How Your Gut Bacteria Influences Your Biology: With Dr Jason Hawrelak

Alrighty. Welcome everyone to yet another episode of the Boost yout Biology podcast. Today I'm joined in with a very special guest, a man who really is pioneering the microbiome field and a lot on gut health and probiotics. He's the lead researcher and founder of probiotic advisor.com so the man himself, Jason Horolak. Welcome to the show.

Thank you, Lucas. It's good to be here.

Fantastic. So I guess maybe for my listeners, did you want to give them a little bit of an insight into how your, I guess, naturopathic journey really all started?

I can do that. Yeah. And I was one of the people that grew up in a. I grew up in Canada and I grew up with parents who were probably pretty typical of parents at that time. That time point of not having a great idea of what good health was and how to, you know, they did their best, obviously. But, you know, I had numerous courses, antibiotics, like probably two or three year on average in those early years. Ate a lot of junk food, a lot of junk food. And, you know, I didn't have great health at my early, early years, you know, and it was really when I, when I started traveling, decided to be a backpacker and travel, make my way around the world with my idea. I didn't get too far before I arrived in Australia. I think it was my third country in my around the world trip. Fell in love with the country. And when I arrived, I arrived in northern New South Wales around Byron Bay in the early 90s. And it was a pretty transformative place back then. And it just really got me in contact, an awareness of good health and what we could be doing to look after oneself, which is really something I think nothing about leading up to that. So, you know, went through those phases of essentially implementing naturopathy personally. And then just seeing this absolutely huge change in my life. My asthma, allergies, hay fever, energy levels, infection levels, all those things changed dramatically and just felt better. And that was living naturopathy. And then I later worked out that you could study this to become a naturopath and help other people because, you know, I'd never heard of such a thing when I was in Canada. You know, I never heard of naturopaths or herbalist. I was very much in that Western medical model as my family was and as I was as a child. So I studied naturopathy at Southern Cross University. And then in my final year of study, essentially I had a lecture given by Dr. Steven Myers talking about leaky gut and dysbiosis and this to me was like one of those pivotal turning points where I had, you're pretty generalist in your naturopathic training and I love herbs and I love nutrition. Those are my core things I always kind of take with me regardless. But it's just having that, that lecture really stimulated something and it really grabbed me that he sends, he brought together the information that was around there, around the importance of gut integrity and the consequences of leaky gut on a range of other health conditions and this dysbiosis. And this was back in 1999, you know, so naturopaths have been essentially talking about leaky gut and dyswadic ecosystems from the, well, for a long time, but certainly pretty heavily from the 1980s sort of onwards, you know, so it's. For naturopaths, it's not a, a new concept. What's new perhaps is the knowledge levels and development and the testing. Those things have certainly moved. But talking about good gut health and healthy ecosystem are things that we've been talking as a profession for decades. But it's really. His lecture really stimulated me so much. I went and spoke to him right afterwards and said, hey, I want to do my honours degree and hopefully PhD in this area. And that's essentially what I did. So from 2000 onwards, I did my, you know, clinical trial looking at the microbiome, what we called the microflora at that point in irritable bowel syndrome patients, we looked at leaky gut and IBS patients, designed a treatment protocol with herbs and prebiotics and probiotics to treat these patients with IBS. And then that foot onto my PhD, which we kept doing in a similar vein, really trying to work out ways to benefit, modify the ecosystem. And it's been pretty amazing to be in the gut and gut microbiome field since that point, because that's where from the early 2000s, where it really started to boom dramatically. And you never would have guessed it back in the 1990s, or even probably 2000, 2001, that it was going to boom the way that it has. But yeah, it's been an amazing ride along that way and to just see, for me, it's just been amazing to see the changes in technology and the tools that we have as clinicians have access to look at ecosystems now are like light years away from where they were 20 years ago. And because of that evolution of tools, it means that researchers around the world can actually see more of what's going on than what we could 20, 30, 40 years ago, where the tools were Using culturing were very crude and we couldn't really see nuanced changes and sometimes even big changes. You can put people on like all vegetarian diets or all meat diets and they don't like it. They couldn't even see real much difference in their ecosystems back in the 80s and 90s when they did those experiments. And now we know that there's dramatic differences from that, but we just didn't have the technology to see such things back then.

Yeah, it's fascinating. You mentioned one of your earlier research projects was analyzing or assessing the micro flora of IBS patients. Curious to know like what, what did.

You find in that in the early stages?

Well, this is one of those pivotal turning point stories again in that we were doing cdsas comprehensive digestive stool analyses on these patients. And what was trying to think, my main takeaway was that those weren't very accurate. That's my main takeaway from my honors year at that point. They were based on culturing and we were giving our patients 100 billion lactobacilli for a supplement that was designed just for my clinical trial. So it was weeks old, like it was. They are made, sent to me, given to patients. There's no die off of microbes there. We're giving them two different prebiotics and the test we were using was unable to tell any changes before and after. We're looking at the gut ecosystem and to me that was just like unbelievable because we knew there's bugs in the supplement. We knew that they're giving therapeutic doses of prebiotics because they were farting like mad. They had like a lot of flat, a lot of gut action going on. So they were working the way that we'd expect them to and they were unable to determine any real shift and that was a huge red flag and certainly maybe want to go down and investigate like the different types of stool analysis we should be doing and why we should get away from culturing as a way of assessing gut microbiome health. And thankfully 20 years on we're generally there, but there's still some labs and still some practitioners holding on to the culturing because they don't want to move along with the times. But I think from memory, having a deep search really back memory, memory banks, it was probably low. Bifidobacteria I think was one of the things we did show up in our IBS patients and we, and we certainly found them to have a higher instance of increased intestinal permeability too.

