How Your Microbiome Shapes Your Body and Mind with Dr. Jack Gilbert

Jack: 
You can imagine a future where you have data streams coming out of you in the morning that you can track like your watch tracks your blood pressure and your heart rate and your number of steps. You can also track the microbial community inside your intestine, or on your skin, or in your oral tract or your denal tract, and use it to create personalized advice, like you mentioned, on a day-to-day basis.

Bret: 
The microbiome. It’s a mystery, right? Forty trillion organisms living in our intestines that somehow affect our health and are influenced by our diet and our lifestyle. But what is a healthy microbiome? Do we need to have fiber? How can exercise impact your microbiome? It all comes down to maybe the mitochondria, too, and how does it influence mental health and metabolic health?

So many questions, but luckily, we have the expert, Dr. Jack Gilbert, is here to discuss all these aspects and more about your 40 trillion cells living in your intestines.

All right, Dr. Gilbert, thanks so much for joining me today at Metabolic Mind. 

Jack: 
Ah, nice to be here. 

Bret: 
Yeah, so I’ve got to start with the story of how we connected, that we were introduced by Dr. Jong Rho at a conference here in San Diego in Coronado. And we talked about getting together for an interview and then went our separate ways.

And then my son came home with a science test, and we always have to sign their science test to say we looked at it. And one of the questions was, according to Dr. Jack Gilbert in his book, Dirt Is Good, which of the following? And I read that question. I said, hey, I met him. I have to reconnect.

So, I’m so glad we’re here today to talk about the microbiome. And when I reflect on the microbiome, when I was in residency and fellowship, like we, there wasn’t much about the microbiome. There was a whole bunch of cells in your intestines, but we didn’t really know what they do now. We’ve learned so much about the microbiome, and it seems there’s so much more to know.

So, with that as the primer, how’d you get into the microbiome and what is your journey? How do you see how the field has changed while you’ve been in it? 

Jack: 
I got into the microbiome, initially, in about 1995, when I was given a textbook in the first year of undergraduate school at King’s College.

And I really enjoyed reading about these incredible beings, which I didn’t know much about from my high school days. But these incredible beings that were able to adapt to anything and do anything and had all this metabolic potential. And I thought, this was incredible. And then I ignored it for about three or four years, and then came back into it during my PhD when I was sent down to Antarctica to isolate bugs, bacteria that had the ability to make ice smaller, make ice crystals smaller.

This was mostly for frozen food applications, if you can believe that. Working for the company, Unilever, and that really put me on a journey to understand how the microbiome could be used to deal with problems, right? And hypervaried problems.

I started out in frozen foods and then got into agriculture and marine ecosystems, and then I moved to University of Chicago in 2010. And I was sitting in my office and a surgeon booked a time to come and talk to me, and I was like, this is strange. And his name was John Alverdy.

And, he said to me, yeah, I really, I’ve been doing some stuff in human microbiomes with some colleagues and collaborators. And he said he really wanted to, he had this really difficult problem and he thought the microbiome might be involved in it. And I said, alright, okay, let’s have a look at this.

And it turns out he was getting blamed, all the surgeons were getting blamed whenever anybody got a surgical infection. When they had gut surgery, and they get these pathogens that were making their guts swell up and then explode and then cause problems. And he said, I just, we do everything perfectly, everything’s great.

And I said, okay, let’s have a look at this. And turns out, two, three years later, it turns out actually, the bacteria that were killing the people were inside their intestines already and were part of, were being promoted by the diets they were eating. And this blew my mind.

I was like, oh, my gosh, we got so many opportunities here to use microbiome understanding, to use mechanism of action to understand how things work. And use that to change practice, to change minds, so maybe make people healthier. And yeah, then I went off in about 50,000 other directions. 

Bret: 
Yeah, all right. That’s a, that’s an interesting journey from ice crystals in Antarctica, all the way to clinical and human applications of microbiome. Now, one thing about the microbiome though is we hear these stories like a trillion organisms in your intestines, and it just seems so vast, like to hard, hard to even wrap your mind around. How do you explain it to kids or to people who don’t know about much about it?

What is the microbiome? How do we wrap our heads around it? 

Jack: 
it’s actually pretty difficult, and also quite simple. And it depends how you look at it. So, we did a Netflix documentary recently called, Hack Your Health, and they used little felt animals that were living inside your intestine.

