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cover of episode 577: The gut-brain axis, inflammation, & fecal transplants | Charles Akle, M.D.

577: The gut-brain axis, inflammation, & fecal transplants | Charles Akle, M.D.

2025/1/26
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Charles Akle, M.D.: 我认为我们实际上是我们微生物群的一部分,没有微生物群我们就无法正常运作。免疫系统和微生物群之间的联系至关重要。微生物群的关键在于多样性,每个人的微生物群都像指纹一样独特。免疫系统对我们的生存至关重要,它具有防御和创造的双重作用,而没有微生物群,免疫系统就无法发挥作用。我认为城市生活方式、饮食习惯、过度清洁和抗生素的使用都会对我们的微生物群产生负面影响,降低其多样性。我们需要接触一些“脏东西”才能生存,这有益于我们的健康。环境中的微生物,特别是分枝杆菌,是触发有益免疫反应的关键因素。农村社区或经常接触狗、猫和“脏”哥哥的社区,过敏性疾病的发病率较低。阿米什人和胡特尔人的生活方式差异导致了哮喘发病率的不同,这表明环境变化对健康有重要影响。

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Welcome to the My Buddy Green podcast. I'm Jason Wachub, founder and co-CEO of My Buddy Green and your host.

This episode of the MBG podcast is sponsored by IMI. Most of us only start thinking about our immune system once we're already feeling under the weather. And while a thriving immune system does help us keep healthy during cold season, it does so and so much more. That's why folks are turning to IMI, a daily supplement that supports your immune system and overall health by reintroducing healthy bacteria back into your gut microbiome.

A healthy immune system plays a huge role in your overall well-being, from better mental health to enhanced resilience to improved inflammatory status. IME's hero ingredient is an ancient bacteria strain we used to have in our microbiomes naturally, but that's been lost to modern living. It acts as a conductor for our complex immune system, thereby improving our inflammatory status, supporting the gut-brain axis, reducing the body's stress response, and enhancing gut health.

So if you're looking for a natural, effective solution to help your immune system fight off sickness and address inflammatory status, mental health, and overall resilience, this is your solution. Retune your immune today at immi.co. That's immi.co for more information. I can say to my new Samsung Galaxy S25 Ultra, hey, find a keto-friendly restaurant nearby and text it to Beth and Steve. And it does without me lifting a finger. So I can get in more squats anywhere I can. One, two, three.

Three. Will that be cash or credit? Credit. Galaxy S25 Ultra, the AI companion that does the heavy lifting so you can do you. Get yours at Samsung.com. Compatible with select apps. Requires Google Gemini account. Results may vary based on input. Check responses for accuracy.

Did you know your gut microbiome is as unique as your fingerprint and is one of the most crucial aspects of your health? Today we're exploring the fascinating world of the gut-brain axis, inflammation, and immunity with Dr. Charles Akel, a leading surgeon and immunologist with over 40 years of experience.

Charles explains the intricate connections between your gut and your brain, shedding light on how your microbiome orchestrates immune responses, influences stress, and even impacts your longevity. In today's show, we'll discuss the hygiene hypothesis, the surprising role of mycobacteria in supporting a balanced microbiome, and how modern life is disrupting our health.

We'll also dive into actionable tips for nurturing your microbiome, from embracing nature to making smarter dietary choices and discussing the promising future of bugs as drugs in personalized medicine, as well as fecal transplants. Yes, you heard it right, fecal transplants. Whether you're curious about cutting-edge research, intrigued by the future of microbiome-based medicine, or just looking for practical tips to support your gut, this show is packed with insights you won't want to miss.

So remind us, what is the role of the gut microbiome on our overall health? Well, the simple answer is that we are part of our microbiome. We're not just one organism, we're a whole multitude of organisms.

And the microbiome is really, as you all, and I'm sure our listeners know, the bugs that live in, on, and around you. And without that kind of interaction, we can't function. We really cannot function. And the key element that controls that is the immune system. Therefore, the linkage between the immune system and the microbiome is the fundamental of everything.

and this is what we've learned more recently than before. And so the microbiome is something that

really hinges on diversity. It's not just one bug. There are companies out there desperately trying to search out the 4, 5, 10, 20 organisms that might make a difference. In fact, it's 40,000 to 50,000, and each one of us has a unique microbiome, like a fingerprint. You could actually identify an individual from their microbiome if you looked hard enough.

So, it's diversity that is the key.

produces diversity and regulation, if you like, in our immune system, which is what keeps us healthy. And it's really more important to ask about the immune system because that's what helps us to stay alive. It has a defensive role and a creative role. And without the microbiome, it won't function. - So you mentioned the immune system and everyday life is brutal in the 21st century, to say the least.