Interesting. So I guess maybe we can transition over into an area that you're obviously very passionate about and that is understanding probiotics, just in general understanding probiotics and their effect on, on humans. So do you want to sort of talk about how your interest sort of like shifted in towards understanding probiotics a little bit better?

Yeah, and that really started back in 2000 when I was doing my honours degree where we really had to design a probiotic supplement as one of the components to treat these patients with ibs. And then that followed through with my research I did as part of my PhD. So that gave me a chance to really delve into the probiotic literature. And you know, as a naturopathic student, we certainly get taught around use of probiotics and certainly far, far more so than any other sort of health profession. But there were still big gaps, as it turns out. And that was certainly around stuff around strain specificity. And you're probably quite familiar with this concept, but I can tell you back then, no natural, but strain specificity, it was like very new concept and industry that was quite ignorant about it too. In general. To me, that was one of the biggest takeaways that I learned in the first couple years was this idea that, okay, within a species there's actually a multitude of strains that could actually display different characteristics and have different therapeutic actions. And that was pretty mind blowing. And it really changed the way that we put together probiotic supplements for my study because we tried to find ones that had the right actions or the right activity for patients with ibs. And then that obviously flows through into practice because I've stayed a while, so I've been doing research. I've always been a clinician as well. So you can't not put that information that you learn into practice. You trying to source and find the best research on what strains are good for what conditions. And that sort of we. And then I've always been. I've been teaching from probably 2000, probably 2001. I started teaching at Southern Cross doing a little bit of stuff around probiotics and gut health in the nutrition units. And that allowed me to sort of start developing teaching resources around that. And you start off with very small documents that were a couple pages and then there's two, two or three documents. And by the time 10 years goes on, I've got giant documents used to have to give to students. And then eventually I decided I should ship that into a database. And that's where the Proactive Advisor database came from because it just meant that there's so much information that Built up over, you know, 15 years that I could put it all into a searchable space and make it far easier for people to access that information. Because it is really finding the right probiotic strain that has the action that you're after to change the physiology or the disease process you want to shift. It's not unlike with herbal medicines where we choose the herb that has the action. So someone's got gut spasms, we choose an antispasmodic or someone's anxious, we choose something that decreases anxiety, anxiolytic or same way that people got pharmaceuticals, it's after an action. And that's really what the research is showing around probiotics too, is that they are, should be really used in the same way of sort of disease specific and strain specific? For the most part.

Absolutely.

Yeah. I mean, when I, when I started researching probiotics, I was really trying to understand more about, I guess, not only whether or not they have the ability to colonize, but also some of the epigenetic effects that they, that they may have, like changing sort of gene expression. So, you know, when people argue this probiotic doesn't work because it has no, it just goes straight through your, you know, there's people that sort of say you take a probiotic, it doesn't do anything. So do you want to sort of explore more on how even though we might consume a probiotic, we're sort of neglecting the effect that it may have on gene expression or, you know, certain enzymes and things like that?

Well, I think part of the problem in the probiotic realm comes and you see newspaper articles and media articles around the two. Like a study shows that probiotics don't change the ecosystem. And it's like for people that have been researching products for a long time, like myself, we've known that for a long time. It's not why people are giving it necessarily. I mean, there will be occasions where post chemotherapy, right after radiotherapy, during and right after antibiotics, where often they do shift the ecosystem because it's a very in flux environment and we can, their presence then can actually shift things in certain ways. But once an ecosystem is much more established, probiotics have pretty minimal impact on shifting that ecosystem. But that doesn't mean that they're not useful or they're not therapeutic. And I think that's the key takeaway here too is that there are hundreds of studies showing that probiotics have therapeutic actions independent of the capacity to colonize or stay in the gut for any length of time. Will they stop Having that action when you stop taking it. Yeah, sort of like if you're taking antihypertensive medication for your high blood pressure, you stop taking it and you're not doing anything else to fix why you've got hypertension. Well, your blood pressure is going to go up. It's the same way. And there actually even are some probiotics that help will decrease blood pressure. And if you take them, they go down, you stop taking, and eventually go back up if you haven't treated the underlying cause, you know, So I think it's that realizing that probiotics have specific actions and how they can interact with us and how they might interact with certain other microbes in the gut, for example, that go beyond this concept of colonization, and then that's the only thing that matters, because it really doesn't matter. You know, we've got all this research showing that these probiotics work despite the fact they don't permanently colonize, despite the fact they only stay around for short periods of time and transitory effect.

Right.

You mentioned that certain probiotics have, you.

Know, specific actions in the body. And so do you want to maybe explore a little bit on some of.

The, I guess, funky or unusual actions that people may not be aware of, such as potentially anxiolytic effects or antidepressant properties and things like that? Do you want to look at some.

Other interesting aspects there?