And then the food, felt food comes down. And it comes down to your intestine, and they jump on it, and they munch up this food. And then they poop out other things, which your body has evolved to need. And when I was growing up, my parents knew nothing about the microbiome and I was told that basically poop is just made up of the byproducts, which our body doesn’t want.

And, therefore, it’s dangerous and you shouldn’t touch it. But it turns out that poop can actually be life-giving. Now that we understand the power of fecal microbiome transplants, and that the microbial community is actually 40 trillion cells that live inside your gut are part of a symbiotic relationship that we have with the world, right?

They’ve actually evolved to live in the really complex and wonderful ecosystem that is our intestine. They’ve also evolved to live on our skin, which is a whole other ecosystem. It seems pretty banal, but it’s actually a deep city-like ecosystem that goes all the way down to the depths.

And then, we’ve got our urine genital tracks. We have our lungs, even our eyes, we have microbial communities anywhere that we are exposed to the outside world. And that’s fascinating. And I think, once you describe that to people, and you say you are literally in a symbiotic relationship with these 40 trillion organisms. And they’re helping to support your health, why?

Because your body got used to the fact that they were there and decided to harvest them. Like a gardener working in their garden, growing vegetables and pretty flowers. We have developed an immune system, which gardens this microbial community inside us and chooses the bugs that it wants so it can get the benefit from them that it needs.

Bret: 
That’s a good description. Yeah, and it takes, there’s probably a hurdle for some people who have this concept bacteria equals bad, bacteria equals infection that needs to be treated and gotten rid of. No, not always because there is this whole community of helpful bacteria that, like you said, we’ve gotten used to and have become part of us in this symbiotic relationship.

But the question comes up time and time again in research, in when clinical discussions about the microbiome. What is a healthy microbiome? And I know it’s maybe not so black and white. That there’s one definition, but what are the concepts that you think of when you say, okay, how do we define a healthy microbiome?

Jack: 
It’s an interesting problem, right? So, there’s there’s the Anna Karenina ideology, right? Dostoevsky, I think, or is that Tolstoy? Anyway, the opening line to Anna Karenina is, all happy families are the same, all unhappy families are unhappy in their own way. So, all healthy microbiomes tend to have very similar traits.

We see that across developed societies, but we also see it across developing societies, communities that may be living different lifestyles to our own. And no matter where in the world we look, we see quite similar functional traits to that microbial community, which are generally associated with a healthy phenotype.

Our bodies are healthy, our microbiome therefore reflects that. But disease is quite unique. There are different perturbations of the microbiome that are associated with inflammatory bowel disease. There are different perturbations associated with colorectal cancer, different perturbations associated with type II diabetes, with depression, with atopic dermatitis, with bacterial vaginosis. Wherever we’d look, we start to see differences in how this beneficial microbial milieu, which is quite complex and crazy, but generally is a high diversity ecosystem where you have a lot of connectivity between all the pieces, like a rich rainforest where everything is reliant upon each other and it’s all in this dynamic relationship.

To one which is fragmented, and you’ve got one organism that dominates, and think a destroyed rainforest where you’ve got a couple of trees. And maybe they’re now farming cows, and it’s not functioning properly and there is no feedback loop. And it’s all broken, but the brokenness is quite unique depending upon what disease you have.

And so we use this term dysbiosis to refer to a non-healthy microbiome, but it’s really just a breakdown in that symbiotic relationship between your microbial community and your body. And when that breakdown happens, it can affect the onset of disease. But it happens in myriad in unique ways, which is fascinating.

But horribly complicated to study. 

Bret: 
Yeah, and I think another issue when we talk about the microbiome is this question of chicken and the egg, cause and effect. That it’s affected by your diet and your lifestyle, which is going to affect your health. But then it’s going to change your microbiota, which can also affect your health.

So, is it the microbiome and the bacteria and the specific makeup that is affecting your health, whether it be obesity, type II diabetes, potentially mental illness or is it the lifestyle changes that affected the microbiome that are also affecting your health? So, that seems to be this constant push-pull.

So, how do you explain that? 

Jack: 
It’s both, and there’s no black and white answer for this. It’s both. So, let’s say you eat a high saturated fat, high sugar diet. Let’s say you eat, go burlock on us and eat McDonald’s every single day for an entire month.