And so can you talk about how 21st century life is negatively impacting our microbiome and thus affecting our immune system? And then we'll get into the gut-brain axis as well. Well, in fact, there's an excellent paper by Bach in 2002 that demonstrated very clearly that in the last hundred years, there has been a dramatic reduction

infection in serious infectious diseases like tuberculosis, measles, etc. Although now they're beginning to pick up because of vaccination issues. But the incidence of asthma, diabetes, multiple sclerosis, inflammatory bowel disease has rocketed. The graph just goes straight up. It's terrifying.

That really prompted people like Graham Rook, Chris Lowry, some of these great, great thinkers, and have written on the microbiome extensively and still researching it, to suggest that this is to do with a change in our environment and our relationship with our microbiome. Diversity, what I was talking about, seems to be the case. If you live in an urban jungle,

With the sort of diet we have in the West, with the cleanliness that we have with the West, the antibiotics that we're taking that damage and change our microbiome dramatically. If you compare that to the diversity of somebody living in the Amazon or in Africa and places like that, it's dramatically different, as is their health.

That raised the issue of what we call the old friends hypothesis, what was known as the hygiene hypothesis. Probably the hygiene hypothesis is easier to understand. A bit of dirt. You need to have a bit of dirt to survive. It's good for you without going too far. The old friends expands that into the microbiome.

The interaction with infections that you pick up in infancy, which actually, if they don't kill you, make you stronger.

and the interaction with your environmental organisms, which include worms, by the way, and in particular the mycobacteria, which is the interest of mine. The mycobacteria in our environment are present in almost all the Earth's soil and mud and water, and they are a major element to triggering microbe.

beneficial immune responses. So, these rocketing incidences of asthma and eczema and whatever, just as an example, are quite interesting because if you look at communities which are rural and urban or communities that have exposure to dogs, cats, dirty older brothers and things like that, you'll find that the incidence of allergic diseases is far lower.

A classic case are the Hutterites and the Amish. This was published in the New England Journal of Medicine and in Nature. If you look at the lifestyle of the Amish and the Hutterites, who share genetic backgrounds, because the Hutterites are more modern, they have four times the incidence of asthma because of the dust in their houses being different to that in the Amish community. In fact, if you take the dust from an Amish household

and you put it into a Hutterite household, they improve. If you take the dust from the Hutterite household, you put it into the Amish household, they get asthma. So this is all an environmental change that's taken place because of modern life. Wow, fascinating. So it sounds like you want to be exposed to the elements, so to speak, but it's got to be the right environment.

elements, specifically the mycobacteria, and that's short for, I'm going to butcher it, can you do it for me? Mycolysebacteria. We only call that because it's a subclass of the mycobacteria. When you mention mycobacteria, it can scare people because, of course, tuberculosis and leprosy are mycobacterial illnesses, but they account for

two out of some 200 bacteria. And the Mycolici bacteria, by definition, are entirely non-pathogenic and benign, which is where imi, our mycobacterium, mycobacterium aurum, Aogashima, fits in. That's why we use it. It's completely, completely non-pathogenic and has this

common soul effect, right? So that's very important to understand that. And this urban-rural thing is very important. Listen, you don't want to go and be eating...

any old dirt and ending up with typhoid or cholera or something stupid like that, which, by the way, is where fecal microbial transplant, which I'm sure some of our listeners will be familiar with, is terribly important. And it's part of a research program I'm looking at because the effect of doing a fecal transplant is

on a patient who is quite ill can be dramatic. The response rate's fantastic, but you need to be careful. - Let's talk about that one, 'cause I remember a decade ago, we were talking about fecal transplants and how exciting they were. So what is the update on fecal transplants? Where are we?

In terms of the efficacy, and maybe just give a primer, because some people are probably watching or listening and saying, whoa, is that what it is? Is that what it sounds like? And so maybe define what it is. Well, the FDA approved indication for fecal microbial transplant, which is where you take

feces from a healthy person who has been very carefully screened and put it into a sick individual is the treatment of a condition called hospital-acquired infection by Clostridioides difficile. It's a hospital-acquired infection because you had too much antibiotics, you're immunosuppressed, and it looks like somebody's taken a blowtorch to your colon. I mean, I'm so old as a surgeon.

We used to have to remove the colon to try and save these people, and we ended up killing them. So if you have C. diff and you give antibiotics, there's an antibiotic called vancomycin, for example, you get something like a 40% response rate with conventional treatment, 40%.