Well, this has been amazing to watch the last, really, 15 years where we started using probiotics. I'd say even goes back to 1999 was the first study that I think they really looked at using probiotics to prevent eczema. And it was a. Maybe the study was done before that was published in 1999 in the Lance. It was like a pretty huge thing going, oh, my God, if we give probiotics, we can actually prevent eczema developing in these kids, prevent this allergy sort of pathway. And that I think really opened the gates of going, oh, my gosh, we can use probiotics for more than just gut or vaginal issues, which is really where they had been researched up until that point. So it's been great to see all the, again, the booming area of probiotic research where there's clinical trials for cervical dysplasia from ingesting probiotics, for endometriosis from, again, orally ingesting probiotics, as well as for things like natural vaginosis or vaginal candidiasis, for example, or prevention of UTIs. So that's the sort of Female repro area, you could argue. And then there are clinical trials for using probiotics have been shown to decrease anxiety, to improve mood scores, to benefit cognitive scores in people with Alzheimer's disease, as well as for more classical stuff around irritable bowel syndrome, more inflammatory bowel disease and lower cholesterol levels. Probiotics used in Europe to decrease high blood pressure, to give you, again, a decent spread of actions that were or indications that human clinical trials have shown probiotics can be useful for. So it's not even just in vitro research, not just animal studies. These are all human clinical trials showing that specific probiotics can be helpful for those conditions. So it's it for me, they're a core. Group of tools that I use in my practice. Yeah, just like I've got herbs, I've got probiotics, I've got nutritional supplements. You know, I separate them out because you can't just go give a probiotic. And that to me is always something that's very frustrating. When you read something say, I'll just take a probiotic. It's like, yeah, that's useless advice. It's like, take, take a herb, take a drug. Which. Her. Which drug? You know, it's like, you've got to be specific here. What action are you after? What are you trying to achieve? This is what we need to be focusing on when we make our choice around probiotics.

Exactly. Yep.

So I guess maybe we can transition back into exploring more of the impact of diet and how specifically certain food groups, or I guess lack of certain food groups can impact the microbiome. So maybe we sort of start out with, I guess at the moment a lot of the. My US audience, you know, it's quite big in the US Is the carnivore diet. So perhaps we can sort of start with analyzing what we know so far about, you know, what happens to the gut when we remove fiber completely, such as on the carnivore diet.

Yeah. And I suppose I'm looking forward to probably more systematic research around that question. I mean, I think we can look at, okay, what happens when we go ketogenic? What happens when we go high fiber, sorry, high protein, low carb, and essentially cut out most fiber? There is research around those, those aspects of things and I think there's theoretical ideas of what's going to happen too when we take that another step further. Because essentially what microbes are living in our gut really depends on what we feed them. I think that's sort of like, you know, makes sense and we kind of resonate with that. But when you think about that's really important because you might have 160 species down there. Some will eat bile, some will eat protein, but a whole bunch, particularly ones we generally see as beneficial species, are fiber consumers. And if we essentially don't feed them, their populations go down. And there are consequences to that. And that's what we do see in research and I certainly see in patients that have been following sort of more extreme ends of, you know, animal based ketogenic versus you know, having more plant fibers in there too is you will get a decrease in butyrate producing bacteria.

Right?

And the research showed even within two weeks you can have a 50%, you know, pretty massive decrease, a decrease in Bifidobacteria and a decrease in Faecalobacterium, which is a, a key butyrate producing bacteria that has other anti inflammatory effects in the gut as well. So for me that's, that's a pretty dramatic impact and that does impact on things like gut integrity over the longer term because your, your colonocytes, your colon cells have essentially evolved its relationship with gut, our gut microbes, and that about 70% of their energy needs are met from the gut gut bacterial metabolites like butyrate and other short chain fat acids, but primarily butyrate. 70%. So what happens when we don't feed those colonocytes butyrate anymore? They don't function the way that they should, you know, and you start getting leaky colon and you start getting inflammation that's going on, then they can't really heal up properly because we're so reliant on that. And it's pretty amazing to think about the fact that we've evolved, you know, those cells have evolved this relationship with the microbiome and particularly with the butyrate producing microbes that are there. And those ones are very much dependent on dietary fibers, resistant starches, oligosaccharides and polyphenols. I would say to essentially be able to produce butyrate and be able to function, eat and live. And if we take all those things out, essentially we don't feed them anymore. What we do feed is ones that eat protein and we're often feeding ones that eat bile. And those ones are more problematic. And that in general we're feeding more Proteobacteria, we're feeding more Allostipes, more Bacteroides, ones that actually tend to thrive on more protein and bile. Because when we eat more fat, we produce more bile. More fat, more bile, more fat. More bile. So they're not eating the fat directly, but they are responsive to fat intake. This is something I see clearly when you see this rise in lithypes and this rise in bilophylla, which are key bile loving organisms. And they eat their primary bile acids and they produce these things called secondary bile acids, which are then pro inflammatory in the colonial as well. Linked to increased risk of colon cancer, for example. And through that process of protein putrefaction. Because that's essentially what's happening is you're feeding more. If you're cutting out the fiber and having essentially much more protein, more of the protein reaches the colon to be putrefied is the technical term for it. And there's a reason why they use that term instead of fermentation, because it's not a clean burn. You know, like fiber is a clean burn that you get gas like hydrogen. Hydrogen gas and short chain fatty acids. Yep. And then some hydrogen gas will be consumed by something else, like methane producing microbes, for example. But the ptfaction of protein gets a little bit of gas, not very much, a little bit of short chain fatty acids less and certainly not much butyrate. But you do get ammonia, you get amines, you get indoles, you get phenols, you get hydrogen sulfide gas. And many of these things are toxic in higher amounts and you can cope with it for a period of time. But things like hydrogen sulfide gas for example, we know has got the capacity of causing visceral hypersensitivity. It prevents colonocytes from being able to utilize butyrate as a food source. Even though the small amount of butyrate is being produced, it can't be utilized properly because of the increase in hydrogen sulfide gas production and causes that sort of colonic leakiness that I alluded to earlier. But that doesn't happen over two days or two weeks. That builds up over months and months. Yeah. And this is where you see this increasing gut sensitivity. Like I had a patient who came to see me that essentially was. She was just eating two chickens a day. That's it. Nothing else. She had been eating a little bit more, but. But as her gut got more and more inflamed, she essentially was cutting out anything that produced gas. And in the end she's getting bit of gas from potatoes. So Petra said, okay, we'll cut out potato. She did that. And then trying to get her to have anything that was remotely fibrous, even like the tiniest bit would cause her excruciating pain. Because essentially we did A microbiota analysis and her like lithes were off the charts are very high protein bacteria and extremely low butyrate producing bacteria, which is you'd expect because they're not feeding it like it's not. Not a surprise. But it was interesting to see the, the total amount. I think her butyrate producing bacteria made up like 2% of her ecosystem and usually we're looking at 40% is what we're looking for ideally. So like really, really low. And her degree of visceral hypertensitivity was intense. You know, she was in excruciating pain every single day. When she could feel the bit of her bowel movement essentially scraping its way going through her gut, it's causing excruciating pain. And this is one of the more classic endpoints that you see where we're starving off butyrate producing microbes. We're starving off bethyl bacteria, the ones that are important for promoting integrity and decreasing inflammation in the gut. We're feeding microbes that are causing inflammation in the gut and causing that increased hydrogen sulfide gas production, increase of secondary bile acid production which again increases inflammation and cause having such a severe degree of inflammation in the colon as a result of that.

