150: The Microbiome’s Role in Aging and Healthspan
Dr. Sean Gibbons joins Dr. Buck Joffrey to discuss the complexities of the gut microbiome, its evolution, and its significant role in health and longevity.
He explains how our microbiome is established at birth, how it changes throughout life, and the impact of diet and lifestyle on its composition.
The discussion also covers the challenges of modifying the microbiome, the potential of precision nutrition, and the emerging field of fecal transplants.
Dr. Gibbons emphasizes the importance of butyrate, a beneficial short-chain fatty acid produced by gut bacteria, and the future of microbiome research in developing targeted interventions for health improvement.
Learn more about Dr. Sean Gibbons:
https://isbscience.org/people/sean-gibbons-phd/?tab=biography
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Transcript
Disclaimer: This transcript was generated by AI and may not be 100% accurate. If you notice any errors or corrections, please email us at phil@longevityroadmap.com.
When we are born, we're born sterile, so there are no microbes in and on our bodies when we're in our mom's womb. Um, and as soon as we're born, we are instantaneously inoculated with trillions of microbes.
Welcome everybody. This is Buck Joffrey with Longevity Roadmap, and uh, today we're gonna talk about a. Um, about the microbiome a little bit more. Um, this is an area that I still find very confusing. I know a lot of influencers out there, um, that you hear about, have an answer to all of what ails us through the microbiome, which obviously, uh, is not the case.
Um, it's not that, not necessarily the case, that the microbiome is not responsible for a lot of things. It absolutely is. But controlling that. Microbiome is another thing, uh, entirely. I don't think there's one panacea for everybody, not one probiotic, you know, no specific, uh, panacea that's going to correct all that ails us.
And so today I've got a guy who specializes in this stuff, who they are doing a lot of research on, you know, trying to figure out. How the, uh, microbiome evolves with age. You know, what goes wrong in some people and how you can potentially redirect it, uh, with various therapies. And it's not as simple, again, as simply just, you know, grabbing a probiotic off the shelf and taking it.
It's actually pretty complicated stuff as I find this entire topic, but it's, it's incredibly important. Because the microbiome is responsible for a lot of our health and, uh, therefore responsible for a lot of things that aile us as well, like, like inflammation in our bodies, people with um, inflammatory bowel disease, things like that.
Um, there's even been reports on autism that have shown, um, benefits with fecal transplant. Anyway, really fascinating interview with Sean Gibbons and we will have that. For you right after these messages. Hey, longevity enthusiast. It's time to take you to the next level. I've been fine tuning my longevity regimen for years, and I look better and feel better than I did a decade ago.
In fact, my blood work is even better than it was back then, and it's all because of my data-driven regimen. And it's inspired me to create a course and community just for you. It's called the Longevity Roadmap, and I urge you to check it out. If you're tired of your belly fat, tired of being tired, or just wanna optimize yourself for the next 50 years, visit longevity roadmap.com.
That's longevity roadmap.com. Welcome back to Longevity Roadmap. Today my guest is Dr. Sean Gibbons, associate professor at the Institute for Systems Biology in Seattle. And Washington Research Foundation, distinguished investigator. He's also an affiliate faculty member at the University of Washington in bioengineering genome sciences and data science.
He earned his PhD in biophysical sciences at the University of Chicago, completed a Fulbright and microbiology and synthetic biology at Oops, Sala University, and did his postdoctoral work at MIT studying eco evolutionary dynamics. Of the human gut microbiome. His lab focuses on understanding how our gut microbes evolve over a lifetime, and how we can design personalized interventions to promote health and longevity.
Sean, welcome to the program. Thanks, Bob, for having me. You know, I just wanna kind of start out setting the stage here. I think a lot of your research revolves on the idea that the gut microbiome isn't just an active passenger. It is. Uh, or I'm sorry, a passive passenger. It's a, it's active, uh, changes with their environment, diet, et cetera.
Uh, I guess the question for you is, I think for perspective, I was thinking about this myself. A lot of people end up with messed up microbiomes. I'm probably one of them. How are we born? Are, are people born with a good microbiome? Inevitably that. Can be altered and go wrong, or what happens at birth and as we grow?