Not good. If you do a fecal transplant from a healthy patient, response rate, 94%. 94%, which is spectacular. You're essentially just taking the stool from someone who's healthy and

and essentially inserting the stool right up there to the person who needs it. And that is 94% effective, whereas antibiotic treatment for C. diff is 40%. Wow. And that is FDA, MHRA English. This is a regulatory indication for fecal transplant. And for example, the stool bank that we're working on at the University of Birmingham in England

has the country's stool bank so that any hospital in the country with a severe case can access the stool bank and we ship the stuff out to them. So that is the indication of pyroxenolase. However, if you look at inflammatory bowel disease, and we're talking about Crohn's disease, ulcerative colitis,

And, indeed, some of the arthritides, the arthritis issues, there is no question that there is a big signal in giving an unhealthy patient a fecal transplant. Even more exciting is, again, our listeners will have heard about checkpoint inhibitors, these new immunotherapy agents. And the papers came out in the last two years showing that if you have

malignant melanoma, nasty skin cancer, and they give you immunotherapy, you've got about a 50% chance of getting cured. I mean, it's phenomenal. Look at President Carter. Although, bless him, he's in a home, he's had brain metastasis since 2016. He should have been dead within three months of that, right? However, 50% respond, 50% do not respond. Why?

And the interesting thing is, if you take feces from responders and you put it into the non-responders, you get a 30% uplift in response. If you take feces from a healthy person and you put it into the non-responder, you get a 50% benefit. Well, now that's just, that tells you something, doesn't it? I mean, how credible is that? It's unbelievable. And so the implications are way bigger than C-DEF. And if I'm listening, I'm thinking,

Okay, maybe I'm struggling with autoimmune. Maybe there are immune issues. I just can't. I'm immunosuppressed. And fecal transplants could essentially solve a whole host of issues that people are facing. But you have to be careful what you wish for. I mean, I think that's absolutely... Oh my God, I don't think anyone's like, I wish for... I'm like, I'm not going to raise my hand for a fecal transplant.

It may be that every patient who's being treated for cancer needs to have some kind of fecal transplant supplementation, which is where we're headed. But I think that we have a danger as human beings that if you see, well, this thing works for one thing, God, it must be good for everything. It's the panacea. It will be part and a major part of the holistic treatment. I'm a great believer in the holistic treatment of the patient.

But this is incredible though, because we've been talking about this literally, I remember in 2014 having this discussion and here we are, and it feels like it's starting to arrive. It is. The problem has been the delivery. A, collecting the material and having it saved. The second thing is nobody really wants a tube stuck down their nose.

and into the jejunum, to put it, or a colonoscope, or even an enema, there is a much easier way of getting it in. But I tell you what's even more interesting, Jason, and that is everybody thinks it's the bacteria.

that is involved, which is, again, a simplification. There's something very strange going on because there is a term which I used ages ago and has now been written into a book called dark matter. And again, the listeners will know about dark matter in the universe and how much of the universe is dark matter. I think in fecal transplant,

And this whole microbiome story, there's a big chunk of dark matter we don't understand. So with C. diff, for example, if you filter, you do ultrafiltration of the stool. So you take out all the bacteria and you put the ultrafiltrate in, you still get an 80% response rate. So you have to explain that.

Now, you can say, well, of course, there's viruses, bacteriophages, there'll be fungi, yeast, and extracts. But there's all sorts of new bacteria out there. For example, there's a thing called the candidate phylum radiation.

which you can go and look up. But that's a 40% component of life on Earth and some 40,000 new bacterial-type species, which we can't culture. We've only been able to culture two of them. There's some very strange bugs out there. You go down to the depths of the ocean and you find giant viruses. You find organisms that can survive in a sort of fumarole, a volcanic fumarole. It is...

There's so much out there that we don't understand. And that's why you have to be rational and careful. And you've got to do your own proper studies. The papers I mentioned about the checkpoint inhibitors and immunotherapy are in very, very serious journals. It's not the Outer Mongolian Herald or something like that, or the National Enquirer.

This is big, big papers. So I think we have a lot to learn. But what we do know is that you need to have modulation. The key thing about the microbiome is the diversity. And I don't care what the diversity is, so long as it's there. You get the diversity. But like the analogy we use at IMI, which is the orchestra. So you have all these different instruments.

musical instruments in the orchestra, but somebody has to put it all together and get the music so you get beautiful music. And that's the conductor. And that's where we find the Mycolysis bacteria, of which Imi is one, has a critical role. And that's why the exposure into the environment, to the rural environment, you need exposure to mud and dirt.

to get contact with these organisms because they act as modulators. They act as immunoadjuvants. They are tuners. They're brokers, if you like, of the immune system. And I can go into more detail with the gut-brain axis in a moment, as we will discuss. Just one thing before we go. I want to go to the gut-brain axis. How do you view diet?

versus environmental factors? Are they equally weighted or is it we all unique when it comes to this? What's your take? That's such a great question. And a few weeks ago, I would have said, well, you've got to eat all the different kinds of fruit, vegetable, et cetera, to vary the microbiome.

Do you know a recent paper in Nature just a few weeks ago, only 3% of the bacterial variation in your microbiome comes from the food you eat?

