Probiotics, Prebiotics, And Gut Testing With Dr. Jason Hawrelak

Okay. Welcome to the podcast, Dr. Horlack. It's. It's an honor to be able to speak with you again after what's probably been a couple of years since we last spoke on a podcast.

I think it has been. It's great feedback, Alex.

Yeah. And I'm looking forward to our chat. We've got some sort of similar questions, I guess, in some ways. So I really wanted to pick your brain on maybe two different topics really. One a little bit more around the testing side of things and then one around the supplementation side of things. So it probably makes sense to start with kind of the testing and then we can kind of make our way into interventions from a supplement and perhaps dietary perspective. But one of the things that I really wanted to start with, if you're happy to, is around sort of stool ph. And when we have that within our stool testing, what are some of the things that we might want to be thinking about when we're seeing an excessively acidic or alkaline stool? Diving into the knitting gritty straight away.

Yeah, I like stool ph, and I'm glad that most tests just like, you know, more of the comprehensive digestive analyses are still doing it, but not all are, sadly, and I think we miss a bit of information, we don't get that. And I still like getting the, you know, shorthand, fatty acid percentages, et cetera, and the amount of butyrate. Like, I think those are still key markers too. But I think with people, ph helps put it in context because we know we can tell a few things from ph. One of the things is potentially transit time. In general, a lower PH is suggested, a quicker transit time and a more alkaline pH, a slower transit time. So we can get a bit of data around that. Obviously the determinants of ph is really around short chain fatty acid production and absorption. So those things come into play there too in that obviously with, with a quicker transit time, you could have a more short fatty acid being produced but not absorbed so much. So hence when the fecal matter comes out, the ph is quite low. And you could also conversely have people that are producing a fair bit, but because the transit time is so slow, they're absorbing most of it and their, their PH comes out more, more alkaline, you know. And then obviously from. From a interpretation or production perspective, we're looking at, at, you know, fermentable substrates primarily are the core drivers of short fatty acid production. So that would be include a range of different fibers, mostly soluble fibers, prebiotics, resistant starches, Other industrial oligosaccharides and you know, sort of mist sugars, mist protein can also contribute a little bit as well, but far less than the other compounds that we mentioned. You know, so those things I'm always got the back, back of my mind when looking at that. And having someone's diet in the context of their ph is helpful too because you're looking at, okay, does it make sense in terms of their fiber load, their fermented of substrate load, in terms of what the PH is telling me? I would always look at the PH in relevance to their bowel transit time as well. I always do this with patients in a very low tech way, inexpensive way of having meat corn on the cob or black quinoa or red quinoa or sesame seeds essentially not chewed. You know, they swallow that, they take note of when they take it, ingest it. And then we look for it in their poo, you know, when it first starts coming out and when it finishes coming out. And I think that is a very simple test we can do that provides so much information because I've had patients who are doing, you know, type four Bristol, you know, beautiful, perfect poo once a day, never miss a day. And it took them 10 days for that corn to come out.

Wow.

And if I hadn't have done that, I would have assumed is solely on the basis of one stool a day, type four stool, that they didn't have a slow transit time, you know, and then conversely, you've got patients who only poo in every three times a week. You're going to expect it to be slow. But I've had patients where it was 26 days before that corn made its way out the other end. And you're like, well, I knew it was slow, but I didn't know it was that slow, you know, so. So you're looking at ph, I think in the context of that transit time too, because the opposite of that is like six hours or four hours, you know, and if it's that quick and the PH is four or four and a half, you're like, yeah, that, that fits. And obviously a transit time issue. Things are moving through too, too quickly. So I think that's one thing we have to look at in relation to ph as well as their diet history or diet diary as well in terms of like optimal ranges. For me, I probably hear more that I prefer it a bit more acidic than I do alkaline. So for me, five to six and a half is where I'd be happiest and Anything from six and a half upwards, I see, is too alkaline. And we know that essentially those more alkaline or neutral environments are more conducive to the growth range of pathogens, bacterial pathogens, fungal pathogens, protozoal pathogens, et cetera. So really we wanted to shift the ph to keep it in a range where it's less conducive to the growth of pathogens and pathobions. For me, that's lower than 6.5 and sometimes even lower than 6. But it's looking within context of symptoms, signs of malabsorption, signs of failure to thrive or something like that. They're just not keeping on weight as well. Because you can have a ph of 5 on a stool test in someone that's immensely healthy, eating tons of fiber daily, lots of prebiotics, and I'm not worried. But if I have someone who's eating McDonald's and they're losing weight and the pH is 5, then I am worried because something's not quite lining up. It doesn't make sense. There's some, some pathology going on that explains that quick transit time, like celiac, for example.

