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Autoimmunity and the key role of the gut microbiome with Lisa Costa-Bir and Dr. Brad Leech

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Autoimmunity and the key role of the gut microbiome with Lisa Costa-Bir and Dr. Brad Leech

Dr. Brad Leech, Clinical Nutritionist and Herbalist joins fx Medicine Ambassador Lisa Costa-Bir to unpack the intricacies of autoimmunity and the connection to the gut microbiome.

Dr. Leech shares a wealth of clinical pearls for practitioners with autoimmune patients by unpacking the clinical relevance and meaning of functional gut testing markers. Dr Leech examines how practitioners can use testing as a tool to identify inflammatory risk factors associated with autoimmunity and individualise treatment protocols for patients using diet, lifestyle, and supplemental support.

Dr. Leech describes the clinical significance of establishing balance and healthy diversity within the gut using food as medicine, rather than focusing on elimination.

Together, they also explore lifestyle factors that impact the gut microbiome, and how managing stress and using targeted supplementation to achieve a balanced gut microbiome can contribute to lowering autoimmunity risk factors in our patients.

Covered in this episode

(00:26) Welcoming Dr. Brad Leech
(02:28) The link between autoimmunity and the gut and modifiable risk factors
(04:49) Dietary interventions for patients with autoimmune conditions
(09:26) Gut dysbiosis in autoimmunity
(15:34) Autoimmunity and gut microbiota species and genus
(22:42) Pathobionts
(24:07) Gut markers for investigations in microbiome testing - zonulin and calprotectin
(32:33) Fibre tolerance and the microbiome
(35:16) Hydrogen sulphide
(39:05) Gut markers for investigation summary
(42:03) Inflammation markers for systemic inflammation
(46:36) Therapeutics for inflammation
(48:00) Saccharomyces bollard for inflammation
(51:42) Other probiotic strains
(53:20) Other beneficial supplements
(54:23) Lifestyle strategies
(59:46) Metagenomic testing 
(61:01) Thanking Dr. Leech and closing remarks

Key takeaways

  • Patients with autoimmune diseases have similar gut microbial status: less diversity and more abundance of certain species 
  • By eliminating major food groups such as FODMAPS, digestive enzyme production is impacted, potentially causing further intolerance to such foods 
  • Prebiotics and probiotics help to crowd out pathogenic bacteria and re-balance the gut microbiome without the need to kill off certain microbiota.  
  • Cruciferous vegetables block the conversion of TMA to TMAO 

Suggested therapeutics to support a reduction in inflammation 


Resolution of inflammation 

Omega 3 Fatty Acids 

Reduction of inflammation 

  • Microbiome modification to reduce inflammation 
  • Consider a diverse range of prebiotics to ensure microbial diversity 

Immune modulating effect, support microbial diversity, and reduce inflammation

Saccharomyces Boulardi 
  • Reduction of inflammation, gut permeability, and immune dysregulation 
  • Supports microbial diversity and increases secretory IgA 
Vitamin D 
  • Regulates the immune response 
  • Supplemental support when low, but when above 100 nanomoles per litre encourage safe sun exposure 
Chanting Om 
  • Vagal nerve activation to support stress management and gut/brain connection 
Colouring in 
  • Changes brainwaves to support parasympathetic nervous system activation 

Functional inflammatory markers 

  • Acute phase marker for intestinal permeability. 
  • Zonulin will only increase when it’s actively being stimulated.  
  • Activation of zonulin is an immune system defence mechanism 
  • Zonulin levels need to be assessed in conjunction with other autoimmunity and inflammatory risk factors and markers
  • A sign of inflammation and gut permeability when above the optimal reference range 
  • You will not see calprotectin at zero. 
  • To be considered in relation to other gut inflammatory markers 
  • A sign of inflammation and gut permeability when above the optimal reference range 
  • You will not see lactoferrin at zero. 
  • To be considered in relation to other gut inflammatory markers 
Hydrogen sulphide 
  • Can indicate a level of gut permeability, inclusive of other risk factors. 
  • High cysteine-based foods fuel hydrogen sulphide production 
  • Can indicate a level of gut permeability, inclusive of other risk factors. 
  • Short chain fatty acid 
  • 24% of acetate will be converted to butyrate 
  • Short chain fatty acid 
  • Works on signalling the immune system and modulating gene expression 

Resources discussed and further reading

Dr Brad Leech

Connect with Brad: Instagram

Mentoring Program

Research: Diet, Digestive Health, and Autoimmunity: The Foundations to an Autoimmune Disease Food Pyramid - Part 1
Research: Diet, Digestive Health, and Autoimmunity: The Foundations to an Autoimmune Disease Food Pyramid - Part 2

Gut microbiome and autoimmunity

Journal: Autoimmune pre-disease
Article: Gut dysbiosis in autoimmune diseases: Association with mortality
Article: Gut dysbiosis is associated with primary hypothyroidism with interaction on gut-thyroid axis
Article: Gut microbiota and Hashimoto's thyroiditis
Article: Gut microbiome metagenomics analysis suggests a functional model for the development of autoimmunity for type 1 diabetes
Article: Microbial dysbiosis in the gut drives systemic autoimmune diseases
Article: Role of microbiota short-chain fatty acids in the pathogenesis of autoimmune diseases

Intestinal permeability and gut dysbiosis

Article: All disease begins in the (leaky) gut: role of zonulin-mediated gut permeability in the pathogenesis of some chronic inflammatory diseases
Article: Hydrogen sulfide toxicity in the gut environment: Meta-analysis of sulfate-reducing and lactic acid bacteria in inflammatory processes

Mental health and gut dysbiosis

Journal: Association of Loneliness and Wisdom With Gut Microbial Diversity and Composition: An Exploratory Study.


Lisa: Hi, and welcome to fx Medicine where we bring you the latest in evidence-based, integrative, functional and complementary medicine. fx Medicine acknowledges the Traditional Custodians of country throughout Australia where we live and work and the connections to land, sea, and community. We pay our respects to the elders, past and present, and extend that respect to all aboriginal and Torres Strait Islander peoples today.