3%. It's only 3%. And that blew me away, right? 3%, I mean, if you ask anybody, you'd say, well, it was 90% or whatever, right? But 3%. Now, if you're a baby, it's 50% because you're getting it from your mother. You're getting your mother's milk and what have you. So it's 50% in a baby. And then it drops as you get older down towards the 3% mark. Well, that means that some 97% must be coming from somewhere, right?

Of course, a big chunk of that's going to be environmental contact. The way you touch people, you get it from other people, from animals, from the environment, the soil. All these other sources of interaction with your environment have become that much more important and relevant.

So it's not just the food that you eat. You've got to eat the food. No question. You've got to farm, as I always say, your microbiome. But you must remember that there's a lot more going on and we've only just scratched that surface. Isn't that fascinating? It is because I think there was a school of thought that you must have, you know, diversity in terms of how you eat and you must eat a certain number of foods.

fruits and vegetables. You must have probiotic foods in a certain amount every day. And like, look, I think everyone agrees you should eat whole foods. Don't eat ultra processed foods. But I think it takes, alleviates some of the pressure for someone who takes this seriously. It's like, oh, you know, I only had blackberries today, you know.

Yeah. Well, I mean, I think that's exactly right. I still think you have to farm it. I still think you have to have your fibers so that the bacteria that are there can be nourished and do their thing. I think you need that variety and eating lots of different fruits and vegetables. It's not just the bacteria because, of course, as you know, a lot of fruit and vegetables contain so many other chemicals.

So the polyphenols, you know, that's why things like the black fruits and berries are so good. Curcumin is so good. But on the other hand, a lot of your microbes produce very helpful nutrients.

material, you know, chemicals that are actually very good for you. So, but you, you know, that 3% probably is, is, is much more important. It, it, it, um, it sort of bats above its, uh, it bats above its average, but that's where it all comes from. Isn't that, it's just fascinating. It is. And it really makes the case for getting outside in nature.

Absolutely. You've got to get out there. And the proof of that, as I said, is, for example, the Amish Hutterite thing. But in Germany and in Finland, for example, and particularly in Finland and Scandinavia, the children's playgrounds, they take forest material and they put it all over the playground. So the kids are playing around, not on concrete, but they're playing around with turf.

It's all got the bouncy turf now, which I get, you know, but. Yeah. I mean, there's a wonderful joke by a great American comedian that when he was a kid, the playgrounds had broken glass and concrete and nobody got hurt. Now with the bouncy turf, they'll break something. But that's a joke. But, you know, having mud and forest material and stuff like that reduces the incidence of asthma and stress, stressors.

stress in those children. And the inflammation and stress are intimately linked, very, very intimately linked. We know that as an example. Acute stress we know is quite good for you. So if, for example, you're walking along in the savannah as our ancestors did and a lion comes to you,

Well, you get acute stress, right? Your adrenaline shoots up and the fight or flight, you run like hell or you get...

And then when the lion's gone away, everything comes back to normal. And we've repeated this experiment, by the way, with urban and rural subjects in Germany. We took 40 patients. This is Stefan Reber's work and Chris Lowry. Took 20 subjects who are city slickers.

never have dogs, never been in the countryside. We took 20 people who lived on farms and exposed animals, stressed them with emotional stress, measured their

levels of cytokines, particularly interleukin-6 and these other measures of inflammation. There's no question that the city slickers are chronically inflamed and they don't respond well to stress. The rural people respond really badly, but they come back to normal.

So, the analogy of that which I teach is it's like going down into the woods. If you're going to the woods and you think, "Oh my God, behind every tree there's going to be a bear that's going to come out and jump and eat me," right? And you never get rid of that fear that there's a yellow cab going to run you over or somebody's going to mug you in the underground or whatever. The bear is behind every tree.

And so you get scared and you get chronically excited. And then eventually you attenuate and you think you can cope with it. But actually, the stress factors on your body are still there and it doesn't do any good. Have you still getting around to that fix on your car? You got this. On eBay, you'll find millions of parts guaranteed to fit. Doesn't matter if it's a major engine repair or your first time swapping your windshield wipers.

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eBay. Things. People. Love. Eligible items only. Exclusions apply. Found. Is there a minimum effective dose in terms of nature and or is, you know, a certain type of soil better than white sand at the beach?

versus the ocean, or do we not know any of this yet? - Oh, no, we know quite a bit. There are a couple of factors that come to mind. One is that any soil that is natural and things is great. In fact, there are some traditions, there's this church at Chimayo in New Mexico

where miracles are supposed to be linked with eating the soil, for example. And they eat the soil to get miracles. And spray, by the way, on the beach contains mycobacteria. You have mycobacteria in the spray. So any rural exercise is healthy. But as always...

