Dr Brad Leech and Emma Sutherland discuss key microbiome concepts, emphasising the importance of distinguishing between pathogens and pathobionts, the latest on testing methods, microbial richness vs diversity, and the safe use of antimicrobial herbs, including Brad’s four rules for clinical practice: Test, Reflect, Protect, and Regenerate.
Dr Brad Leech shares updated clinical knowledge on supporting the gut microbiome focussing on antimicrobial herbs and supporting the gastrointestinal environment during antimicrobial treatment. Joined by fx Medicine ambassador Emma Sutherland, together they define specific terminology related to microorganisms, the significance of differentiating between pathogens versus pathobionts, and the relevance of accurate testing in microbiome assessment. On the subject of testing, they delve into the value of various testing methods, including culture tests, qPCR, 16S sequencing, and shotgun metagenomics, highlighting their pros and cons. Microbial richness and diversity and the impact of mucin degradation on gut health are addressed and Brad explains his preference for extracts/tinctures over oils for microbiome health.
They elaborate on the mechanisms of antimicrobial herbs and their potential impact on commensal microbes. Rounding everything up, Brad share’s his Four-Rules for clinical practice: Test, Reflect, Protect, and Regenerate, providing guidance on microbiome assessment, patient care, and maintaining gut health.
Expect to get the latest information on functional testing and treatment options for maintaining optimal gut health in this clinically relevant podcast.
Covered in this episode
(00:26) Welcoming Dr Brad Leech
(04:40) Naturopathic principles in treating the gut
(06:27) Difference between a pathogen and a pathobiont
(10:17) Gut microbiome testing: to test or not to test, and when to refer
(14:00) Different functional gut testing methods
(20:41) Terminology: diversity and richness
(26:15) Antimicrobial herbs
(29:10) Antimicrobial herb dosage and timing
(33:35) Treatment rationale for using antimicrobial herbs
(35:40) Brad’s key antimicrobial herbs
(38:30) Brad’s four rules in using antimicrobial herbs
(45:07) Common findings in microbiome testing results
(48:00) Thanking Brad and final remarks
Key takeaways
Terminology update:
- PATHOGEN: strains (or genetic variant) that cause disease
- PATHOBIONT: species associated with negative health outcomes
- OPPORTUNISTIC PATHOGEN: disease causing strains to susceptible individuals (immunocompromised, elderly, infants etc.)
- COMMENSAL: species associated with a positive health outcome
TESTING – before you test ask yourself “will the test change my clinical treatment?”
- Culture tests: limited as only 5% of microbes from our gut can grow on agar culture. Susceptible to false positives
- qPCR: highly sensitive but can be costly due to test devices being specific to the microbe or set of microbes they’re designed to assess
- 16S: limited due to detecting only to the genus level and not species/strain
- Shotgun metagenomics: able to assess a wide range of species via DNA sequencing. Linked to presence of live microbial activity
- Microbial richness reports on the number of species per sample
- Microbial diversity is a combination of richness and balance in the sample. Diversity can be scored by the “Shannon Index”
- High mucin degradation can indicate a compromised gut barrier lining
Refer when patients present with bloody diarrhoea, acute abdominal pain, watery diarrhoea, vomiting, or fever
Clinical Case Studies
- Pomegranate extract – more selective than others and has a prebiotic benefit
- Use extracts/tinctures over oils – gentler than oils on the microbiome
- Pulse dosing in weekly timeframes for a limited timeframe
Update on antimicrobials – most times they’re non-selective and can impact the commensal microbes. They’re herbs or compounds from herbs that can inhibit function or kill microbes. They work by disrupting microbial cell membranes, interfering with metabolic processes, and inhibit microbial growth.
Effective and safe use of berberine. Metagenomic sequencing shows that 500 mg/twice daily for 3 months, increases hexa LPS and reduces beneficial microbes and their metabolites.
Brad’s 4 rules for gut treatment:
- Test – will this test aid in advancing your treatment for the best clinical outcome? Are you dealing with pathogens or pathobionts?
- Reflect – on the patient picture for the best clinical outcome for them
- Protect – against potential widespread damage to the microbiome via prebiotics from various sources
- Regenerate – fibres, fermented foods
Resources discussed and further reading
Dr Brad Leech
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Connect with Brad: Instagram |
Intestinal Permeability
| Research: Clinical Practice Guidelines for the management of increased intestinal permeability |
Pathogens and Pathobionts
Transcript
Emma: 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 their connections to land, sea, and community. With us today is Dr Brad Leech. Brad is a PhD-qualified clinical nutritionist specialising in chronic autoimmune conditions and complex gastrointestinal disorders. After entering the profession in 2008, Brad has taught and developed subjects at leading universities and conducted research on intestinal permeability, autoimmune disease management, and food-based probiotics.
