischemia this is where your blood vessels and if you have diabetes the blood vessels in your periphery your hands your feet can become diseased right they can they can get infected by bacteria and that can lead to gangrene and it can lead to having an amputation right um so we had people coming into clinic um who were pre-ischemic they they they didn't quite have these infections yet but they were really close and we knew within six months we'd be bringing this person in to have an amputation that's a highly motivated group we could only get 30 of them to change their diet to reduce their risk. People are wedded socially to food and in your south african version we're dealing with built on we're dealing with bulwarks we're dealing with stockies you know these are these are very very good lovely yummy yummy yummy foods and they they also might be poisoning us right but there is a social dynamic associated with food we we have a holiday celebration that's predominantly focused on food about to come up next week. How do you take that out of the equation? And so social science is a really key precept here. How do we alter somebody's social intentionality around their diet? I can eat a horse to water, but I can't make a drink necessarily. So I need to be able to figure out better ways of providing people with an active dietary program to support their gastrointestinal health, metabolic health, endocrinological health, and immune health. And that is not an easy solution. We run dietary intervention studies all the time, including in people with familial polyposis syndrome, which it sounds like your patient had. And we still get not everybody sticking to the diet, even when we buy the food for them. A great example of this is, if you have children and I provide you a particular diet plan, what are you going to do? Just eat that yourself and then cook food for your kids that's completely separate? That adds a huge social pressure onto you. We have to find better ways of making people access, having better access to that food.

Sheena:

Yeah. And although some of that might be helped by your clinician actually having good coaching skills, because there's a big difference between your success rates if you just do a brief intervention, which is what the majority of doctors would do in this kind of situation when you want to affect change. And then using proper coaching skills that would involve taking a little bit more time with that patient to try to encourage change. Um and there's definitely more success with the latter um and and that i think is one of the reasons why you know medics are generally not as successful with with lifestyle change um and of course the british society of lifestyle medicine the american society of lifestyle medicine are trying to change that uh by making sure that more doctors are you know skilled in coaching techniques and able to help their patients in this way. And I think that's part of the solution. But the other part of the solution is the food climate out there. Some people live in areas where there aren't any good food choices. And you're living in America and where about 70% of the American diet is ultra-processed. It's actually really hard to avoid processed foods in America. I remember going over to Boston and New England And after several days of typical American food, I actually felt so ill with it, I started going to Whole Foods. And we basically ate all of our meals out of Whole Foods because I was so sick of the restaurants and things.

Jack Gilbert:

I have patients who their primary grocery store is a 7-Eleven. I mean, that's the food they have access to.

Sheena:

There's nothing in there, nothing fresh.

Jack Gilbert:

No, it's nothing. It's all processed. And it's not healthy, 100%. I mean, this is almost de rigueur now. We all, hopefully, everybody knows that eating those things is not great. In the UK, you've had a much easier time of it, I think, in terms of changing the cultural phenotype around food. I know from my relatives that still live there, a lot of them have a much better understanding of nutrition um and a much clearer understanding of what they should eat even if they don't always do the right thing they know what they should eat over here yeah the education system and the health care system is fundamentally different and is fundamentally flawed um to support these kinds of preemptive food is medicine and accessibility problems we we need to change it That's a given. How we do that and how we do that in an equitable and accessible way is an unsolved issue for a country this complicated, this divided and this big.

Sheena:

Yeah. And what does the American gut look like, the average American gut?

Jack Gilbert:

You know, that's a complicated question. I can answer it in two ways. If we compare it to other people, it is a lower diversity, less species present, and generally associated with lower fermentation pathways. So the bugs that are there are less likely to be able to use complex carbohydrates in our diet, like plant fibers, than, say, a gut microbiome from somebody living in rural Ghana or even parts of Europe. So from that perspective, it's a multi-generational insult practice, antibiotics. Different birthing strategies, constant processed food for the last hundred years, that has led us to have a microbiome which is less able to provide the health benefits that our body has evolved to depend upon from our gut microbiome. Um it's uh it's it's a problem there's a great example bifidobacterium longum infantis this this uh bifidobacterial organism is uh is ideally evolved to consume all of the complex sugars in mother's breast milk that's i mean it's it's almost tailor-made for it it evolved explicitly to deal with mammalian milk and our particular subspecies has dealt is evolved to deal purely with mother's milk in humans. That's an incredible evolutionary advantage, and it provides massive health benefits for the baby. It's missing from 60% of women growing and children in America. They do not have it in their gut, and the babies do not have it in their gut. So babies often have sloppy stools, right? There's the diaper, or nappy. The poop is generally quite sloppy, which is not normal. It should be fermented and it should be quite a chunky fecal mass. But we don't have that because we've intergenerationally lost those bacteria that provide that health benefit. And that's improperly.

