Adapted from episode 155 of The Perfect Stool podcast and edited for readability with Clinical Nutritionist and Herbalist Dr. Brad Leech, PhD, and Lindsey Parsons, EdD.
Lindsey:
So we talked about focusing on antimicrobials. So I want to start by asking you about what not to do, which is to say, the most common antimicrobial herbs that are used traditionally for gut healing and issues that are harmful to the gut microbiome, and what the research says about that.
Dr. Brad Leech:
So this is an interesting one, and we need to consider that over the years, the way we evaluate the impact on the microbiome, the way we evaluate the effectiveness of herbal medicine, has changed because we’ve changed the way that we sequence the microbiome. We’ve gone from culture to shotgun metagenomics. So our understanding of this whole ecosystem in the gut has shifted hugely in the last especially 15 years, but more so the last 30 years. Now historically, and I’ve got a background in herbal medicine, and I love my herbs, and use herbs day in, day out with my patients- but something I started to notice five plus years ago is this over prescription of antimicrobials whereby it wasn’t just practitioners prescribing high dose antimicrobials. It was, and I’m speaking from the viewpoint of the Australian market, consumers would just go into a pharmacy, a health food shop, and they would get over-the-counter, high-dose berberine, high-dose oregano oil. And we’re using it for things, yes, related to the microbiome, but also metabolic health, or bloating, or anything in between. And I was getting patients upon patients where you’d look at their microbiome report, and it was shocking, there would be a reduction in diversity. There would be changes to these beneficial species.
And at that time, going into the literature, there were indications to say that these herbal products were beneficial. There was culture and PCR-related studies to show that when you take berberine or oregano- the limitations in the research were huge, because they were saying it was a good thing. But it wasn’t until two studies that came out in 2020 and 2021, now these two studies, one by Zhang et al. and the other one by Ming et al., 2021 which actually utilized metagenomic sequencing to measure the microbiome in herbal medicine intervention studies. Now for those listeners who might go, hold on, what’s metagenomics? What’s shotgun metagenomics? Very briefly, there are different ways to measure the microbiome. You’ve got culture, which is basically growing the microbes. You’ve got PCR, which is looking for a specific microbe with a probe. You have 16s, which is accurate down to the genus level, not so much to the species level. And then you’ve got shotgun metagenomics, which can look down to the species level to understand what species are changed. We’re not at the strain level yet. So it’s just down to the species level. To get down to the strain levels, we need something called nanopore technology, which is basically just you crack open the microbes and you pour out the full strain of the DNA to get access to it. They’re utilizing this in some research settings.
We are 15 plus years away before we can look down at the strain level. But species, we’re there, and we should be looking at the species. So these two studies, they really jumped out at me when I was doing a bit of a deep dive in and around the time that they were published, around 2021, and so forth, because they utilize this metagenomic sequencing. So broadly speaking, these two studies, they were well-conducted studies: multi-center, double blind, randomized control trials, where they had around three to 400 participants where one group were diabetic, the other group were hypoglycemic patients, and they prescribed anywhere between 500 to 600 milligram grams of berberine twice daily for 12 to 16 weeks. So this is definitely a higher dose of berberine than what many practitioners would prescribe, but it is at the dose that you can buy over the counter. There are many, many supplements on the internet where it’s around that 500 milligrams of berberine.
Lindsey:
Recommended for people with type two diabetes. . .
Dr. Brad Leech:
Exactly. It’s very effective when it comes to high cholesterol and type two diabetes. But we, as functional medicine doctors and naturopaths and everyone in between, have this concept of first do no harm. So the interventions that we prescribe, first and foremost, shouldn’t be causing any harm to the patient. So, and I’m going to tell you in a moment, the negative impact that these studies actually showed. So after the 12 to 16 weeks of around that 500 to 600 milligrams of berberine twice daily, what actually showed in the microbiomes was an increase in hexa-LPS producing species. So LPS, your lipopolysaccharides, and we’ve got this subgroup of lipopolysaccharides called hexa-LPS, and they are the pro-inflammatory microbes. So taking high dose berberine resulted in hexa-LPS increasing.
But the other thing that was found were particular species that were linked up with disease outcomes. So Klebsiella pneumoniaes, E. coli, actually increased, which we weren’t expecting. Then the plot thickens, whereby these high-dose antimicrobials, and this is something that I’ve been seeing in practice for years now, they actually were shown in the research studies to reduce butyrate and commensals within the microbiome, including a lot of your bifidobacteriums, in addition to reducing diversity within the microbiome. So, thinking about that for a moment, we’re taking an intervention that shifts the microbiome to a more negative state, a way that is more resembling disease outcomes rather than health. So I now question when we utilize antimicrobials, and that’s not to say that we shouldn’t use antimicrobials, but we should use them based on the microbiome, and we should use them in particular clinical situations, and we should be utilizing more selective antimicrobials.
Lindsey:
And so were there also studies on oregano?
Dr. Brad Leech:
Not oregano. There are in vitro and animal-based studies showing positive impacts, and so we can only speak to berberine, but they have very similar actions, antimicrobials. What I’d note with oregano is the actual herb, so using it in the cooking, amazing, lovely. But when we actually use the oil of oregano, it’s much stronger. So it’s much stronger to the microbiome and has a non-selective action, meaning that could actually impact the good and the bad. So when selecting antimicrobials, going for the extracts, or maybe the tinctures, and utilizing something called pulse dosing, we might use one week on, one week off, or two weeks on, one week off. Other antimicrobials that we may consider utilizing may be nigella or black cumin. Pomegranate husk extract* is an excellent one, and even garlic* has been shown to be a bit more gentle, but still effective as antimicrobials.
