Link Between Leaky Gut and Microbiome with Dr. Brad Leech

This episode is brought to you by Nourish Me Organics, your gut health superstore. Nourish Me Organics is the premier online store for all things gut health, including probiotics, prebiotics, natural health supplements and home fermentation kits. So head to www.nourishmeorganics.com and use the code Happy Gut for 10% off. Join Criben Govinda, a seasoned food scientist and gut health expert, as he sits down with Dr. Brad Leach, a clinical nutritionist with a profound understanding of the microbiome.

Hey guys. Criben governor from the Gut Health Gurus podcast. I've got a background in food science and today I have this legend over at my house to talk Dr. Brad Leach, Brad Leach or Brad Leach, Brad.

Leach L C H. So I nailed it the first time you did.

So welcome to the show, Brad.

Thank you. It's a pleasure to be here and a pleasure to be chatting all things about gut health and the microbiome.

And what I like to do at the start of the podcast is to get it straight from the lovely gentleman who is Dr. Brad Leach.

Who am I right? I'm a, I'm a PhD, qualified clinical nutritionist. I've got a background in ayurvedic herbal medicine, background in nutrition. I've worked a lot with supplement companies, pathology companies and I work currently in clinical practice, both seeing patients and and mentoring practitioners all in the area of the microbiome and gut health. So really focusing on how can we improve gut health through the microbiome and improving the environment within the gut health. In addition to that, I've, I've worked alongside universities, I've developed different courses and I'm now currently the, the lead clinical educator at Microbar. Involves educating practitioners and consumers on how we can understand the microbiome and how we can understand what we can do to improve the microbiome from a very evidence based perspective, but a clinically relevant. So rather than giving a recommendation that is so difficult to implement, such as consuming 60 grams of dietary fiber a day, which is very difficult to do, bringing it down and translating it to say, okay, how about we aim for 30 grams of, of dietary fiber. That's something that you as an individual will be able to tolerate without becoming too bloated or sacrificing other macronutrients in.

Your diet, that's a great introduction. We kind of jumped into, right into the meat of the discussion today, which is going to be a lot about the microbiome. But what I'd like to understand A little bit more, Brad, is what fostered this passion of yours for the, for getting involved in the microbiome space. What was that pivotal moment when you developed this burning passion, which, which I, which I can clearly see, you know, on your, on your face when you talk about it. So what was that moment for you?

So I. In traditional ayurvedic medicine, they've got this large emphasis on your digestive system. You know, all disease begins in the gut. So yes, my initial education was very much focused on supporting with digestive health, but I, I'm very much interested in autoimmune conditions and I really thought my career directory focusing on autoimmune conditions. As I ventured into my honours and PhD, I wanted to find the cure of all autoimmune conditions. And as researchers will be well averse, you can't find the cure for all autoimmune diseases in a PhD. And so my, my supervisors, they sat me down, they go, brad, I know you want to accomplish and achieve so much, but you need to choose one small, tiny little element when it comes around to autoimmune disease. And at that point I stumbled across a paper by Dr. Fasano who discovered the protein zonulin contributing to this increased intestinal permeability. And he basically theorized that we could stop an autoimmune disease development by modulating the release of zonulin and stopping this intestinal permeability. And that kind of led me down this track of, of gut health and intestinal permeability. So I did a whole PhD on that. And then by the end of my PhD, I came to the conclus illusion that it's like, hold on, it's not just about barrier integrity, it's about everything that goes on within the gut, including the microbiome. And that's when I really started to do these deep dives to go. We have this basic understanding as clinicians on what we think a healthy gut may be. But when you actually dive deeper and deeper into the research, you understand the different ways to measure the microbiome, you understand the different types of prebiotic fibers, you go, hold on, this is a lot more complicated. There's a lot more to it when it comes around to improving the microbiome. So that's, that's a bit of a long way to come and answer your question in relation to coming back to the gut microbiome.

That's fascinating to see about your journey on how you fell into the space. We all fall in it in very different ways. So thank you for sharing that. That's amazing. So how about we kick it off by giving a basic description of what the microbiome is.