Sheena:

Yeah, it is. And that's been lost because of birthing techniques and loss of breastfeeding, do you think?

Jack Gilbert:

Among many things, as I say, antibiotics, problems with processed food, just eradicating these bugs. If they do not have the nutrients, then they can't survive. And if, you know, mother takes antibiotics, they might wipe that out so it's not transferred to the baby. But yeah, you know, if you don't breastfeed, this bug does not have its food source. So it cannot survive.

Sheena:

It's concerning. And yet you can actually buy that as a supplement, Bifidobacterium infantalis, can't you? So that is available as a supplement for infants. Is that something you would recommend for babies who are not being breastfed or have had C-sections or perhaps even just mothers that are worried that they might not be giving their child this?

Jack Gilbert:

I mean, the bug in itself is pretty much useless unless it's also being fed the breast milk. So it's a two-stage problem, right? If you can get human milk into the baby, and then you add in Bifidobacterium lungum infantis, there are a little over 45 double-blind placebo-controlled randomized clinical studies which have demonstrated that it can be highly efficacious in supporting immune health and also physical and physiological development of an infant to add this back in. But you need the breast milk as well.

Sheena:

You need the HMOs, the human milk oligosaccharides.

Jack Gilbert:

Precisely. It can be breast milk from a donor. That's a very important part of it. This bug only eats those human milk oligosaccharides. It needs it. So if it's not there, you're just adding another probiotic into the system, which really all the probiotics do the health benefit from the vast, vast majority of probiotics is stimulate our immune system. Our body got used to eating fermented foods, right? Our immune system got used to seeing these foreign organisms coming into our body. And so it positively responds immune health-wise to the presence of those bugs. That's really all those probiotics are. It's just unfortunate the vast majority of probiotics are pretty undiverse. You really need more complex probiotics that have a lot more diversity so they can stimulate the immune system in different ways. And that will support improvement in health.

Sheena:

So taking a whole ecosystem rather than which is f which is fmt or you know uh.

Jack Gilbert:

Well yeah that's a fecal transplant but you know fermented foods right why why can't we just go back to eating more fermented foods and i see i see that um when i do return to england i see it more commonly in the shelf and i you know i'll say that uh tim specter's probably had a significant role in helping people to understand that i think if he has any public service um award it should be around getting people to consume more fermented foods because that's a natural probiotic.

Sheena:

It is indeed. I should mention here that you've actually got quite a lovely book that you and Rob Knight wrote together called Dirt is Good. Actually, I've been reading that the last few weeks. It's a great book, sort of question-answer format all the way through, just trying to answer all the questions around microbiome science that you might sort of be encountering as you're bringing up children. And I think it's lovely in that way because being a parent's really tough. And I've got three kids, so I know. And you don't get it all right. And there's so many things that I think you can do to really enhance children's microbial balance as they age. And that's a brilliant book to help you along the ride. So, yeah, what was your main motivation for that book?

Jack Gilbert:

A lot of it was sanity. So giving microbiome lectures around the world to the public and to other scientists, we just got an inordinately large number of questions. People are desperate out there for solutions, right? Modern healthcare is not providing them with a lot of the solutions that they want or a lot of the information that they crave. And so when you're pretending with something as seemingly simple to engage with, like the microbiome and diet, people get excited about it. So every single lecture I gave, I'd get bombarded after the lecture by questions. I once gave a lecture at the planetarium in New York, and I was held up for three and a half hours after the lecture with this group of 200, 300 people just queuing up to ask questions. And I was like, this is bad for my mental health, so I need to write all these questions into a book and answer them so people can access it I would say I've probably been asked more questions than copies of the book I've ever sold but that's it that's irrelevant right at least now if somebody has questions they they can go and answer they can go have them answered by this this book but it's a it's yeah that was the motivation to give people access to the real knowledge now we need to build it into a chat gpt format so that people can ask simple questions and the information they're provided is accurate based upon the current understanding of the field um so people don't have to be able to read scientific papers they can access that information more effectively we are working on on that kind of structure right so a website where people can actually ask sensible or you know or insensible questions about their health, about their children's health, and then get the right kind of answers back using large language models to predict it.