Let’s just say lots of carbohydrates, lots of salt, lots of sugar, and those sugary drinks and lots of saturated fats, which can be beneficial in certain situations and non-beneficial in others. Okay, but you eating this stuff, you’re an average Joe, whatever. Now, a lot of that food is going in your mouth and a lot of it’s getting absorbed in the stomach and the duodenum.

And it’s affecting some microbes in there but not a lot. But the absorption is saturating your blood with sugar and fat and causing health problems that are associated with that consumption. But it’s also what we don’t absorb is going down inside our intestine. You are now flooding your microbial garden with these nutrients, which are selecting for the weeds, which would normally come up.

And so where you were trying to grow carrots, now you’re growing prickly, unpleasant thistles. And where you are trying to grow your flowers, now you are suddenly growing an invasive species of vine that’s taking over and killing everything. And that’s what’s happening, right?

It’s a double whammy. Your body’s absorbing all of those unhealthy nutrients, potentially leading to cardiac disease, but it’s also promoting a microbial community inside your gut, which starts to pump out these chemicals. Because they’re consuming that food and when they consume things, the end product in all life is poop, right?

But their poop is little molecules. Those molecules actually are absorbed by your body through your colon and your large intestine. And they go into your circulation, and they can affect how your different organs work. So, for example, we demonstrated that high saturated fat, high sugar diet can promote bacteria ,which produce a compound called hydrogen sulfide.

That’s the rotten egg smell that you smell when you are, if you have a heavy night the night before. You might have a lot of hydrogen sulfide in your diet, right? And that will get into your bloodstream, and it affects how your liver processes hormones in your body.

And that can actually lead to how it changes in how your body distributes weight, energy, leading to more adipose or fat tissue generation, and also, fascinatingly, changing how your brain perceives satiety. So, how hunger, making you more hungry for longer. So, it’s in that one little situation, you’ve got the food affecting your health, but affecting the microbial community, which feeds back upon your body and makes you hungrier, persistently hungrier, and makes you more likely to put on fat tissue rather than burn it up in your muscles.

So, that’s a double whammy. So, it’s both, but lifestyle, yes. Lifestyle’s incredibly important. 

Bret: 
Yeah, it’s fascinating how it’s all interrelated and interconnected that way. And you had brought up fecal transplants, which they talk about in the Netflix documentary that you’re involved in, Hack Your Health.

They talk about fecal transplants there to explain it to the kids. And that I thought was pretty fascinating in terms of just demonstrating the power of the microbiome, especially if it’s a C. diff-type infection where it can be used clinically, but also for people to lose weight with a fecal transplant like that.

When I first heard that, that kind of blew my mind. So how does that work? 

Jack: 
It’s the same way, it’s like saying, going back to Anna Karenina, happy families are all the same, unhappy families are all different in different ways. You’ve got a disturbed microbiome. It’s sitting inside your intestine, and it’s pumping out these chemicals, right?

So, you’ve eaten the wrong food, you’ve done the wrong kind of exercise, or you’ve taken the wrong kind of medicine. And not necessarily wrong, but it’s had an bad effect upon your microbiome. Now, you’ve got a disturbed microbial ecosystem. And now, when you get a disturbed ecosystem, things can move in.

That’s when you get invasive species coming in. So, when we talk about fecal microbiome transplants, the only FDA-approved therapeutic for, the only FDA-approved clinical application for fecal microbiome transplants is for treating recurrent clostridioides difficile infection or C. diff. This causes chronic and sometimes lethal diarrhea, which can be a massive problem in people.

And our first line defense is antibiotics, but the antibiotics don’t always work. And the bug keeps on coming back and back and making people’s life hell and often killing them. So, we take that ecosystem, which is damaged and is allowing this C. diff bug to constantly reinvade and sprout up and start to cause hell, right?

We take that ecosystem, and we replace it with a fully functioning rainforest that we put up it back inside your intestine. And this rainforest is like, yep, I’ve got all my friends around me. I’m feeding off of these plants and these animals and these birds and these bacteria and everything’s great.

It’s amazing, and I am robust. And then the little C. diff bug comes back in like a little houseplant, tries to get back inside your gut and it can’t. It just dies, and it gets pooped out again. So, it’s about replacing that ecosystem inside you with something that’s robust and can stop invading organisms from taking over.