Joining us on the line today is Dr Brad Leech, an internationally recognised integrative medicine practitioner. After entering the functional medicine profession in 2008, Brad has taught and developed subjects at leading academic institutions in integrative gastroenterology, naturopathic medicine, nutritional and dietetic medicine, and public health research. Brad is the lead clinical educator and co-creator of Co-Biome. In addition to his research and working with patients, Brad offers practitioner support through his mentoring programme, Brad's Brainiacs. Welcome back to fx Medicine, Brad.

Brad: Lisa, it's fantastic to be chatting with you again. It's always a privilege to be here on fx Medicine.

Lisa: Oh, we love having you, and we always learn so much. So, today we're talking about autoimmune diseases, which we know are on the rise, and current statistics suggest approximately 5% of the population worldwide has at least one autoimmune condition. Now, while some of the factors that predispose an individual to an autoimmune condition, such as genetic susceptibility, are largely out of our control. Other risk factors such as optimal gut health, are very much modifiable. In fact, 2,500 years ago, Hippocrates stated that all disease begins in the gut. And certainly, gut health is a logical place to start when trying to modify an autoimmune disease. And that's what we're going to explore today.

Brad: Mm-hmm.

Lisa: Mm-hmm. So, Brad, you have published a research article on digestive health and autoimmune disease. Can you tell us a little bit more about your key findings and also what led you to look specifically at the link between autoimmunity and the gut?

Brad: I read a paper by Dr Fasano and basically, he proposed that if we corrected one of these potential risk factors for autoimmunity and that is increased intestinal permeability, then the autoimmunity wouldn't continue, and it would reduce. And so, I spent a number of years focusing on intestinal permeability, and that just, kind of, led on further and further to all the other components of gut health and autoimmune disease. So, now, yes, I have fallen into the cliche of a practitioner focusing on gut health, but I've been doing it for years and years and years and I can tell you all disease begins in the gut.

So, with that said, I was involved in the research paper. Now, it's a two-part article called Diet, Digestive Health, and Autoimmunity: The Foundations to an Autoimmune Disease Food Pyramid.

Let's say Part 1 explains what we refer to as modifiable risk factors for the development and exacerbation of an autoimmune disease. Now, we went in with a very open mind going, "Okay, what are all the potential risk factors that we as practitioners can address in our patients who have an autoimmune disease or at risk of having an autoimmune disease?" Now, we looked through all of the different literature and we came up with four modifiable risk factors, and they include increased intestinal permeability aka leaky gut, inflammation, dysbiosis, and immune dysregulation. And so, these four modifiable risk factors, they almost feed off each other in the sense of, when there is inflammation, that can drive permeability. When there's dysbiosis, that can drive immune dysregulation. So, they have this crosslink between each other where they all drive one another. Now, that was Part 1.

Part 2. We then looked at all of the different diets. And so basically, we did a literature search and going, "Okay, show me all of the dietary interventions in patients with an autoimmune condition." We opened it up to all autoimmune conditions because we know, as integrative practitioners, that if you've got inflammatory bowel disease, it's not just about working with a gastroenterologist. It's about looking at the whole picture. And so, we group these autoimmune conditions as one, okay, in a sense. And so, we looked at different diets, the Mediterranean diet, the vegetarian diet, the vegan diet, the gluten-free diet, the paleo diet, and also the low arachidonic acid diet also known as the anti-inflammatory diet.

Now, based on this research, we actually put forward what a food pyramid may look like for an individual with a autoimmune disease. We know here in Australia and in other developed countries, that we have food pyramids or plates, but they're not targeted at disease states. Let's take cardiovascular disease where they give recommendations about reducing saturated fats and reducing salts and so forth, but no one's actually gone and gone, "What does a diet look like for a patient with an autoimmune disease?"

So, to summarise, what we found was somebody with a active autoimmune disease, the most effective diet would be a gluten-free diet, which is high in fibre, that has plenty of seafood and has a max of 150 grams of arachidonic acid containing foods each day. Now, while in practice, if a patient has an autoimmune disease, I will address these four modifiable risk factors: intestinal permeability, inflammation, dysbiosis, and of course immune dysregulation.

Lisa: Okay, very interesting. So, with those recommendations that you just suggested, so less than 150 grams of arachidonic acid producing foods, what are some arachidonic acid producing foods and what would that look like in terms of specifics like x amount of cheese or meat or so on?

Brad: Arachidonic acid for those who don't know is call it the opposite of omega-3. Omega-3 is anti-inflammatory broadly speaking, and arachidonic acid is pro-inflammatory broadly speaking. So, some of the most richest sources of arachidonic acid are going to be things like eggs, and turkey, goat, lamb, chicken, and so forth.

Now, there's different varying amounts. So, to give you an example, what we're trying to achieve here is 90 milligrams or less of arachidonic acid per day. But if you go telling that to a patient and they need to count it, it's going to be too difficult. So, what we've done is we've taken the mean average of arachidonic acid containing food, which is basically land-based animals. And we've gone, "What's the mean average of that?" So, for example 100 grams...no, sorry, 150 grams of chicken eggs contains about 50 to 60 milligrams of arachidonic acid where something like 100 grams of beef will contain about 200 milligrams of arachidonic acid, so it varies.

Lisa: Mm-hmm.

Brad: So, we came up with this 150 grams not of arachidonic acid but of arachidonic acid containing foods. So, rather than having this 300-gram steak with dinner, we're just going to reduce that. Rather than having 12 eggs a day, we're just going to reduce that. The exception here is seafood, because seafood won't contain these high levels of arachidonic acid. They're going to be containing the omega-3s and the ant-inflammatory fats, so we can consume more of that.

Lisa: Okay. Wonderful. So, it's not about eliminating altogether. It's just about reducing and increasing fibre and things like that too at the same time.

Brad: Yeah. So, it's about changing the cellular membrane of the arachidonic acid to omega-3 ratio. So, I'd be bringing in the fish oils if they've had a history of consuming too much arachidonic acid. I might go testing their bloods to see what is their makeup of different fats on a cell membrane and go, "Well, we need to increase omega-3s or the plant-based omega-3s or fish-based omega-3s."

Lisa: Okay. So, you were talking about... You mentioned dysbiosis, intestinal permeability, inflammation, and immune dysregulation as those four modifiable risk factors and that perfect storm for an autoimmune disease to take place. Is there always dysbiosis in an autoimmune condition?