So the microbiome. So we can have a microbiome on our skin, in our lungs, a microbiome vaginally as well. Not myself, but females. But I think we're going to be focusing on the gut microbiome. So that's microbiome within your, your mouth, your, your stomach, your small intestines, but mainly within the large intestine. So the large intestine is where the vast majority of the microbiome is. Is there. Because that is where a lot of the fermentation occurs. What I find really fascinating is at our current level of understanding, we can actually measure and sequence over 28,000 different species of bacteria. 28,000 different species. That is a huge number of different species that we can identify. For many years, probably about 10, maybe 15 years ago, we were under the influence. You know, we're only looking at the genus level of bacteria. We're only looking at a few celebrities of the gut, you know, bifido bacterium, longum or Lactobacillus rutii, you know, really targeting on a few different species or genus. But when we have this more advanced understanding of the microbiome, we go, hold on, it's not just a few. There's so many. Now, on a individual perspective, we can generally see around that 174 different species within the gut. So of that 28,000 that we could sequence and see within the environment, within the gut, within our skin, on average, there's around 4 to 6,000 different species which could be in the gut. Most people wouldn't have that number of species. If they did, they would be superhuman or they'd be very ill. Most people generally have around that 176. To put this into more of a realistic perspective, I have patients, really ill, ill patients with inflammatory bowel disease who have actually got like 20 species in the gut. 20 species. And when you dig deeper into those 20 species, the vast majority of them are detrimental species. But then you go, someone like myself, I've been vegetarian most my life. I've never taken antibiotics, I've never taken NSAIDs. I was born vaginally. I grew up on a farm. You know, all these key things that we're, we're looking for, we're trying to promote in, in, in our patients or you as an individual. I've got about 250 species the last time I checked, which I'm like, I'm very Proud of. But if we actually take a step back outside of the western, western world and look at other microbiomes. I came across a paper probably about two or three weeks ago which was published and it looked at the microbiome, the tribes in Africa. And what was absolutely fascinating was the tribes in Africa on average had 750 species in their microbiome. So although I'm very proud to say, oh I've got 250 species in my microbiome, there's still a long way to go for a microbiome like sub Saharan Africa and rural parts of Africa.

That's incredible. That's amazing. When we think about the, the progress of society moving from a, almost a, like a hunt hunter gatherer to more a structured society that we have now and then we see the potential degradation of these species over time. So are there any factors that you think are really driving the, the reduction in the number of species? And the term that we love to use in the microbiome space is diversity.

Yes. You know I can, I can list a few. We've got alcohol. I want to go on record as a prediction, when it comes around to alcohol in 10 to 15 years we will view alcohol the same way as we view smoking as a contributing factor to chronic disease. It doesn't just increase the risk of cancers, it can impact our microbiome. So when we have large quantities of alcohol that's going to reduce diversity in our microbiome and impact our gut integrity and impact this environment within our gut. Medications, so antibiotics, NSAIDs and even antimicrobial herbs, very controversial topic in relation to the impact antimicrobial herbs can actually have on our microbiome. So they can actually impact microbial diversity. So reduce the number of, of species found in our gut. A low fiber diet. So when we don't have sufficient fibre in our diet, our microbiome are starving. They, they need fiber for the fermentation of microbial metabolites. They need fiber to produce beneficial compounds. When there's insufficient fiber they start to die off or they will start to utilize mucin with that mucus layer within the gut. And a few other examples are urbanization. Is that a word where, you know, we're taking a step away from being out in rural communities where you know, there's cattle and, and other wild anim there in a small apartment in Sydney. I spent five years in Sydney, Australia doing my PhD where I was in a very small, you know, 13 square meter apartment. It was, you know, single bed, it was very, very small I'm sure my microbiome suffered because of that. So not getting out there in nature, believe it or not, when my patients have low diversity, when they've got an in a reduced number of species in their gut, I give a number of recommendations. I tell them to get out there in nature, to go for a walk in a national park, be surrounded by the rainforest. Another one that I like to tell them is to get out in the garden. So to actually to get your hands dirty in the compost and in the veggie garden, really get the dirt under your nails. Patients love that. It may have a number of other benefits outside of supporting with microbial diversity can bring down stress levels. So when there's high amounts of stress, we're in this fight and flight response that is going to impact the release of digestive enzymes. When there's a reduction in digestive enzymes, it's going to reduce the ecosystem we call our microbiome, thereby potentially contributing to a lack of diversity within our gut. Are there any other big ones that you can think of when it comes around to factors that can impact microbial diversity which you often speak about?

Yeah, sure. I think I'm pretty much on board with every, everything you talk about. I think also the amount of chemicals that are present in our food. Things like a glyphosate that is a highly prevalent sort of herbicide that's sprayed onto crops, that's sprayed onto park gardens in the local neighborhood. So it's kind of ubiquitous throughout the environment. So just small levels of these, these kind of chemicals are damaging the, the microbiome diversity impacting certain species. The wide use of antibiotics in, in meat, not, not so pertinent for yourself. But meat is, is commonly pumped full of antibiotics with the primary means of really increasing the, the amount of muscle mass and, and weight. Whether it's fat mass, it's just, it's just a, an economical reason why it's used primarily. Also you can argue for the health, health issues with the, the cattle and then also just a plethora of things like artificial sweeteners highly damaging to the gut microbiome, all sorts of preservatives eat numbers chemicals, you know, things that probably are our great grandparents would never have been exposed to have permeated into our food supply which is the primary means of getting exposed to these chemicals. Also with our cleaning products, our shampoos, personal health products. You know, you're swimming in, in these chemicals in the modern world. So those are the ones that kind of at the top of my, my Mind and, and going, going on with that just not eating enough. Diversity in plant foods, I would say, is a big driver as well.

Huge, because we know that each individual plant product has got a, its unique makeup of different prebiotic and dietary fibers. Different species in our microbiome will utilize different prebiotic fibers as a fuel source. So if we, if we met our 30 grams of, of dietary fiber every day, but we got it from just potato or rice, that's going to reduce microbial diversity because there isn't that diversity in the different prebiotic fibers. We've got inulin, gauss, foss, there's a lot of different dietary fibers, beta glucans, which are found in a variety of different foods. And so if we can. And the common thing I tell patients is to consume 30 different fruits, vegetables, nuts and seeds and grains every single week. Now, most people can get to 2020, no problems, but that last five, they really need to, really need to think and go, okay, what additional food product could I be incorporating into my diet to really ensure that there is diversity?