And for weight loss, it’s the same. Again, that idea that the way we eat changes the microbiome, which can make your body more likely to be hungry and more likely to put on fat. Okay, so your gut microbiome is now changed. It’s very hard to shift it back toward diet.

For example, one study done by a group in Israel, estimated it would take about nine months on a high fiber, high polyphenol, really healthy diet to shift the microbiome back to a state where it was that robust, healthy rainforest that would not promote obesity after you’d abused it enough to get it into a state where it does promote obesity. So, you take a fecal microbiome transplant of this rainforest and you pop it back in there, it’s like a quick fix.

Instead of having to do nine months of eating this healthy diet, now you’ve got a healthy gut microbiome there. But the problem is human beings are not very good at listening to advice. I, myself, tend to eat a burger probably too frequently. And, I know I’m not always, I don’t always listen to my own advice, probably tend to drink too much.

In doing so, I erode the benefit of that now healthy ecosystem. So, you are constantly playing a cat and mouse game between replacing the microbiome to make it robust and healthy, and then your lifestyle trying to erode it. And the best thing is pop a good, healthy microbiome there, now live a healthy lifestyle.

And trust me, 95% of the time, that’s going to work wonders to make your body healthy, and it’s a double whammy. But if you don’t, you’ll have health benefits for a short period of time, and then as your lifestyle erodes that healthy microbiome, your disease will start to come back, whatever that disease is.

Yeah. So it’s, you can lead a horse to water, but you can’t make them. 

Bret: 
Excellent analogy. So, then you mentioned a couple specific foods. Let’s talk about the healthy microbiome foods. And the joke is you can study the microbiome all you want, and the answer is eat more fiber and eat less ultra-processed foods.

All roads lead to Rome is the joke like, yeah, but how true is that? 

Jack: 
It’s true in as much as generally around the world, when we look at communities from pretty much every part of the ecosystem, people eating more fiber tend to be healthier. It’s a rule of thumb, right? But there are people for whom certain types of fiber actually do cause significant gastrointestinal inflammation and can cause damage to the microbiome and to the body.

And there’s some people for whom it takes a long while to get their gut ready to actually receive fiber in that way. And there’s communities that have evolved over time, such as the Inuit in northern Canada and what is now Canada and what is now Greenland, who do consume fiber, but it’s more fiber processed in the intestines of other animals.

And then they consume that alongside quite a rich, high-fat diet, right? But their bodies have evolved, receive that information, and their microbiomes evolved alongside that in order to maintain a healthy homeostasis. The health effects of their food have evolved with them. And so what we see is that it’s, there’s no one size fits all solution.

The rule of thumb can be for anyone growing up in pretty much Africa, Europe, or even Southeast Asia. These dietary or, and quite often we see similar traits in certain parts of the Americas and native populations there, if you are eating more fiber, you’re going to be healthy. But other people, it may not be true.

And we need to therefore use the microbiome to figure out what they might need in order to stay healthy, what might be appropriate for that individual, and or that community. So it’s not an easy solution. But on the whole, if anytime I, somebody asks me, I say, try to get 30 grams of fiber in you a day minimum.

Try to eat the rainbow. Eat as many colored fruits and vegetables as you can. Try to cut out refined sugars. Try not to eat too many processed foods. And try to exercise a little bit, and those, will all have health benefits. Exactly what your mother told you to do 20, 30, 40, 50 years ago.

Just listen to your mom, and you’re probably going to be okay. 

Bret: 
Yeah, I like how you mentioned also to not eat sugar and ultra-processed foods because what we don’t eat is just as important as what we do eat. And so the specific example that we think about a lot here at Metabolic Mind is people who are eating a very low carb ketogenic diet or sometimes even a zero carb carnivore diet, and seeing amazing improvements in their health from metabolic health to mental health to autoimmune conditions.

And on the surface, it’s exactly the opposite of what you should be eating for a healthy microbiome because there isn’t all that much fiber, although there certainly can be in some ketogenic diets with plenty of fiber. But what you’re not eating is the sugar and the ultra-processed foods and the refined carbs.

So how do you juggle that with a relatively low fiber diet, having incredible health benefits, and what kind of impact where does the microbiome fit into that? 

Jack: 
You have to understand it’s not like those, it’s not like a carnivore diet is just about meat. A carnivore is eating herbivores.

And the, if you are eating the right kind of meat, it’s actually full of quite nutrient dense, compositional material, which your body and your microbiome can then disassociate and process in different ways. Meat is a, let’s say beef or lamb or something where the animals have been eating out in the field.