That's a great question. Um, so we're not far back to go, I guess about birth. Yeah. Birth, but even before that, right? Evolution? Yeah. We're multicellular organisms and we're, we're living in a microbial world, right about 2 billion, 2 billion years before u carry outs and multicellular organisms arose. There are microbes and they can kind of do anything metabolically speaking.
And so they colonized us just like they do everything else. Um, and we had to learn how to live with them. We were either walking happy meals, uh, to be eaten by them or, um, we could cooperate with them. There's all these ways we could interact with our microbes, and so over a long time periods, we've sort of evolved a stable interaction.
The vast majority of these microbes, in and on the human body are either benign. To us or even beneficial. Um, whereas a very, very small minority of things are pathogens. Uh, when we are born, we're born sterile, so there are no microbes in and on our bodies when we're in our mom's womb. Um, and as soon as we're born, we are instantaneously inoculated with trillions of microbes.
Mom is sort of the sourdough starter culture. She kind of gives us our first dose. They get, uh, if we're vaginally born, we're, we're exposed to vaginal microbiota. It's also a little bit of poop there, right? Mom's poop a little bit when they give birth usually. Um, so you really get a kind of diverse inoculum from mom.
Um, c-section born babies, their microbiomes actually look more like the skin for the first few weeks of life. Uh, so you, you definitely get more of an inoculation from skin associated microbes. You know, as we grow and develop from infant hood to early childhood, um, we create sort of a self-assembled ecosystem.
You know, uh, we we're sampling microbes from our environments, from the people around us, but also from the dirt or from touching the dog's nose or what have you. Um, and if you look at, you know, two people's microbiota. They're very, very different. They're, they're one of these things that makes us very unique in addition to our genome and even identical twins, um, who share the same genome, have microbiomes that are almost as divergent as two complete strangers.
You know, it's interesting because you, you think that, you know, most children, um, start out with, you know, this is just my perspective. You know, most children don't start out with issues with their gut. Right. Uh, maybe, maybe that's true, maybe it's not, but that's just my impression. Just in terms of how things seem to evolve, older people seem to have more issues to develop over time.
Is that true or is that just not true? It, it depends. Right? Like CO is a common condition for babies. A lot of time that's due to bloating and gas and, and pain. It's hard to pin it, pin it down, but I think some amount of that is gut related. You do see that babies born via cesarean section or vaginal birth show variable outcomes.
Also, kids that have different exposures to antibiotics throughout their childhood, like kids with chronic ear infections, for example, receive lots of antibiotics throughout their childhood and that perturbs your gut microbiota in addition to everything else. Um, we see the kids who are born by be a cesarean who don't.
Breast feed or who are exposed to a lot of antibiotics and all of those things can be kind of a perturbation on that. Early life microbiota, a lot of those kids show elevated risk for certain, um, overactive immune system disorders like autoimmunity, asthma, allergies, food allergies, so forth. Yeah, it, the other thing that comes to mind, and I doubt there's a study on this, but you would think that you would.
Be able to link some things in these children from their mother's microbiota. If, if that's the, you know, if they're coming through natural childbirth. And that's our first exposure. Do we have any, uh, data on that? We do. There's a lot of cool studies on this, um, sequencing the mom's stool and vagina and skin and, um, and looking at the babies.
You for sure see exact strain transfers. So the exact same strain of e coli or whatever bug that was in mom is making it into the baby. Um, but it's less than you would expect in to, in terms of like the total composition of the microbiome. Maybe only like a couple of percent or a few percent of the strains in the infant are coming from mom and, you know, 90 some percent are being derived from somewhere else.
And we don't quite know exactly how that sourcing's happening. Um, we see, uh, siblings, mom and dad, um, these, um, close social interactions do give rise to exact strain sharing. Um, whereas it's very, very unlikely that two strangers who've never physically interacted share the, the exact same strain.
Interesting. What are some of the most important changes to the gut microbiome? As people age, and, and maybe that's, maybe that's not the right question from what you're saying, but is there a natural change or progression of the microbiome that is attributable to the, the aging process? Yes. So there's a few phases that you can separate your life into.