I'm with you. And then the other thing is, people might not be realizing is polyphenols. So things like coffee is a controversial topic, but polyphenols in coffee, green tea, different types of juices like cranberry juice, pomegranate juice, and all these very unique polyphenols, herbs and spices also. So it's not that difficult to boost up your, your plant, your 30 plant foods when you consider all these other polyphenols as well.

Yeah, so, so in, in addition to the 30, you know, fruits and vegetables, nuts and seeds and grains, it's also eating the rainbow. So making sure that you're eating every single color every single day, and then also every single part of the plant. So we've got the roots, we've got the stem, the leaves, the N feeds the flowers. Each part of the plant has got different polyphenols, different prebiotic fibers, and then that will support with microbial diversity and the number of species found within your microbiome.

Let's, let's dig a little bit deeper because diet is a highly nuanced topic. Now what we've been speaking about is very general. So how do you deal with a patient from a nutritional point of view when they present to you with an issue like IBS or not being able to eat a lot of fiber because they get bloated? So how do you tackle that?

And this is one where I've really delved deep into the literature and then also just trial and error. I've been seeing patients since 2008. I've made some, I've had learnings where I've given too much fiber too soon or I've done things where I've learned from my, I don't want to call mistakes my, my doings. And I've really changed the way I, I treat patients so they, they don't have reactions. The trick here, and the end goal is to go low. Sorry, go. Yeah, go low, go slow. So in relation to a small amount building up over time. So I give an example. If someone can't tolerate oats or particular legumes, we need to get a better understanding of why. Is it a sibo type picture? And if it is a sibo type picture, can we support with our own microbiome's capability and gut capability to produce antimicrobial compounds to balance out the gut? Can we support with microbial diversity and also peristalsis and motility? Okay, so we can address the placebo then. The trick here is to start at a very low dose. So what I'd commonly do is once they can tolerate it, I'll go, all right, let's add in a teaspoon of well cooked canned legumes. So just, you know, lentils. The trick here, make sure you wash them really, really thoroughly. Start off with a teaspoon which has been cooked. Now you want to do a teaspoon maybe every second day and slowly work your way up. So that's the first week. The second week you might do 2 teaspoons or 1 teaspoon every single day. And the trick here is we're feeding up the microbiome which consume these different types of dietary fibers. If you were or had an intolerance to different dietary fibers and prebiotic fibers and you added in a large amount of, of fiber into your diet in one go, you're going to end up with bloating, you're going to end up with maybe diarrhea or constipation. So it's really important if you're one of these sensitive individuals to start at a very low dose and go slow.

How do you. A lot of these, these gut ailments are often a sign of some form of damage to the, the gut, whether it's the so called leaky gut or some sort of issues with intestinal permeability damaging mucin layers, you know, the different barrier properties of the gut. How do you balance that out with your dietary advice? If someone presents with that in relation.

To what element I will treat first, whether it's the microbiome or gut integrity. Correct. I like to do almost a synergistic approach. We're treating multiple different avenues all at the same time, because we know that gut integrity is influenced by the microbiome, we know that the microbiome can influence gut integrity, vice versa. And so if we just treat one element or ailment, then it's not going to have this synergistic approach. So really making sure we remove any triggers from the diet, we slowly incorporate dietary fibers and then we can use targeted therapies to support with leaky gut or increased intestinal permeability if there's evidence for it. So a lot of patients, unfortunately, 10, 15, 20 years ago, there was this quite uproar about everyone having leaky gut syndrome. I'll clarify here. There's no such thing as leaky gut syndrome or. Although I've done a PhD on leaky gut, leaky gut syndrome isn't actually a thing because syndrome eludes the fact that there's a group of clinical symptoms that can diagnose the syndrome, when in fact, my own research has shown that there isn't a group of clinical symptoms to say that there is leaky gut syndrome. Leaky gut or increased intestinal permeability is a reaction that happens within the small intestines. So it's really important to address that at the same time as the microbiome, because they can impact one another.

Great. Thank you for clarifying because it is a controversial topic in the space. So it makes complete sense that there is clearly there is patients that are presenting with damaged guts, whether it's that mucin or the actual junctures between them, which leads to things like LPS leaking into the gut. So this is a perfect segue to talk about lipopolysaccharides because they're so pertinent if someone presents with a damaged lining. So firstly, what is, what is a lipopolysaccharide? And then how do you define that when you, when, say, for instance, someone hears a type of, of lipopolysaccharide, which microbe of the company that you work for is so, so much, so much having so much expertise in this space of actually defining what a hexapolysaccharide is.