Interesting. So obviously you mentioned a little bit on butyrate and I know butyrates probably been. Is it. Would you say it's one of the most well studied short chain fatty acids. I know there's acetate and propionate. So there's the. They're the main three. And then is butyrate the one that's had. They are research.

I'd say more recently. Yeah. Because again I can look back to look back at my honors thesis and where I had to review on short chain fatty acids and I reckon acetate actually had a fair bit around it back in the late 90s or you know, which is where the literature I was looking at for my first honors thesis. But I think the research on butyrate has really boomed since that point. So there's certainly stuff on acetate, certainly stuff on propionate too, but a lot less than butyrate. And I think the. There's been a lot more focus on butyrate because of the. Not just because it's the main food source for colonocytes, because we've known that for a long time, but because it has other systemic benefits that have only recently arguably been teased out beyond just its impact on the gut. And that's the other aspect that you argue with the negative consequences too that if we're not getting that. If there's very little butyrate being produced, clonicides are going to utilize everything that's there and even not have enough for them. And you're certainly not going to get any sort of systemic absorption of that butyrate to get the other action that butyrate can produce, which are the neuroprotective anti inflammatory actions. They improve insulin sensitivity, so they help with blood sugar control. For example, they can help heal a damaged blood brain barrier, help essentially increase serotonin production the gut by decreasing inflammation in the brain. It's like all this amazing stuff that Beta 8 does. It is very much a potent neuroprotective agent, but we have to produce enough in the gut to have a chance of getting enough in the circulation to get those additional therapeutic effects.

Yeah.

I know there's a few products on the market that actually sells like exogenous butyrate in a supplement form. So curious to know your, your thoughts on exogenous short chain fatty acid supplementation.

Yeah, my first goal is always to enhance endogenous production.

Yeah.

You know, feed up the indigenous producers because they're most people, they're there. Even that that patient had 2%, there are still some there, you know, and there was still enough. If we could eventually get to the point when she has actually expanded her diet quite considerably since then from a fiber plant food polyphenol perspective and her butyrate producers would have gone up as a consequence of that. But there are some of those people who have that degree of severe gut sensitivity that we might use exogenous butyrate as a substitute. Because at the moment, the tiniest pinch of any sort of plant food worsens their already severe gut pain. So we have to deal with that stuck in this conundrum because if it stays like that, the inflation's gonna get worse and worse. Yeah. So we've got to try to expand their dietary approach. There's more fibers, polyphenols, distant starches, etc. Slowly at the same time decreasing that, that inflammation that's, that's currently present. So they can, they will tolerate those things better. Yeah. And I think exogenously supplied butyrate, so supplemental butyrate can play a key role there. And that's probably where I use it most is in that situation. And ideally something that slow release that releases in the colon rather than supplements that might release in the stomach and upper gut and you absorb that butyrate and you don't get the local effects in the colon, which is what I'm really after in that instance, because there is good research showing butyrate can help decrease that visceral hypersensitivity and obviously promote healing of a damaged and inflamed colon.

So with that visceral hypersensitivity you just mentioned, is that something that's just common across ibs, ibs, C, different types of ibs. Can you explain what that actually is for my listeners? They may not be aware.

Yeah, essentially get. Good point. So visceral hypersensitivity is where the nerves in the gut are hypersensitive and essentially how they. I always tell my patients this, but how they research it in research circles, luckily not in our clinical practice, is putting these special balloons up their butts and pumping up these balloons. And people with visceral hypersensitivity complain of discomfort and bloating when the balloon is this full, whereas normally it would be this full before I would get the same degree of discomfort as what they're experiencing. Essentially the nerves are just hyper responsive and even a small amount of stimuli and that can be feces moving through, that can be any bubble, gas bubbles being created. The pressure on those nerves triggers a much more exaggerated pain response, and that's what they're experiencing. It is very common across IBS patients and it's considerably one of the core underlying drivers of irritable bowel syndrome as well. And it's certainly not uncommon in ulcerative colitis. And certainly with number of patients that I'm working with that have got a fair degree of inflammation, that area. It's pretty common. I'm thinking of one patient that had to do an enema before bed every single night to clear out any feces so they could sleep. Because just the presence of feces just sitting there overnight was enough to cause enough pain to prevent sleep, you know, and that's again, a more exaggerated response.

Cool. So do you want to maybe explore a little bit on the implications of sort of excessive antibiotic usage and sort of like what the research has shown? I know there's some people, you know, discussing the fact that certain antibiotics can wipe out certain bacteria for for many months or even up to a couple of years of red. So do you want to explore sort of how we've gone about that sort of research?