In addition to being an adjunct fellow at the National Center for Naturopathic Medicine and creating gut and autoimmune disease courses for the public, Brad offers practitioner support through his mentoring program, Brad's Brainiacs. Today, we are going to deep dive into the use of anti-microbial herbs when optimising microbiome health.
Now, Brad, I am so excited to cover this topic with you because it's such an important one for all the practitioners working in the area of gut health, which is really all of us. And I've been in clinical practice about 20 years now, and I have seen a lot of trends over the years. And over the last 10 years, gut microbiome tests have become more user-friendly and available and, I guess, as a result, there's been an increase in the use of antimicrobial herbs to treat bacterial overgrowths in parasites and yeast. But my thinking around this framework has really started to shift over the last three years. And I would love to pick your brains on the dos and the don'ts of using antimicrobial herbs. And I think we all need to just get ready to challenge our preconceived ideas and potentially our current protocols.
Brad: So, Emma, it's fantastic to be here. And yes, I am thrilled to be talking all about the microbiome and antimicrobial herbs. And I might start off with to say I am a herbalist. I love my herbs. So, if I say anything that might push a few buttons for the practitioners listening, forgive me, and I'm only going to be stating what the research is saying. So, don't blame me. Blame the research.
Emma: Yeah. Don't shoot the messenger, right?
Brad: Exactly.
Emma: So, on a personal note, Brad, why and how did you become interested in gut health?
Brad: Well, I never actually intended to focus on gut health. It all just happened by accident. I really wanted to, and I still do a lot of autoimmune disease, and I wanted to get into very serious health conditions. But from my very early training in Ayurvedic herbal medicine, there was such an emphasis on digestion and how your gut functions. And I thought, "Oh, yeah, that's well and great, but what does nutrition and naturopathy have to say about the importance of gut health?" And as I was going through my degrees, and even my PhD, and working in clinical practice, I came to the conclusion that, hold on, gut health has this huge importance within clinical practice. And if we support gut health, everything else will become so much easier to manage.
So, although many praccies got into gut health because they had gut-related problems, I never had gut-related problems. I like to refer to my poop as the golden poop because it's of high quality. So, I'm very much from the perspective of the reason I focus on gut health is because that's what I've been seeing for coming up to 15 years now, that there is so much benefit in addressing the microbiome and addressing gut health to supporting overall optimal health.
Emma: I would agree with you. And that ripple effect of once the gut starts to shift, everything else seems to soften. Now, let's go back to our naturopathic roots and remember our philosophies, and our most important one is, first, do no harm. So, how does this philosophy tie into treating the gut?
Brad: Well, as we commonly say, all disease begins in the gut. And it's one of these concepts of, yes, first, do no harm, but we also need to ensure that we're addressing the root cause when it comes around to any pathology or any ailments that the patient is presenting with. I like to think of the analogy of, if I was on a quiz show and it was a quiz show about can you link this condition to gut health? I reckon I could link absolutely every health condition there is, some way or another, to gut health.
Now, from a very clinical perspective, what I find here is if we address and support gut health first, then everything else becomes easier. I give the example of, let's say, detoxification. Now, within Phase II and Phase I liver detoxification, there are so many essential nutrients that are required, so many herbs that are going to be beneficial. But if our gut can't absorb and thereby utilise these nutrients, how are we, as practitioners, meant to support with optimal detoxification pathways if our gastrointestinal system can't actually absorb the nutrients efficiently?
Emma: Yeah. A huge problem. It's the missing puzzle piece with a lot of patients, I feel, that aspect.
Brad: Yes. Exactly.
Emma: Now, just to set the scene for us today and just put us all on the same page, can you explain the difference between a pathogen and a pathobiont? I just want to get the terminology correct so we're all understanding things here.
Brad: Yeah. And that's a great place to start, because some of these terminologies, historically, we've been using them interchangeable. But in fact, they're not. There's a line in the sand to say, "Well, this is a pathogen and this is not a pathogen." So, to start off with, a pathogen, a true pathogen, is a microbial strain that can cause disease. So, hear that I just said strain, not species. It's a strain that can cause disease. An example of this would be E. coli 0157. That is a strain. So a pathobiont is a microbial species which is associated with a negative health outcome. An example of one of these species could be Prevotella copri or M. Smithia or E. coli. They are pathobionts that are associated with a negative health outcome, so an increased risk of a particular reaction within the body or a particular disease.
Now, there are other terminologies that are worth noting as well. You've got an opportunistic pathogen, right? So, this is, just like a pathogen, a microbial strain that can cause disease in susceptible individuals. So, individuals with compromised immune systems such as HIV or AIDS or the elderly or the very young. So, if I had an opportunistic pathogen, I might be fine. But if my elderly grandmother with Stage 3 liver cancer, if she got a opportunistic pathogen, that might actually be a lot more serious.