Yeah. So lps, I say it, lipopolysaccharides, that could be my, my accent when it comes around to that. But lps, lipopolysaccharides, they're a component of some bacteria. So some bacteria will actually have this on that the outer layer cell membrane. And we can actually look at something referred to as hexa lps. Hexa LPS is a different, let's say, subgroup of lps. Now when you look at all the different subgroups of lps, it's hexa LPS which is more pro inflammatory and is more linked with, with chronic disease. And so that's why we're really focused on this hexa lps. So we can have a increase in hexa LPS being absorbed within the gut that can contribute to systemic inflammation. But within the gut, hexa LPS can actually induce intestinal inflammation and intestinal permeability through the TR4 receptors within the gut. So it's one of these things where it in itself is linked with intestinal permeability, but also with different types of gut inflammation. Now, from a clinical perspective, we really want to reduce this microbial metabolite, this production from the microbiome because it's linked with a number of different health conditions, inflammatory bowel disease, ibs, whereby those who have these chronic health conditions, we have higher abundance and higher amounts of hexa LPS producing species within their microbiome. And thereby, if we can actually reduce it, but bring it down, it will translate to an improvement in clinical symptoms. So you think of gut inflammation, systemic inflammation, you've got clinical symptoms such as pain, you could even have maybe some bloating, some cramping. You know, they're all indicators or even loose stools of gut inflammation. When there's gut inflammation, the microbiome is not happy. They can't thrive in an inflamed gut. So we really want to bring down any types of gut inflammation and one of the contributing factors can be this hexa lps.

So the hexa LPS microbial is a sequencing company that people send in a stool sample. They have a very high level of testing. Whole genome shotgun sequencing gives you a very good picture of the different types of species strain, right down to the strain level. So very good idea of what's in that stool sample. So what species is the key driver of hexa lps.

So there's a lot of different species that can produce hexa LPS and a lot of your common species. So a lot of E. Coli can produce hexa lps, Klebsiella can produce hexa lps. There's so many, I want to say there's at least 40 to 60 different species that can produce hexa LPS. So it's not just looking at individual species, it's understanding collectively how much collectively hex LPS are all of the species in your gut being able to produce. So rather than just looking for oh, you know, my patient has E. Coli, thereby they've got high levels of hex lps. I've seen many reports in my patients where they have E. Coli, but their production of hex LPS compared to a healthy cohort is actually less so or the same. Thereby it's not, not overly a huge concern. But when you actually dive into other species, you know, different club ciella species and so forth, that can produce hex lps. When you combine them all together, then it's like, oh, hold on. There's actually a quite a large abundance of, of species known to produce XLPs.

If the, the gut is well functioning, meaning it's, it's, you're producing enough mucin, the, there's no injury to the, the walls of the, the cells. Is hexa LPS a concern?

Depends on how high it is. So if it is elevated, you know, above what we've seen in a healthy cohort, then it can go on and contribute to gut inflammation, systemic inflammation and increased intestinal permeability and being linked with a number of different chronic health conditions. So it is one of those markers. There are so many different microbial metabolites. You can view, you've got branch chain amino acids and IPA and which are all part of our microbiome. But hex LPS is one of these that I personally call me biased because you know, I love increased intestinal permeability. But I'm always looking for, to check or does my patient have hex lps? Yes or no? Okay, we need to do something about that.

That's, thank you for the clarification, Brad. So how do we tackle hexa lps?

It's one of these things and maybe in the past five, 10, 15 years ago we would have gone, okay, there's an E. Coli, we're going to give an antimicrobial herb, we're going to come in with, with high dose berberine, high dose oregano oil or different antimicrobial herbs to kill it. Okay, that, that's been our mindset for many, many years. But just recently in the last two years, research has come out which have, which has used metagenomic sequencing, shotgun metagenomics to look at the impact of taking antimicrobial herbs on the whole microbiome. Rather than doing like a cell culture or looking at particular species, which has been all the past research, this research looked at the impact of taking these antimicrobials on the whole microbiome. What was absolutely fascinating. And when I came across these two research papers, I was blown away. I read them two, three, four, five times because I was like, I really wanted to make sure I was reading them right. What they actually showed was those who took, took berberine supplementation for a period of, it was a thousand milligrams for a period of three months. They had a reduction in butyrate producing bacteria and an increase in hexa LPS producing species. So no, taking antimicrobials is not going to be the most appropriate course of action when it comes around to, to hex lps. So, you know, I put on my research hat and go, okay, what are the other interventions that we can utilize so we can change fat ratio in our diet? So if we have a more balanced fat ratio, so we consume less saturated fats below that 10% of total energy intake and consume more omega 3s, that's going to reduce the absorption of hexa LPS from the gut into systemic circulation. Now that's, that's going to reduce the impact within systemic, systemic health. But there's still going to be hex LPS within the gut. Believe it or not, I stumbled across this research using GOS to actually change the microbiome to reduce hexa LPS producing species, including E. Coli. So what the study involved was individuals, older individuals taking gauss supplementation around that 4 grams of GOs for a period of three months. And what the study actually found was there was a reduction in hexa LPS producing species. So rather than coming at this from weed seed feed, so, you know, trying to kill it and feed up the microbiome, I like to view hex LPS as a feed, feed, feed approach. So we're nurturing the gut, we're supporting those species that are already there to nurture them, to bring them up to overcrowd. So then these detrimental bacteria, which our gut will naturally, you know, dissipate, can die off and then thereby we've got a more diverse, a more balanced and more healthy microbiome. A couple of things I'll mention in relation to how I've been prescribing GOS in clinical practice for these hexa LPS patients, the vast majority of them have been quite sensitive. So, you know, they've got a variety of different health conditions going on that, you know, they, they're not just a healthy individual, but they've got high hex lps. They've got a variety of different health conditions. So really Starting at a low dose when it comes around to goss. So I'm generally prescribing about that one gram a day and slowly working my way up. So maybe depending on the individual, I might do one gram for a week, then increase that to one gram twice a day for the next week. Or I would do one gram for three days, then increase it by one gram for three days. There are very few patients, I would say, oh, just, just add in 5 grams of GOs, because they're more likely to cause bloating. I mean, for myself, I can take 5 grams of gauss, no problems at all. My microbiome loves it, but I've got a very healthy microbiome. People come to see me. They don't necessarily have a healthy microbiome, so we've really got to nurture that. When it comes around to the use.