Yeah, and this has been a fascinating area to watch too. I did a systematic review, I think it was about 2004, where we grabbed every single study that looked at antibiotics and their effect on the gut microbiota, which was 100, and some studies extracted all the data into the tables to get an idea of what was doing what. And every single study done to that point had used culturing and as I said at the very beginning, not that accurate to tell us what's going on. And generally they would show, yeah, there's a massive change for maybe a week, two weeks, at worst, four weeks, then it's going to look pretty much similar to what it looked before. So I remember reading that data at that point going, my God, maybe they're not that bad. Maybe they're only impacting things for like two to four weeks and then things seem to look more normal again. And that was really a limitation of the tools that we had. That was the key thing there because there was one research study that showed that even, you know, 16 months after course of antibiotics, the metabolic activity, the functionality was different. And that was the first study that was the early 2000s to suggest that maybe it looked normal, but the functionality was different. But luckily, as we moved over to using modern microbiology techniques, we could actually see that the impact of antibiotics was far, far, far greater for the most part, than what we assumed before. Interesting study published in Gut last year. Single course IV antibiotics, nine species went extinct, extinct.

What do you mean by extinct?

Extinct, gone, never to be seen again. And this person's got. Yeah, and that was IV antibiotics in one single course, one single dose even. It wasn't like, you know, like a lot. It was just like this. Sometimes some antibiotics have got absolutely massive changes to the ecosystem. And in this case they had a species that went from like.00 something percent Borg Falkii went up to 92% the day, the next day after the antibiotics, you know, because it could survive, it could survive that antibiotic. And the competition didn't. And it was like, I got spoon, I got space grew into that and it even this bug didn't even know existed before they named it after the researchers Bork and Falk, but joined it together. Bork, Falkii. Very funky name. Yeah. But you know, so that, that in itself was interesting, just that change and then it did sort of settle back down and the bark folkii went back down to much lower level. However, it was the nine species being lost and there was a 10 species that was missing for I think it was nine months. And then eventually it came, came back on the radar. But even two years afterwards, those nine species were gone. So I think that really needs to be flagged for patients and practitioners is just the potential impact there is not as mild as we once thought. And what are the repercussions of the loss of nine species, we don't know. I think that's the key thing, is that some of these species we have not named yet, we don't know what role they play in the gut, but they have evolved with humans for thousands upon thousands of years. So arguably they play important roles or they might well do. And there is a degree of what we call functional redundancy in the ecosystem in that a number of species can do the same task. But there's some cases there's not. And I think a clear point, clear example of this is Oxalobacter formigenes. So Oxalobacter eats oxalates. We know that we get in spinach and almonds, you know, those sort of foodstuffs. Now there's research showing that people who took a triple antibiotic cocktail for Helicobacter pylori, you know that microbe that causes, potentially causes stomach ulcers in some people, given that antibiotic cocktail, 66% of them permanently lose extinction level events of Oxalobacter after that. Yeah. And from that point it means that that microbe that was eating your oxalates and preventing you from absorbing them, it can't do that. And that oxalate is now being absorbed and now you have a high risk of kidney stones. And I mean there's all this discussion around oxalate issues now. That wasn't around 10, 15, 20 years ago. It wasn't. Yeah, we had oxalates and kidney stones totally, but not all these other issues there. And I really think this has got a lot to do with that loss of that species where we don't have that functional redundancy, that that is the only species in our gut in some of these people that can eat oxalate. And it's gone. It means that you absorb that oxalate and you weren't before, you know, and it means if that was for, let's say a 20 year old woman who gets treated for H. Pylori and she, before she has kids, she can't pass on that species to the next generation. So this is, we're talking about intergenerational effects. And I think this to me is the other thing that's a huge issue. Concern for me is that what we're doing to our ecosystem now impacts generations moving forward because we can only pass on what we have. And that that person that lost their nine species from that course of antibiotics will no longer be able to pass it on to the family line. What we see for Westerners is this dramatic decrease in diversity with every generation because we're getting C section birth, we're getting formula feeding, we're getting lots of antibiotic use, crappy Western diet. Then they have this, they can pass that on to next generation and they go through the same process and get thinner and thinner and thinner because we're wiping out the species that can't tolerate the antibiotics that need polyphenols and dietary fibers to live, you know, for example. And we're just getting stuck with a much smaller, less diverse ecosystem. And there are people certainly arguing that that's the reasons what some, at least a key reason why we're seeing this boom in allergies and this boom in autoimmune disease diseases and boom in neurodegenerative conditions is because of this change in our ecosystem that we see in Westerners, that there's. If we keep moving the same way, there's no hope of really easily shifting that because, you know, we're still giving. People are still getting antibiotics for viral infections. Now there's a study published in Medical journal of Australia 2018, I think, showing that 90% of people presenting with viral bronchitis to their GP got prescribed antibiotics. 2018. This isn't like going too far back in time, you know, so we still haven't addressed that there's some of those key drivers of loss of species presence. And, you know, antibiotics save lives and save limbs and we should use them for those conditions we shouldn't be using for viral infections and we shouldn't be just playing with them going, oh, let's just try antibiotics to see if it works. If we have got no evidence that they actually are safe and effective in that condition.

Yeah, super fascinating. I was never aware of that specific Oxalobacter. You said Oxalo.

Oxalobacteria.

Interesting. That's. Do you have much of that on your. Is that like an area that you're going to be researching more and more or.

Which. Bit a few different tangents there.