We humans, if one of something is good, 10 must be 10 times better. Not true. If you look at elite athletes, the kayakers particularly, there's a paper on kayakers, Olympic row men, racehorses. These are

Elite athletes, they over-exercise. You can do too much exercise. And when you reach the peak, you become immunosuppressed. Your interleukin-6 levels become so high that after your big race or whatever, you're very susceptible to viral infections and all sorts of stress issues. And so you can do too much. I think you just do enough exercise to raise a sweat, just a gentle sweat, a little bit of a sweat once a day.

Go out in the countryside, have a walk, think about it. I've just been doing this up in Scotland. It's just wonderful. Just good for the soul. And if it's good for the soul, it's good for your microbiome.

I love it. And so I want to come back to, we started to go here but didn't quite fully finish the thought, the gut-brain axis. Okay. So the gut-brain axis was something we didn't really understand. I have to tell you, as an old surgeon, and I'm a very old surgeon, back in the 60s and 70s, if you were anybody, you actually had a duodenal ulcer, which was due to stress and excessive acid secretion. And I spent a significant portion of my early life cutting the vagus nerve on these patients

to reduce the acid secretion and cure their ulcer. We don't see duodenal ulcer, interestingly, so much nowadays. And that's perhaps a blessing and subject for another discussion. But the point is that the gut-brain axis works on two messaging systems. One is LAN,

If you have a computer, you can plug it into the wire and the information goes up a wire, which is where the nerves, the vagus, and the whole sympathetic immune system works and parasympathetic system. Or you have Wi-Fi. And Wi-Fi is the blood-borne and lymphatic system where the cells circulate in the blood and go off to the brain. So both elements are extremely important.

What we now know is that in the gut, the gut is your biggest immune organ. It's by far and away the biggest immune organ in your body, which not a lot of people fully appreciate. And most of it is concentrated in the last 18 inches of the small bowel just before it joins the large bowel and near your appendix. Your appendix is stuffed full of immune tissue, which is why it causes problems every so often.

So in those immune cells, there are specialized cells called M cells, microfold cells, which have little fine filaments that go through the mucus and sample the environment. And they will specifically detect bacteria such as Shigella, which is, as you know, is a bad gut organism, cholera, salmonella, you've heard of the salmonellas, and microbacteria.

And that is why you need only a tiny dose of any of these, in particular, our mycolysis bacteria, IMI, is detected in minuscule amounts, in picomolar amounts by these M-cells.

The M cell then talks to a dendritic cell in the submucosa, in the wall of the bowel. The dendritic cell is the border guard. He's the guy who, when you arrive at JFK, wants to see your passport and your fingerprint and all the rest of it. So he decides, okay, yeah, I've seen this guy before. And one of the great things about the gut is tolerance. You need to have the induction of tolerance so that you don't react differently.

to every single person who comes in. Not every person who arrives at JFK is an international terrorist, right? They're not all cholera. They're not all Shigella. The great majority are decent citizens who just want to go about their business. And you don't want to waste resources on that. So the CD1 dendritic cell

If he senses danger, he then talks to the adjacent CD141 cell, which is another dendritic cell, which I guess is the FBI or whatever you want to call it. He then circulates the information. Part of it goes through the nerves and all lymph nodes and all the gut is very richly innervated. That goes up the vagus.

to the brain. It's the insular cortex, the island cortex. We know that data is then stored in the insular cortex, which is sufficient

to, if it's needed, to go back down the vagus. That's only just been proved in the last couple of years. It goes back down the vagus and it informs virgin, naive immune cells to react against whatever is needed. How that happens on a digital system, I don't know.

I'm very interested to see how the guys get on with that. But it is brilliant that the brain can actually store the information about your immune responses. So that completes the natural cycle which all biological systems work on.

That's where stress becomes an issue because, on the one hand, stress can affect your immune system and your immune system will affect your stress. They're completely interlinked. There's no point discussing about one without the other. Your microbiome is constantly feeding information into the immune system. It normally would induce tolerance or a reaction against a hostile and enemy threat. Every so often, something goes wrong.

and the gut sees something that it hasn't seen before and it thinks, well, this could be a threat and it reacts and you then end up with a big battle going on and chronic inflammation. So the bear in the woods who is, you know, you're frightened behind every tree there might be a bear, that's chronic inflammation, never settles down, you never calm down. And so that sets up the

cyclical reaction of bad immunity and whether it results in stress, whether it results in autoimmune disease, whether it results in cancer, all these things are closely interlinked. It's a flywheel. There you go. And so are there, I'm sure someone's listening and myself, I'm asking the question, I've done microbiome testing.