So the first is going back to being a baby. Um, our diet is very unique as mammals. During that early phase, we're breeding milk. That's the predominant source of energy. Um, and in the human gut, uh, there are these organisms called actinobacteria, specifically bifidobacteria, which have evolved to consume the polysaccharides, the human milk oligosaccharides that are present in milk.
It turns out that mom actually. Produces a bunch of these HMOs or human milk oligosaccharides. A large fraction of the total energy content of milk is made up of these oli oligosaccharides, which the baby cannot digest. So these are molecules that we've evolved to put into milk that exclusively, um, cultivate specific types of bacteria in the gut.
In particular, these bifidobacteria. And so being, having high levels of bifidobacteria in the first several months of life while you're breastfeeding is very healthful and very good. It suppresses pathogens. Um, and as we transition towards solid food, you see a flip in the ecosystem where the actinobacteria decline precipitously.
You get an enrichment in these other two major clays of anaerobic bacteria that belong to. I think now it's called the Basta phylum and the boid OTA phylum gram-positive and gram-negative anaerobes that, um, tend to be dominant in the adult human gut. These rise into prominence by about a year or two of age, and then your microbiome kind of stabilizes to an adult proposition and that adult composition is very stable.
Some people call it our second genome. Like, I just sequenced my microbiome again after seven years, and it's about identical to what it was seven years ago. So the ecological composition of that adult microbiome is, is very, very stable and steady over long periods of time. Uh, and so that's most of your life, but then towards the end of your life, as you get, um, into later middle age, like fifties, sixties.
You do start to see that there is a bit of a shift that occurs, and this is actually recent work from our lab where we've characterized, uh, that there are actually kind of multiple trajectories of aging towards the end of life. And those have variable associations will with health. And I guess the question question is how much control of that do we have?
I mean, that, that obviously leads into, you know, a number of, of health related issues. How controllable are those changes? That's a great question. And we don't quite understand the mechanistic drivers for what, what is driving these, these different signatures? So maybe I'll first describe what those signatures are.
Mm-hmm. So when we look at data from older humans, um, we see there's a certain subset of people who kind of maintain a microbiome that looks like it did when they were in their twenties and thirties and forties. You see a very high prevalence of these gram-negative anaerobes, like the bact Dota. Um, and then, you know, also a mixture of these basta, these gram positives.
Um, and if you maintain that composition into later life, that maintenance of a or youthful microbiome is actually associated with worse health outcomes, right? Those people aren't doing as well. Alternatively, there is this, uh, pattern that's gonna observe in centenarians and in healthier older people.
Used to get this steady decline in the Bacter Dota phylum, the grand negative anaerobes are kind of going down in their dominance in the ecosystem. And you see a, a relative rise in the dominance of these, uh, bas to the gram-positive like Clostridia, um, butyrate producing taxa. They're kind of rising in prevalence with, with older and older age.
Uh, what is driving, this is still kind of unknown, um, but there are a few things happening as we age. One. Um, you know, we have kind of menopause, menopause, hormonal changes in the body. Some of these are affecting things like transit time, like how fast we're pooping. Um, sometimes that kind of slows down a little more as we get older.
Um, appetite declines a little bit, so maybe, maybe taking in a little bit of food than we used to. And that's gonna affect the microbiota. Um, our gut produces mucus, which lines the, the interior of the gut and kind of acts as a barrier. Or a wall between us and our microbes. Um, our ability to produce mucus actually declines as we get older, and so that wall starts to get thinner.
The gram-negative anaerobes that we're talking, I was talking about like the, the bacter genus, for example, some of the, many of these bugs can eat the mucus layer, and so their presence could maybe even lead to thinning of this eroding mucus layer as we age. So having lower levels of these guys could be beneficial in that context.
Um, I suspect that the, these variable patterns are being driven by healthy lifestyle. So people who are maintaining the high level of dietary polysaccharides are probably enriching for these clusteral taxa with age as the niche or the gram-negatives is maybe declining due to these physiological processes that are associated with aging.
Talk about these changes that are occurring with age. Makes me wonder a little bit again, just on this idea of like, how much can you actually change the microbiome with things like, you know, probiotics, prebiotics, postbiotics, things like that. I mean, is there, is there a certain level of resistance to those changes that develops over time as you have that steady state microbiome?