The other one worth mentioning here is a commensal. So, a commensal is a microbial species associated with a positive health outcome. So, an example of this could be akkermansia muciniphila, a species that we talk about that has a positive health outcome. So, it could be reducing the risk of chronic disease through, let's say, cross-sectional data, or modulating the microbiome to produce beneficial compounds. These are commensal species within the gut.
The thing that we as practitioners really need to consider here is not to call a pathobiont a pathogen, because a lot of the times we pull up a very basic microbiome report and say, "Oh, you've got this pathogen and that pathogen," when, in fact, what we're referring to as a pathogen isn't actually a pathogen. They're pathobionts. And they require a different treatment approach, and they are identified through different ways. And we as practitioners need to view them in a different light because they present differently from, let's say, clinical symptoms, and also from a treatment perspective.
Emma: Yeah. I think it is the terminology, it does need to be more precise because we do tend to use all these terms interchangeably. So, a pathogen is a microbial strain that can cause disease. A pathobiont is a microbial species associated with negative health outcomes. The opportunistic pathogen is the microbial strain that can cause disease in a susceptible individual. I love the analogy of your grandmother because it's locked it in my brain. And then the commensal is a microbial species associated with positive or good health outcomes. So, yeah, okay.
Brad: Exactly. You have it. Fantastic.
Emma: I really love that you're setting the scene in that way. Now, let's move on to testing, now that we've got our language in correct. First of all, when should you test, and when should you not test the microbiome? First of all, the decision is, do we or don't we?
Brad: And that's a really good point, and it does come down to the individual. The first thing I'll mention here is when to actually refer to the GP. So, sometimes, we as practitioners, a patient presents to us, and if they present with serious clinical symptoms such as bloody diarrhea, acute abdominal pain, watery diarrhea, vomiting, fever, although they may be suggesting a dysbiotic state or something going on with the microbiome, whether or not it is a pathogen, we actually need to do our duty of care and we need to refer that patient to the GP so we can do a qPCR panel that can be turned around within a 24 to 48-hour window. So, then the patient can start on antibiotics, if required, or go on to further investigations, if required. So, that is if they present with those very acute symptoms.
Now my rule with all functional testing, so this is microbiome analysis to DUTCH testing, hormonal testing, testing that is out of pocket, is we need to ask the question, "Will the test results change my treatment recommendations?" If the answer is yes, then we should be testing. If the results are not going to influence and change how you are going to practice, then no, we shouldn't be measuring. So, of course, we have these classic digestive conditions such as bloating and diarrhea, constipation, flatulence, loss of appetite, dyspepsia, nausea, headaches, that may be associated with a dysbiotic state, which may justify the need to measure the microbiome, there are other systemic health conditions that I would often go, "Oh, I want to measure the microbiome." We've got things like hormonal conditions. So, when there is that estrogen dominance or that PCOS maybe endometriosis picture, we're looking at things like beta-glucuronidase. Is there that reactivation of estrogen and/or drugs within the bowel being reabsorbed? So, we're considering that. I'm also thinking about cardiovascular disease. I'll give you an example here. I had a patient about a month ago, maybe 2 months ago now, and he was the eldest living member in his family, and he was 46 years of age.
Emma: Wow. Okay.
Brad: Because his father, his uncle, and his brother all passed away from a cardiovascular event before the age of 45. Okay? So, he comes to me, I'm like, "All right, let's measure the microbiome." He had this microbial marker called trimethylamine, or TMAO, which has been linked with cardiovascular disease. Now, his reading was four times higher than I have seen in any other patient. It was so high that I can say, with almost absolute confidence, that that is a driving factor for why his family might have this increased risk of a cardiovascular disease. His microbiome is driving that potential risk, right? He doesn't have digestive-related symptoms, but he has a history of cardiovascular disease in his family.
Emma: And that would have, of course, changed your recommendations based on that testing. And I think that's a good framework for working out do we or do we not test because these tests are out of pocket. They are expensed at patients, and I feel, as an industry, we tend to overtest. We need to be careful with this. But if the test is going to change your recommendations, and you explain it to the patient, then it's probably an appropriate test to be doing. But can you explain the different types of gut tests available, and their pros and cons? Because it is a little bit confusing, really.
Brad: It's very confusing because it was not taught at university. I was not taught it at university. And when I was teaching at university, I didn't... Well, no, in the later subjects at Southern Cross University, I did teach it. But at the other colleges in my earlier years, I wasn't aware of the different methods. So, let me actually give you an analogy because sequencing of the microbiome, it is so foreign to healthcare practitioners. Let me give the analogy of blood pathology because I feel like we have quite an advanced understanding when it comes around to blood pathology.