Sheena:

Um and is that successful so far because i've heard that with um the ai um projects ai can start to make things up after a little bit of time.

Jack Gilbert:

Hallucination is real absolutely yeah so i you know you can you can tweak large language models to be more or less hallucinogenic um but more importantly the information the database the knowledge base that it is calling upon is really important so you can turn off its ability to hallucinate which makes it kind of boring to talk to but um with the right database at the back end it can intuit um connect its knowledge from that knowledge base and provide that back to participants um it's very very much in the developmental phase at the moment but it's something we are extremely keen to do so people can have a better precision health for themselves yeah.

Sheena:

I think that would be really useful um i think one of the main problems i see at the moment is that um medics are generally quite interested in this field but it's daunting for them i mean if they were to pick up uh an article on anything microbiome related there's a whole load of terminology there's a whole load of um, just, you know, even the examination techniques, even the investigative techniques that you're using in microbiome science will be quite alien to a lot of clinicians. And, you know, that's why Siobhan and I have written a course on microbiome science for clinicians, but not everybody wants to sit and, you know, do a lengthy course. So it is a bit of a barrier at the moment in terms of getting that knowledge base to our day-to-day practitioners um do you have any solutions any ideas on how we fix this.

Jack Gilbert:

I mean as you said you have to understand it from a physician's or a clinician's perspective right how can they access how can they get access to this information and use it in the clinic and a lot of that is ensuring that the right information is provided to them and then they have the right solutions to apply from that knowledge so just like a participant a physician needs a chat gpt kind of interactive capability to facilitate them being able to integrate this knowledge into their practice i do not need clinicians becoming microbiome experts that you know as you found out that's just number one not possible and number two not useful what we need is people to be able to use that information in their clinical practice most most clinicians are not experts on blood chemistry. Most clinicians are not experts on MRI signatures, right? We allow people to be able to access the data coming out of those particular tests in a way that enables them to make decisions. That's the reason we're trying to push for more effective translation into clinical practice. We need these technologies to be embedded in the culture of patient care. Not teaching people to be excellent people. What you're doing is actually very good, by the way. You're enabling people to... Understand the importance through your course to understand the importance of this new science but the only way it will become deployable is by integrating it into the culture and the practice of healthcare and that that it requires them not necessarily being experts but understanding it as yet another tool in their toolbox to treat a patient.

Sheena:

Yeah so we've got a bit of a way to go with all of this.

Jack Gilbert:

Um um.

Sheena:

So how do you see things over the next couple of years what would you like to see happening in the world of microbiome science but also in the medical world.

Jack Gilbert:

There are currently um there are 13 phase 3 clinical trials over here in the united states and a couple in europe that are focused around different indications for microbiome based therapies for for treating those indications so i i think we're on the cusp of significant translational potential there's a an additional 30 or so phase two and phase two three trials that are that are on on it currently ongoing so we're at a stage where people are already um trying to get this technology to the point where it can be approved and integrated into clinical practice one of my colleagues uh uh charles chu up at university of california san francisco already deploys old omics analysis so metagenomics so where we sequence all of the dna from a stool sample he already deploys this in um predicting uh disease risk in an individual you know identifying whether it's a virus identifying whether it's a bacteria identifying what kind of antibiotics that bacteria might be resistant to that's happening right now right it's already there, so this is going to happen we're going to get more and more and better and better technologies that will facilitate us being more effective at driving clinical practice.

Sheena:

Okay um and can you allude into a little bit more depth on any one of those areas that we can um you know that you think will be translating into the clinical world in the next year or two um which areas of practice.

Jack Gilbert:

Yeah, well, it's a really good question. So in the next year or two, I think we'll be at a stage where if when a patient comes into the hospital, we will be able to sequence their microbiome and detect the most likely causative agent that is driving their risk of metastasis in cancer treatment. We are very close to having biomarkers, which we could deploy. It will still require a new drug license for clinical practice, but it's there. We have these biomarkers, and they can be deployed to help people, to help clinicians understand if a person is at risk. Now, what we do about that, once we made that prediction, will take longer, but we're definitely at a stage where we can integrate microbiome data into a cancer patient's health journey to facilitate them and the clinical team from having a better understanding of of the uh the future trajectory of that health journey so that is that's an important piece i'd say you know by 2020 and in 2026 beginning in 2027 we'll be in a space where we can do that regularly now which health care systems it will be deployed will be very much dependent upon local regulatory drivers, right? The British healthcare system is very different from the French one, very different from the United States, very different from Burkina Faso. You know, you have to work with the system you have, but we'll at least see it starting to be integrated into those practices.