Are we there yet? Because everything I've heard is it's helpful, but it's a snapshot of a day. I mean, people have made a fortune. If I had a dollar for every one of those, I could, I could fund some of my cancer research, which I'm desperate to do. But, but, you know, uh,

There's something in it, but the truth is they test your microbiome and say, well, you need a bit of Acominensis or you need Thermicutes or you need this or you need that. You don't need all that. I've just told you it's only 3% of your microbiome is linked.

to your food. So why not just go and do those things anyway in the same way that you just go and do exercise? And I don't care what exercise you do as long as you build a little sweat. You don't have to be a big sweat. Do a little sweat every day. And that you eat healthily, you enjoy your food, you don't smoke, you don't drink too much. You know, there are all these... You don't eat the processed food, the junk food that I deprecate. I hate that. So...

All these companies will go and test your microbiome, say you need this, that, and the other. And then they always say the same thing. Well, you need a bit more beans and you need a bit more fiber and you need this and you need apples and you need stuff. Well, eat them anyway. What's your problem? So I think when I tell you that there's a lot missing,

the other 97%, you need a lot more stuff out there. And one of the things that you definitely need is a broker. And that's where IMI comes back in again. - Let's go there. Let's talk about IMI and how it's different than other immune supplements that just focus on the microbiome and a standard probiotic, if you will.

Yeah. Well, so, Amy, the whole story goes way back to, funnily enough, tuberculosis and the vaccine for tuberculosis, which is known as BCG, Bacillus Calmet-Guerin. BCG is an attenuated, weakened form of tuberculosis, which was used as a vaccine, right?

And today, in America, we don't use it as a vaccine. We tend to avoid it. In Europe, it's standard. You know, the kids get it. And of course, in places like Africa, you need it because in sub-Saharan Africa, HIV-AIDS is very high. You then get this drug-resistant vaccine.

multidrug-resistant tuberculosis, and that's what tends to kill the AIDS patients more than anything else, and not just in Africa. So BCG is also used in bladder cancer as an anti-cancer agent because it has pro-inflammatory effects.

Now, when I was a kid in the '60s and '70s, and we had a malignant melanoma, say, on your arm, we used to inject BCG into the tumor to try and stimulate an immune response and kill it. The first time you do it, it was good effect. The second time, not so good. The third time, you actually made it worse.

And we know, for example, that if you give BCG under the age of three, it's a good idea. It works very well. And after three, it doesn't work very well. The great thing about giving it below three, fascinating, is that it protects the kids from a lot of other infections during that first few years of life. It has what we call a bystander effect, a bystander immune effect, and in later life,

There's data occurring to show that it prevents cancer, certain cancers in particular, the lymphomas and breast cancer. BCG has this protective effect.

So we've known that there's something in these mycobacteria. And then basically, to cut a long story short, I've done 25 years work on this, trying to find it, to use it as an agent, A, to support BCG in those older patients where it doesn't respond, they don't respond well, and also as an anti-cancer effect because...

There was a great man called William Coley who, in the 1890s, worked in New York and became interested in infections inducing an immune response against certain cancers, particularly bone cancers. He's the father of immunotherapy. We think that inducing an immune reaction using... This is why BCG was tried, but it's too toxic. Inducing a reaction using these non-pathogenic...

Mycolysis bacteria has had some very interesting effects. We've done a batch of clinical trials on the sisters of IMI. The reason we don't do it with IMI, we have to be careful with claims, is that we already spent 80 million pounds, about $120 million, trying to develop those other things. Can you imagine the cost to the patient of trying to recoup that investment?

Whereas IMI we've done as a dietary supplement, and our aim is at $1 a day. I don't want to make money out of the misery of my fellow man. It's not what I went into medicine for. I hate that. But at $1 a day, most people can afford it even in sub-Saharan Africa. And so we don't want to go through that extremely expensive regulatory stuff, whereas we have got a lot of

very, very good scientific data and research data on the activation on human cells. The mycobacterial story, the precursor was called Mycobacterium vaccae. It's not cow vaccae. It's not actually Mycobacterium vaccae. It's slightly different. The other one was Mycobacterium obuensi, which is from Japan also, like Aurum is.

And, we found that we had quite a dramatic response. And the most interesting thing was, because we were hampered by the way clinical trials are done, to this day, double-blind control clinical trials are the wrong tool for immunotherapy. There are so many variables. You're only allowed one variable in a double-blind control clinical trial, really.

You have so many variables in immunotherapy that it just doesn't work and we need a new tool. But basically the point is that if you really want to try and get a response,

You need to have a holistic approach to what you're trying to do. You need to treat the whole patient. And what we found was that the patients who we tried to blind, as it were, you know, so we gave them a placebo, we couldn't do that because the minute the patient walked into the room with advanced lung cancer, we did a lung cancer trial, for example. This has been published in the literature.

When the patient walked in, you could tell immediately that that patient was on vacci or oboensis because they had a smile on their face. They coped with their illness. You tell somebody you're going to die from cancer very soon, they're usually a bit miserable, right? These patients felt well. And by the way, they didn't lose weight as much as the other patients. They just coped. And we thought there's something very, very interesting going on here.