Brad: Interesting. So, it's one of these perspectives where a lot of patients with a advanced autoimmune condition, especially if it's within the gut, will have some form of dysbiosis, right? But is it the chicken or the egg? Which one comes first? Does the dysbiosis drive the autoimmunity or does the autoimmunity drive the dysbiosis? And I would actually say it goes both ways in the sense where, once that autoimmune disease has developed, then, yes, there's going to be significant changes to the microbiome. But we know from the research where changes in someone's microbiome will pre-perceive the onset of an autoimmune disease diagnosis. So, we know that there's changes in the microbiome before an autoimmune condition is actually diagnosed.

Lisa: Mm, okay, so I want to talk about this a little bit more because I was having a little look at the research, and I also noticed exactly what you're saying that so many of the researchers are observing that clusters of patients with the same autoimmune disease have similar patterns with regards to their microbial status, so with regards to their gut. So, they're seeing reduced diversity and abundances of certain microbiota when compared to healthy controls.

So, for example, a 2023 paper examining gut dysbiosis in autoimmune disease observed faecal bacterium, was commonly depleted in individuals with autoimmune conditions such as lupus, multiple sclerosis, and Sjögren's syndrome. And basically, the function of that faecal bacterium they were saying was to maintain homeostasis of the gut immune system because that bacteria secretes short-chain fatty acids such as butyrate, which is anti-inflammatory, which I just thought was so interesting. So, when we don't have enough of that faecal bacterium, then we see alterations in immunity increased inflammation, which then predisposes to these autoimmune conditions, which I just think is super interesting that they can see that on a test. Have you seen similar patterns with your patients and in the literature?

Brad: So, yes, a lack of butyrate is going to be very common in in many chronic health conditions. But something that I will highlight here is looking at butyrate production is a lot more clinically important than focusing on a few butyrate-producing species. So, we as practitioners need to collectively assess how our patient's microbiome, how their capacity is to produce butyrate, and whether or not there's sufficient fuel source to feed those species to produce the butyrate. So, it's more about the group of species and their abundance rather than classifying it as this one particular species. Is there too much or not enough of that?

Now, what I find is a lot of practitioners are focusing on a few select genus rather than the whole microbiome. So, this causes this mentality around practitioners is I need to increase X species or X genus. Now, I mentor lots and lots of practitioners, and they bring to me a variety of different microbiome reports, and they go, "My patient doesn't have Akkermansia," or, "It doesn't have Lactobacillus. I need to increase this."

Lisa: Yep.

Brad: What I will tell you here is I'm sure we've spoken about my gut microbiome before. I like to say I've got...

Lisa: I know. I wanted to mention this. I wanted to refer to you as the man with the golden stool.

Brad: The golden stool.

Lisa: And not the stool that we sit on.

Brad: The running joke. I grew up on a farm. I was vaginally born, grass-fed. I eat more plants than most people. My dinner last night, it had tempeh, and lentils, and chickpeas along with cruciferous vegetables. It was like jam-packed. It also had brown rice that was cooked and cooled. We digress.

Where I'm going with this is I have measured my microbiome multiple times, okay, and I measure the whole microbiome. I do not have any lactobacillus in my gut, right? So, it's not about trying to increase one particular genus, it's about, well, let's take a step back and look at the whole microbiome and see how that microbiome functioning and what we need to do to support that whole microbiome rather than targeting a few genus here and there.

Lisa: So, why don't you have any lactobacillus?

Brad: I don't need it. My microbiome has adapted in the sense of... It's this common misconception. It's a whole can of worms when it comes around to the classification of lactobacillus. So, a number of years ago, what's happened is lactobacillus has actually been reclassified into over 25 different Genuses and species. So, what we thought was lactobacillus in research, which is older than 10 years old, isn't actually going to be lactobacillus because it incorporates 25 other Genuses. So, I probably do have a number of those other Genuses within my microbiome, but I don't technically have the lactobacillus genus within my microbiome because we've reclassified lactobacillus rather than looking at how it acts underneath a microscope. We classify it on a DNA perspective to go, "Okay, what is the DNA and where does it fit within the hierarchy of bacteria?"

Lisa: So interesting. So, interesting. Now, I want to ask you about Hashimoto's because obviously I've got an interest in it, but I do think it's one of the most common autoimmune conditions that we see within clinic. I was reading a 2020 study which observed that most individuals with Hashi's have gut dysbiosis. No surprises there for most of the clinicians listening. They found that the short-chain fatty acid producing ability of individuals with hypothyroidism was decreased resulting in increased serum LPS levels. Another study I read observed decreased Prevotella 9, which is known to enhance anti-inflammatory activities by reducing Th17 polarisation.

So, what you're saying is we would not target specific bacteria, but we would look at the microbiome as a whole in these patients. Is that right?

Brad: Yes, that's correct.

Lisa: Okay. Fantastic. So, then if we were doing a gut analysis and we see things like low Prevotella or low butyrate, basically this sort of testing is we're able to inform ourselves and I guess our patient that they could be at risk. So, they haven't been diagnosed with Hashimoto's yet but we're seeing low butyrate. We're looking at this marker and thinking, "Okay, this marker when it's at the right level is usually anti-inflammatory. This patient's got low levels. Possibly, we're seeing an increased risk for autoimmune disease."

Brad: Okay. So, there is some confusion here, and I think where you're applying is some particular genus or species have been linked with autoimmunity. So, they're generally classified as potential autoimmune disease triggers.

And I believe a study that you quoted earlier on was Chang 2023, and that was the one looking at all of the different genuses and linking it up with different autoimmunity. Now, something to consider here is that particular study and a lot of other studies are only linking up genuses. So, the genus of the bacteria, not the species.

So, yeah, I give you the example of streptococcus. In that particular research as I recall, they linked streptococcus, so high amounts of streptococcus, the genus, not the species, the genus, to multiple sclerosis, lupus, and rheumatoid arthritis. Now, streptococcus is an interesting one because, yes, we could potentially contribute as a trigger for autoimmunity but, it can also be what we refer to as a oral species.

Lisa: Yeah.

Brad: Now, when I say oral species, these are microbes that are found within your oral cavity. What happens is they can actually be found within a stool test. How do bacteria from the mouth transit all the way down through the stomach acid, through the intestines, and be found in a stool test? It comes down to high amounts of oral species on a stool microbiome test can actually indicate a lack of stomach acid.

Lisa: That's exactly what I was thinking.