Sheena:

Okay, that's exciting to hear. And what about in the drug world? You mentioned before about, you know, being able to predict your response to drugs. You know, the pharmacomicrobiomics world is a really interesting one because, you know, as a prescriber of medicines, I frequently see people having side effects, problems with medicines. And it would be so useful for me to know if somebody was at risk of reacting to certain types of medicines before we actually give them these. How is that world coming on?

Jack Gilbert:

Um it's it is coming along we already have uh um uh you know we we know for example if someone's going to respond to certain types of heart medication already based upon microbial signatures in their stool um we're getting more accurate at being able to pinpoint those particular biomarkers with new tests but that that is happening but you know there's a cornucopia of drugs out there of pharmacopia of drugs and uh and um the interactions which those drugs have with different bacteria in different people in different regions is many, multifactorial, right? So it's very, very complicated, myriad of connections. So we have a long way to go in being able to say that this connection is universally applicable across populations. So we need more effective strategies at recruiting individuals from diverse backgrounds, from diverse ethnicities to support uh understanding how their microbiota might be interacting with that drug um and so that that's part of uh the ethical development of this field but it's it's it's something we're working on but yeah drug interactions are key.

Sheena:

Yeah, that's really interesting. But as you say, if we could get people to improve their lifestyles, perhaps we wouldn't need so many drugs. That would be a world I'd be quite happy in.

Jack Gilbert:

Right. I mean, just cutting out refined sugar from your diet can have a profound effect. I know this. Still, every time I'm in the UK, I crave a dairy milk bar and I will eat it.

Sheena:

Oh, even with the new supplement in it?

Jack Gilbert:

Yeah, I don't know. is just sugar and fat and it's delicious how do you know how can i ask people to be so diligent with their health and their nutritional journey when when i cannot do that and it's a really that's a complicated problem but you know it's the same in the 1960s with doctors smoking and telling people not to smoke.

Sheena:

That's right that's right and and fifth and when i did my diploma in lifestyle medicine we were quoted because it was an international diploma i did we were quoted that over 55% of medics in America were overweight or obese. So, you know, how do they get anybody to change their, their dietary habits when the patients are just going to look to the clinicians? And, and that's probably part of the problem as well, because, you know, we have to lead the way as clinicians and scientists, we need to show people what is possible and how to live your life in a really healthy way. I'm sure you have made other changes. You don't look too unhealthy, Jack.

Jack Gilbert:

No, I mean, you know, yeah, I eat a very high fiber diet. I mean, that's something that actually helps to balance out a lot of other things. So I can occasionally sneak a candy bar and not worry about it too much. But yeah, high fiber diet, a significantly increased amount of fermented food in my diet rather than processed preservatives and ensuring that I do things in a diverse way. So not just one type of fiber or one type of plant, but you asked earlier what our primary finding was from the American Gut Project. The primary finding for the American Gut Project was eat more than 30 species of plants a week and you will have a diverse microbiome and a diverse chemical profile in your stool and your blood. It was purely, taken hold over the over the over the world in uh netflix documentary we did recently to uh to um, tim specter's you know programs in the uk that one finding has resonated with the public um and it's it's you know it's a rule of thumb yeah just try and eat more diverse plants and and fungi and you'll be better.

Sheena:

Yeah yeah it's a great message.

Jack Gilbert:

Whether it's true university we're not as hard to know and.

Sheena:

And that's that's the kind of messaging that we keep repeating again and again to people um i think it's so key as you say um you know and it's not that hard to do i mean my i make my own breakfast cereal these days so i make my own muesli and there are nine plants in my breakfast muesli um just between all the seeds the nuts um the type of grains um so it's not hard to achieve and if you you constantly change the types of fruits and vegetables that you eat and add in lots of herbs and spices uh it's it's she it's quite easy to achieve that.

Jack Gilbert:

It is if you have access to it um and if you have access to it absolutely you have the financial resources to be able to do it also you know as you say you've got three children um well you know a lot of people struggle to get their children to even think about addressing that So this is a social science problem. We can't, I cannot work in isolation anymore. I need to work with social scientists to understand the social fabric of the communities I work with. That's the only way we'll be able to make a big impact upon people's lives. And I think the work that you're doing in integrated medicine is, is a key example of that, right? It's, it's embracing the fact that people live in a social fabric and understanding how to integrate the science into that social fabric.