Lindsey:
What about uva ursi? It’s commonly listed if you do the old tests with the culture, they often would list what the sensitivity is for these antimicrobials. And they always put berberine, I think oregano, garlic and uva ursi on the list.
Dr. Brad Leech:
Yeah, I can’t speak to that one. I haven’t looked into it, unfortunately.
Lindsey:
And then other plant oils, like thyme or cinnamon, are those also sort of along the same line, considered very strong?
Dr. Brad Leech:
For those it’s the oils. When it’s the oils, it’s a much stronger antimicrobial. And in some situations, when there is a true pathogenic infection, yes, we may utilize it for a true pathogenic infection, but what a lot of practitioners are utilizing it for are pathobionts. So pathobionts are things like M Smithi , Klebsiella pneumoniae, B. wadsworthia, E. coli. Things that aren’t causative of disease, but associated with disease. Antimicrobials can safely be used for when it’s a pathogen, and when I refer to it as a pathogen, I’m referring to things like Bali belly, Dehli belly, food poisoning, where there’s quite obvious loose stools, abdominal discomfort causing a pathogenic infection.
Lindsey:
I’m laughing because in Australia, the closest place where people frequently get food poisoning is India. In the US, we call it Montezuma’s revenge, because the closest place is Mexico.
Dr. Brad Leech:
I love that one, I might use that in future.
Lindsey:
Yeah. So, basically, if you go get an ova and parasites test at the doctor, that list of the really bad ones, like Campylobacter or salmonella, or these kinds of things, the very pathogenic E coli, C diff, like this list of things?
Dr. Brad Leech:
Exactly, exactly. So, I mean, it really depends. And I know the healthcare system in America is not one to rave about, but in some situations, when it’s quite acute, loose stools in Australia, that’s a referral to the GP. Go to the GP, get your antibiotics, but if there is a lack of clinical symptoms, but these pathogenic infections are still identified, so they’re suboptimal. That’s when we can really come in with the anti-microbials.
The other thing that I might stress here is, at the same time of eliminating the infection, we want to protect the microbiome. So there’s things that we can do to protect this ecosystem, one of which are going to be your HMOs*, so your human milk oligosaccharides, a type of prebiotic first isolated from breast milk, and it’s there to feed up the microbiome. Now the research on HMOs show that it exclusively feeds the beneficial species, while reducing the adhesion of pathogenic bacteria to the lining of the intestines. So it brings up this environment in the gut. Dosage wise, you’re looking around that two grams of the HMOs in addition per day. In some cases, you could do two grams twice a day. But the thing to note is HMOs are very expensive, so that adds up very, very quickly. The other one that we may utilize is your SB, so your Saccharomyces boulardii*, fantastic around that 200 milligrams a day. And then we’ve got a probiotic strain called Bifidobacterium lactis BB12*, and that’s been shown to survive and be still effective during antimicrobial and antibiotic use, so it’s one that we can take alongside the stronger antimicrobials.
Lindsey:
So I don’t know if you’ve heard of the whole protocol involving MSM* as an antimicrobial, any sense of that?
Dr. Brad Leech:
What I can say is there are many antimicrobials out there. Resveratrol*, on the outside of grapes, is an antimicrobial. Turmeric* is an antimicrobial. Their secondary actions can be antimicrobials. MSM* is not one that I would typically think of as an antimicrobial, but there are many lower dose or weaker antimicrobials. We’ve just really got to consider when utilizing antimicrobials- are they impacting the species that we want them to impact, or are they actually damaging the beneficial species? And unless we have research to confirm that, I’m always a bit cautious to go, I would rather cause less harm than more harm to the microbiome.
Lindsey:
Yeah, no, I asked because I had heard about it on Nirala Jacobi’s podcast*, there was a doctor who came on and her protocol for everyone was MSM, work your way up to 32 grams a day. And once you hit that level, usually the bloating is gone. Everything’s fixed. She doesn’t even test the gut. So, I’m going- okay, I’m not going to recommend this protocol, but I’m going to try it on myself. I have post-infectious IBS, so I’m a great test case for whatever, because whatever I have, it’s always coming back. I can knock everything out, but it’s coming back. So, I did, and, I mean, it was great. Like every other anti-microbial regime, it knocked out everything and I was great. I didn’t bloat for maybe a week or something. And then everything started coming back. So I just started taking a little bit every day. So I’ve been holding off on a stool test to see whether it’s decimated my good microbes or not, because I’m kind of at the point where, so when you have post infectious IBS, probably what’s overgrowing is going to be something that’s LPS producing, right? So I’m thinking it’s better for me to just kill stuff than to just continue to let this inflammation potentially hover in my body.
Dr. Brad Leech:
You raise a really good point here. Those studies that I show described just before are in a clinical setting where participants did nothing else other than take high dose antimicrobials. I know for myself and my clinical practice, I never just prescribed one thing. I am recommending a variety of different supplements. I’m recommending a change in diet and lifestyle. And I’ve spoken to a number of practitioners in this area, and they would utilize higher-dose antimicrobials for SIBO management, but they would also, alongside it, give the PHGG* and the kiwi fruit and no snacking. And they’ll do these interventions that would actually have a positive effect on the microbiome, along with prescribing these things like the HMOs, the S. boulardii, the BB12, to protect the microbiome, and then thereby, what they see in their practice is less of a negative impact to the microbiome. So yes, this study is a very sterile study in the sense of it is just looking at one specific aspect and in clinical practice, that’s not really how we work. But it does illustrate the potential power of these herbs. They are very strong. They’re very potent, and we need to utilize them in the right place.