Emma: For sure.
Brad: So, we have a patient in front of us, and we want to evaluate whether or not they have low iron. Do we rely purely on the patient's diet? Probably not. That's not going to give us the full picture. Do we rely on a hair mineral analysis test to determine iron levels in hair? Oh, probably not. Do we rely on just ferritin alone? Probably not. We rely on multiple different markers to form this complete picture of that iron status; hemoglobin, ferritin, transferrin, CRP, all of which can contribute to understanding; where is this low iron coming from? And so that's that complete picture, right? So, just like that, there's different levels when it comes around to measuring the microbiome. There's different sequencing methods, so different ways that we measure the bacteria in the gut. And different methods will provide completely different results.
So, the first that I'll describe is culture. Okay? So, that is very simple. That is where we send off a sample, and it is applied to an agar and it's grown. The problem that faces with culture is only about 5% of the microbiome can actually grow on a Petri dish, okay? So, it's not actually telling us the whole microbiome. It's not telling us everyone who's there, and it's not telling us what the function of the microbiome is. It's really just a very limited component. Now, I guarantee you, if you are utilising culture in practice, you are seeing streptococcus quite commonly, or even candida, quite commonly on a microbiome report.
I am actually going to say that that's actually going to be a false positive because when we send a stool sample away and it's not kept cool and it's not to the lab within a very timely manner, what's going to happen is things are going to start to grow within the sample, and we're actually going to get a false result, right? So, it's really important, when doing any microbiome analysis, to ensure that the sample gets to the lab in a timely manner and it's kept cool for a lot of, let's say, sequencing methods.
Another method which is being used is qPCR. Now you're thinking, "Oh, qPCR, that rings a bell." Of course. We've just been through a pandemic, and that was the method that we used to identify COVID, the qPCR test. The beauty with a qPCR test is if there is a probe, so a particular probe, we can identify a strain or a species quite accurately. We can go, "Ooh, that is going to be there." We can say that with quite a lot of confidence. The problem here is a probe. So, you need a different probe for different species and strains of bacteria. Each requires a different probe. Thereby, it's quite costly.
Now, there are so many different bacteria in the gut. It's actually impossible to have a probe for every single bacteria. That would cost $1 million just to sequence one person's microbiome. The other thing is, yes, it does a really good job at saying, "Okay, this individual is here," but it doesn't actually give us the picture of the whole microbiome. It just tells us, "Okay, 20 or 30 different species, okay, it is there."
The next up is 16S. Now 16S, we don't really have access to this in Australia. It's very big over in America and the UK. And it does look at DNA, but it looks at the rRNA, and it can only accurately identify down to the genus level. So, remember the hierarchy of when it comes around to looking at bacteria, it goes genus, species, strain. 16S can only look down to the genus level. So, it's somewhat inaccurate because it's not going deep enough. Okay?
The last method is metagenomics or shotgun metagenomics. Now, this uses a really unique method to look at the DNA, so the genome of the bacteria, and go, "Okay, looking at the genome, this is most likely going to be a akkermansia muciniphila species. Right? That's what's going to be there. And because it's looking at the DNA of the genome, it can measure all the bacteria. When, in fact, there are so many different species that could be measured. Upwards of 28,000 different species could be measured using metagenomics because it's not restricted by growing the bacteria or having a probe. It just looks at the DNA.
Something that I will note here is a lot of pathology companies will say they use DNA to measure the microbiome, but it's misleading. It really needs to say metagenomics.
Emma: Right. So, it's that, once again, going down to the terminology and getting the accuracy there and being careful which test we are doing. Yeah.
Brad: Exactly. Because different tests will provide completely different pictures and will drastically change how you treat the patient.
Emma: Okay. Well, that was a really good explanation of the pros and cons between culture, PCR, 16S, and the metagenomic. Yeah, because it's a bit mind-boggling with this stuff. It's very technical, so thank you for distilling that so easily for us lay practitioners out here. Now in relation to microbiome testing, there's a couple of terms that I want to reference and get your explanation on, and that is diversity and richness, because they sound like the same thing.
Brad: They're very similar. So, there is a difference. So, microbial richness actually measures the number of species in a sample, okay? I want to put this into perspective for you. On average, there's anywhere between 110 to 244 different species in a individual's sample. Now, the mean average is going to be 176, okay? Let's put this into perspective. At the beginning of the podcast, I referred to my gut as the golden poop. And I say the golden poop because I've got over 250 different species in my gut. Now I grew up on a farm. I've never taken antibiotics. I was breastfed. I was born vaginally. All these key things that we're looking for for a healthy microbiome. So, let's say, okay, 250, that's great. That's fantastic. I have patients who have fewer than 100 species. I once had a patient that had 20 species of bacteria in the microbiome.