Brad: So, here's the thing. Is it actually the microbiome or is it further up going, "Hey, we need to address stomach acid," right? The other one here, when it comes around to linking particular Genuses, not necessarily species, but particular Genuses with an autoimmunity is how we name species. A lot of species contain the wrong name. So, when you actually dig into the methodology of a research article that's looking at microbiome sequencing, we want to evaluate what database they use to name the species. So, there's a number of different databases. The two main databases is what's referred to as the GTDB. It's a database set up by the University of Queensland, and it's actually regarded as the most accurate and comprehensive database for accurately naming species of bacteria.

But we've also got this database called the NCBI, right? And that's what a lot of labs will actually use to name their bacteria and what a lot of researchers will use to name their bacteria. But they actually misclassify so many different species. So, the research article might say Prevotella copri, but is it actually Prevotella copri or is it active or is it something else?

Lisa: Oh, my gosh, that's insane. It's so confusing.

Brad: So, where I'm going with this is, from a research perspective, we've got to look at the methodology and understand what database they're using. And then when we're interpreting a microbiome report, we've got to understand what database are they actually using because they may be reporting particular genus or species but in fact, it's something completely different.

The other one here is this linking particular species with a particular autoimmune disease. It sets up this mentality for practitioners where they go, "I need to kill this..."

Lisa: Yes.

Brad: ...where they go, "Oh, my patient has klebsiella pneumoniae or Prevotella copri. I need to kill it." So, I'll give you the example of Prevotella copri. Now this is quite common, I want to say, about 5%, maybe 10% of individuals will have what we refer to as a Prevotella copri dominant gut. That is where more than 10% of the microbiome is Prevotella copri. Now, this is classified as a pathobiont in the sense of it's linked up with a number of chronic health conditions and so forth.

But there's interesting research out there that is almost going that next stage where going Prevotella copri might have an array of different strains. Remember, Prevotella copri is the species. They may have further strains, which we just don't know yet where, when they're fed a healthy wholefood diet, it's actually beneficial. But when you feed it a typical Western-style diet, it's going to produce negative compounds.

Lisa: So, similar to candida, right? Different strains.

Brad: In a sense. I mean, that's another kettle of fish when we're talking about candida and whether or not candida is actually there or whether or not it's candida that is grown because there's cross-contamination and it's sitting in the post for too long. So, yeah, when somebody has high Prevotella copri, it's emphasising a wholefood, healthy diet to ensure... Because that's Prevotella copri. It's not going to go anywhere. It's going to stay. We want to feed it the right amount of food.

So, to kind of get back to that original question on, can we link particular bacteria with autoimmunity and Hashimoto's? Where I like to go here is with pathobionts.

Brad: So, a pathobiont is a microbial species which is associated with a negative health outcome. So, it's been seen in cross-sectional data to be higher amounts in Hashimoto's or Crohn's disease or so forth compared to healthy individuals. What I want to express here is everyone has them. I have pathobionts. Even...

Lisa: Man with the golden stool.

Brad: ...the practitioner with the golden poop has got pathobionts. It comes down to how much space they're taking up in the microbiome. So, all of my pathobionts... How about we say my healthy patients? When they have pathobionts, they have it in a low abundance, right? But when they are higher, I'm talking maybe two standard deviations higher than what we see in unhealthy individuals or healthy individuals, that's when it becomes a bit of a problem. That's when we go, "Well, hold on, why is this growing?" And one of the biggest things that we've actually found in the research is to address these pathobionts rather than coming in with that killing perspective is if we actually feed up the beneficial bacteria and that's going to change that level. So, yes, in autoimmunity, I'm always looking for whether or not there's high amounts of these pathobionts. And if there are, I'll want to reduce their abundance by increasing the beneficial bacteria.

Lisa: Yeah, I love that approach. And that's definitely the approach I take as well. So, when doing a gut microbiome analysis, what markers in our gut can tell us that there is intestinal permeability, and dysbiosis, and inflammation? And how can practitioners apply these results?

Brad: Okay. So, we've got a number of different markers here. So, why don't we break it down? What I will do is I'll start off with my favourite, intestinal permeability, and then maybe we can dive into inflammation.

Lisa: Sure.

Brad: So, intestinal permeability, it is what I've dedicated many years of my life to. I feel like when it comes around to evaluating intestinal permeability in clinical practice, yes, you've got stool zonulin. Something I want to classify here and re-educate practitioners on is the reference range for zonulin. So, as we see in, let's say, blood pathology, we have what we see on the pathology report and then we have our own integrative reference ranges, which are a bit more narrow. When it comes around to GI markers, such as zonulin, calprotectin, lactoferrin, how they are calculated is there is a line in the sand. If you're above it, you have it. You have permeability. You have inflammation. But if you're below it, you're not. The reason I bring this up is I see practitioners either in my mentoring programme or even on social media saying that somebody might have leaky gut when their zonulin is at 50. And we know that the cutoff point is 107. If somebody has zonulin at 50, they don't have intestinal permeability, right? It's not a scale you've got to be over. Of course, if there are 106 or even 100 being very close, I'll classify that as intestinal permeability, but you will not have zero on zonulin. You will not have zero for calprotectin. That's just not how these markers work. Everyone has them. We need them but it's when they become too high.

Lisa: Yeah. So, similar to even thyroid antibodies, people will always have them. It's just that they shouldn't be over the reference range or even close to that reference. There will always be some degree. Okay. So, with zonulin, calprotectin, we should expect to see some. It will never be zero, but it just shouldn't be over the range.

Brad: That is correct. And zonulin is one marker when it comes around to assessing gut permeability, and we want to assess these markers in patients with autoimmunity because that will give us that indication of do we need to address intestinal permeability in clinical practice. Not everybody with intestinal permeability will have elevation in zonulin.

Lisa: Oh, that's interesting.

Brad: So, zonulin will only be increased when it's actively being stimulated. It's what we refer to as an acute phase protein, meaning that it has a relatively short half-life. So, you've got to stimulate it for it to be found. That is why I rely on other markers to give clues to whether or not there's intestinal permeability. These are going to be things like high secretory IgA, right? Other compounds such as LPS within the microbiome. Butyrate, of course.