Lindsey:
Okay, so let’s dig in a little bit more on the ones you did mention. How do you use in particular the Nigella. Is that the black cumin?
Dr. Brad Leech:
Black seed oil or black cumin. So Nigella is a very gentle antimicrobial. I’d be utilizing a combination of the Nigella*, the pomegranate husk extract* and even the garlic* when there is a pathogenic infection. When there’s a pathogenic infection, I’d be utilizing a combination of antimicrobials, whereby, if it was, let’s say, an overgrowth of a pathobiont, which was really impacting the microbiome. So let’s say a particular E coli flexneri was dominating the microbiome, about that 5%, 20% type of picture, really dominated the microbiome. I would then utilize pomegranate husk extract as a gentle antimicrobial alongside, and you’ll find this very interesting.
An effective way to reduce E. coli in the bowel is actually with GOS*, so your galactooligosaccharides is a prebiotic. You can get it in food sources, but also as a supplement, Bimuno GOS*. This GOS has the research behind it that’s used in a lot of these studies, and a dose range of around four grams per day has been shown after 12 weeks to bring down E. coli species. Side note here with GOS, you really want to go low, go slow, because if you jump in to four grams or five grams per day, you’re going to get bloating. You know it will really go because it’s a FODMAP. It is a fermentable carbohydrate. It feeds up the microbes. So we want to slowly, slowly introduce it. There are definitely some individuals who can’t tolerate GOS and who shouldn’t be taking GOS, but those who can, it’s a great, great tool to be utilizing to change the microbiome.
Lindsey:
And we talked on the pre interview call about the Mediherb pomegranate husk extract. They have the 300 milligram pills? Well, it turns out it’s not available in the US, but they’re working on getting it available by Standard Process. So yeah, at this point, if you’ve ever tasted it, you probably know pomegranate husk powder is perhaps one of the vilest things ever. You can mix it into a smoothie and hide it, but you’re not going to put it in water, it’s just going to sit there as a film on the top, and then it’s like, you know…
Dr. Brad Leech:
It’s not enjoyable. And we need to, especially with compliance with patients, we need to have it in a way that’s going to be easy for them to take.
Lindsey:
Yeah, yeah. And so how much of the Nigella do you use?
Dr. Brad Leech:
It really depends on the extract. I actually really use the seeds in cooking. So you can get them from an Indian shop, and they bring out such an incredible flavor in your cooking. The trick here is to actually put them in with the onions at the beginning, or in that first part of a stir fry, or in a curry, and it just extracts all of the flavor. And that’s one of the ways that I like to utilize the Nigella.
Lindsey:
Okay, so you’re not talking about the oil?
Dr. Brad Leech:
No, not, not necessarily the oil. No, yeah.
Lindsey:
Okay, yeah. And would cumin powder be just as good in that sense, or do you want the seeds?
Dr. Brad Leech:
So black cumin and cumin are different. I imagine you can get black cumin, so that’s like, almost like the layman’s term to describe it, but it’s similar to cumin, but different. I imagine you can get Nigella powder, and you can get it in a capsule, and there are many supplements that have it in the capsule, and in some cases, yes, I would go for that.
Lindsey:
Okay, yeah, how about SBI’s- Serum bovine immunoglobulins?
Dr. Brad Leech:
So your serum bovine colostrum?
Lindsey:
Well, in this case, it’s the extracted immunoglobulins. I don’t know if that’s available in Australia at this point.
Dr. Brad Leech:
We have got something called Serum bovine colostrum. So it’s a colostrum from the blood of cows, and it actually binds on to the byproducts of pathogens.
Lindsey:
Right! I think we’re talking about the same thing, right? Similar thing here, because it’s dairy-free. It’s from the plasma.
Dr. Brad Leech:
Right, yes. The thing with the serum bovine colostrum is it’s really great when there are high levels of hexa-LPS within the microbiome. So when there are Klebsiella and E. coli’s in the microbiome, it does a great job at binding onto it. So the dose that I generally utilize is around that 2.5 grams, so around a head of a teaspoon. And it’s quite potent. It’s quite strong and effective as well.
Lindsey:
Yeah, that’s one of the supplements that I actually sell, but only in the US, because it’s too much of a pain to try and figure out how to export and all that. So when you use the pomegranate husk pills, I guess the extract is somewhat different from the powder. I think it’s more potent.
Dr. Brad Leech:
We’ve got pomegranate husk extract. So that’s the extract of the husk. And yes, it is much stronger compared to, and it’s very different to the actual pomegranate juice powder. Pomegranate juice powder isn’t an antimicrobial. Pomegranate juice powder is a polyphenol, and it’s actually going to feed up the microbiome, and it’s actually going to increase Akkermansia-based species as well. So really potent, I believe that a 300 milligram capsule of the extract is equivalent to three grams of the husk. So it’s about equivalent to almost a teaspoon.
Lindsey:
Yeah, the pomegranate powder. And, yeah, what other polyphenols do you recommend for building up those? And if you use the GI Map and go down the GI Map test and, everything’s looking good and zero Akkermansia and zero Faecalibacterium prausnitzii . Yeah, those are always the two that were knocked out after people had done antibiotics or antimicrobials. So what polyphenols or other prebiotics do you like to use?
Dr. Brad Leech:
Another thing to consider is with tests that utilize PCR, they’re looking for just Akkermansia muciniphila. They’re looking for just that one species whereby there are many, many other beneficial Akkermansia species which may not be identified. So it’s kind of giving that false indication as to well, is there actually Akkermansia, or is there not, or is there no Akkermansia muciniphila, but Akkermansia others.