Yeah. Okay. So, yeah. Am I right in saying that sort of, that the mal digestion piece is a factor here as well? So if there is kind of, sort of, I guess, partially undigested food entering the large intestine, then that can lead to excessive production of certain fatty acids or metabolites that pull ph down, or certainly that will.

CELAC is another perfect example here that they see that patient undiagnosed, it will tend to have a lower stool ph. And that's because they're malabsorbing things in the small bowel. More of everything in terms of sugars and things that otherwise be absorbed if the villi were intact or not. So they reach the colon and they get those extra fermentation compared to normal ph goes down more. So there's certainly a component of that present for sure. And I think it's something we need to have on our radar when the PH is low, of going, okay, what's the reason for that? As I said that, that, you know, my personally and I assess mine on a conference statistical analysis. It was like 5.2 or something like that, you know, was I worried? No, because I'm, I'm eating tremendous amounts of fiber. I'm intentionally eating things to nurture my gut ecosystem. You know, that's when I'm choosing any of my food sources. What am I feeding, what bugs in my ecosystem are Going to be well fed from this particular meal.

So.

And then I'm taking prebiotics on top of that as well. So you know, that would be totally normal in the context of me, but it may not be normal 5.5.2 in the context of somebody else, you know. So I think we have to be aware of, you know, normal, but then aware of what impacts that and whether it's a problematic outside the normal range or not.

Okay, no, that makes a lot of sense. So you've mentioned that you like ph as a marker. There are some other markers like butyrate status. Are there any other markers that sort of just quickly come to mind that you feel are particularly important? Just when we're thinking about, I guess, gut health or colonic health?

Yeah, I think the inflammatory markers like fecal calvitectin is key and that's just a good tool we can use to help differentiate between more functional conditions and pathology like ulcerative colitis or Crohn's disease or even diverticular flares, diverticulitis, for example, fetal carpeting will go up and that we can use that to separate from ibs, for example, or more functional causes of diarrhea, etc, that might be harder to discern solely on symptoms. But with that marker we can go, okay, it's definitely gross inflation present. You can still have mild inflation without much of a rise in calprotectin. That seems to be the case for sure. But when there's gross inflation present, then I think we'll see that rise in calprotectin. That's a good marker to have flagged. And I think things like fecal fat can be helpful too. And levels of protein putrefactive byproducts too. But again, you need to look at them in the context of diet because I think sometimes we get very fixed and going, oh my God, they're fecal fat. But they might be eating tablespoons of coconut oil on top of a higher, you know, relatively high fat diet already. And like that's it. It's not because they're necessarily malabsorbing anything, it's because they're eating train some mouse. And same with protein putrefactor byproducts is like, well if they're, they're eating a very protein heavy diet and then taking protein supplements on top of that. We know a percentage of protein gets malabsorbed in. If you eat 200 grams of protein versus a hundred grams, you're going to get twice as much reach in the colon where it's going to be putrefied, you know. So I think again, looking in the context of the diet as well as looking at the ecosystem too, and looking at things like stool ph too. Because another reason why I like lower stool ph is you prevent, it's kind of like you bring up the better behavior of certain microbes like Bacteroides, for example, which is one of those path of balance. Having the right amount is good, but too much is problematic. And having a more acidic environment tends to keep population down, which is good and I would say a healthier zone. But two, it brings on their better behavior. So they're not producing beta glucuronidase, they're not producing, they're not putrefying protein and you're not getting those protein putrefactor byproducts that are, are harmful, you know, so that's another. You look at ph when you're looking at things like beta glucuronidase and ph, when you're looking at protein putrefactive markers as well.

Okay, so just see if I can articulate this question. So, because I presented a webinar recently on hydrogen sulfide, for example, and obviously one of the things they talk about is the amount of sulfurous compounds entering the large intestine being a substrate for those sulfate reducing bacteria. So within the context of someone who is eating lots of protein and you're seeing elevated levels or high levels of putrefactive metabolites or products, is that always problematic? Would be my assumption. So even though they're on a high protein diet, it's still problematic. And therefore we would want to be thinking about either optimizing the digestive process or reducing the level of protein. Is that correct or yes.