Something to note here with butyrate is that there's two ways to assess butyrate within the stool. We can look at the microbes that produce butyrate, and then we can also measure actual butyrate. Now, unfortunately, when we go measuring actual butyrate, this can actually be greatly impacted in a negative way based on a patient's transit time, okay? In the sense of if you have a patient with constipation, a lot of the times their butyrate is going to come back as low, right? If you have a patient with diarrhoea, a lot of the time the butyrate don't come back as high. That is not to say that somebody with constipation has got low butyrate. That is to say that somebody with constipation will be absorbing more butyrate because there's slower transit time and staying in the colon for longer, right? With somebody with loose stools, it's going to be coming out. It's not going to be absorbed. So, it's not giving us an accurate depiction on butyrate status. Whereby if we measure the microbiome, the capacity to produce butyrate, that's not going to be impacted by transit time, and it's going to give us a more accurate way to go, "Do you have species to produce butyrate and do you not?" And you combine that with the data from their diet. Are they consuming enough resistant starch? Are they consuming enough prebiotic fibres to feed up these species to produce butyrate, right?

We can also go a bit deeper here. Now, of course, hydrogen sulphide, another marker which is elevated can be indicating intestinal permeability. But I really like to take butyrate and hydrogen sulphide, their results, together. Hypothetically, if somebody had normal butyrate or on the lower end but still within range but they had high hydrogen sulphide, I would still support their butyrate. This is because hydrogen sulphide will reduce the absorption of butyrate within the bowel, which is just...it blows your mind where we need to collectively...

Lisa: So detailed.

Brad: ...look at all these markets rather than just one at a time. The other example here is going to be acetate. Now, acetate being another short-chain fatty acid. We haven't been able to find definitive links between acetate and intestinal permeability, but what we know is 24% of acetate will be converted to butyrate. So, if somebody has super low acetate and sub-low butyrate, I'm going to be saying, "Hey, I need to even further support this patient's butyrate because acetate isn't going to be helping out as much."

Lisa: And so let's just go back to butyrate and talk about its role in autoimmune disease because I was doing some reading on it and I went down a massive rabbit hole as usual. I got so excited about it. It's a short-chain fatty acid. It's anti-inflammatory, right? It's an immune modulator. And so if we don't have enough of the bacteria that produce it, then again, if we see that on a blood test...not a blood test, a stool test, we would be thinking, "Uh-oh, foreseeing problems." Would you say that's right?

Brad: Mm.

Lisa: Yeah. Okay.

Brad: And in the sense of... Butyrate is one of the I would say most important markers when it comes around to... I won't say autoimmunity but just within chronic health. And sometimes we fall into the relaxed approach of, "Oh, they're butyrate. We'll just give some prebiotic fibres to increase it," but butyrate is so important where it works on signaling the immune system, modulating gene expression. It can impact the inflammatory cascade to butyrate. Even when suboptimal or even when optimal, we do need to continue to address it.

Lisa: Can I ask you then, because you've brought up a really good point, where I'm getting at is that I had a patient with low butyrate and I was talking to colleagues and they were saying, "Oh, you can just get a butyrate capsule and take it." And I was thinking in my head, "This doesn't make sense to me because they're not getting the food or the prebiotics." But then I was looking at some research and they do give butyrate capsules. But again, I didn't go there because I was kind of like, "Oh, my God, I'm talking to Brad. I'll just ask him."

Brad: Well, first of all, in Australia, we don't have access to butyrate capsules, but they are available elsewhere in the world. What the research shows is, yes, they are very beneficial in the sense of it will have the same action as butyrate. But at our core philosophy is address the cause. We are integrative and holistic healthcare practitioners. And if it takes a little bit longer, it takes longer but I want to address the underlying cause.

Now, something that a lot of practitioners will struggle with is my patient can't tolerate fibres, right? Now, I'm on a bit of a bandwagon at the moment on we need to increase fibre in the diet. I'm reading Fibre Fuelled at the moment. And from a practitioner perspective, it's basic but from a patient perspective, amazing. I very much support a lot of what he's saying in the book.

But where I'm going with this is our microbiome, if we don't provide it with that diversity, with sufficient fibre, it will actually lose the ability to break down fibre. A lot of the enzymes required to break down fibre are found in our microbiome, not within ourselves, right? And we know here that the release of digestive enzymes is a positive feedback loop. The more that we put into our body, the more that it will signal our body to release these enzymes. If we remove FODMAPs, if we remove major food groups from our diet, our body will produce less and less of these digestive enzymes. That's one component. And then the other one here is our microbiome will forget how to digest and break down fibres.

So, I described my dinner last night. I'm going to be able to just tolerate this, no problem at all. I'm not going to get any bloating and, sure, but that's because I eat it on a regular basis. If I had a patient who suffered from bloating, digestive issues, and if they consumed that fibre-rich meal, they would be in agony. Where I'm going with this is we need to start low and slow to the point of starting with an eighth of a teaspoon of well-cooked lentils and over a one-year period, increasing that to half a can.

Lisa: Okay, so it's a long-term thing, a one-year period.

Brad: Look at true food allergies, right? Eggs. We can now have children who are anaphylactic and allergic to eggs. We can actually retrain their immune system to be able to tolerate eggs. But what they do, they start off with an egg that is boiled for 15, 20 minutes, and you eat an eighth of a teaspoon. And that's what... You do that every single day. You just slowly work your way up along with probiotics and so forth and a gut repair, but you get to that point where you can eat a nice, runny egg on sourdough bread.

Lisa: Yeah, super interesting. So, it's about building up slowly that tolerance and the immune system becomes more capable.

Brad: Yes, exactly.

Lisa: Great. So, then can we talk more about hydrogen sulphide? Because I didn't actually know much about it till I did a bit of reading. And basically, it's metabolite produced by bacteria, right? Hydrogen sulphide.

Brad: Mm-hmm.

Lisa: Is it responsible if... I mean, I know we're going to do the stool test, but if a patient was getting gas that smelt like sulphur, could we assume they have an excess of hydrogen sulphide-producing bacteria or is that a bit too much to stretch?

Brad: Listen, we've got to go with the rule of three. If we evaluate their diets, if we evaluate what they say about bad gas. Where I'm going with this rule of three, 100% if someone can't afford a microbiome test, I will use these clinical indications.