Okay, so yes, I love the pomegranate. So I initially started doing actual pomegranate juice, advising patients to consume pomegranate juice, but it was quite difficult to buy and then you got the sugar content, and it was just a burden for the patient, was too much. And then you can actually get frozen pomegranate, the little seeds of the pomegranate, you can get frozen pomegranate, and that’s really nice to go on to a salad, to go into a smoothie, but accessing it is also an issue, so pomegranate juice powder* is the way to go. So it’s an extract of the powder. It’s very potent. You only need around that 250 milligrams of the extract of the powder to be effective. It’s an expensive product as well, but I love the aspect of the polyphenols feeding up the microbiome, especially when it comes around to those who may be unable to tolerate prebiotics.
Polyphenols are an excellent option because they have these actions and in fact, all polyphenols, they have three mechanisms of action. They are anti-inflammatory, so they can reduce your CRP, Interleukin six (IL-6), Interleukin eight (IL-8). They are also antioxidants, so they can support that antioxidant aspect. And they’re also antimicrobials. So we mentioned before that curcumin, resveratrol, quercetin, can also be an antimicrobial and even an extract of green tea. So these polyphenols, they are incredible. So your grape seeds, your bilberry, your cranberries, aloe vera, pomegranate, as we mentioned, are all excellent polyphenols, even curcumin. We love curcumin as a polyphenol.
The way that I like to get this into our patients is through diet. Diet is going to be number one when it comes to polyphenol prescription. We can take all the expensive polyphenol supplements we like, but we can get a huge amount in our diet. A couple of things I tell patients is diversity, diversity, diversity, and not just diversity in the foods, but diversity in the color. We want to have five different colors on our plate in each and every meal. Okay? The next one is going to be berries. Incorporate berries every single day, the amount of berries that we actually need to be therapeutic is around that 200 grams. So I don’t know what that is in ounces [7.05 ounces], but it’s about a punnet of blueberries a day. Yes, expensive, but frozen is perfectly fine. So you can get frozen, and they need to be organic, because the herbicides and pesticides they use in the berries will actually reduce the polyphenol content.
Another one here is, rather than using sauces in cooking, is to actually use your herbs and spices per gram per teaspoon. Herbs and spices have the highest amount of polyphenol compared to all other foods. Yeah, other ones here are switching from other oils, whether it’s vegetable oil, canola oils, butters and so forth, to olive oil which has higher amounts of polyphenols. Coffee will also have polyphenols. But even incorporating things like green tea, there’s studies to show that two cups of green tea is significant enough, and this is high quality green tea as well, is significant enough to bring down intestinal inflammation. Flax seeds are another great polyphenol. Grind them up, adding them into a smoothie. Adding them into oats is a great way to bring in more fiber, but then more polyphenols. And then lastly,
Lindsey:
Flax seeds have some conversion to EPA and DHA.
Dr. Brad Leech:
Yeah. And then the last one I might add in there would be chocolate. We can’t go without chocolate. It is an excellent polyphenol, but there are no polyphenols in white chocolate or very little. We need to go for that dark chocolate. I was at my mother in law’s last night, and I looked in the fridge and she had 100% cacao, and that is incredible. And I tasted it, and it’s so incredibly bitter. I’m only at about that 85% cacao. That’s my threshold. My wife loves 90% cacao, but 100% cacao, if you can handle it, fantastic.
Lindsey:
Yeah, I’m sort of at 70. That’s kind of my max. So you mentioned in the list of polyphenols- grape seeds. And I always think of grape seed extract as a super strong which could wipe out your microbiome kind of thing.
Dr. Brad Leech:
And that’s the thing, yes, it can be a stronger antimicrobial when it comes around to the grape seed. Yes, it does have antioxidant capacity, yes, it’s anti-inflammatory, but it’s also going to be antimicrobial as well.
Lindsey:
Yeah, okay, so when you pulse, the stronger things, so let me back this up a little bit and say that I often see people who have tried the SBIs, if you’ve tried the lighter stuff and they’re not getting better- they’re miserable, they’re bloated, they’re saying, “Can I just get oregano oil or berberine, or whatever?” They want to take something stronger. So, you feel like, at this point you’ve tried the lighter stuff. You have to do something. So then you do try and pulse. But then sometimes I see this, there’s a regression in the week off and then it seems like it never is quite as effective after you’ve pulsed. Have you experienced that at all?
Dr. Brad Leech:
In some situations, yes. That’s when I’d probably do the two weeks then one week off. It’s still that aspect where let’s take SIBO, when we use antibiotics to treat SIBO, 40% to 60% of the time, within six months, it’s going to come back. So it’s not necessarily the answer. It’s going to resolve short term, but it’s not getting to that underlying cause. So we’ve got to consider, okay, if we’re going to be utilizing these anti-microbials, how can we ensure that the patient doesn’t come back to see us in six months’ time with the exact same picture, and then we need to do it all over again. More antimicrobials, in essence, antimicrobial herbs are going to be better for the microbiome than antibiotics. But we, yeah, we’ve got to be cautious here. That’s why protecting the microbiome at the same time, lifestyle factors, cleaning up their diet, having that synergistic action whereby you do everything that they’ve tried before, but at the same time as stress management. You’re not eating too late at night, you’re eating easy-to-digest foods. And then you bring in the antimicrobials and hope that that’s going to have a more sustained effect.
Lindsey:
And do you have testing in Australia for vinculin antibodies?
Lindsey:
Which antibodies are those?