It’s full of incredibly valuable molecules that can help your body to stay healthy and also can, your microbiome can, process certain processed meats, lack most of that beneficial nutrients. So it’s complicated and the ketogenic diet, yeah absolutely, shows amazing benefits for people with certain neurological conditions and that can be incredibly valuable.

And that’s part of this matrix of understanding that we’re trying to deal with now, yeah. Are these things traditionally associated with a beneficial microbiome? No. But then, the Inuits up in northern Greenland would also say, actually, we don’t necessarily need all of this fiber.

We’re mostly eating seal meat, and gannets, and fermented foods, and that’s where it all comes down to it. A wonderful study demonstrated, from the Sonenberg labs up in Stanford did a study where they demonstrated that people, if we take somebody whose gut microbiome is not ready, and we put them on a high fiber diet, it can actually make the problem significantly worse.

So, what they did is they demonstrated that if we put them on a fermented food diet, first of all, where we’ve already got microbes that have been taking food and digesting it and producing lots of lovely chemicals in a drink or in a food substrate. And then we put that inside the body, it actually promotes an improvement in the microbial ecosystem and makes their body ready to receive the fiber.

The microbiome is now primed to be fiber consuming. And I look at some of these communities where they eat a lot of meat or they eat a very high protein diet, and they often also consume a lot of fermented foods. Why? Because they had to, right? They had to preserve things. So, a lot of times they’re eating the meat, or they’re eating the high protein in a fermented form. And so, they’re actually getting a lot of those beneficial microbial products that from this fermentation process, that’s helping their body and their microbiome to stay healthy.

So it’s a complicated scenario, but I’d say if you can’t eat fiber, stay away from starches. Absolutely stay away from complex and processed carbohydrates. But if you cannot eat plant fiber, for example, then try and eat fermented foods alongside your otherwise carnivorous diet. It can actually be beneficial.

Bret: 
Yeah, all right. That’s a good take on that. One thing that has occurred within the realm or the world of the microbiome, is it’s gone from the research setting to the commercial setting now. And people are coming up with these microbiome testing kits and precision nutrition to say you can change your diet based on what we find on your microbiome.

And I’m curious like what you think about that as someone who’s so deep into the research and knowledgeable of the microbiome? What do you think of those commercial kits and precision nutrition based on it? 

Jack: 
It’s complicated. And I will note, I used to be on the scientific advisory board of DayTwo, which was one of those companies that was taking the microbiome and predicting a diet to reduce your blood sugar spikes and troughs after eating food.

And I do have a lot of connections. So, for example, our citizen science program, American Gut, formed something called British Gut and that became a company called Zoe in the UK, which does a very similar thing. And so we’ve got a lot of connections with a lot of these companies. I’ve got no problem with them using the data they generate in order to provide people with actionable advice.

So as long as they are publishing the results and demonstrating that their program works, and it actually has an impact. That’s absolutely fine. I know a lot of companies that don’t appear to be publishing or appear to be publishing very low quality articles, which are very questionable, and that really worries me because it means that they are potentially just selling snake oil. If they cannot prove that their product works, then why are they selling it? And why are people buying it? I would go with companies that prove that their product can work.

In the scientific field that it’s peer reviewed, and that people have looked at it, who know what they’re doing. But that being said, if you’re a clinical doctor and somebody comes to you with a microbiome profile and says, I got this from a website. And it says, look, I’ve got these bugs up here and these bugs are low, and how can I use this?

Can you use this in your clinical practice to help diagnose me or provide a prognosis? 99.999% doctors are going to be like, no, not really. So we’ve got to, we have to go a long way forward in order to be able to integrate that kind of data into something which is useful for clinicians. For example, the current research spike that we’re trying to deal with right now is to use AI to take all of the incredibly rich, diverse, and enormously large data sets that we currently have available over the last 10, 15 years of research and to use AI, and I use that term broadly because we’re using 15 or 16 different AI mechanisms, but use AI to try and take a single microbiome profile, compare it to the 5,000 thousand microbiome profiles we have available and say what features in your microbiome profile might be predictive of disease risk, and what is the, precision and accuracy of that claim.