And that's why we then twigged

We understood that there's something very interesting going on between the gut-brain axis, that the brain is having this tremendous effect in allowing you to cope with a very serious situation. And that's why we've gone this way, to try and make it available to everybody. And so for Emmy, and I think this ladders up to just our immune health more generally, you shouldn't wait until you're sick. I think we tend to think of our immune system as, okay, I got to do something.

I don't feel well. Why should people, you know, take ME or really care about their immune system every single day, even when they feel great?

Well, you know, if you're taking exercise, you live in the countryside, you're getting exposed to mud and soil and all the rest of it, that's fine. But it's a bit like oxygen. You know, you can say, hey, listen, I'm breathing. I'm fine. Well, stop breathing for a while and see what happens, right? You're not going to do very well. And this is why the IMI, by the way, you have to take every day because unlike...

other bacteria that culture, that grow inside the gut and remain there. E. me is pooped out. Whether it's alive or dead doesn't matter. In our case, it's dead. But you poop it out and you need a constant exposure to it. Now, if you're feeling well and fine,

That's great. You're doing all the right things. But if you become exposed to a stress response of one sort or another, whether it's an illness or psychiatric or whatever, you need all the help you can get.

If you're already pre-tuned, then you're less likely to have the same amount of damage. If you're on the staff and you travel and you're in a group, and we've had this reported to us both in the cancer patients but also with the IMI cases.

If you go out and everybody eats something, they all get vomiting and diarrhea, they've picked up an infection. Generally, the people on MA don't have a problem. Or if they do, it's relatively minor.

It's the same as all the cancer patients said in the winter. They said, "You know what? I went through last winter, the English winter. I always get flu and colds and stuff. I've had none of it. The rest of the family have come down with it, but I haven't. I should be the one who gets it because I'm the one with the cancer and all the rest of it."

The lesson is that prophylaxis is better than treatment. You've just got to look after yourself. Otherwise, it's much harder to fix it if you then break it.

I'm sold. You know, in the context, you know, longevity, we talk about longevity all the time. It's a hot topic. We cover it quite extensively. It feels like we're at this stage where we can optimize longevity through. It's not just, you know, it's not just VO2 max and...

some of the more intense longevity protocols, but we can do this through the gut microbiome and the gut-brain access. We're just not quite...

- No, and we're not quite there yet with the whole thing anyway. I mean, every billionaire wants to live forever and all the rest of it. And I always tell the story, one of the great things you learn at IMI is again, a holistic education. So I'll tell you about my Greek, you know, classical education among other things. You have to be careful what you wish for. And there's the wonderful story of Eos, who is the goddess of the dawn.

And she fell in love with a beautiful young man called Tithonus. And Tithonus was mortal, but she wanted him to become immortal and live forever. So off she goes to Zeus and says, listen, I want you to make my boyfriend immortal. So he says, yeah, okay, fine. So he makes him immortal. Well, after a few years, Tithonus gets older and older and wizened, you know, and has all the problems and eventually turns into a shadow.

And Eos goes back to Zeus and says, "Oi, hang on a minute. I wanted him to have eternal youth as well." She said, "Well, you didn't ask for eternal youth, did you? So I can't help you." So she turned him into a cicada. And that's why cicadas squeak in the morning, because she's the goddess of dawn.

Sorry, it's a long, roundabout way of telling you. It's all very well you wanting to live forever, but if you've got dementia and you, you know, there's no joy, there's no benefit. You need to have the youth. And that's where, if you like, if you can maintain your body as a functioning thing and your brain working well, well, then that's going to be...

um, part of the deal. You don't just want to stay living, you know, as a shadow. You want health span. You just don't want lifespan. Absolutely. And, and, and it's the quality of life that is everything. Uh,

I think, to me, it's the same in cancer and things. It's quality of life that matters. You don't want the treatment to be worse than the disease. Equally, you don't want to spend your whole life as some of our famous billionaires go off and they have, I don't know, plasma transfusions and they connected to this machine and that machine. They spend half their life being treated. And, you know, I think, well... There's a tension, you know, I think,

Look, there's what you can control and what you can't control. And I've joked on the show, you could optimize it and you should as much as you want to. And one day you get the perfect lab results. And then the next day you get hit by a bus.

You can't, you know, there's only so much within our control. Absolutely. Yeah. Yeah. If you could wave your magic wand and get funding and limited resources for any study and it could happen tomorrow, what would it be? I,

What drives me is cancer. Before I shuffle off this mortal coil, I'd like to knock it down. I've given it a bloody nose with the Mycobacterial Programme. I'm involved in

some cancer research work that we're trying to do. We've got some funding for what we call intralesional treatment using the mycobacteria as an agent. I think I would like to put quality of life as you get older the priority. Whether you live any longer or not in terms of totality is another matter, but I'd like to get the quality of life

as the priority. And I think then the length of life will follow. If you've got a good quality of life, barring accidents and things, as you just mentioned, and buses and what have you, I think the longevity will follow. We see this in the so-called blue zones. You know, you heard of the blue zones across the world. Sure.