Of GoS, is there a difference between the different types of gauss? Because often you'll see something like beta gauss. So what's the, the difference?

That is a really good question and one I actually want to get your opinion on from the perspective of, I know a little bit, but I think you could actually educate me on, on the benefits of the different gosses.

Sure. Well, the, the clinical studies on gos are primarily based around the work of a brand called Bimino, which is very difficult to get your hands on here in Australia. But it's, it's basically a fermentation process that involves milk peptides and the like with some different other sort of substrates. And then the end metabolite is something called Beta Gauss. So Galactoolsaccharide, a very potent, as you mentioned, prebiotic supplement. But I would always steer people to use something like Beta goss, whether it's from Bimino or my company, Nourish Me Organics, because we know that it's effective in a clinical setting based on those studies. So. And look, there's, there's some great prebiotics on the market as well. Sun fiber. I'm not sure you've ever come across a sun fiber or phgg or partially hydrolyzed guar gum. Do you use that in your clinical settings?

I use a variety of different prebiotic fibers. I use inulin, I use HGG, I use GOS a lot. I use HMOs. So it's really about choosing the right prebiotic fiber based in the microbiome for the individual to ensure that it's having that desired effect.

When would you use phgg? Is that of interest?

Now phgg can support with the production of butyrates. It's also in more clinical symptoms. So if somebody has constipation, it's one of these fibers which are quite gentle in the gut. A lot of people can and that supports with bulking of the stool, supporting with peristalsis and motility. And I'm giving it to those constipated patients. So generally around that, maybe around that 10 grams at night to support with bowel motions. I would dabble in a bit of PhD into my smoothies each day. But because I personally don't have any gut related problems, I prefer diversity. So rather than focusing on just one prebiotic fiber, I will have a little bit of Gauss and a little bit of PhD. I'll take my HMOs to ensure that I'm feeding a variety of different species. Although we know that GOS feeds the vast majority of species within our gut, they can utilize GOS as a fuel source. We also want to make sure that we're still utilizing different types of prebiotic fibers.

For sure. I'll tack on to that things like fosinulin or even GOS for someone that's really sensitive can, as you mentioned prior, cause bloating, depending on the dose level. So firstly is again, as Brad mentioned, start slowly. But what I, I find is if someone's really sensitive, it might be apt to start off in PHGG because it's FODMAP friendly. As you know, a lot of IBS cohorts, they will follow a low FODMAPs diet for a short period of time to help alleviate some of these symptoms of, you know, like bloating, just digestive discomfort. So, you know, phgg in that setting is, is a good one to explore as well. But from a hexa LPS standpoint, I love the studies that you've just shared on in relation to gos. It's amazing. So how about we move on? That's a, that's a good, good time to talk about your testing. So I don't think we fully explored the microbial testing. So what does the test actually give a patient?

Yeah, what I'll speak to is the technology around the testing and maybe provide a bit of clarity around metagenomic sequencing and shotgun metagenomics. To put this into perspective. There are so many different ways we can measure the microbiome. We can measure the microbiome through culture, we can measure the microbiome through 16s through QPCR and metagenomics in Australia. The vast majority of ways we can measure the microbiome is culture, qPCR and metagenomics. 16s is more US and UK based. And 16s is looking at genus level, so it's able to look at all the variety of genus within the gut. It's unable to look down at the species level accurately. So culture, I'll start off with culture. The reason why I'm not utilizing culturing in clinical practice is because it's only able to measure about 5% of the microbiome because it's exposed to oxygen. And we know within our large intestine there's no oxygen going around. Thereby, if we take a stool sample out and we expose it to oxygen, we grow it, what's going to happen is there's going to be a higher prevalence of things like Candida. Not because Candida is growing in our gut, but because Candida loves growing in an oxygenated environment, thereby it's giving us false information. Now, qpcr, it's depending on what probe is used. So you can utilize different probes to go, okay, I want to look for Akkermansia mucephili, or I want to look for, you know, Streptococcus genus. It's very accurate to go the amount of Akkermansia there, but it's not telling you who else could be that. So there's only around 100 different probes identified to use in QPCR technology. But, you know, most microbiome reports, you generally see about 20 or 30 different species. I like to use the example of if we were to compare QPCR testing to metagenomics, if I was to go into a room and had a flashlight and look around the room, I could go, oh, there's Cribbon, there he is. But, but that's qpcr. So we can target and say, okay, that's who's there. But with metagenomics, we're able to turn a switch on and see the whole room. So metagenomics looks at the DNA of the bacteria and because we look at the DNA of bacteria, we can understand, oh, okay, well, that's the, the DNA of Akkermansia mucephili. Great. But then we can also dive deeper into the DNA and go, oh, Akkermansia mutophilia is responsible for consuming mucin as a fuel source. It can produce this metabolite and that metabolite. So not only can genomics produce results on species level information, it can tell us what their function is. So with metagenomics, we can see all of the different XLPs producing species and combine them based on the genetic profile to say this person's microbiome can produce a lot of hexa lps. Now, there's a variety of different other microbial metabolites that we can look at using metagenomic sequencing. And that includes, okay, yeah, we've got hex lps, we've got branch chain chain amino acids, we have ipa. Now, not ipa, the drink. I'm referring to IPA as in three indole propionic acid, a very beneficial compound. We've also got tma, which can get converted to tmao, which can contribute to that risk of cardiovascular disease. We have methane, we have hydrogen sulfide. So we can actually look at the function of the microbiome rather than just who is there, because we're looking at the genetic DNA, a understanding of the microbiome that's amazing.