Yeah, I'm really captivated by that. I was never aware that we even had bacteria that could help to offload the negative effects of oxalates. I always thought there was certain nutrients, such as B6, you know, citric acid, things that help with elimination, but I wasn't sure. I wasn't aware of bacteria that could help to combat the oxalates. So that's really fascinating.

Yeah. And certainly most of my patients that I see, if not all that have oxalate issues, have lost that species.

Really? Yeah.

Not all, but Most, most have. There's other dietary factors that you've mentioned and other things that can increase absorption of oxalates from the colon, irrespective. But that is a certainly key, a key factor in many patients.

It's fascinating. So what about. So obviously we spoke a little bit about the lack of fiber, but I want to explore a little bit more on the lack of polyphenols in I guess maybe the carnivore diet, because that's something that I want to, I want to see more people discussing and you know, talking about how these polyphenols, these are or whatever you want to call them, sort of things that will help re establish certain bacteria in the gut. But do you want to explore, I guess, some of the implications or the effects of certain polyphenols on the microbiome?

Yeah, and this is an area that is currently being teased out in much greater detail than we knew ever knew before. But you know, for those people that aren't aware, polyphenols are in general, we'd see them as brightly colored compounds that we find in blueberries and raspberries and blackberries and cherries, eggplant skin, black rice, red rice, black beans, for example, adzuki beans, to give you a bit of an idea of what foods they're in. And obviously purple potatoes, purple carrots, red cabbage, red lettuce, those are all the old plants. If you haven't seen that pattern, then come see there. But 90 to 95% of dietary polyphenols are too big to be absorbed. So they essentially reach the colon and this is where they interact with our microbiota. And generally the sort of more gut healing, anti inflammatory species are the ones that actually interact with those polyphenols. But we get this win win situation from it and that they convert that polyphenol from something that's too large to be absorbed to something that is smaller and can be absorbed and therefore has a therapeutic effect once absorbed. But because they're eating it, they actually grow too. So we're actually feeding beneficial species and at the same time they're nurturing us in return by creating these smaller polyphenol molecules which we can then absorb. And this is even important for medicinal herbs too, as you know, for herbalists, herbs like ginseng. Panax ginseng is a good case here to look at too because the compounds in Panax ginseng essentially are too large to be absorbed and they need to be converted by a number of different species, including some of the B28 producers. Including some things like bifidobacteria to make the compound that we then absorb that has a therapeutic effect. Yeah. But we know that these polyphenols tend to have broadly speaking antioxidant and a range of anti cancer, anti inflammatory effects in the system. And so I think the anti inflammatory aspects are a pretty huge one because there's how many diseases that we see in Western nations that aren't driven by inflammation. And if we sort of take out these anti inflammatory factors in our food, there's a consequence, let alone the direct consequence on the microbiota as well, whose species are dependent on consumption of those polyphenols as well.

Super interesting.

So I think that's another huge thing. There's the fibers, resistant starches, oligosaccharides, and there's a polyphenol that were essentially on that sort of very restricted diet. You are preventing any of those microbes that eat those things from being fed and essentially eating, feeding the ones that eat protein and bile.

Super fascinating. So I want to, I want to discuss a little bit about potentially a little bit on bile because I know like, I mean I've spoken about it like trying to educate people on the importance of eating the bitter foods to stimulate bile, pre digestion, things like that. And you mentioned that 95, was it 95% actually get reabsorbed back into the small intestine.

I didn't, but we know I was talking more around the polyphenols and their lack of absorption, meaning that they all reach the colon. So I didn't talk too much around enterobiotic recycling of bile acids. It's good leading, it's all good.

You want to discuss maybe like you mentioned, so the protein that can be putrefied in the, in the lower intestine, but what happens with the bile.

Yeah, and it does depend on the composition of that bile as well because we change the composite of our bile to suit the types of fat that we're consuming. Yeah. So there is ample evidence showing that to deal with dairy fat, for example, we produce a much higher sulfur based bile and we actually feed different microbes from this amount of dairy fat than we do with this amount of olive oil or avocado oil or not seed oil, for example. Yeah, it's something very. Listen, when it comes to things like Allostypes and Bilophylla, which are the two species we'd see as being key consumers of bile acids, they do seem to, their population seem to be very dependent upon not only total fat, which Has a part of contribute contribution but types of fat. So dairy fat, lard, animal fats more broadly, ghee butter which obviously dairy fat, but just want to clarify that. And coconut oil actually seem to be things that can drive the increase in Bilophylla and, and I don't see that with olive oil. I don't see that with people eating lots of avocados or nuts and seeds. Yeah, you know they eat lots of olives and olive oil. I don't see that. It's really the foods in those categories that produce that more higher sulfur based bile which then can be used by things like Bilophylus specifically.

Fascinating.

So maybe we can delve a little bit into. Had a few notes here, I guess. All right, there's one. So in terms of understanding the ratio between the firmicutes and the bacteriodoides, so that's something that's talked about quite a lot. So do you want to sort of explain what are these different types of bacteria?