Emma: Wow. Goodness.
Brad: Twenty. Now, when you look at these 20 species, the vast majority, 80% of them were pathobionts. They were negative species. So, their microbiome was completely kaput. Now, I did just say that I have a golden poop of 250 species. But I read up an article just 2 months ago that showed that, over in sub-Sahara Africa, where it's the most diverse microbiome, their stool samples, on average, have got 750 species.
Emma: Wow. Mind-blowing. Oh, my goodness.
Brad: So, I think we have a long way to go. Maybe the amount of EMF I'm exposed to and maybe eating out and maybe some inflammatory oils are actually impacting my microbial richness. That's the number of species.
Next, we have microbial diversity. Now, this is a combination of two different markers, a combination of richness, and then also evenness. So, it takes into the account how many are there, and the evenness, so whether or not there's 10% relative abundance. So, whether or not there's a Prevotella copri dominant gut where there's 20% or 40% of the microbiome is of that one particular species.
So, it utilises this concept of a Shannon index. So, a Shannon index is a very accurate way to take into the account the richness and the evenness to provide us with a score that is used within the literature, which is used within microbiome testing to go, "Okay, this is your score, your Shannon index." So, upwards of that. 4.5 is really a good place to be. Once you start heading down to that 3, 3.5, that's really going to be indicating that it's not ideal.
Emma: Okay. So, the richness is the number of species in the sample, whereas the diversity is the richness plus the evenness. So, there's balance or harmony within the gut. And I love that there's an index to measure that, that we get a score based on that diversity, and we want to look for 4.5 or above.
Brad: In and around that area. Four can be fine as well.
Emma: Okay. All right. Super interesting. But what I've always wondered is this one thing I'd love you to answer for me, how can you tell if the DNA picked up on the microbiome test comes from a dead or a living bacteria or parasite, i.e. do you need to treat it or do you not need to treat it?
Brad: And now, Emma, this is something that research is still trying to debunk in itself. I did a little bit of digging around on this to try and find where we are currently standing with this. What I can tell you is the bottom line is if it's being picked up with metagenomic sequencing, so remember that's looking at the DNA, what that tells us is that there's a large enough proportion of the genome to say that it's dead, to say that it's alive. Now, if it was dead, the genome would be highly fragmented, meaning it would be broken up into multiple different pieces, and then thereby would not actually be showing up on the result.
Emma: Right. So, if it was just a PCR test, then it could be dead, more likely.
Brad: It could be dead, but it could still be alive. That is correct.
Emma: Yeah. Okay. Oh, gee, so much confusion in this space, isn't there?
Brad: I think we almost need a degree at university where it's like Nutrition, Naturopathy and the Microbiome. So, a combination of microbiology and naturopathy to form the two. I would love to teach that.
Emma: Yeah. Well, that, I'm sure will be down the pipeline for some university out there to take that opportunity.
Brad: Exactly.
Emma: Now let's look at the antimicrobial side of this conversation. So, once again, I want to get the technicality correct. So, what is an antimicrobial herb?
Brad: So, an antimicrobial herb, it's a plant or a plant extract that contains a compound which is capable of, let's say, inhibiting the growth or killing a microorganism such as bacteria or viruses and fungi and parasites. So, these herbs, often they produce these compounds to protect themselves as a plant. Now, antimicrobial herbs typically contain bioactive compounds such as phytochemicals, essential oils, and secondary metabolites that can exhibit a antimicrobial action. Now an example of these antimicrobial herbs are going to be garlic, and goldenseal, and oregano, just as a few examples.
Emma: Okay. But how do they actually work? Can you talk us through the mechanism of action? And are there any indications or contraindications or safety issues that we should be thinking about when taking these herbs?
Brad: Okay. So, there's a few that I can recall. Now, the first I'll mention is a disruption of the cell membranes. So, some antimicrobial herbs contain compounds that can disrupt the cell membranes of microorganisms. An example of this is allicin in garlic can disrupt the bacterial cell membranes leading to cell death. Another example is certain herbs can interfere with metabolic processes in these bacteria and parasites. An example of this could be berberine, found in goldenseal, can inhibit the enzyme that is necessary for the microbial energy production, right? In thyme, thymol, I think it's referred to, can actually inhibit the enzyme involved in microbial growth as well. So really interesting. There are so many different actions it could have.
Now in relation to interactions, each and every herb will have their own unique potential interactions, whether it's with breastfeeding and particular medication and about pregnancy. But the one thing that all of these antimicrobial herbs will have in common is the potential impact on the microbiome. These herbs are very, very powerful. And although sometimes we as practitioners view them as selective when, in fact, a lot of the times, they're actually non-selective and can actually impact our commensal microbiome.