And also so it gives you a basic profile of the, the organisms that are present at a very high resolution. Probably the highest of technologies available right now. And based on the potential to produce different types of metabolites.

Exactly.

So. So it's just almost looking at bacteria as little factories that produce chemicals.

Yes.

So there's other metabolites like B vitamins.

For instance, or folate, short chain fatty acids. It's one of these things where if I was to either give up a practitioner or an individual, a list of their 184 species, you would look at this list and go, go, I don't, I don't know what am I going to do with this information? But if I provide you with the function of your microbiome with, oh, you're not producing enough butyrate, you're producing too much hexa lps, you're not producing enough ipa. We know that they're linked with, you know, gut inflammation, motility, systemic inflammation. You can take a step back and go, okay, well how can I reduce hex lps? How can I increase butyrate, you know, increasing those resistant starch? So it's more of a, a user friendly way to look at the microbiome rather than being overwhelmed with all of these different species. Now, I've been looking at gut health for 15 years, I still don't know everything. Single species. There's 28,000 different species. I'm learning as I go. But it's not humanly possible to know the function and the treatment of every single species. You're better off to go, all right, let's look at these microbial metabolites and treat it that way because it's going to be a much more user friendly way to approach the microbiome.

I agree with you Brad. It's such a novel technology that microbial in a sense are discovering new species. So sometimes we look at a stool profile and there'll be some random code that's assigned to a particular strain or species of bacteria. And the reality is we just don't know enough about this particular bacteria now, now. So it's extremely a new field emerging and as Brad mentioned, we're learning, right?

Yeah. And that's the thing because we're looking at the DNA, there's multiple in every report I look at, there's species which have never been documented in the scientific literature. But you're able to look at well, that function of that particular species. Although we know nothing about this species, we can look at the DNA and go okay, well it's producing short chain fatty acids. So okay, it could, could be, could be beneficial. Yeah, so it is. Looking at the function is such a more clinically useful way of looking at.

The microbiome that 100% resonates with me with myself looking at patients and looking at stool profiles when they present with certain disease elements. It's so useful to have an understanding of where the deficiencies are. Firstly, it's great to start with the wins. I love to start with wins when I'm dealing with patients. You've got a great species here. It's unique, you know, it's producing some great metabolites. It just makes the whole conversation a lot more balanced. And then you can tackle some of the deficiencies in that particular stool profile and look at the metabolites and say the hexa LPS is a little bit too high. Here are some dietary recommendations or some supplement recommendations, something like GoS that we could use to bring those levels down. And then it also highlights that, you know, things like B vitamins. You know, if, if you producing a lot of B vitamins in your guts innately then perhaps you can save a bit of money and not fussing too much about your B vitamin supplements.

You know, it's a really interesting one, the B vitamins where of course our microbiome can produce a number of different B vitamins, including folate. But the research out there on whether or not they're absorbed systemically and we can utilize it or whether or not it's the, the microbiome is utilizing those B vitam we're still learning. It is an area where we still don't quite fully understand. But the microbiome can produce B vitamins, which is incredible to think about.

B12.

B12, yes. Great for you.

But I hear you. I mean, it's such an early, an early field. So we have to approach this caution with caution. And then there's the whole methylation story as well when it comes to B vitamins and how we absorb and utilize.

Yes.

So it's a complex area. So Brad, what's, I'm fascinated to hear, you know, you spend so much time digging through literature, reading studies, you're at the forefront of nutrition in the microbiome. What's exciting you right now in the science?