Lindsey:
Vinculin for the post-infectious IBS?
Dr. Brad Leech:
So, we have ways to look for antibiotic-resistant genes. So we actually look at the microbes to see what genes they are resistant to, and based on those genes. So there’s 20-30 plus genes to go, oh, it’s resistant to this type of antibiotic or this type of antimicrobial. So utilizing the DNA aspect. The thing to consider is when we do these studies where we have the microbes and we apply the anti-microbials, which is done in a lot of research studies, that’s just looking at the effect on that particular species, and it’s difficult to determine whether or not that same effect will occur when we consume it and it goes down into the gut with, let’s say, biofilms, and everything else is happening within the gut. So it’s one of those things where we’ve got to consider, yes, that could be effective on a piece of paper, but is it actually going to be effective in clinical practice?
Lindsey:
Yeah, what I’m talking about is something different. This is from Mark Pimentel’s work on the IBSsmart Test, but I’m guessing you can’t access that in Australia. What test do you like for analyzing the microbiome? Do you use breath testing at all? Or do you use stool testing?
Dr. Brad Leech:
I’ll utilize stool testing and shotgun metagenomics. So where it utilizes metagenomic sequencing to look at all the species in the microbiome. That’s the test that I’m going for, because when you’ve got that species-level information, it gives you an indication as to what’s going on. Let me give you an example. Have you ever seen a microbiome report where they’ve got Streptococcus, or Streptococcus sp., whereby you don’t actually know what species it is. You just know, well, there’s the genus of Streptococcus. Within the Streptococcus genus, we have Strep A. So Strep A is a true pathogen. We also have Streptococcus thermophilus. So Streptococcus thermophilus is found in yogurt and is a commensal. There’s really nothing wrong with having that streptococcus in our microbiome. You also have Streptococcus salivarius, so an oral microbiome. You’re identifying species in the microbe in the oral microbiome, in the stool. Now when we identify down to the species level, it will really govern treatment direction. So for Streptococcus thermophilus, we’re not doing any treatment. That’s fantastic. We don’t need to treat that streptococcus. Yeah, when it’s Streptococcus salivaris, we’re not coming in with an antimicrobial. We’re not trying to kill that.
An increase in oral species in the microbiome is actually an indicator of lack of stomach acid. So we can actually utilize high levels of oral species. When there’s four or more oral species in the microbiome, it can actually allude to a lack of stomach acid. So they’ve done these research studies. Those taking PPIs, your proton pump inhibitors, had an increase in oral species in the stool because there wasn’t sufficient stomach acid to break down these oral species. Now, that type of understanding of species-level data is only available with metagenomic sequencing, and that’s why that would be my choice of testing. The other one here to consider is how we can go about supporting that stomach acid. Yes, we can come in with betaine hydrochloride, but we also need to consider, well, is it stress governed? Should we be supporting stress management? Are there particular herbs like ginger and gentian and black pepper to really support with bringing up that stomach acid? So I think yes, to answer your question in a roundabout way with an example, I’m utilizing metagenomic sequencing in my practice.
Lindsey:
And what companies operate in Australia that you can access?
Dr. Brad Leech:
There’s one company called Cobiome by Microba and they were founded out of the University of Queensland. So two researchers, Professor Jean and Professor Phil, were actually the ones who first published research on metagenomic sequencing back in 2004. Cobiome by Microba are the ones that are available in both Australia and the United Kingdom. In the UK, you can access that as well through a company called In Vivo.
Lindsey:
Okay, and is this something that people can order themselves, or is this exclusively by practitioners?
Dr. Brad Leech:
Because the tests contain diagnostic markers-it contains markers like pathogenic infections-it can contain calprotectin, lactoferrin, markers for inflammatory bowel disease, it actually needs to be ordered through a practitioner. But these tests are the gold standard for measuring the microbiome in Australia. Any practitioner who is educated in the microbiome, that’s their preferred method of testing.
Lindsey:
Yeah. So you mentioned seeing the Streptococcus salivarius- what other commensals from the mouth, or pathogens from the mouth might you see that clue you into low stomach acid?
Dr. Brad Leech:
There are over 450 species which can be identified in the stool. Would you like me to name them all? I’m joking.
Lindsey:
I just thought there might be some common ones?
Dr. Brad Leech:
I can’t name them all, because there are so many, a lot of Streptococcus. So a lot of Streptococcus, Streptococcus mutans will be one. I actually can’t recall all of them. I can’t recall many of them, purely because, on metagenomic sequencing tests, they have a button, where it says the number of oral species. So they do all the calculations for you. So then you’re not looking for, oh, which one’s an oral species? Which one’s not? It would just say there are five oral species, and list the oral species, and some of them are just weird and wonderful names, but they have been identified within the oral cavity.
Lindsey:
Okay, yeah, we don’t have, well, at least not any of the ones I’ve been using. I’ve been using this one called the Tiny Health Pro, because it’s got the metagenomic sequencing plus all those markers, which is nice, because most of the other metagenomic sequencing ones are just sequencing. You just get the species. And obviously I want to see the markers too.
Dr. Brad Leech:
There is a database, and I can’t recall the name of it, but there is a database with all the oral species. So maybe there’ll be a bit of manual handling on that one as well.
Lindsey:
So you mentioned the ways to bring up stomach acid. And, yeah, I often get this situation where you have someone who just has persistently low stomach acid. They can take five Betaine HCl at a meal, they feel nothing and, their blood tests keep coming back with all sorts of markers of low stomach acid. So how do you address that? Let’s get into a little more detail.