Yeah. So we've got different ways of classifying microbes. And most of the species in the gut will belong to either Firmicutes or Bacteroides. Not all. There are some like E. Coli, Klebsiella, Oxalobacter that belong in the Proteobacteria grouping. There is Akkermansia, that belongs in the Verrucomicrobia phyla. And then there are Arbifidobacteria that long belonging to the Actinobacteria phylum. But most people's ecosystems are dominated by trimicides and Bacteroides. To a great extent you will get people that are exceptions to this but in general that's the way it is. Now do those microbes within those groupings have a lot in common? Not that much. It's sort of like, you know, us with things with spinal cords or something. You know, it's like yeah, we've got something in common, but there's a lot of differences between them too. It's the same way with these microbes that you can say okay, well all Bacteroide are gram negative microbes and all gram negative bacteria produce lipopolysaccharide as part of their structure or endotoxin. Yeah, it's okay, they've got that in common. And I think you could see that as a potential driver of inflammatory conditions in patients. I certainly do. Firmicutes, again it's a wide group of different species. Now most in fact, almost all of our B tray producing bacteria belong to the firmicutes. Phylum. So there's a lot of good guys in there. And there are some in the Bacteroides that I'd say are more in the pathobiot category. So pathobiolent is where species, when they're in the right amount are doing good things for us, they're great, they're very helpful for us. But when they get too high is when they come more pathogenic or disease causing. And I'd say that there's probably more arguably in the Pacterodides file who've got that, that capacity like Bacteroides as a genus, which is probably essentially what the name came from for Bacteroides tends to be one of those species that in the right amount is great, is quite helpful for digestion and production of short chain fatty acids. But too high amounts, it produces ammonia, putrefiles, protein, produces things like beta glucuronidase, which enhanced enterohbatic recycling of toxins and things your body's wanting to get rid of and hormonal products, for example. Yeah, so not that great. But I think where the focus really came from was a study done in 2005, 2006, where they showed that link between essentially that an obese microbiota, we could pass on obesity from obese rats to thin rats, thin mice by taking poo, despite no change in calories, no change in exercise, these things would get fat. And it was again one of those groundbreaking papers that really showed how important the microbiota was for your body's metabolism, that we had no idea how important it was up until that paper was published. Now that paper suggested that there was an imbalance bacteroidities firmicides ratio associated with obesity. Yeah. And that's what they found these rats. And that's the found in the human population they looked at in that small cohort study that they looked at, they published at the time. And that really gained a hell of a lot of media attention for good reason because it was a pretty groundbreaking paper. But in my opinion it's meant that people have got too attached to the firmicutes bacteroides ratio because there's been a number of studies even within the realm of obesity and metabolic dysfunction that have not found the same thing around that ratio or found the opposite, that having higher frequencies is better than having higher. Bacteroidetes and other found no association. So I think from a metabolism perspective, I don't put any weight, I focus on that, on that ratio or even more broadly, I'm looking at what's the components of could they have too much, too much endotoxin. This was. Maybe that's the way I'm looking at Bacteroides, because they're endotoxin producers, releasers. It's like, okay, how big of a component of the gut are they and how much might not be driving that inflammation in this patient? And how is their diet and lifestyle influencing where that's at? And then again, I'm looking at funicles mostly because of all the butyrate producers from those categories. So I wanted to make sure that there's a good amount of butyrate producing bacteria in someone's ecosystem. But I'm not attached to that ratio.

Yeah, yeah.

And I don't think we should be based on current data, of course.

And obviously you said that there's other bacteria that lie outside of either the bacterial or firmicutes. And one of them you mentioned was Akkermansia.

Yes. Akkermansia is one of those recently introduced species that we didn't know existed before that unhealthy guts make up between 1 and 3% of what's there. That seems to play a pivotal role for metabolism, help maintain good weight, maintaining good blood sugar regulation and metabolic control as well as just gut integrity in general. That it seems to be. You can see the function it performs in the gut is to maintain good gut integrity. I think that's a good takeaway. And the flow on of that is improved metabolic health. That's the other takeaway. So, yes, so that's one of those genera that very few people are aware of, Akkermansia, probably more so, I must say, because I remember I've done enough talks over the years that I say, how many people in the room have heard of Akkerman, the euphoric Alibactum? And it used to be like nobody, one or two people. Now most people put up their, their hands to like the awareness of that, that specific genius has increased dramatically over the last know, five to seven years, mostly based around that and this. The Akkermans, interesting microbe because they can actually eat a few different things. Yeah. It can eat mucus. Got mucus. It can eat fruit, oligosaccharides and other sort of indigestible oligosaccharides. It can eat polyphenols. Yeah. So that is one of the species that doesn't necessarily get negatively impacted by like a carnivore or ketogenic diet. Yeah. The reason being is because um, such diets can can essentially induce more inflammation in the gut, which means more mucus is being secreted, which means Akkermans, it continues having a food source.

Yeah.

And sometimes you'll see have people who the Akkermansia, like 15, 20% of that ecosystem and that's released. And they're usually people that are pooing out tons of mucus with their bowel movements, for example, which is a clear sign that there's inflammation there. The body's trying to deal with that by secreting more mucus. And the Echomandia is like, oh yeah, I got lots of food. And then it grows to a great, great degree in that situation. So that's one population, because of its ability to eat a few different food sources, can actually go up or stay stable on our carnivore type, ketogenic type diet, versus the other sort of beneficial categories like bifidobacteria, fecalobacteria and butyrate producers that tend to go down.

Fascinating.

Yeah.

Just from on the Akkermansia front, I think I saw some, some pretty cool research on if you're familiar with Cordyceps mushroom. Yeah, yeah, I was like, I was, I was an in vivo study. I wasn't obviously humans, but it does, does actually promote the growth of Akkermansia. So that's how I first heard about. I was like, well, cordyceps is able to help the growth of that. And like, what's Akkermansia? What else increases Akkermansia?

Yeah, well, luckily, I mean, things like cranberry, those red polyphenols tend to do so. And certainly I'd say most consistently a prebiotic like immune inulin type fructans like inulin and fructosaccharides oligofructase tend to increase the growth pretty consistently across the board. In fact, in everybody. Lactulose is another prebiotic I use a lot in practice. Will increase Akkermans in most patients, but not all because I think some Akkermansia don't seem to have the right enzyme for lactulose. Most do. Whereas in human fast it does seem quite well geared to and it does bring up the population pretty consistently.