Sheena:

Yeah, no, that's really interesting. We've touched a little bit on testing at home. How long do you think it will take till we have a system whereby people can actually get access to microbiome testing more routinely? I know, obviously, the NHS is going to be way behind America on this, but what do you think in terms of what's realistic?

Jack Gilbert:

I think what's realistic, taking a step back, right now if someone gives me a microbiome test, as I said before, the only thing I can really tell them is, yeah, you look like somebody who could use more fiber in your diet, right? That's a universal truth, whether I've got the microbiome data or not. So currently, it's very hard to make accurate predictions other than for nutritional intervention from the gut microbiome. That has to change before people or organizations and companies or the National Health Service will leverage at-home testing in an effective way because 99% of all the clinicians and the GPs in the UK if you gave them a microbiome test result they wouldn't have a clue what to do with it if you give me your microbiome test result I have a much more nuanced understanding but still it's hard to predict a therapeutic outcome right so um we're not there yet so there's no.

Sheena:

There's no point then in in the average person who's listening to this podcast thinking i need to go and pay for a private uh microbiome test just to see what my gut looks like.

Jack Gilbert:

Yeah i know the only examples where i would say there is credible evidence to support having the microbiome test is companies like Zoe, where they will be able to provide dietary recommendations which are backed up by peer-reviewed clinical studies. That's one of the few examples. In, you already have a good example of that. There is one of them over here in the US as well. But for the vast majority of clinical outcomes that patients are interested in, right now there's very little reason.

Sheena:

Yeah, and of course, Tim Spector's work with Zoe, he's been able to combine the microbiome testing with your continuous glucose monitoring and that really helps as well to aid your decision-making around diet. Um so yeah i've got tim coming on the podcast in a couple of months time so i'm looking forward to hearing his his take on all of this as well um so if we're not going to be checking our microbiomes just yet unless you're doing it for scientific research um then what can we um what can we do to manipulate our microbiomes in other ways you've mentioned obviously diet and fermented foods and things so we won't hash through that again but um what do you think about probiotics.

Jack Gilbert:

So um well i'll say before i jump on the probiotic story exercise is also important you know light exercise you need to go crazy but walking is important also the environment's important we we run in clinical studies right now with children where we randomize them to receive outdoor schooling in a forest right and the the immune stimulation that the children get from being exposed to soil and plant and animal bacteria and antigens in that ecosystem appears to significantly reduce their chances of developing immune disorders metabolic health is improved and even neurological and and cognitive health is improved in children that are experiencing that so. Walking is a great way of getting out into the world. Gardening is a great way of interacting with the natural world. And your body has evolved to need that kind of immune stimulation from the environment. So those are, diet's great, but being able to get outside and access the natural world from an immune perspective is also really important. And I'd say probiotics are just and almost a clinical gateway example of that, right? They are an easy thing to do. You can go to the store and buy some probiotics and take them, and they may help, right? There's lots of double-blind, placebo-controlled, randomized clinical studies, which is our gold standard, which demonstrate that some probiotics can be effective in treating some diseases. But they also do essentially the same thing as fermented diet does and going outside and interacting with the natural world does. It just stimulates your immune system. There are a few key examples where, like Bifidobacterium longum infantis, where that's more mechanistically interacting with diet, but not many of those. So I think that's what we should do. Go out, go walk start gardening get outside and try and eat healthily if you can.

Sheena:

Fantastic right and what about fmt uh fecal microbial transplants um what's your what's your feeling on that at the moment and and are you involved in any research on fmt.