Dr. Brad Leech:
It really depends on the individual in front of us. Some of the options that I could utilize would be apple cider vinegar. It’s simple, but it’s effective. So taking about a tablespoon in warm water with a meal- that’s going to be acidic. My top herbs will be ginger, black pepper and gentian. Yep, I don’t utilize betaine hydrochloride frequently because it’s just adding in the stomach acid. I would rather come out of the approach of naturally stimulating it. So through those herbs, and then also through vagus nerve stimulation. So, stimulating the vagus nerve with bitters, but then also you can get different devices to stimulate the vagus nerve, even singing, singing from high pitch to low pitch can stimulate the vagus nerve. Chanting, om which is that vibration can stimulate the vagus nerve. I was in India a number of years ago, and you see these, these monks and so forth. You know that they’re almost there on the side of the road drinking chai tea. Now, in the chai tea there is more sugar than humanly possible. It’s basically tablespoons upon tablespoons of sugar. I am thinking how are you living to 100 years of age when you eat so much sugar? And I put it down to they chant on for hours a day, stimulating the vagus nerve, bringing up stomach acid and regulating inflammation. And I wonder if we all just chanted for hours per day, could we eat more sugar? Maybe? Who knows?
Other ones here are going to be hypnotherapy, so we can utilize something called gut hypnotherapy. Now, gut hypnotherapy is a process whereby you reconnect this bi-directional link between the mind and the gut. Really effective for visceral hypersensitivity IBS. And in fact, there’s been a study, a multi-center study from Australia, the US and the UK, where they compared gut hypnotherapy with a low FODMAP diet in IBS patients. They found that the gut hypnotherapy was more effective short term and long term than the low FODMAP diet in IBS patients. So it’s one of those things where, rather than putting my IBS patients on a restricted, low FODMAP diet, I’m actually leaning towards gut hypnotherapy. It’s a six-week program to reconnect this link, and then also bring down this visceral hypersensitivity and support with the symptoms of IBS. But where I’m going with that is that it can also support stomach acid production. And then there are particular probiotics, Saccharomyces Boulardii, L rhamnosus Rosell*, that can be effective to bring down oral species in the microbiome. It’s promoted as a product to change the ecosystem in the mouth when there are high amounts of oral species causing dental problems.
Lindsey:
Okay, so you mentioned black pepper. Are you talking about the piperine they add to the curcumin supplements?
Dr. Brad Leech:
That can be an option, or even just black pepper, yeah, but both can be an option. Here so in traditional Ayurvedic medicine, you have pippali. It’s like a long pepper, and it’s slightly sweet. But in some of the products that I’m using it’s just black pepper extract, a very small amount, but to stimulate those digestive secretions.
Lindsey:
Okay, so back down to the testing. What do you think about the accuracy of markers for things like pancreatic enzymes or steatocrit or secretory IgA on the functional stool tests?
Dr. Brad Leech:
I can tell you so much about this. So there’s a couple of things to consider. Pancreatic elastase, it is well known within the published literature that the accuracy to diagnose pancreatic insufficiency is extremely poor. Yeah, the sensitivity and specificity for identifying pancreatic insufficiency is quite terrible. And there are articles upon articles stating the exact same thing. So it’s when it becomes really, really, really low. And what’s the reference range that you’re using in the US?
Lindsey:
So a lot of markers will put 200 at normal but, sort of generally we think of 500, even though that’s further up, that’s really the more optimal.
Dr. Brad Leech:
So similar ranges here in Australia, anything above 200 is okay. Anything below 200 is indicating pancreatic insufficiency. But really, to accurately diagnose pancreatic insufficiently, correctly, it’s more like below 50. Now that’s just what I’m seeing within clinical practice. The literature is saying below 100 but it’s in that range between 100-200, where it’s not definitive in saying that I will always provide a digestive enzyme and stomach acid support and bitters to support that. And I see that marker does increase, but it’s once it goes down below that 50 mark, that’s when I’m referring to the GP to actually do further assessment for true pancreatic insufficiency, which requires lifelong medication of digestive enzymes, not the digestive enzymes that naturopaths can access. I’m talking strong, pharmaceutical grade digestive enzymes,
Lindsey:
Hardcore ones like Creon, and what if it’s sort of in that middle range, like it’s 250, it’s 300 or something.
Dr. Brad Leech:
Because of the test being less sensitive when it’s above that 200 mark, you say that it’s okay, and you also go off clinical symptoms. Yeah. So what was the other one you said, secretory IgA? So the thing with Secretory IgA is it is very sensitive to temperature and heat. Now I’ve been involved in a number of lab comparisons where we’ve sent one sample, so we had an individual provide us a stool, and from that one stool, we’ve sent it off to multiple different labs in Australia, in the US, and compared the results. Very, very interesting in the sense of the results. One of the things that came back was secretory IgA, and what it actually appears, and the literature confirms this as well, and the labs know this as well, is secretory IgA, when it is exposed to high temperature or is not processed in a timely manner, can start to break down.
So what can actually happen is low-quality labs will be reporting low secretory IgA more frequently than labs that have a higher duty of care and higher standards. So I know, growing up doing my degrees, it was always low secretory IgA. That was always going to be the issue. But that’s because at that point in time, back in 2008 the labs were pretty poor, and it was just, it was actually secretory IgA breaking down in the post. So here in Australia, especially in Queensland, there can be heat waves, really hot temperatures and so ensuring that you’ve got the ice bricks and temperature control to ensure that it is getting back to the lab in a timely manner. So secretory IgA, it is accurate, as long as it is back to the lab in a timely manner. So generally, within 48 hours, 72 hours, anything more than 72 hours, it’s really going to start to break down. And also, you don’t want it to be exposed to high degrees of temperature. So you actually want a temperature control method in the parcel that you send back to the lab to ensure that it doesn’t go above that threshold where it starts to break down.