And if. If you try to alter it because some people you know may not have a healthy microbiome, how difficult is it actually to meaningfully change that ecosystem? It's difficult. It's actually frustratingly difficult. Hmm. Um, you can definitely change your microbiome with radical shits to your diet and lifestyle.
So if you were eating a pure carnivore diet, then you switch to a high fiber vegan diet, you would definitely start to see. Shifts happening in the ecosystem. Um, but there's a lot of, um, kind of priority effects in the gut. So once an organism is in there and establishes, it becomes difficult for another competitor to dislodge it.
Yeah. So that, that adds sort of a inertia or hysteresis to the composition of the microbiome. Um, and then, you know, for a new bug to come in and. Get access to a, to an emerging niche, it needs to go through the bottleneck of the stomach, right? So there's this, this bottleneck that's trying to kill everything that's coming in through our diet.
So if only a few cells can make it through, they happen to hit the right spot and bloom and, and get in there. So you sort of have to wait around if you change your diet for these organisms to kind of get in and colonize those niches. So there's a lot of slowness to the process and there's also. Um, uncertainty as to like, how do we rationally engineer or select prebiotics and probiotics?
Yeah, that's a lot of actually what our lab is working on currently, our modeling tools to kind of build a digital twin or representation of the gut microbiota, metabolism, and ask, you know, of all these probiotic organisms that I could add to the system, which one would I predict would be most likely to grow in your particular microbiome, in your particular dietary context?
And we have some recent papers kind of showing some efficacy for those types of models. So I think that's the future where we will have to maybe design targeted or precision. Prebi and probiotic and dietary interventions to be able to change and, and adapt the microbiota at will. Well, let's jump into that a little bit more.
In terms of what you guys are doing, you've developed methods to, uh, essentially reconstruct dietary patterns from stool DNA. Right. Um, how do you do that and, and I guess what, what kind of, um, output do you get from those studies? Yeah, so that is actually a recent method that just came out on how to infer diet from gut sequencing data.
So the basic idea is, you know, we're eating things with DNA in them when I eat a corn, corn on the cob, that corn has DNA corn DNA in it. Um, and some amount of that DNA survives passage through the digestive tract and ends up in stool. Now the problem with that though, is that the vast majority of DNA in stool is coming from bacteria, um, by weight stool is about half bacterial cells.
By DNA content, it's something like 99.9% of all the DNA is coming from bacteria. So when you're sequencing it, it's like finding a needle on the haystack to find the, the corn DNA in this fast soup of microbial DNA. But we figured out a way to, to do it. Research scientists in the group, Christian Diener built a bio bioinformatic workflow that takes in the shotgun sequencing data from, um, DNA extracted from stool.
Um, maps it to a, a large database that includes something like 400 genomes of all the plants and animals and fungi that are in the human diet that have been sequenced, that are available. Um, we then sort of extract that information and also kind of the abundance information of how many sequences are mapping to each organism.
And then reconstruct a, a matrix of, you know, here are all the different organisms we're detecting in your stool, and the counts of how many DNA sequences we found from that organism as kind of a relative abundance metric for those things. And that can be used to map to a different database that contains, um, information about, you know, for every gram of beef.
There are x number of grams of alanine and cystine and thine and all these other things. So you can get kind of nutritional information from the biomass information. Um, and together you can get both composition of diet in terms of what types of organisms you're eating and nutritional content of diet in terms of what are all the macro and micronutrients.
Um, then we did some benchmarking with some controlled feeding studies, and it works pretty good for certain contexts. Uh, for, for some things it doesn't work so well. But we're, we're kind of continuing to develop the method to make it better. It, it sounds like, you know, this is kind of headed towards this, I guess it's a popular term, but precision nutrition type of thing.
Right. Um, what does the look like, like when you use this data, what is the ultimate goal? I mean, it looks like you're basically able to look back and see what people are eating from the microbiota. What do you do with that? Or what is the goal ultimately to apply this, uh, in a, in sort of a precision health model?
Yes, great question. So this actually relates to a different method we've developed, um, called MyCom, which is a port mento of microbial and community. It's MyCom and it's, it's essentially we're, we're taking a method called Flux Balance Analysis. And it's a mathematical framework for taking a biochemical reaction network.