Yes. Yeah, you get the high incidence of centenarians. They live happy lives. They live a good life. And they don't have cancer. They don't have the arthritis. Their brains are good. That's what I'd like to try and create.

But I think inflammation, to me, the one thing that is the underlying problem is chronic inflammation. It so happens that cancer is my interest. Others, it's stress and things. But all these things are interlinked. Stress produces chronic inflammation. Chronic inflammation is stress. Yeah.

And of all the drivers of chronic inflammation, what do you think is the biggest? Oh, modern life. We live in a concrete jungle. We're running around like lunatics just to stand still. You know, we have stresses that come at us every way. And, you know, how do you deal with that? And we're still learning.

I think modern life is in concrete jungles. That's why I live out here in rural Herefordshire near the Welsh border. We're right by the river. I get my feet wet. I get mud on my hands. I only eat muddy potatoes.

Enjoy yourself. You've got to have a happy life. I mean, at the end of the day, you don't want to turn into some kind of hermit or an ascetic. I like my wine, but I drink good wine and I drink maybe two glasses at a time. I don't drink two bottles of wine. I don't smoke. I take reasonable exercise. I don't run marathons because that's crazy. It ruins my cartilages. But on the other hand, I do enough exercise.

We have a dog, you know. So, you know, you've got to enjoy it, right? I wholeheartedly agree. So in terms of the microbiome, where's the future? Where are we going to be in five years? Is it fecal transplants are widely accepted and part of...

a cancer protocol? Paint us a picture of what you think the future is going to hold here. Well, I think part of the future is already here. We already know that we have abused antibiotics, as an example. And that may be part of the problem. In fact, almost certainly is part of the problem. So when I was young, as a doctor, every patient who came along almost demanded antibiotics. Whatever was the matter. You had a headache, you gave them antibiotics, right?

And so we've got to learn to be much more appropriate in the way we do things. I think the microbiome is still absolutely a mine of information that we haven't completely understood. I think fecal transplants or the equivalent that we're working on are...

I think every single patient with cancer, for sure, needs to have supplementation. I think ordinary people will know that they have to supplement the way that they eat, that they farm, F-A-R-M, their microbiome, that you give it.

the seeds, which is the probiotics, et cetera, and the prebiotics that you need. Increase your fiber intake. And by the way, as a colorectal surgeon, fiber is great because most of my patients had bowel problems and things, you know, giving them fiber cured most of them in, you know, it was wonderful. And I think we need to know how to deal with stress. So I think

the two things are linked, but stress, there are other factors in stress, as you all know, and I think society needs to address that. But from the microbiome point of view, I think the way forward is that we will understand the microbiome much more and we will know how to farm it and look after it and adapt it. And I think most of modern medicine will be done through manipulating the microbiome.

You will get the bugs to create the very chemicals and drugs. And in fact, there is an initiative, by the way, with the National Institute of Health that is out called Bugs as Drugs. And bugs as drugs is a really good term, right? And they are funding research into that whole arena. And interestingly, some new work that has come out with the collaboration we have with the MD Anderson in Houston.

on what's called single-cell transcriptome. Basically, we look at the genetics of some of the immune cells and their responses to exposure to IMI. And each cell, can you imagine, each cell, you only look at one group of cells, they produce 60,000 data points. 60,000 data points.

So, trying to analyze that as a human being, it blows your mind. But that's where AI comes in. So, we get the data, but we then spend the next six months putting it through the supercomputer and AI to try and get the data. So, I think bugs as drugs maybe summarizes where I think we'll be in five years' time. I love that. We covered so much today. Is there anything we didn't cover that you'd like to touch on before we wrap up?

Well, you're very kind. I mean, as you probably gathered, I could talk for another five hours on the whole subject, but I won't, I promise. No, I think, listen, be happy out there. You guys enjoy it. Don't listen to the siren song of, you know, this one drug cures everything. And you've got to buy a ticket in the lottery of life. So you need to make a bit of an effort to

Don't smoke. Do some exercise. You have a varied diet. But, you know, your environmental micro bacteria are really important. I think IMI seems to help an awful lot of people. I'm very proud that we've done something that is affordable to everybody and may well be

may well change how we live in the future. So if nothing else, that would be a good legacy. I'd be quite happy with that. Well, I'm sold on EMI and I'm also sold for incorporating more environmental exposure for our family, especially our kids. They get a fair amount here in Florida anyway, but wow, that's 3%.

Wow. 3% diet says it all. Yeah. Charles, thank you so much. Jason, it's a pleasure. Thank you for having me on your show.