Lindsey:
Okay. And so are the results of the study you’re talking about, where you sent it off to different labs published?
Dr. Brad Leech:
That was for some education programs that I put together, where I wanted to compare different labs, and we went through that. It was a really interesting exercise comparing all these different labs. What I can say is it’s very difficult to compare, because different labs will call species by different names. They will give different measurements as well. So they’ll use different databases to name different bacteria. So broadly speaking, we have a number of different databases. We have a database called the GTDB, which is the gold standard for naming microbes, so that’s based on their DNA. So that’s the GTDB database. But a lot of research studies and a lot of older labs will utilize a database called the NCBI, which is completely inaccurate when it comes to naming families and genuses and species in the microbiome. It just gives it completely different names, because it’s an old version of naming microbes. So, there is this change in recent years on how we name microbes. The microbe in itself isn’t changing, but the name that we provide it is changing because we’re naming it based on the DNA, rather than looking down a microscope and going, oh, this is producing X compound- It’s a lactobacillus. So we’re changing how we name these species.
Lindsey:
So I’m curious, though, with the labs in the US, was there one that sort of came out as the best one?
Dr. Brad Leech:
I don’t want to negatively put down labs.
Lindsey:
That’s why I asked for the best, I didn’t want to ask for the worst.
Dr. Brad Leech:
What I would illustrate is any lab utilizing metagenomics, shotgun metagenomics, fantastic, great. Any lab that’s utilizing PCR, I’m sorry we’re so far past that we don’t just want a list of hey, here are the 30-40 species that we can identify. But, are they in your gut? Yes or no, that is not microbiome assessment. That is just looking for a few key species. We want to be looking at the whole microbiome, rather than just a subset of a few species which that particular lab can measure.
Lindsey:
Yeah, as I’ve started to use metagenomic sequencing more and more, I’ve begun to realize that I was sort of operating in the dark when I was not using it, because there were definitely species that were coming up that were just not on the list. So, with hydrogen sulfide SIBO too, I’m seeing that there’s some species that are not on one report that have these three, but not all four or even more. So it’s not ideal, it’s interesting.
Dr. Brad Leech:
I get patients from Australia, UK, America, they come to me. They have microbiome results and generally, and the US market, very interesting patients that come from the US. They’ve done so many different tests, okay? And they’ve probably done four different microbiome tests with four different companies. And I’ll actually say I’m actually not going to look at those results. I’m only going to look at the results using metagenomics because, well, I understand the accuracy. So there’s this concept called identification bias. Identification bias is whereby, if we see something that is positive, we believe that that’s the problem. So for instance, if we identify Streptococcus, or if we identify Blastocystis, or if we identify something and everything else is okay, we believe that that’s the problem. And what’s happening, especially here in Australia, GPs are going, yes, all the microbiome, but they’re just doing really standard gut tests, and it’s not giving all the solutions, and they’re just identifying one marker and treating that one marker rather than really considering what else could be happening in the whole microbiome.
Lindsey:
Yeah, so new topic as we sort of get towards the end. What do you think about leaky gut? Is this a condition in and of itself, or secondary to other issues?
Dr. Brad Leech:
Yeah. So background, my PhD was on leaky gut. I spent the better part of five years reading every single article on intestinal permeability. What I can say here is intestinal permeability, it isn’t a syndrome, it is not a condition. It is not a syndrome. It is a reaction, okay? It’s a reaction that can occur within the gut, so disassembling tight junctions within the small intestines.
Lindsey:
Is it everything, or is it a driving factor?
Dr. Brad Leech:
I believe it’s a driving factor, rather than the sole focus that we as practitioners need to give it. Many things can drive up intestinal permeability, particular medications, microbes in the gut, stress can be a massive one. And I used to say gluten was a driving factor for leaky guts. But the research actually has come out to say, no, it’s not an independent driving factor for leaky guts. And I know many people would be like, hold on, what are you saying here? And even a colleague of mine, Dr. Fasano, who discovered Zonulin, is in agreeance with this, whereby, in the early days, we did these studies with a cell line, where we had individuals with celiac disease, non-celiac gluten sensitivity, Crohn’s disease and healthy individuals. And we added a bit of gluten to all of these cell lines, and permeability increased. But now we’ve got actual clinical studies where we had individuals and we gave them gluten to determine whether or not that resulted in permeability, and they didn’t always increase permeability.
There’s a few exceptions to the rules. It appears that there’s this threshold with the amount that you can tolerate. So it’s about equivalent to a tablespoon or two of gluten. So that’s not a gluten product, but of actual gluten. So around that 15 to 18 grams of actual gluten, which is about two pieces of toast. Yeah, but those with the celiac genes had greater permeability even if they didn’t have celiac. So I’m always looking for those celiac genes and recommending gluten free. In that case, there are some conditions like Hashimoto’s, inflammatory bowel disease, and non-celiac gluten sensitivity. And many others where I’d be advising a gluten-free diet.
But what I do focus on is when you eat gluten and you have clinical symptoms- Why is that ? Is it the fructans? Is it the glyphosate? Is it what else is going on in that product that is driving up those clinical symptoms, and the goal in some of my patients is to actually bring grains back. And I know, for years we’ve been saying grains are the devil, but I guarantee, if you look at someone’s microbiome who’s avoiding all grains, it is a terrible microbiome. It is a starving microbiome. It’s got really high mucin-degrading species in the gut, because there’s not enough fiber in the diet. It is very difficult to get enough fiber purely from plants, sorry, purely from vegetables. So we need to be considering grains. They could be gluten-free grains, by all means, or they could be gluten-containing grains, but I just, I thought I’d throw that out there as a bit of a novel approach around leaky gut.