Now, hydrogen sulphide, really, really interesting. The big one here is going to be cysteine. High cysteine-based foods is the fuel source to produce hydrogen sulphide. Now, this is where it gets really interesting, NAC, N-acetylcysteine, one of my favourite amino acids for insulin resistance and detoxification and you name it. It's an amazing amino acid, but I've had a few patients who have adverse reactions to NAC. They can't tolerate it, or their rotten eggs...

Lisa: The gas.

Brad: The gas smells more like rotten eggs. And it comes down to they've got too many hydrogen sulphide-producing bacteria in their gut and then they're adding in this cysteine, which is feeding that up. So, before I prescribe NAC or even high cysteine-rich foods, I will double-check their microbiome to go, "Oh, can you tolerate that? Yes or no?" And then I'll prescribe that. So, that's one of the biggest things that we can do if somebody has high amounts of hydrogen sulphide is to reduce cysteine-based supplements, to reduce cysteine in the diet. But the other alternative here is FOS. So, FOS being a fermentable carbohydrate. The research does indicate that increasing that in the diet will reduce these hydrogen sulphide-producing bacteria.

Lisa: Ah, interesting. So, that's fructooligosaccharides.

Brad: Yes.

Lisa: Mm-hmm. And what do you usually use in clinic in terms of dose and length of how much someone has to take for how long?

Brad: I'm with FOS. I usually do it through the diet. From the perspective of it's available. There are so many different foods that contain FOS that are just... Just eat a diverse diet. Eating 20 to 30 different plants each and every week will address that.

Lisa: Mm-hmm. So, I want to go back to hydrogen sulphide again and just, I guess, emphasise that it is associated with increased gut inflammation, isn't it? Like, higher levels.

Brad: Mm-hmm. Gut inflammation permeability.

Lisa: Yeah. So, if we see that on the test, that's not a good thing.

Brad: That's not a good thing. No. We don't want... I mean, we want a little bit, but we don't want too much. If it's there, fantastic. But if it's too high, then we want to bring that down.

Lisa: Okay, good. And we use the FOS for that.

Brad: Exactly.

Lisa: Mm-hmm. Do you think that some patients with IBD symptoms post-consumption of sulphur-containing foods, then that that's less to do with the FODMAPs and more to do with increased hydrogen sulphide or something different?

Brad: It could be either in the sense where... It really could be either. My patients are so unique that it could be both.

Lisa: All right. So, if we do a little summary, so zonulin, if we're looking at intestinal permeability in these markers, zonulin has to be completely... Well, it needs to be out of the reference range. It's an acute phase marker for intestinal permeability. And activation of zonulin, we could think of, is a defence mechanism by the immune system to flush out bacteria. I think I've read some studies say...

Brad: Yes, that's correct. Yes.

Lisa: The other thing I actually thought of is last time we spoke, you really emphasised that zonulin has to be measured in the gut, not blood.

Brad: Yes.

Lisa: As a lot of research papers do, they measure blood.

Brad: Yes. Yeah, and that's the thing. The abstract might say zonulin, but go down to the method section and go, "Was it stool zonulin or was it serum zonulin?"

Lisa: Have you ever had a patient with an autoimmune disease where you've done their stool test and they haven't had any notable gut symptoms but there have been major discrepancies on their gut analysis?

Brad: Mm. Okay. So, it comes down to how accurate and comprehensive the test being used is, which will determine that. So, I recall in my early years in practice, I'm talking 2008, 2010, 2012, when metagenomic sequencing just...it wasn't available. There was no tests globally, I believe, or definitely not in Australia that offered metagenomic sequencing. So, I would be utilising our data and data methods for measuring the microbiome. And there would be many reports where it would come back either of two things where it's like, "Oh, this doesn't mean anything," or, "Your gut is fine." But now that I actually use, and we have access to metagenomic sequencing, it's providing that more accurate and comprehensive information. I'm able to use this information to direct treatment approach and to get that further understanding of the microbiome.

So, yes, there's a sense of about 40% of my patients that I do a gut test with will not have digestive issues, right? We often think digestive issues got to do a stool test. But in a lot of cases like hormonal cases, mental health, poor immunity, even the worried well, when there's a autoimmune condition outside of the gut like RA, multiple sclerosis, lupus, I will be using a gut microbiome test to give me an understanding. This is because we can see markers within the gut which are linked with systemic inflammation. We know that systemic inflammation is linked with mental health, hormonal issues, rheumatoid arthritis, and we can understand whether or not the microbiome is driving systemic inflammation.

Lisa: That's so interesting because I think, for me as a practitioner, I often do blood testing, and ESR/CRP markers of inflammation often show up normal, even though someone can have a raging autoimmune condition and the patient reports feeling very inflamed. So, the gut can obviously inform us not just about intestinal inflammation but also systemic inflammation, it seems.

Brad: Yeah. So, one thing that I'll note here is ESR/CRP, they are really the only markers that we can do through the GP, but you can do a more comprehensive panel where you're looking at all of these different cytokines. What I've observed using that type of panel is sometimes there'll be markers out of range. But when somebody's on the verge of not really inflamed, then there's not going to be markers out of range. So, if ESR/CRP are, kind of, like, suboptimal, then I may do this panel to see inflammatory markers, but I'll also evaluate the markers within the gut microbiome that can indicate systemic inflammation.

Lisa: And what are some of these?

Brad: Yeah. So, some of these markers that we can look at... So, these microbiome metabolites that our microbiome produces can be linked with systemic inflammation, will be things like your branched-chain amino acids. So, there was a a research study and the title was association of plasma branched-chain amino acids with biomarkers of inflammation and lipid metabolism in women. And what this particular article found was there was an association with systemic branched-chain amino acids and a variety of different inflammatory markers such as CRP.

Now, our microbiome produces these branched-chain amino acids, which can then drive systemic inflammation. So, that's one marker that I'll look at. But when it comes around to that marker, it's important to evaluate their weights, their level of exercise to really determine what direction of treatment you might go. So, if somebody is overweight, it's going to be about increasing their exercise to be able to utilise those branched-chain amino acids. But if somebody's having a very healthy diet and they are exercising quite often but they've got elevation in branched-chain amino acids, then it's actually not a problem because it's not going to be a risk factor. It's when we apply these results to the individual.