Emma: And I think that is a good consideration, and I know we are going to do a little deep dive into this because you and I are both passionate in this space. But, yeah, mechanisms of action, really important. They disrupt cell membranes, interfere with metabolic processes such as in the enzyme needed for energy production. Mother Nature is just mind-blowing. But, yes, the selective or the non-selective. I think it's a good point that these antimicrobial herbs are much more powerful than we may be giving them credit for. But are these antimicrobial herbs dose-dependent, and is there an optimal duration of use for these herbs? When is it too much or when is it too long?
Brad: And you know what, this is something...because I've been presenting on this topic for almost a year now. Looking for the golden paper. I spoke about the golden poop, I look for the golden paper. And when I say a golden paper, I'm looking at a crossover, randomised control trial that utilises a variety of different whole herb extracts, oils, and also uses metagenomic sequencing to measure the microbiome.
The problem we have here is the vast majority of research looking at the impact of antimicrobial herbs on the microbiome is done through qPCR or culture and actually does not provide the evidence or the information I need to accurately go, "Okay, this is the dose that I'm looking for. This is the length of time that is needed." So, it actually falls back to us as clinicians to put our grassroots research hats on to go, "What are we finding in clinical practice? What is working, what is not working?" So, with the limited research available, I really utilise what I see day in day out in my own clinical practice.
And I've got a few clinical pearls for you when it comes around to prescribing antimicrobials. Okay? So, from my clinical experience, there's a few points. First of all, to utilise extracts or tinctures over oils. Now, extracts and tinctures, they're going to be less impactful on the whole microbiome compared to an oil. An oil is going to be very concentrated, very strong. Now, you might utilise them in some situations, but extracts and tinctures, they're going to be a little more gentle on the gut. We could also utilise pulse dosing, so that is one week on or one week off, okay, to ensure that it allows the time for the microbiome to almost bounce back a little bit. But the key, out of everything here, is short-term.
Now, short term is key. When we start doing long-term, that is more than a few weeks, then we get into this realm of, should they really be taking that? And I know that there are some, let's call them health coaches, because they're not practitioners, some health coaches, they have this protocol of everybody gets antimicrobial herbs. And yes, there is going to be clinical changes in their symptoms, but what is going to be happening to their microbiomes long term? I'm not just worried about short term. If someone wants short-term changes, then go take a Panadol. That's going to result in short-term changes. I am focused on long-term changes. I'm focused on long-term health, not just what are some short-term changes in their clinical symptoms that I can change?
Emma: Yeah. And I think we've all had the patients walk in the door who have seen multiple other practitioners before and been on really long courses of antimicrobials. I had one patient last week who was six months on oregano oil and berberine. And I really think your point here is so important. And these pearls of using extracts or tincture over an oil, I love that one because I see oregano oil used so extensively and at high doses. The pulse dosing is a great way to let the microbiome rest in between. And that short-term use, less than three to four weeks, I think you mentioned somewhere around there, I think we all couldn't take that on board and review our protocols that we're currently using.
Brad: Exactly.
Emma: And if you think about your testing, like gut testing, what kind of presentations or what sort of test results would you be looking for to rationalise the use of antimicrobials in your treatment plan? What makes you go, "Yes, we are going to go there?"
Brad: And just to reiterate what I said, there's been no research to confirm the impact or the effectiveness. But when there's a lack of research, we've got to rely on our clinical experience. What I suspect...now this is just my personal view as to the use of antimicrobials, is when there is a true pathogen, okay, in some situations. So, in some situations, it is a referral to the GP. In other situations where, well, hold on, could strong antimicrobials be as effective as antibiotics but be less impactful to the gut? Okay. That's what I'm thinking. So, when there is a true pathogen. So when there is some form of pathogenic E. coli, when there is other... I don't want to say... C. diff, it's a reportable, we need to send that off for antibiotics, but it's one of these things, depending on what the patient is saying.
Also coming down to clinical symptoms. So, if a patient has a pathogen with clinical symptoms, we may actually utilise antimicrobials in some situations. You've really got to ensure that you are a well-trained herbalist or naturopath if you're going down this avenue, and you've got advanced training because there's this delicate balance where if it's a pathogen, we actually need to get rid of it. We know that some antibiotics will get rid of it. And if we're very confident that these antimicrobials can do the same job without causing further harm, and we're well trained, then yes, in that situation.
Emma: Okay. All right. Some really nice guidelines there. And let's pick your brains a little bit more. What are your key go-to antimicrobial herbs, and what's the evidence for these, whether it's traditional or scientific? What do you see working well in clinical practice?
Brad: And I used to use antimicrobial herbs a lot more than what I do now. But there is one antimicrobial herb that I'll still utilise here and there within clinical practice, and that is going to be pomegranate extract.
Emma: Yeah. Nice.