And that is saying, look, we now have enough data that we can use statistical approaches exactly the same way as we do in clinical practice generally to make these assertions, to make these prognosis, to make these predictions or diagnoses. We can now say that if your microbiome looks like this, there is X percent risk of this disease or X percent chance that you will respond to this medication in a beneficial way or x percent chance that your body will respond positively to this diet.

We are getting there and we’re getting much closer to that reality, but it’s taking time. So, I’m confident that there are companies out there that can do this.

I’m also confident that we are on the cusp of a clinical revolution where we will integrate this data into clinical practice exactly the same way as we would take a blood pressure cuff or a lipid, blood work panel and determine and predict your chances of cardiovascular disease or type II diabetes.

This is happening. It’s happening now. It’s just, it takes time. We’ve only been doing this for 15, 20 years. And the ecosystem takes time to mature before we can actually put it into clinical practice. I have an article coming out in, we just submitted it to Nature Medicines. Me and the great and the good, I gathered all of my colleagues from around the world, who work in this translational space, and, we wrote an article where it, we go into detail about that particular problem. How do you translate this monstrously large quantity of information? There are currently now, we have two FDA-approved clinical therapies.

One’s called VST, one’s called Rebyota. Both of them are used to treat recurrent C. difficile infection. They’re refined microbiome therapeutics. We have 8 or 10 phase 3 clinical trials, but using products which are relevant for various diseases that are all microbiome-based therapeutics.

And there’s another 9 phase 2 clinical trials, which are in a similar state, right? So, it really is, we are really at this cusp, this inflection point for translation of these research-based therapeutics. Now, whether a direct consumer, customer facing company is going to have the ability to deliver these therapeutics, no, I don’t think they are.

But if you are integrated into clinical trials, and you’re interested in putting this in the hands of medical practice, that’s great. But there are other products which will never be valuable in medical practice, and then we need to have a direct to consumer route, right? Probiotics are a great example of this.

We need to figure out why probiotics work in some people and not in others. There’s a lot of phase 2 and phase 3, double-blind, placebo controlled, randomized clinical trials, grade A clinical trials, which demonstrate that these things can be effective in certain people. So, that’s a way of making sure that the public can get access to the benefits of these therapies, and that they aren’t locked behind a firewall of insurance.

Bret: 
Yeah, and complicated, is complicated. Medicine, unfortunately, likes guideline-based care. Treat everybody the same, XYZ. Here’s your protocol, yeah. Whereas, what clearly what we’re seeing is that does not play in the real world and certainly with the microbiome. A lot of the research that we see right now with ketogenic therapies, metabolic therapies for treating mental illness.

One of the questions is how do we predict who responds amazingly well, who responds moderately well, who doesn’t respond? So, could the microbiome be part of this? It sounds like that’s what you feel like we’re on the cusp of doing with all this machine learning AI to process all that data.

So, do you think the day will come where you show up with your microbiome test and your other blood work, and you say, okay, you go to the ketogenic diet, you go to a plant-based diet, you eat Mediterranean diet, or that degree of specificity? Or would it be like you take this specific probiotic to bump up your bacteroides and you take this specific one to bump up that? I’m just curious kind of what direction you see this going.

Jack: 
You got two directions. You can either say everybody has to go back and live on a farm and become a granola eating hippie and get back to nature, which I think would be great. And I love it. 

Bret: 
Sounds pretty good, yeah. 

Jack: 
Just give me away from all of this craziness. But I think it’s unrealistic in our current culture and our current society to expect that.

So, what I’m trying to do is make sure that people, that we can package up the benefits of eating healthy, of living healthy and put it into therapeutic applications either direct to consumer or into the clinic that where we can have a real effect on people’s health. We’ve launched a product called, The Gut Lab, through a company, which I did co-found, I do hold equity in, that will monitor your microbiome daily at home or in the clinic.

And so we, this is deployed into clinical trials right now, but you can imagine a future where. you have data streams coming out of you in the morning that you can track that can, like your watch tracks your blood pressure and your heart rate and your number of steps.

You can also track the microbial community inside your intestine, or on your skin, or in your oral tract or your genital tract, and use it to create personalized advice, like you mentioned on a day-to-day basis. I do my data dump in the morning, and the signature that comes out suggests that I have a risk of a depressive episode, which is being tied into my clinical records, which stipulate that I do have a family history of depression.