Like all the enzymes, for all the metabolic reactions that are happening in one organism's genome, you can pull out those enzymes and build a reaction sort of matrix. Um, and then include sort of a dietary or environmental, uh, constraint matrix. So like how much of all these nutrients are available to this biochemical network?
It's like you're pouring these things into the network and looking how they filter through it and predicting what, how they're blowing out the other end. Um, so we take that kind of a modeling framework and we extend it to complex multi-species communities like a gut microbiome. So we can build these, these models that have hundreds of organisms in them, each in their own little compartments with internal metabolic reactions occurring.
Transport reactions happening across their membranes, and then an external dietary milieu where they can exchange metabolites, consume and produce metabolites and cross feeded with each other, and then feed things to the host, which is, which is us. Um, so it's, it's these big unwieldy models that we can now create and I can initialize them with sequencing data, say from Norco.
So I sequence your microbiome. I see which tax are there and their relative abundances. I can use that to initialize one of these models of your particular system. And then for the dietary input, which is another constraint, need to layer into the model. We can use what I just talked about, which another method we call medi, uh, metagenomic estimation of dietary intake.
We can take that dietary intake estimate and we can turn it into a model accessible diet. Together, we can then predict, you know, if, if you eat this, this diet that you're currently eating, what microbial metabolites are being produced. Um, and we have a few that we've focused on for validation. So butyrate was one we recently published on, um, to a First Approximation.
The microbiome is this bioreactor that takes dietary fiber, um, and ferments that fiber into organic acids, right? The kind of things you taste when you drink like kombucha or. Eat sauerkrauts, these sour tasting molecules. Our microbes are producing these things in our guts all the time, and these have a really positive healthful effect for our bodies.
Now in the developed world, we are very much underexposed to these organic acids because we don't eat as much dietary fiber as we used to. Back in the old days, we probably ate a hundred grams of fiber a day as hunter gatherers, and today we're lucky to get 10 grams of fiber in the modern American diet.
So, you know, turning up these organic acids is really key to preventing a lot of chronic diseases that seem to arise from this, this missing fiber in the diet like diabetes or auto inflammation and, and so on. Um, and so what, what we wanted to do with our model is to predict butyrate production in particular, which is one of these organic acids that have a really potent health effect in the body.
The problem is if I feed a banana to 10 people. Very, like up to 10 times, different amounts of butyrate will come out at the other end. Um, so what we did is we tried, we showed that our modeling infrastructure could predict this variability so I can predict your butyrate and my butyrate production. We validated these predictions using, uh, we call them poop soup experiments.
So we could take fresh stool from a person in the lab, incubate it in the lab with say a, adding a dietary fiber, and then measure the butyrate production. And do that for, you know, a hundred different people and then model those same interventions and show that, that you align very well. So basically to your original question, how do we use this information?
You know, if I could turn up your butyrate level at will, I could probably reduce your LDL cholesterol. I could improve your insulin sensitivity. I would lower your risk for cancer in the long run. Um, and any number of healthful effects, right? It's this very potent molecule that has myriad effects across the body.
Uh, and so at this point, we've done some of the preclinical validation. We're now thinking about moving into human clinical trials where we try to predict, personalize, prebiotic, probiotic, and dietary interventions, um, that perform better than a standard of care intervention. Like maybe eating a Mediterranean diet or something.
Yeah. So in, in this situation is the primary. So it sounds like the primary endpoint, at least for the stuff you've talked about, is butyrate production. Is that right? If I had to pick one molecule, that was maybe the most important thing that our microbiome is producing day to day it, it would be butyrate.
So that's why we focused on that one. And then we generated some validation data showing that we could indeed accurately predict personalized production rates for this molecule. The downstream effect of that molecule. We were able to assess in a lot of different ways. Like there's a lot of literature on butyrate and what it does in the body, but we had a cohort where we had paired poop samples and clinical chemistries.
You can get measured at the dock, something like 130 of them. And we associated all of these with our predicted butyrate fluxes, and found that about, you know, 30 or 40 of these chemistries were significantly associated with predicted butyrate, and they all showed the directionality we would expect. If you're predicted to produce more, you have lower LDL, you have better insulin sensitivity, you have lower inflammation, so on and so forth.