What is exciting me? I'm really passionate about two different areas at the moment. The impact of antimicrobials on the microbiome, as I mentioned before, and how we can go about treating a pathogen and a pathobios. And then also this concept of functional dysbiosis. So maybe I can speak to those if you'd like. So functional dysbiosis is a new way that I'm trying to display this common term of dysbiosis. So as clinicians for many, many years, we've gone, you've got dysbiosis, you've got dysbiosis. I want to change how we refer to dysbiosis and say you've got, got functional dysbiosis and that comes down to the function of the microbiome. So if I was to say you have a functional dysbiosis with a low potential to produce butyrate, that provides you as a clinician, you as a practitioner with a lot more information rather than just to say my patient has dysbiosis, what type of dysbiosis, what's going on? So functional dysbiosis is a bit of a term and a phrase I'm interested in using now to display a more evidence based understanding on the different categories of dysbiosis. And then the other area I'm quite interested in at the moment is pathogens and pathobions and how we as practitioners and consumers can go about treating different pathogens and pathobionts within our microbiome. So for many, many years we've had this understanding of pathogens in our gut. But I believe many practitioners and even consumers, when consumers order a stool test themselves, look at a particular species or genus and go, I have a pathogen, I've got to kill it. But a true pathogen is a pathogenic strain. So not a species, it's the next level down, it's a strain. Now these pathogenic strains, these are, they need medical referral. When someone has a pathogenic strain such as a E. Coli strain 01597 where it's causing acute diarrhea here. Yeah, I'm not going to be playing around with, with, with prebiotic fibers. You know, let's support the microbiome. I'm going to write a referral and send it to the GP to get antibiotics to, to kill that pathogenic strain. But there's this concept of pathobionce. So a pathobionce is a microbial species associated with a negative health outcome. And this is a lot of what we're seeing in metagenomic research where, where we've got all of these different species, we're seeing them statistically significantly higher in those with chronic disease. Now they, they're not a pathogen, we're not trying to kill them, but we can see through cross sectional data that it's a pathobionce. Now some practice, get confused between pathogens and pathobions and start treating pathobions like they would a pathogen going, oh, we've got to kill this, we've got to kill this. But when in fact, fact, you don't necessarily need to kill it, you need to nourish and support the microbiome. So if somebody came to me and in their microbiome report had a variety of different pathobiants, you know, there's, there's red saying, oh, you know, these are associated with negative health outcomes. I'm going to be a looking at the abundance, are they actually high? Because believe it or not, sometimes, you know, healthy individuals will have a pathobinds but it just might be in a very low level. So it's not no problems at all. But how I would go about treating this is to understand the different causes and then to treat the cause. So I'll give you an example of let's say Streptococcus. So the genus Streptococcus can have oral based species. Now when there's a higher abundance of oral based species, these are pathobion. So these are species found in your oral cavities, your nose, your throat, your mouth, and they're actually identified in your stool. So riddle me this, how can, can species of bacteria in your mouth survive this whole transit all the way down to your anus intact? It's because there's a lack of stomach acid. So when there's a lack of stomach acid, there's going to be a higher amount of oral species in your microbiome. So myself as a clinician, I use that in my, my tool belt to go. Oh, rather than trying to kill this potential streptococcus saliva species, I'm going to go. The cause is because it's from the oral cavity. The patient also suffers with bloating, impact in motility and other digestive problems. I'm going to support with stomach acid production. I might do some bitter herbs, apple cider vinegar, digestive enzymes, hydrochloric acid, zinc and so forth to support with stomach acid. Thereby oral species aren't going to be found in the intestinal microbiome. The other factor when it comes around to pathobiome management is, is feeding up the other beneficial bacteria. So incorporating beta glucans found in oats, incorporating fermented foods into your diet are all key strategies to bring up the microbiome, to feed the microbiome. So then these pathobions aren't going to take up much space in our gut.

That's brilliant. I love that approach. It's like the, the old, the old style used to be kind of like you nuke the gut and then you start again from scratch. But when you look at it like in any ecosystem, you know, if we went to a, like a wild rainforest and then nuked the whole thing and tried to start again from scratch, it's highly unlikely that it's going to grow back into a vibrant rainforest because there's so much complexity and there's so much that we don't understand about the interactions between these different organisms. You know, we were speaking earlier in the preamble to the podcast about blastocystis, so how about we, we tackle that a little bit because I think your, your point of view is very valuable.

It's, it's an interesting. So parasites such as Blastocystis defagellis a number of years ago, before we had this more advanced understanding of, of the gut microbiome, even myself, I, I can admit that at one point in my career I would get a letter from, from the patient has blastocystis. I need to treat this and I would, I would be using antimicrobials, I would be using garlic, I'd be using all of these interventions to treat and kill this blastocystis. And I wasn't overly successful. I think I caused more harm than good. But now with the change in understanding the microbiome, we can actually view blastocystis and D. Fagelis to two different parasites as just part of the ecosystem. It's when the environment in the gut but it's compromised and under an Impact, that's when they. Not they become an issue, but an issue occurs. So just because they're there doesn't necessarily mean it's an issue. So I've got D for jealous, and I'm proud of it. I've got no gut problems, no problems at all. So I know some patients still to this day, even last week I had a patient come to me saying, I've got blastocystis, or my blastocystis is flaring up. And then we need to take a step back and go, okay, you've got blastocystis, but what else is happening in your gut? Are you stressed? You know, are you having a regular bowel motion? Let's not try and pinpoint blastocystis as the cause. Let's look at other potential causes, because from my experience and from what we're seeing in the, in the research, actually trying to kill blastocystis is very, very, very difficult. It's going to compromise the microbiome. And when you do kill it, there's not a change in clinical symptoms. Symptoms.