So, another one here is going to be TMA or trimethylamine. Now, our microbiome can produce TMA from consuming carnitine and choline within the microbiome, whether it's through supplements or whether it's through the diet. It goes into circulation, and it converts to TMAO, okay, a compound which has been linked with cardiovascular disease, inflammation. I actually had a patient who had huge levels of this. I'm talking the highest levels I've ever seen. Now, he was a 46-year-old male, and he was the eldest living member of his family because his brother, uncle and father all died of a cardiovascular event before the age of 45.

Lisa: Oh, my gosh, wow.

Brad: So, could the microbiome be contributing to heart disease? Mm, I wonder. We know that our microbiomes are very similar within families. Interesting. So, what did I do for this particular patient? Well, we know cruciferous vegetables will actually block the conversion of TMA to TMAO. So, whenever we're having a carnitine-rich meal, a choline-rich meal, we want to be incorporating broccoli, lots of broccoli, some kale, if you enjoy that, cabbage, brussels sprouts and so forth. We can also take DIM if it's quite high as well to stop that conversion.

And then other markers for systemic inflammation from a microbiome perspective is hexa-LPS. We know a lot about that. And then also microbial diversity, so low diversity. Something to note here is, yes, there's a few research articles out there to link low microbial diversity with systemic inflammation, but there are hundreds of research articles linking low diversity with chronic disease. What's that underlining factor for chronic disease? It's going to be inflammation.

Lisa: Do you ever use omega-3s then?

Brad: Of course, when there's obvious inflammation, especially when it's evident on blood tests, I will use a combination of omega-3s and also your SPMs to really resolve that inflammation and bring it down, because whenever there's inflammation there, we know that biochemical pathways, everything else is just going to exacerbate. As I mentioned before, the four modifiable risk factors for an autoimmune disease, one of them being inflammation, we need to bring that down. And, yes, your SPM molecules, your omega-3s, they are going to be amazing at resolving...so, A, resolving the inflammation but then B, changing that cellular structure, that makeup of fatty acids, so then there's less inflammation for years to come.

Lisa: Yeah, and probably the SPMs are more indicated in that autoimmune picture than the omega-3s because often I think where there's that low grade inflammation or even high grade inflammation, we're not converting them. We're not converting the omegas to the SPMs.

Brad: Exactly. So, what I would generally do is SPMs first, bring down that inflammation. Once things are under control from an inflammatory perspective, utilising blood tests. Then, I would then transfer them to just omega-3s.

Lisa: Okay. So, we're at the therapeutics. Let's talk about SB, Saccharomyces boulardii, because for me, it's such a multitasker when it comes to autoimmune disease. How do you use it and how...?

Brad: I love SB Saccharomyces boulardii. It's in most of my treatment plans. It's one of those core recommendations that I give, especially when there's gut inflammation, when there's intestinal permeability, when there's immune dysregulation from so many different perspectives. So, in patients with, let's say, inflammatory bowel disease, sometimes they're on and off antibiotics. So, very important in and around antibiotic use. And it's one of those things I tell them, "Keep it in the cupboard. If you feel some pain going on in your gut and you know that you'll have to go on antibiotics soon after visiting the GP, start taking the SB."

But when it comes around to intestinal permeability. There's a lot of conflicting evidence out there for a lot of different supplements, but there were a few and SB, glutamine and zinc were the main supplements that, kind of, shone from that perspective of there is high-quality evidence to support their use for intestinal permeability. We know that SB will support with microbial diversity. It supports with increasing secretory IgA. It can prevent the adhesion of pathogenic bacteria and even pathobionts onto the wall of the intestinal cell wall. So, it's one of those really essential interventions that we can utilise.

Lisa: Yeah, I love it for that. So many different functions. And I had a look at the research and there's not a whole lot of research in specific autoimmune conditions. They're starting to do some research in humans with multiple sclerosis, but there's not that many papers where they've given just the Saccharomyces boulardii. But coming back to those four points that you talked about in your paper, the inflammation, dysbiosis, intestinal permeability, and immune dysregulation, as you said, there's lots and lots of research there. What do you do or have you encountered this in a patient—I'm thinking about a patient I had last week—who I've given SB to, and they are reacting with bloating and things like that. Have you come across that?

Brad: Interesting. What I can say is all patients are unique. It comes down to, whenever there is a reaction, I will say pull it out. Okay, give it three to five days. Wait to see if their reaction reduces. Now, I will always try it again. As long as it wasn't like an IgG immune response, try it again. Because sometimes what can happen is after a patient sees us as a practitioner, they change quite a lot in their diet. They change this in their diet. They take that supplement, they start exercising more. A lot's going on, a lot's changing.

So, sometimes the combination of all of them can contribute to that. I haven't seen SB in itself contribute to bloating per se, but it's one of those things we'll maybe start at a slower dose or take it after a meal or, when someone is more inclined to have a reaction, I will prescribe it at night and then I find that to be less impactful because they're sleeping.

Lisa: That's a great idea actually, nighttime prescription. I do think it was dose-dependent because it was a high dose that she was inclined to take it because it was just a one-a-day kind of situation. But I think maybe for her, the lower dose more frequently would have been beneficial. So, then what about other probiotic strains?

Brad: Yeah. So, this is a really interesting one. Of course, we need to move away from this perspective of, "My patient has low lactobacillus, I've got to prescribe lactobacillus," because we know that they don't necessarily stay. They're quite transient in saying that probiotics are incredible at changing the environment in the gut. If we change the environment in the gut, then the species, your microbiome, will then flourish. They will have more favourable environment to grow and thereby the beneficial species will grow.

So, I'm more of a prescriber of probiotics. I use them all the time and a nice multi-strain, well-researched probiotic for a gut health protocol but not necessarily to add lactobacillus in but for it to have an immune modulating effect or to increase the creatinine IgA or to impact intestinal inflammation, I'll do it to change the environment in the gut.

Lisa: Lovely. And how long do you do generally with your SB and your probiotics? Do you start off with just SB and then do probiotics? I'm interested in your regime.

Brad: So, this is quite interesting. So, I did some research on this very topic a number of years ago in the sense of how long should practitioners be prescribing a gut repair protocol for. My gut protocol will be three months. I might slightly chop and change things about two months. but they will generally be on a gut protocol upwards of three months.

Lisa: Mm, lovely. Okay. So, any other supplements you think are worth mentioning that you use?