So, you know, to like a clinical endpoint, what would you look at in a trial? I think you could kind of pick your poison to some extent, but I, I would focus on like a cardio metabolic endpoint. Probably like hba one c or blood pressure, um, something like that. But whatever we do, we're trying to find that first proof of concept to show that.
Microbiome guided personalized intervention is optimal and does better than some standard intervention, um, just specifically to butyrate and, and notice it. It's often in various new nutraceuticals. Now, is there a problem with getting that butyrate to where it needs to go when you take it, uh, by mouth?
Yeah, so that, so the, that's like a post biotic, they call this, right? Yeah. So you take a product that the microbes are making and you just manufacture that as it's as a drug and you just give it to people without worrying about the microbes. This is something that can be done. Actually, last week I knew, this, people I know of published a paper on Butyrate Panama showing that they dropped blood pressure by 10 points in a randomized placebo controlled trial.
So we know it works, right? Um. If you give a high dose enema that that works. There are studies that have shown taking pills with butyrate in them, um, can or may or may not have effects. So it seems that if the butyrate is delivered to the small intestine, it doesn't necessarily have as potent of an effect as if that butyrate gets delivered in the colon, or a lot of the receptors are there for detecting that butyrate if you're responding to it.
So I think spatially where you deliver that butyrate is really important. So that's one challenge. The challenge for the enemas is that it stinks to high habit, right? Butyrate is very stinky. Patients actually don't like getting butyrate enemas 'cause they smell like a garbage can for a day after they get it.
Um, so that's a problem. And uh, finally I'll say that, you know, in order to have, you know, a, an optimal effect, I think you need large amounts to be produced or to be delivered continually. Short of some like tube that's like feeding it in all the time. Um, I would argue that why not leverage our endogenous microbiota to be constantly producing it in situ?
Sure. You know, we've been talking about, I think you mentioned this with digital twins, uh, the concept of digital twins, basically these virtual models that can test interventions before trying them in real life, right? Isn't that sort of the concept there? Yes. So. It sounds like to me from what you're saying so far that, you know, sort of the standard, you know, just grab a probiotic, prebiotic, post biotic, all that stuff may not be terribly effective in the end.
Is, is that right? It depends on how you think about it. You know, um, there's a lot of clinical trials that have been done on say, high fiber diets on fermented foods, various probiotics. Many of them do show, um, a significant effect on some phenotype. But, um, you know, inevitably there are responders and non-responders to all of these integrations.
This isn't just true of the microbiome. This is also true for pharmaceutical drugs, right. Um, and so what I think what these precision algorithms are helping us do is to rescue the non-responders. There's, there's always a subpopulation that would be, would benefit from a different intervention. And if you cannot priori rationally predict what those are, you essentially rescue those non-responders.
I mean, I, and I would say like most people, general advice of eating a whole food, high plant-based diet that contains a lot of fiber, eating fermented foods. Um, if you follow those rules, you're probably gonna be doing pretty okay. But in our models, there are still some people that don't respond all that well, even to those interventions.
Sure. So there's a lot of buzz these days about basically fecal transplants. Right. Um, from everything from gut disorders. Uh, gosh, I've, I've heard people talking about autism, which, you know, I, I don't think that that's probably. It's something that has that much scientific rigor to it. But what's the real promise of fecal uh, transplants?
I mean, obviously you talked about how your delivery of butyrate, uh, directly, uh, through enemas seems to be beneficial. The idea that here, I guess is taking somebody who has a so-called sort of very healthy microbiota and, uh, transplanting, um, now. Basically just transferring some of their, uh, uh, some of their poop over and seeing if you get the, you know, a similar microbio.
Tell us a little bit about that. Yeah. Um, this is actually the first case of, you know, clinical translation, uh, in the microbiome space. So I did my postdoc with a guy named Eric Hall at MIT, and he started the first stool bank, uh, in, in the country called Open Biome. Um, and you know, at the time. They were using fecal transplants to treat a condition called recurrent cluster DD diff seal infection.