Brad: All right? Because it's going to be more selective than others and it has actually been shown to be a somewhat prebiotic to actually support with Bifidobacterium species. So, if I was to choose...if I had to use an antimicrobial, I would be going down the avenue of pomegranate husk extract.
Emma: Okay. I love that. That's a very nurturing framework there, Brad. But I want to deep dive into berberine because it is the most commonly used antimicrobial herb that I see practitioners using or a patient's been taking. And, of course, there are so many aspects to this herb because it is now, as we all know, being used for insulin resistance as well as antimicrobial in the gut. But, first of all, let's look at the impact that berberine, as the herb, that we're talking about has on the rest of the microbiome. And the question I have is, can you actually protect the rest of the microbiome and still eradicate these microorganisms that you want to get rid of?
Brad: And this is a great question. So, believe it or not, we've actually got research on berberine. So, we've got great research, using metagenomic sequencing, on the impact of berberine on the whole microbiome. So, berberine, it's a compound found in Phellodendron and goldenseal and other herbs. And what these research studies showed, so there were about 3 months and they utilised around that 500 milligrams twice a day of berberine extract, so it's on the higher dose. What they actually found, looking at before and after on the impact on the microbiome, is that taking berberine supplementation increased hexa-LPS within the microbiome and it did reduce Bifidobacterium, but it also reduced butyrate-producing species in the microbiome. So, having this understanding of, ooh, this antimicrobial herb can have this type of impact, what can we do to protect the microbiome? So, I have my four rules when it comes around to using antimicrobials.
Emma: Woah.
Brad: And that is test, reflect, protect, regenerate. Okay?
Emma: Great. We are going to have to deep dive into these because you know I need to know all the clinical pearls out of each of these. I love that you've got a framework for us to work with. So, yeah, let's do it.
Brad: Okay. So, when I refer to these four rules, test, reflect, protect, regenerate, I'm referring to testing the microbiome. So, when we test the microbiome, we've got a better understanding of who's there, what they're doing, and what type of action we're trying to achieve. Are we utilising an antimicrobial herb because there is a pathogen? Or should we be doing another treatment for a pathobiont? So, testing the microbiome.
The next one is to reflect, and this is where we take a step back from the research, take a step back from the microbiome results, and reflect on the patient. What are they saying? How are they feeling? What are they coming to you for? Looking at them as an individual. So, really reflecting on the patient so then you know that you are writing a prescription for them, not just writing a prescription according to their microbiome.
Emma: Nice.
Brad: Yeah? So reflecting them. Next, we have protect. So, this concept of protect, I almost developed it in response to this research on berberine because I'm like, "Well, hold on, berberine's being used, these antimicrobial herbs are being used, what can we do as practitioners to protect the microbiome so then when these antimicrobial herbs are used in some situations, there's going to be a less detrimental impact on the whole microbiome? So, there's a number of different things that we can co-prescribe. The first I'll mention is let's say resistant starch.
Emma: Yeah. Beautiful.
Brad: The reason I say resistant starch is because resistant starch will feed up butyrate-producing species. So, the antimicrobial herbs reduce butyrate-producing species. We just need to feed them up. We need to protect the microbiome, so feeding up those species.
Next, we have is GOS, okay, so galacto-oligosaccharides, and this is a really interesting one. So, we mentioned earlier about pathobionts and how treating a pathobiont is actually different to treating a pathogen. So, let's give the example, if somebody had a high pathobiont that produces hexa-LPS, so particular species such as E. coli can be contributing to hexa-LPS, even Klebsiella pneumoniae can be contributing to hexa-LPS. If there are these elevations in pathobionts, then we can utilise GOS, because there's been some research to show that supplementing with around that three to four grams of GOS on a daily basis for about two to three months can actually reduce the species known to produce hexa-LPS.
Emma: Great.
Brad: Which is absolutely mind-blowing. So, this GOS falls into the category of protecting the microbiome because, as I mentioned earlier, the berberine increases hexa-LPS, or the species known to produce hexa-LPS. So, if we co-prescribe GOS, potentially this will mitigate the impact.
Emma: Okay, when you say co-prescribe, do you mean at the same time, on the same day, on different weeks?
Brad: Yes. At the same time. So, I would potentially, depending on their microbiome, start off with the resistant starch, the GOS and others, and then bring in the antimicrobials. Co-prescribe, so on the same day, it doesn't need to be at the same time, and then continue on thereafter the antimicrobial use.
Emma: Okay. Great. Thanks for clarifying that.
Brad: Okay. The other one that falls into protect is HMOs, so human milk oligosaccharides. They are a type of prebiotic that can feed up beneficial bacteria while preventing pathogenic and pathobionts from adhering to the wall of the small intestines and the large intestines. So, it's one of these great ones to be co-prescribing. It almost protects the microbiome. Very similar to SB. So, we know when you go to Bali, we always recommend, "Oh, take some SB, some Saccharomyces cerevisiae, because that's going to prevent travellers' diarrhea, and so forth. I'm almost doing a co-prescribing in that situation, SB and HMOs...