Brad: There are a lot that I would use. I do like my prebiotic fibres for changing the microbiome. I think they are key. Something that I will note here is a diverse prebiotic fibre is going to be more effective for the microbiome in some cases than just one prebiotic fibre. So, sometimes what can happen is, if we just use one prebiotic fibre for too long, that can actually reduce diversity because we're only feeding up a select number of species. We actually want to... And this is where diet comes into, but have prebiotics, whether it be a supplement or from the diet a variety of different sources, so then we're feeding up the whole microbiome.

Lisa: Mm. Okay. So, cycling, say GOS and PHGG and things like that.

Brad: Yeah, inulin and beta-glucans either from the diet or through supplement, that's going to be ideal.

Lisa: Lovely. Now, I've seen you jogging. I remember we were at a conference, and I was stumbling to get a coffee, and you had returned all fresh and chirpy from your morning jog. What about lifestyle strategies and the gut?

Brad: Lifestyle factors for autoimmunity, and this is going to be key. So, there's a lot that we can do here.

Now, we know how important vitamin D is for autoimmunity, for regulating our immune response. If it's low, we're going to supplement it. We're going to be supplementing to increase it. But once it's at above 100 nanomoles per litre, we want to ensure safe sun exposure. Now there's apps that you can download on your phone that can tell you, "Go out in the sun for 12 minutes and expose this percentage of your body and that will be your vitamin D requirement." So, I'll recommend that type of app.

The other one that I'll do from a lifestyle perspective is to stimulate the vagus nerve. The vagus nerve is what connects the gut to the brain, the brain to the gut, and there's a lot that we can do. Of course, you've got your bitter herbs, but I love telling my patients to sing, to hum, and to chant the word Om. Actually chanting Om. So, Om. That vibration in the back of the throat will stimulate the vagus nerve.

Have you ever thought about these Indian gurus who will sit around and drink sugar-rich chai tea all day but they'll live to 100 years old? But they spend hours and hours chanting Om. So, I wonder whether or not stimulating the vagus nerve overcomes that high amount of sugar in their diet to the point that they are in an anti-inflammatory state.

Lisa: Well, I know in Ayurvedic medicine, they do believe that we have the sweet taste for a reason. So, yeah, and then the oms. Okay, very good.

Brad: Yeah, and then of course, stress management. I can't emphasise this enough. Now I've started probably for the last six months now, been using a recommendation, and I think you're going to really like this recommendation. And I've had some amazing feedback from patients. So, this recommendation stems from... And you must excuse me, I've forgotten his name. He was a neuroscientist who presented some amazing research at the 8th Annual NIIM Conference down in Melbourne in 2023 on the benefits of colouring in.

Lisa: Mm-hmm.

Brad: Okay?

Lisa: Stan Rodski.

Brad: So, he has all of this research where colouring in will change your brainwaves. So, what I tell my patients is to spend 20 minutes every single night colouring in with your family, if you've got family. It has two things. It supports with a healthy sleep cycle. So, rather than getting on the technology or watching telly, but then it also allows you to bounce back from a stressful situation more effectively than if you weren't, so out colouring in. I actually have my adult colouring book, and I'll show it to patients. They love it. They love the suggestion.

The other one is what I find is whenever I'm mentoring late at night or I'm seeing patients or I'm doing presentations late at night, because other side of the world, I will always go, "Before bed, let's do the colouring in. Bring yourself down because unfortunately, I can't meditate in the sense of my mind runs around at 100 miles an hour." So, my style of meditation is colouring in. My advice is to invest in good quality pencils. I started off with just usual pencils. It wasn't doing it for me, so I spent the money and got good quality pencils. Amazing.

Lisa: Lovely. I do think it's really important for patients to be acknowledging that winding down, that social support, and the impact that does have on their gut. It's definitely what I focus on in my clinic. I see a lot of patients with prolonged sustained stress, and that is the real driver to that immune activation. And we know now that psychological stress does impact the gut microbiome. I think a lot of patients don't realise that. They think it's just about what they're eating, but most definitely psychological stress has been shown to increase intestinal permeability and change the microbiome, increase that pathogenic bacteria, decrease the good stuff. And short-term, that's not an issue, but long-term, most definitely.

I love all those suggestions. I'm having a vision of you colouring in and Om-ing at the same time. I think our knowledge of the microbiome is constantly evolving. It wasn't a thing when I was at university. We didn't learn about the microbiome at all. I'm interested. What is an upcoming area within the study of the gut that you're excited about that practitioners should be aware of?

Brad: Oh, you know what? For the very first time ever, and this is not just in Australia but globally, for the first time we as practitioners, we have access to metagenomic sequencing of the microbiome in combination with functional markers.

Now, you may not think that this is quite a novel area, but this has never been done before in the sense of we've only ever just looked at. metagenomic markets or we've only just looked at functional markets. But for the very first time in clinical practice, we as practitioners, we can access the combination of the two. So, I'm really excited from this grassroots perspective, because we need to acknowledge that our knowledge as clinicians is a form of evidence. I want to know. What are the links between high-quality metagenomic sequencing and zonulin or calprotectin? I want to understand the patterns that we see within the microbiome. This is novel. This is the first time it's ever been done. And in Australia, we have access to it for the very first time and so it's exciting because it's providing a comprehensive assessment of the microbiome and the environment, which is not just comprehensive, but accurate. And I think that we are going to learn so much about this ecosystem from this year and for years to come using this grassroots perspective.

Lisa: Very excited. I'm excited. Thank you so much for joining us today, Brad. As usual, you have been a wealth of information and just so generous with it. I think the key points I'm taking away are increasing fructooligosaccharides to decrease that excessive hydrogen sulphide producing bacteria, increasing cruciferous veggies to block TMA to TMAO, colouring, Om-ing, and of course, looking at the microbiome as a whole rather than focusing too much on just individual species and genus. Thank you, Brad.

Brad: That's an excellent summary, Lisa, and it's been a privilege chatting with you. And I look forward to catching up with you soon.

Lisa: Thank you, everyone, for listening today. Don't forget that you can find all the show notes, transcripts, and other resources from today's episode on the fx Medicine website. I'm Lisa Costa-Bir, and thanks for joining us. We'll see you next time.

Emma: This podcast is intended as healthcare practitioner education only, and it is not a substitute for medical advice, diagnosis, or treatment.


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