Or as a third option is changing the environment in the colon so we don't putrefy any malabsorbed protein. And this is where prebiotics can come into play by changing the ph. So if we take something like lactulose, which is one of those for me, an unsung prebiotic that works very well for lowering clonic ph and it also prevents putrefaction of protein through that mechanism. And this is where it brings out the better behavior, as I mentioned before. So we can use prebiotics like oligosaccharides, lactulose, fructosaccharides to help prevent the production of those of those protein production metabolites as well as focusing on reducing the amount consumed. I think those are two key and I do think that when it's high it generally suggests that we are feeding species that are causing harm. Yeah. And their byproducts are causing harm. And you're right that one of the key things have been known a long time around hydrogen sulfide. Before anybody talked about hydrogen sulfide Sibo, we're talking about hydrogen sulfide production being related to protein and animal protein specifically. And there's research studies going back to the 80s and 90s looking at this, that there's some aspects of the hydrogen sulfide stuff that we talk about now that aren't new. Just was never put in the context of small bowel and never, never really outside the probably research sphere to reach where clinicians are at. But high protein diets, high meat diets, are always linked to high production of hydrogen sulfide gas. And when you start doing microbiota analysis, they're often associated with disulfavibrio population specifically, where that microbe tends to be a very good protein putrefier and who respond with enhanced growth when we give it more food, which in this case is the sulfur amino acids rather than, you know, sulfur from a range of other compounds, which can be problematic too, as you would probably be talking about as well. But I think sometimes we forget that the sulfur amino acids in meat can also feed, and do feed at least what that one species of hydrogen sulfide gas producer, the other one, Bilophila, is mostly, in my experience mostly bile related and hence the name, like Bilophyla is bio loving, but the sulfur vibrio is the other other key hydrogen sulfide gas producer, which is much more related to protein in my experience.

Okay, brilliant. And before we kind of, I guess expand on the pro prebiotic topic, are there any other markers that, that come to mind that you like to see?

Gosh, I think those are the ones that pop into my head at the moment. You know, obviously I'm looking at levels of microbes too, and I don't know if you want to expand it to look at that, but there are certain, you know, and even maybe delve a bit more with short chain fatty acid percentages, because for a lot of people they're always in the range and you don't really pay much attention to it until you get one that's really out of the range. You know, and I would say kids on the spectrum, autism spectrum disorders, there's a percentage of them that have extremely high Bacteroides or extremely high Prevotella as really dominant members of their ecosystem. And those two genera are key propionate producers. So in these kids, you'll often see this altered short chain fatty acid ratio where propionate will be excessively high and then butyrate acetate will be low, you know, whereas. So there'll be so many patients where it's like oh yeah, it's all no range or slow little tweaks in there. And there's others that are like really this is a really important tool that provide data around what's going on for them. Because we know that there's, you know, a number of animal studies showing that X is propionate, you know, alters how the brain functions and causes autistic type behavior in those animals. And that high prevotella or high back to woodies is problematic. And that subset of people and that do seem to have an overproduction of propionate that's problematic. And generally low production of butyrate as well, which we know that all the wonders of butyrate. So that's the other thing you always look at is the amount and how much because you go back 20, 30 years, people are talking about beady being so important for gut health and colon health and the main food for colonocytes. And that's also true. But what's expanded upon that is the fact that it's, it has so many systemic effects. Healing up a damaged blood brain barrier, decreasing neural inflammation, helping nerves regenerate, helping blood sugar regulation to work properly, proving insulin sensitivity, decreasing body wide inflammation, just to name a few things that has far reaching effects in the body. It's an amazing thing that we should ensure that our patients are producing enough of because really only when we produce an excess to what our colonocytes are using that you have a chance of it reaching systemic circulation and then going elsewhere. And if we're just producing a little bit, then our colonocytes are essentially going to grab all of that and you're not going to get the systemic benefits that we were just talking about when it comes to butyrate.

Okay, interesting. And on that certain regards to sort of gut integrity, I guess a couple of trendy bacteria that I thought I'd pick out around Akkermansia and Faecali bacterium. I think as a combination they can make up is it something like 10% of the microbiome? There seems to be very prominent organisms within the ecosystem.