Jack Gilbert:

Well absolutely i mean fecal microbiome transplants have been around for at least 70 years in our current incarnation, but there's Chinese textbooks which talk about taking baby's poop and fermenting it overnight and then drinking it as a soup in order to treat GI diseases. They didn't know what they were doing, they thought it was rebalancing the qi. Either way it worked so this is this isn't this is a useful strategy for resetting the gut microbiome the question is how should it be done and how effective is it at treating certain conditions for example treating obesity we haven't we haven't really been able to use fmt or demonstrate the effectiveness of fmt in treating obesity it appears that taking a skinny person's microbiome and putting it into an obese person doesn't necessarily significantly reduce their BMI or lead to significant weight loss. So it's something more complicated going on there. For type 2 diabetes and other conditions, it proved to be much more efficacious. We are running some studies right now in depression based upon taking the microbiome from a non-depressed person and putting it into a depressed person's gut appears to be able to alleviate neurological symptoms associated with depression so there you know there are there are many ways of thinking about this um and trying to understand how to um to take this treatment strategy and put it into effective clinical practice point to point you know for that the only two fda approved clinical interventions using the microbiome are for uh two packaged versions of fmt one where you take a stool from healthy people and process it in a certain way and put it in as an enema and another one where you take bugs that are selected from healthy people's stool and take it in as pills but both of them are versions of an fmt that are approved for clinical treatment of recurrent clostridioides difficile infection c diff infection in people so it's an effective strategy it's not however the be all and end all it won't fix all problems we have lots of failed FMT trials so there's more work to be done and more nuance to be added.

Sheena:

Yeah, that's interesting. So we'll watch this space on the FMT. That's really fantastic. So what other, I mean, what other areas are you involved in? Is there any other parts of microbiome science that we haven't yet covered that you feel that are, you know, things that you want to share with the listeners? Anything else?

Jack Gilbert:

I think the work that we're doing in neurological health, I think is fascinating, right? We found that the microbiome can actually be associated with empathy. So supporting somebody's effective understanding of another person's perspective. It's fascinating. We found the microbiome can be very attuned to treat depression, not just necessarily with an FMT like we're doing, but also with particular organisms. So we found that people with major depressive disorder are missing very specific bacteria that have very specific immune stimulatory roles, and adding those back in, in our preclinical models, appears to be effective in treating depression. So we're running a clinical trial with a probiotic for depression, which is pretty cool. And so, you know, this whole understanding that what goes on inside your gut can affect your brain is really important, because if you affect your brain, you can affect behavior. And that can be food cravings, that can be lifestyle choices, that can be attention and focus. We can use, essentially, microbiome modulation or modification of the microbiome to help to support people's mental health. And that is a real new frontier.

Sheena:

Absolutely and not just that i mean there's so many areas um with the gut brain access you know your cognition your memory um your pain stimulation um we did a couple of podcasts on pain in the gut microbiome a really interesting area um and and in fact we're we're um presenting at the royal college of anesthetics meeting um in the in the early new year um and i've actually been researching the sort of loss of cognition in the early post-anesthetic period and how the changes in the gut microbiome are actually related to this cognitive impairment that you get really interesting area but yeah that that you know connection all the different connections between the gut and the brain and the brain and the gut that that you know those networks between the nerves the the hormones and neurotransmitters there's so many uh different ways that you can stimulate the brain um and so a lot of people would be really keen to see the outcome of that clinical trial i think because you know depression anxiety unfortunately affects so many people these days um which bacteria are you finding are specifically associated with um depression, Well.

Jack Gilbert:

It's not associated with depression, certain bacterial strains.

Sheena:

Okay, so those are the ones you want to have. The bacterioides and um well.

Jack Gilbert:

Not just bacterioides because that's a.

Sheena:

Massive genus exactly i was going to say which specific ones in the bacterioides well that's.

Jack Gilbert:

Under intellectual property protection.

Sheena:

Oh damn it okay fair enough um so so yeah that's really interesting and hopefully we'll get the outcome of that soon i'll have to have you back on the podcast and you can explain it all when when you publish that um so great and you you're hopefully published i mean i can't believe how many publications you've got actually was it over 450 and that was in 2023 um that you'd been involved in so you're probably the most published scientist i've had on this podcast by far well uh it has me beat by.

Jack Gilbert:

Uh by a few hundred so.

Sheena:

Really oh wow that's impressive he's other than so.

Jack Gilbert:

You know i've got some time to go.

Sheena:

Very good well listen jack that's been really really interesting um i've learned a lot this is um it's just fascinating just how many parts how many aspects of microbiome science you're involved in i don't know how you've got time in the day to be honest adfd.

Jack Gilbert:

Is a superpower.

Sheena:

Great so you're taking you're not advocating treating it, yeah i think you're very important okay um so thanks so much for coming on the podcast today um and i hope the listeners have enjoyed this um please check out jack's book um dirt is good it's a fantastic read and he will basically answer all your questions in that book um thanks again um and we'll hopefully chat to you again soon and uh that's us for today um bye.