Lactulose is in the laxative.

Yeah. You may not have known that lactulose used to be added to infant formula way back in the day as a prebiotic to try to make it more like breast milk way before its time. Because they worked out, you know, back in the 1960s that, you know, like kids fed formula. Their ecosystem was nothing like kids fed breast milk. And they knew that lactulose was a Bifidogenic substance enhances bifidobacteria. So they gave it in formula and their bifidobacteria went up pretty dramatically. And it was way before its time. So it never probably hit much in the way of commercialization at that, at that time point for that. But because it's an indigestible sugar, it can work as a laxative. Yeah, because we don't break it down or absorb it. But bacteria, only the good bacteria do. So it feeds bifidobacteria feedbacker and it feeds Akkermansia consistently. So they will consume it. Their populations go up. So we get, if you get the dose right, it will work as a prebiotic and not laxative. If you give a laxative dose, you'll get prebiotics and laxative dose from it. But the laxative, the prebiotic dose is often like one or two teaspoons a day, whereas you're looking at six teaspoons and one hit for the laxative dose. So it's much more reduced than that.

Wow. All right, well, I wanted to sort of wrap it up with one sort of final question and this one's just, I want to throw this out there and just I guess see where your, how your brain ticks and I guess like where you see the entire, I guess, gut health research space veering. Like what sort of direction do you see it sort of veering into?

I think essentially poo capsules without the poo. Simply put, where I see things moving is that probiotics that are very novel, that are based on species that are found in guts in much greater amounts, that play more pivotal roles in gut health. In fact, the first of that sort of newer generation probiotic has just reached the Marketplace in the US and they're marketing it for type 2 diabetes and metabolic dysfunction. But it's got Akkermansia, got two species of B3 and a few species of butyrate producing bacteria combined. And that's the first of many, you know, so I think that's, I'm a bit excited about actually having, you know, a broader range of tools that we'll have access to with a wider range of microbes in those, those forms potentially have, have a greater impact, particularly with those patients like that, the person who just had chicken and that was it. It's like, okay, here's the chance of introducing some butyrate producing bacteria that, that maybe will have some different effect as they're passing through. Maybe they'll even permanently colonize. We don't know. You know, because what we do know is that with current generation probiotics based around Lactobacilli and Bifidobacteria, permanent colonization is extremely rare. There are the odd exception to that. But, you know, 95% studies show they stay around for a week or two. You're doing pretty good. But I'm hopeful that will eventually develop, you know, newer ones that can actually recolonize in a way that current generations don't in a much more effective way, you know, And I think, you know, fecal microbial transplants are going to be something that's much bigger in the future as well for a wide range of different conditions. But I think there's going to be moves to make that easier and less poo Y. That's the poo capitals without the poo, just the microbes without the other fecal fecal matter alongside that, people will happily be swallowing. Whereas at the moment there's too much issue with swallowing poo capsules more broadly speaking, or doing, you know, enemas, for example, as ways to introduce new ecosystem in. But I do think that that will be a booming area too, of going, okay, well can FMT's help with depression, anxiety, obesity, metabolic syndrome? And there's some preliminary research showing that they certainly can, yes. I mean, I think Alzheimer's, multiple sclerosis, ra. I mean, I think that there's, there's all these things that, that there are is great potential to actually impact through the changes in the gut. And we're certainly at that beginning stages of using more, you know, more FMT as a way of changing that, which is much more dramatic shifts to the ecosystem. That's easy. Rather than changing one's diet or changing one's lifestyle, which you know, we would argue is like a core thing we should be focusing on, but that requires a lot more effort versus than just taking a pill. And for some people might be able to take that pill and get some benefit for six weeks or eight weeks until those microbes die off and they need another dose. But if it's quick and easy, then that might actually take off as a new treatment approach too.

Fascinating. Definitely an area that I'll keep my eyes out in terms of these. I think one of my friends actually labeled them crapsules.

Yeah, yeah, it's well named.

All right. Well, Jason, thank you so much for joining me today. It's been packed full of valuable information for my listeners. They're gonna absolutely love this episode. So do you want to give my listeners a chance to find out more about your services and what you offer and where they can learn more about I guess your resources and stuff like that.

Yeah, I mean I've got a website called probiotic advisor.com and we've got two arms to that. One is a courses portal and we have a range of courses on gut health and the gut microbiota, vagina microbiota, breastfeeding microbiota but just like human microbiota and how we can change that. Gut parasites, fructose intolerance, a few different things there topic areas and then also a probiotic database which is really designed more for practitioners going okay well I want to know what probiotic is best to treat ulcerative colitis to help bring in remission in someone that's doing 10 body bowel movements a day versus which ones are better for keeping someone in remission. What's best probiotic to help treat with work with anxiety for example, you can search anxiety or depression into the database term and it comes up with evidence based probiotics that the research shows are useful to treat those conditions. So yeah, I think that's probably the best area to go to find more information about me. I'm also a clinician at Gould's Natural Medicine as well. Well and absolutely love having a couple of patient days a week to work with people and have a chance to shift ecosystems. And that's the thing that I enjoy most is actually seeing before and after work and objective data from microbiome analysis to see what's actually shifted and then what the flow and effects that might actually be externally from that.

Fantastic. Well that pretty much wraps up another episode of the Boost your biology podcast. Keep a lookout guys. For the show notes, I'll be listing Jason's website probioticadvisor.

Com down below, but again I just.

Want to say a massive thanks for joining me in Jason. It's been a pleasure having you on.

You're welcome Lucas. It's a good chat. I liked it.

Yeah, sweet, thanks.