They're big players. It's a funny thing because we're often talked about things like lactobacilli and we've talked about that for a long time as functional medicine, naturopathic practitioners, but it makes up 0.01% of a healthy ecosystem. It's a really small player, but we were able to grow it a long time ago, you know, and it's also lactoir, commonly found in fermented foods. So it's been, you know, we've talked about it for a long time, but it is a really small player. Then you have something like faecalobacterium that can be anywhere between 5 and 35% of someone's ecosystem. Prostnit CI, you know, and I would argue that 10 to 15% plus would be a better percentage than lower than that because we know it's a key butyrate producer for many of us. And it also produces another anti inflammatory gut healing compound besides butyrate as well. So, you know, it's sort of healing the gut in two different ways. And then Akkermansia, I would say typical levels are like, you know, 1 to 3%. And so you kind of wanting it to be in the zone. And it's not, because you do see people where Akkermansia is raised. And this is something that I've noted over years of experience, more so than what's in the research. But high levels, akamansia are often associated with gut inflammation. And it's not as a cause of gut inflammation, but as a consequence of gut inflammation. Because when your gut is inflamed, it produces mucus. What is the main food source of Akkermansia? Mucus. So if you make more of it, it feeds it up. So you get some patients where their akromansia is like, sometimes it can be as little as 6 or 7%, and you're like, okay, this is kind of double where it should be. Is there a reason why? Yeah, other people be 10 or 12 or 15% or 20%, which is much more rare. But again, for them, when it's that high, we'll always do a fetal calcitectin. Okay, is there some pathological level of inflammation being present or is it more mild? Generally they'll have mucus in the stool when you ask them about it, but not always, but they often will. And I've also seen that sort of slightly raised or slightly elevated Akkermansia being associated with hydrogen sulfide gas issues.

Okay.

And again, you know what hydrogen sulfide gas in excess amount is doing? It's causing colonic inflammation, you know, dysfunctional colonocytes, et cetera. And I think it's your body's pretty smooth amicus to deal with that. And then you end up with this raised Akkermansia. So it's an interesting clinical observation. You know where you're going, okay, the hydrogen sulfide of Bilophylla is high in Akkermansis also get raised too. And that's just like, really just signifying that inflammation is present. So it's not like we're targeting. Well, we need to get that Akkermansia down. No, target the inflammation and then Akkermania will come down.

Yeah. Okay.

So in accord. But it, but it is seen as one of those key species whose job it is, is to look after gut integrity. And by doing that, health with blood sugar regulation and metabolism and body weight regulation.

Okay. So it's really through the integrity of kind of the gut lining that it's having that more systemic benefit primarily.

I mean, I think there is research ongoing now to trying to tease some of these things out, because even I think some, some research in Europe showing dead Akkermansia can help improve, you know, blood sugar regulation too. So there might be more to it than that, but it certainly is seen as a pivotal role that it's playing. You know, just like for me, when you start to take on board the concept that the microbot is part of us and can't really be separated from us, it's like, you know, our neutrophils have a specific role. Well, our Akkermansia has a specific role too. And that's around gut integrity. And if we take that away, you get much more problems with leaky gut, for example, and the flow on consequences of having enhanced intestinal permeability. And it's not that unusual to find patients who are lacking Akkermansia through to dietary things that they've done for years into a western diet for long periods of time. But primarily lots of antibiotic usage, which again is something that we as Westerners are way overexposed to in our lifetimes.

Yeah. Because Akkermans are in our testing, we see it very low a lot of the time. So you obviously mentioned antibiotics and long term dietary habits here. From a dietary perspective, what are some of the things that we might want to be sort of consciously including to try and increase the population of this bacteria?