Mm-hmm. Or, or recurrent c diff. Yeah. Um, and the problem with that was that every hospital, every doctor performing those procedures had to go out and recruit a donor for their patient to give a fecal transplant. But most of us walking around in the world carry opportunistic pathogens in our guts. Uh, they're just suppressed by our endogenous microbiota.
Uh, but if I was to give that to a sick person, that could make them even sicker. And so these hospitals that have to screen dozens of patients before they find the one magic person who kind of lacked any of those opportunists, so it opened, biome did as it turned into a factory. They found these healthy, pristine people, and they just had them poop every day for a year.
Made huge batches of their material, turned it into pill form, and then shipped those out to hospitals, making it essentially very, very easy for these doctors to perform the procedure. The clinical trials on this are crazy, right? It's one of one of those where they have to stop the trial early for ethical reasons.
Because the treatment is so much better than the standard of care that, um, it would be unethical to continue giving people antibiotics. So it's something like, depending on what trial you looked at, between 85 and 99% efficacy for treating recurrent c diff, which used to be kind of a death sentence back in the day.
So super effective. And also now there are two FDA approved fecal transplant equivalent. Interventions that you can get from the doc that are healthcare reimbursable, but, but is, uh, limited to recurrent, uh, c diff infection. It seems to me that again, we're, you know, we're focused on things that you can do to stay healthy and are those things that are potentially available to somebody who's just, you know, who's got a bad, uh, microbiome, who needs he, who needs sort of a, a reboot, so to say, is that, is that stuff being.
Uh, studied in that way at all? Has it been looked at? Yes. People have studied this in many different ways For many different conditions. There's a lot of trials for, you know, inflammatory bowel disease or irritable bowel syndrome, or autism or various things. Right? Um, and the outcomes of many of those trials have been very middling, right?
There's, there's been no example of such a stark effect size as what we saw for recurrent c diff. So these FMTs seem to work pretty well for pathogen suppression. So if you have some opportunistic pathogen in the gut, um, these ecosystem of transplants do really well. But for a lot of these other diseases, it seems like it's just a hammer, right?
You're throwing at the system and it's not necessarily doing what you want it to do. It something more precision is likely going to be required for many of these other conditions, and then, you know, there's not, there's no not a lack of risk for these procedures. So, like I said before, there's been a few cases where patients have actually got sick from fecal transplant material.
It's very rare, right? These are generally very safe interventions, but occasionally you can take up a pathogen. And then there are these other weird side effects that happen. Like some people show that depression is transmissible, the have fecal transplants or other kind of gut brain things. Uh, like you mentioned autism before.
That's actually one area where some of the recent data is looking slightly promising. There's actually a few open, open-label trials that have shown some symptom amelioration in kids with autism. I think a lot more needs to be done to flush that out, but. Um, where these will be applicable or where they won't.
I think there's still a lot of work in science being done around that, but generally seeking, it's sort of a hammer. And I think the, the main application we've sort of found the lowest hanging fruit is picked, and now it's, it's moving on to more mechanistic and, uh, targeted interventions. Yeah, I mean, I, I think from a longevity standpoint too, I think you guys have, you know, found that.
There are different types of chemicals. Uh, you've mentioned butyrate already, but you've also discovered gut microbes that may influence how well drugs like statins work. Right? So what do you think we're sort of closest, uh, to becoming every, you know, part of everyday medicine with some of these new techniques?
Well, that's a good, it's a good question. Um. It's actually surprising how many domains there are clinical trials happening in with the microbiome. Um, you know, one of the big ones I think that's very promising and we'll see something in the next few years is precision nutrition. Mm-hmm. There are all, there've already been a few companies that have come out, um, day two from Israel, and then there's Zoe in Europe.
Um, they both have precision nutrition algorithms that leverage microbiome data to predict blood glucose responses to diet. That's based in solid science. Zoe, I think still exists actually. Day two went outta business, but you can now purchase their service, right? So people can actually, um, track their blood glucose responses and, and diet from the microbiome and get predictions, you know, there's a lot of snake oil out there, but that's one of the companies I think doing it better than most.
Um, but then there's a bunch of, like, NIH has this big push now for precision nutrition. Where they're doing these huge clinical trials, where they're collecting microbiome data, doing dietary interventions. And I think the outcomes of those trials will be used to build these, these models and outgroups to make these predictions.