And I’ve experienced depression in the past. Now, you’ve got two choices. It could say, we think there is in this microbiome profile, this depressive episode may hit. You have a 20, 30% chance of a depressive episode in the next 10 days. These are therapeutic options, which you could implement, right?

Either take an antidepressant or change your diet or take this probiotic or maybe exercise more. We need that interface and chatGPT has demonstrated to us that large language models can be highly effective at translating how doctors communicate, to how patients want to communicate.

And we’ve shown this here at UCSD. Patients overwhelmingly prefer a chatGPT-generated response that their doctor puts in, and then it’s translated into patient-ese. Then they do the original doctor communication, right? We need the same thing for all of this clinical data that we’re receiving.

We need to take all this data in, put it through a crunching machine and put it out in a language and a way in which social scientists can explain to us that people want to hear that can move the needle in terms of their behavior. We cannot expect, and I think we’ve seen this recently, but we cannot expect logic to, or truth to change people’s minds.

So, what we have to do is take data and transmit it into a format ,which can help to move that social needle effectively, allowing people to interact or access the benefits of these health realities. And yeah, I think the future is more along the lines of full data integration and putting information in the hands of participants. 

Bret: 
And when you’re talking about 40 trillion microbes in each individual, that’s quite a bit of data for sure. So, it’s interesting how the rise of machine learning and large computer systems and large data systems is really. Ripe for the microbiome for that reason. 

Jack: 
It’s incredible.

Bret: 
Yeah. one last question that you’ve mentioned exercise a couple times. And, of course, exercise is incredibly beneficial for health, in general. But I’m just curious, do you mention it because it can impact the microbiome or as you mention it for the general health? 

Jack: 
It’s, it is an interesting point.

Okay, so why the hell would exercise affect the microbiome? And I questioned this for years. So, we started doing experiments about 8, 9 years ago, and one of my colleagues, Jarrad Hampton-Marcell at University of Illinois, Chicago, really took this to the next level. But it, what it demonstrates is, okay, so inside all your muscles are mitochondria.

All the cells inside all of your cells inside your body have little mitochondria. These are powerhouses, but they’re actually ancient bacteria. That were captured about 2 or 3 billion years ago by an archaeal cell, and it captured this bacteria, and it harnessed it. And it’s used it to generate energy inside its body.

Plant cells have a photosynthetic bacteria called a cyanobacteria. Animal cells have a heterotrophic bacteria that just can take nutrients and pumps out energy. So, this happened 2, 3 billion years ago. All your cells have these ancient bacteria living inside them, and they speak exactly the same chemical language as the bacteria living inside your gut.

So, when you exercise, you have to stimulate these mitochondria to produce energy that helps your muscles move. But they also pump out chemicals, which get into your bloodstream and actually permeate into the intestine and are chemical, communication pathways, which stimulate and tell the bacteria in your gut to do certain things. And the gut bacteria in your gut, and then pump out chemicals, which get into your bloodstream and communicate with the mitochondria in your muscles.

So, you’ve got this two way communication level, and we can show this. We can take chemicals that the mitochondria pump out and put it into an animal, and it will stimulate the gut bacteria and take chemicals the gut bacteria pump out, put it into an animal’s bloodstream, and it’ll stimulate the mitochondria.

So this is a two-way street. When you exercise, you’re also, you’re allowing your ancient bacteria in your muscles to communicate your gut bacteria, and it produces benefits. Why? We don’t necessarily understand that, but we know it works. So, do a little bit of exercise. Not too much though, just enough.

Bret: 
Just enough. \We’ve had lots of discussions with Dr. Martin Picard and Dr. Chris Palmer, who are really big on the mitochondria, and once again, we see it all comes down to the mitochondria. They are, yeah, mitochondria. 

Jack: 
They’re amazing. And yeah, again, because they’re ancient microbes, I can say that with, and keep my microbial credentials intact.

Bret: 
Nice. Nice. I really appreciate you taking the time to go through all this, which can be a complicated topic. But you, I think you, you explain it in a very graspable way, which I like. And so we already mentioned your book, diet is or sorry, Dirt Is Good, and your Netflix documentary, Hack Your Health.

Where else can people go to find out more about you and learn more about the microbiome? 

Jack: 
I have a website. Just type Jack Gilbert into Google, and there’s lots of information on there. And I’m not the dead poet. I wish I was, but I’m not. I’m the microbiome scientist. 

Bret: 
Excellent. Thank you very much.