Emma: Love it.
Brad: ...to further support and protect the microbiome.
Emma: I love we have so many strategies in the protect section. This is great news.
Brad: It's much easier and more beneficial, both for you as the practitioner and for the patient, to protect the microbiome than to regenerate the microbiome.
So, that brings me onto the last stage, regenerate. And that really comes down to fibre, fibre, fibre. Now, there are so many different types of fibre, but having a diverse diet, fermented foods, incorporating diversity of different types of fibre in the diet will ensure that we're going to regenerate this microbiome. So, eating a rainbow, eating every part of the plant every single day, eating a variety of different fruits and vegetables, nuts and seeds, will go a long way to regenerating the microbiome.
Emma: I love that. And I love the whole food as medicine aspect of being a naturopath, so that's just like music to my ears. So, really, yeah, the ability that we have as clinicians to really play that protective role in our patients' microbiome I think has been underestimated to date and we've maybe been focusing on the kill, kill, kill approach, but this is a very, as I mentioned, very nurturing aspect and way of looking at supporting our patients' gut microbiome.
Brad: Exactly. And it comes down to the concept of first, do no harm.
Emma: Yeah. Yeah. And I love the reflect side, which is going back to our roots, which is actually looking at the clinical signs and symptoms, and what is our patient looking like, telling us, feeling, is so critical in this whole entire picture.
Brad: Exactly.
Emma: Now, a couple of things I wanted to ask. I know we're almost out of time, but I wanted to just ask if you can share with us maybe the most common pattern you see on microbiome test results.
Brad: When it comes around to, let's say, chronic disease, there's two main things that I'm seeing in a lot of patients with chronic disease, and that is that low diversity and richness. So, you're seeing a lack of species or a low Shannon index. The other one is a high mucin degradation. Now, I'm sure yourself and the listeners are like, "Hold on, what is a high mucin degradation?" That is a way we can measure how much of the microbiome is using mucin as a fuel source.
So, remember, the microbiome can use fibre, mucin, and protein as a fuel source, as an energy source. When there is too many species utilising mucin as a fuel source, what can happen is a compromised barrier, gut inflammation, because this mucus layer is protecting our gut, and when there's too many species eating that as a fuel source, that's going to lead onto food sensitivities, intestinal permeability, gut inflammation, and those very clinical pictures. So, really, those are my two, diversity richness and also a high mucin degradation. So, those are key species utilising mucin as a fuel source.
Emma: A really interesting insight there. Thank you. Thank you. And obviously, when we are working with gut with our patients, sometimes, it's a really important part is how do we actually counsel our patients on what changes to expect with a treatment protocol. And we want them to adhere and get great results, but how do we help coach and counsel them on the way through, or to set their expectations? What tips can you share with us?
Brad: So, because there are so many different types when it comes around to what a microbiome will look like, it's really important to tell the patient, to say, "Based on your result, I'm not sure what I'm going to be prescribing. It comes down to, what does your microbiome say? And depending on the result will really determine treatment direction." There are hundreds of different recommendations we can be giving our patients, but it really comes down to which are going to be the most important based on their microbiome. So, telling the patient to say, "Hey, we very well could be changing up your supplements. We could be changing up your diet. We could be doing different lifestyle strategies. But it comes down to what does the test say and how do we apply the results of you, as an individual, to the test results?"
Emma: Okay. Goodness me, so much to learn in this episode. Brad, I know you're such a favourite on the podcast, and there's plenty of reasons for that. So, thank you for joining us today.
Brad: Emma, it's been an absolute pleasure, and I look forward to chatting with you again in the future.
Emma: Great. So, some key points that I've taken today, there's been many, but off the top of my head, I think looking at the judicious use of antimicrobial herbs, and that could look like aiming to utilise extracts and tinctures over an oil. We could do some pulse dosing, one week on, one week off. We could limit the time, like, having shorter periods of time for our patients on these antimicrobial herbs. And considering your four rules of test, reflect, protect, and regenerate. And knowing that the research is clear, that doses like 500 milligrams of berberine twice a day does have a detrimental effect on the microbiome. So, we need to be careful with what we are doing here.
Brad: Fantastically summarised, Emma.
Emma: All right, Brad, enjoy the rest of your day.
Brad: All right, bye-bye.
Emma: Thank you, everyone, for listening today. Don't forget, you can find all the show notes, transcripts, and other resources from today's episode on the fx Medicine website. I'm Emma Sutherland. Thanks for joining us, and we'll see you next time.
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