And I think our lab is contributing to this as well. So that's a big area. Um, another area that's something to look out for is cancer immunotherapy. So one thing that the microbiome is really good at is modulating your immune system. Yeah. Um, butyrate is a good example. It actually affects your T-cell differentiation and, um, kind of systemic immune state.
And, um, there's a lot of great evidence that pcal transplants or, uh, probiotics can actually influence the outcomes of immunotherapy and augment, kind of take non-responders and convert them to responders. Um, that's super promising. Um, the first cocktail defined cocktail of microbes for treating recurrent c diff is now in phase three trials by this company called Ante.
So this is supposed supposed to replace eagle transplants for recurrent c diff treatment. I think, you know, if that phase three trial goes well in the next year or two, we should see that as an FDA approach therapy. But there's a bunch of stuff. Is is that with microbes? Is that with basically, uh, like a soup of, of, you know, probiotics specifically Eight strains of Clostridia.
So it's a probiotic. Got it, got it. Interesting stuff. Well, um, I guess one, one last question for you. I guess people listening out there wondering in general, what your take on, you know, obviously we talked about high fiber diets and that kind of thing. Do you have an opinion on, you know, people should be taking probiotics, postbiotics, prebiotics, anything like that?
Just as a supplement or not so much? Yeah. Um, it's a good question. I mean, they usually can't hurt. Mm-hmm. Right. Um, one of the issues with a lot of these probiotics is that, you know, you, you, you look at all these clinical trials, there's some efficacy. Efficacy shown. It's a very specific strain, so you have to go to go track down that particular strain of bifidobacterium and phis if you want to kinda have an apples to apples for what you're taking versus what that that clinical trial showed.
So there's a little bit of murkiness in mapping what's out there in the science to the products that you can actually grab off the shelf. Yeah, so that's something to keep in mind. Another thing to keep in mind is most of the probiotics that we have available to us are grandfathered in by the FDA.
They're what are considered. Generally regarded as safe or grass because they are already present in food, right? They're the same microbes that you find in yogurt and in sauerkraut and in kimchi. So they're considered food, and there've been no clinical trials to prove they're safe. They just, it just lets you eat them because they're already at food.
But the dominant microbes that actually live in the, in the adult human gut microbiome, that I think would be useful for actually treating disease and helping people. Those organisms, I can't just take them out of me and give them to you as a pill. Yeah. Um, like fatali bacterium presidency, for example, is a butyrate producing clostridium that, you know, was very dominant in the human gut, but some people lack it.
And if only I could give them that organism, I think that would do them a lot of good. But you have to first run a phase one clinical trial so that regulators won't slap your hand because you have to prove it's safe before you get it to someone. And that costs a million bucks to, to run those trials.
And so I think. Getting these next gen probiotics into the market will require significant investment from companies, which may lead to a slight rise in the price of these products on the market. Um, but I think that's a price we'll have to pay to have more effective probiotics. Um, there are a few of these that are already exist on the market.
Um, there's a company pendulum that sells a few of them, like Akkermansia and some of the Clostridia I was talking about. And, and I think there's a couple other countries in, uh, companies in Europe that that sell similar products, but these kind of organisms, like Akkermansia and Peter eight producers, if they seem to be on the decline in older people who are less healthy.
So if I was gonna tell anyone to take probiotics, I would say people who are over 50. Or 60, maybe start taking these cocktails of like akkermansia and arid as a preventative measure to try to maintain, you know, metabolic health as you age. Yeah. Interesting. But also eat a lot of fiber and get good exercise and that's, that's probably the biggest thing you can do.
Correct. Um, Sean, where can people learn more about this stuff if they're interested? And they wanna maybe find out, you know, some of what's going on, see if it applies to their own situation, that kind of thing. Yeah, you can, you can follow our research, um, at gibbons, G-I-B-B-O ns dot isb science.org.
That's the website. Fantastic. Thanks so much for being on the show today. Thanks for having me. Thanks for listening. A quick reminder that while I am in fact a surgeon, nothing I say should be construed as medical advice. Now, make sure to include your physician in any medical decisions you make, and also, if you're enjoying the show, please make sure to show your support with the like, share, or subscribe.