I'm with you. I mean, it's. It's such a. A complex interaction. I almost look at the microbes now as, as genetics. You know, a form of. A form of an organ with different genes that produce metabolites. At the end of the day, the actual. The benefits being exerted either from the, the metabolites that they're producing or the succession of different bacteria, yeast, fungi, microbes to an end metabolite. So, you know, that particular pathogen or pathobion or parasite, however you want to call it, might be being kept in check by other organisms, or they might be part of a succession where, where one is feeding off the other. So we often try and paint a good guy and bad guy, but I think in reality, the good guys can be bad and the bad guys can be good. So in reality, it's gray. I mean, they're all. Even the bad bacteria are producing beneficial metabolites. So I think the brilliance of microbial is increasing the knowledge and awareness in this space such that that practitioners like yourself, like myself, can make more informed decisions based on the latest evidence that you're providing.

And that's something I always say to whether it's mentoring with students or teaching students, functional testing needs to inform treatment direction. So we need to be able to say, okay, the results of this test is going to change how I treat my patient. And that's why I utilize microbiome testing in my clinical practice, is because. Because I don't Know what's happening in the gut, I could take a stab. I could, I could give some prebiotic fibers, maybe a multi strain probiotic, you know, if I start feeling like it. But based on the report, it's that personalized medicine. We can go you as an individual, right here, right now, this is what your microbiome is doing. Thereby, let's, let's treat that rather than taking a wild guess as to what's happening within an ecosystem that we just can't view.

Great, I love that. I think that's a good place to start wrapping up. It's been such a fascinating discussion. We hit all the key points that we wanted to hit. One thing, one thing I'm interested to know. I forgot to ask this. You mentioned 16s prior. I'm not sure. Have you seen Rob Knight's latest piece coming out with the 16s? No conversion to, or being able to cross talk between whole genome sequencing and 16s?

No, I'm not familiar with that.

That's, that's fascinating.

Yeah.

Because when you look at the 16s was the predecessor for whole genome sequencing. It was a much cheaper one that was used by companies like Ubiome. Very fast and effective test looking at a very small bit of RNA as a marker, the 16s. But now Rob's done some work where the, they can look, take, take a look at all those older studies and then match up with whole genome sequencing. So I'm really fascinated to see how that evolves because initially I thought, well, all the 16s ones are going to be rubbish. You know, it's kind of outdated. But now with the breadth of Data available on 16s and 16s still being very widely used compared to a shotgun sequence, sensing how that sort of brings all those studies now together in a unified way to see what sort of outcomes can be gleaned.

It also depends on the database they utilize. So sometimes researchers, they can use 16s or metagenomics, but their database is so small it's like, oh well that's not going to provide you with enough information even if it is metagenomics. So you've got to dive deep into, to the research to understand what database they're using, how, how deep they are going when it comes around to the reads within metagenomics, how deep that is. And that will provide you with a more robust understanding to see is it just surface level 16s or metagenomics or is it deep level metagenomics?

100%. I mean whole genome sequencing is the gold standard. You know, any modern company should be utilizing that, that technology undoubtedly, you know, with microbial, with all your machine learning, artificial intelligence, cancer activities going on, to glean more out of the data, I think is the gold standard. I'm excited to look at what can be gleaned from retrospective studies. I think the green jeans database was the, I think your, your colleague Phil was involved.

Oh, okay. Well then if Bill was involved and then it's going to be high level standards.

I, I suspect he was the one that to kind of champion that. But with Rob Knight now it's green jeans too. So let's see how that space evolves. It's probably more in that sort of researcher space that might be interested in that development, but I thought I'd just throw, throw it in there for a bit of a nugget.

Fantastic.

Well, let's wrap. And if people love this conversation, they want to reach out to Brad. How do they find you?

I'm on all the socials, Dr. Brad Leach and then online Dr. Bradleach.com I've got a variety of courses aimed at both practitioners and consumers and then also mentoring for practitioners. And then I present a lot on podcasts like here today and then at a variety of different events both here in Australia and globally.

Great. And I love to finish my podcast with the question, if there was one thing you could do for your gut health today, Brad, what would it be?

Diversity. Diversity, diversity, diversity. Brilliant.

Love that. Thank you so much, Brad.

It's been a pleasure.

We hope you enjoyed this episode of the Gut Health Gurus podcast with Dr. Brad Leach. If you found this podcast valuable, leave us a kind review and five stars on Apple Podcast, Spotify, YouTube or your favorite podcasting app. If you want to connect with our host, Kriben Govinda, please follow him on Instagram, Facebook and TikTok gut healthgurus. Also check out our Gut Health Gurus Facebook group. With 17,000 plus members ready to help you on your journey to amazing gut health, this episode is sponsored by Nourish Me Organics. Head to www.nourishmeorganics.com and use the code HappyGut for 10% off. Make sure to check out their range of gut Health supplements. Until next time.