Lindsey:
Yeah, so how are you diagnosing the non-celiac gluten sensitivity then?
Dr. Brad Leech:
Well, that would be through clinical symptoms, but then we also will utilize particular pathology in the bowel. So you would utilize stool’s zonulin as a marker for permeability, along with hexa-LPS and butyrate as indications for that bowel integrity. I’ll also utilize hydrogen sulfide producing species to indicate whether or not there’s permeability as well.
Lindsey:
What is the relationship between the hydrogen sulfide ones and permeability?
Dr. Brad Leech:
So hydrogen sulfide, the research, shows that it can actually break apart those mucin bonds in the gut, and it can actually be a driving factor behind the intestinal permeability.
Lindsey:
Oh, okay, yeah. So I used to be gluten free because I had Hashimoto’s, but I was completely reversed that my antibodies have been at zero. And finally, slowly but surely, more and more gluten comes back into my diet. And I’m just like, am I killing myself here? But I feel I’m okay.
Dr. Brad Leech:
You know what? Monitor the antibodies.
Lindsey:
I did for five years, I was getting more and more gluten, and still was staying zero, still zero.
Dr. Brad Leech:
Yeah, yeah, a little bit is fine, especially if it’s a sprouted gluten or a fermented sourdough.
Lindsey:
I like fermented sourdough with organic flour.
Dr. Brad Leech:
Fantastic. With some avocados, some poached eggs. I love it. Yeah, exactly.
Lindsey:
Okay- one more question-How do you seal up a leaky gut?
Dr. Brad Leech:
That is a great question. So part of my PhD, we published the clinical practice guidelines for the management of intestinal permeability [see bottom on page], where we looked at over 22,000 research studies on the management of intestinal permeability, we evaluated them for their evidence, their risk of bias, their accuracy, and we narrowed down to our treatment recommendations. And you can download this full guide from our website, free of charge, and it’s got all of the recommendations that we have made to practitioners when it comes around to managing intestinal permeability in relation to when to avoid gluten, when to consume gluten, probiotics, prebiotics, everything in between. What I would say are the top interventions based on the research, it would be zinc, glutamine* and S Boulardii. And I know that’s not new or novel to anyone, but they’re the ones that have the highest amount of evidence to show that they are effective when it comes around to healing and sealing the gut.
Lindsey:
Okay, so zinc carnosine*, or just any kind of zinc?
Dr. Brad Leech:
Carnosine, yes, around that 25 milligrams.
Lindsey:
Okay, and, and what is the dosing on the glutamine? Because that’s a subject now.
Dr. Brad Leech:
It’s a controversy as well. Most supplements do not contain enough glutamine. Generally speaking, it’s around five to 15 grams of glutamine per day. Now, most patients can tolerate five grams, no problems. I had a patient just this week email me to say that they had then gone on to increase to 10 grams, and their neurological issues started going through the roof. So we’ve got that issue with too much glutamine. It can go down that pathway. It can be neuro stimulating, and can actually cause anxiety, rapid heart rates and other impacts like that. So yes, the research studies are actually saying five grams three times daily. But in a lot of patients, it’s difficult to get to that dose. If I really feel it’s needed, then I would be coming in with things like L-theanine, magnesium, or even NAC to counteract the negative impact of high dose glutamine.
Lindsey:
Okay, and you were talking about SB, that’s Saccharomyces boulardii, right?
Dr.Brad Leech:
That’s correct.
Lindsey:
Okay, I find that that’s a good ongoing one, a good probiotic to have for protection.
Dr. Brad Leech:
If you’re going overseas, great. Take it. If you might need antibiotics, take it. It’s a great product.
Lindsey:
Yeah, it was, it was on my kind of list of stuff that I always took, and so many other things found their way onto my list of things. I mean, I take 30 supplements a day because I’m just a giant guinea pig for everything, and everybody sends me free supplements. So anyway, it fell off the list. And then, I started having diarrhea. And I’m like, what’s going on? I need to go get some Saccharomyces boulardii.
Dr. Brad Leech:
Just go back with the old friend, great for loose stools. What I have noticed in some individuals, and this only happens to about 10%, is constipation. If you can take SB, in some individuals, you can develop constipation.
Lindsey:
Yeah, yeah. Okay. Well, this has been awesome. So much good information. I really appreciate your time and your knowledge sharing is fantastic.
Dr. Brad Leech:
And I’ve thoroughly enjoyed all the questions and all the topics we’ve discussed.
Lindsey:
Awesome. Thank you so much.
If you’re dealing with gut health issues of any type (diarrhea, constipation, bloating, SIBO, IMO, H2S SIBO/ISO, IBS, IBD, gastritis, GERD, H pylori, diverticulitis, candida, etc.) or have an autoimmune disease and need some help, I see individual clients to help them resolve their digestive issues or reverse autoimmune disease naturally, You’re welcome to set up a free, 30-minute breakthrough session to see if you’d like to work with me. I also have my own two products, Tributyrin-Max, which is particularly helpful for loose stool and diarrhea as it slows your motility and firms up your stool, and SBI powder, which is an all around gut pathogen binder, which is super safe and won’t harm beneficial bacteria, and is usually the first line of treatment I educate my clients about in order to avoid stronger antimicrobial herbs.
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