Yeah, and I would say it probably breaks into two categories. One category would be polyphenols. So that would be like the red compounds in cranberries or, or pomegranates or red rice or raspberries or strawberries, you know, so when I'm trying to enhance populations of Akkermansia, we focusing on nurturing that ecosystem via having more red polyphenol rich foods and more other multiple colors too. But I think the research has been pretty consistent with red polyphenols and dragon fruit. Absolutely love dragon fruit. So and we, you know, you can, they can get that as a freeze dried powder and it's just an amazing vibrant pinky red color. Or at least here in Australia we can get in the is fruit frozen section of our supermarkets too. And if you're very lucky you can in the warmer parts of Australia you can grow it very happily too and eat it fresh. But I think there's those sort of vibrant reds tend to help fit feed, feed Akkermansia. And same with fruit oligosaccharides that you find in onions and garlic. You know, chicory roots, burdock roots, some things that dandelions, some things we don't eat much of these days. But onions and garlic, asparagus, Jerusalem artichokes are things we do have a bit more commonly in our dietary protocols that do nurture that species as well. And it does seem to me quite responsive to Indian floss. Whether that is as a dietary form or as a supplement. To me that is the most consistent intervention to help with Akkermansia population. If our patients can tolerate those eating those foods or having that as supplements, then it generally almost always, I would say almost always because you know, I never want to guarantee anything but it generally almost always works for bringing out backrooms populations if it's there, you know, because some people it's extinct and you can try to bring it back, revive the population, but it's not there.

Okay. Yeah, it's got me thinking really because obviously a lot of people are coming to us because of chronic digestive issues and obviously onions and garlic being probably in our experience two of the most common problematic. So there's this kind of double whammy almost ultimately or at least that kind of the, the reactions that these people are having from a dietary perspective are then contributing to some of what we're seeing within these results.

Yeah, very much so. Because they're cutting out foods that increase gas production often. Yeah. And by doing that they not not feeding the B ray producers are not feeding the Akkerman, not feeding bifidobacteria. So their gut actually worsens because the ecosystem diversity worsens. Ecosystem numbers of the beneficial microbes that we want, like fecalibacteria, macromansia, bifibacteria. If we don't feed them, their population goes down. Feed them less, the population goes down. And as a consequence of that, our gut integrity Gets worse. Maybe our laxation gets worse, our transit time slows down, and then that might result in a bloom of methane producing bacteria, for example. Then that gets into a really horrible cycle where more methane, slower gut, which slows, it makes more methane, which slows down the gut even more, for example. And then they try to introduce onions and garlic and the constipation gets worse. They bloat, distension, pain, you know, it can be hard to come back. In fact, lots of our work is helping people come back from those. Those situations which, you know, I think inadvertently they may have cause themselves harm in the longer term by cutting out things that reduce symptoms in the short term.

Yeah, I'm so glad you said that because it's something I've been reflecting on for a while. This kind of idea of understandably wanting symptom resolution as quickly as possible. But the way to do that is kind of the opposite of actually what we need to be doing for long term gut health. And it's kind of getting that balance, I think, isn't it, between the two ultimately? So we're not creating problems down the road by trying to just get people feeling better in the short term.

Yeah, yeah. Because I think it can be easy to try to grab for a really restricted diet that will reduce bloating, will reduce distension, reduce abdominal pain, but the end result is a less healthy ecosystem that can be harder to refeed and kickstart after six months, then three months or nine months or 12 months. The longer you should eat that way, I think really the worse the inflammation level actually gets. And often in these patients, has been my experience. And the slower it is to get things coming back as well. Yeah. Because if you're feeding, what are you replacing it with? If you're cutting out onions and garlic and high fibrous fermentable foods, you're often, whether by choice or not, you might be probably eating more protein, you might be eating more fat, and those things often result in blooms of dysulfavrio and dilophylla, which we produce more hydrogen sulfide gas, which then worsens just ribosensitivity and causes more colonic inflammation. And then an even small amount of gas from that point causes worse pain and discomfort than it did three months before. But it doesn't cause acute bloating and distension initially. So you're like, yeah, my symptoms are much better, but you're actually making the gut more sensitive to everything. And it's beginning worse condition every single month that sort of passes on in that state.

Okay. Yeah, it's challenging, but it's probably a good sort of segue into the role of probiotics and prebiotics in some of these sorts of conditions. And I think one of the most common questions we get certainly is around sort of the single strain versus multi strain arguments or essentially just query. But also I think, and I'd be interested in your thoughts on that from like a prebiotic perspective as well. You know, often we're using single prebiotics, so phgg or gos. And I wonder whether actually we should be thinking about more broad spectrum prebiotics as a way to kind of really work on this, because are we potentially contributing to issues in the long term if we're using individual prebiotics that are obviously feeding specific populations of, of an ecosystem?

Yeah, it's a good point. I can think of one patient who had been on low fodmap diet for a time. He could tolerate, oh man, it's been a while since I've seen this patient. So maybe you could tolerate gauss. Okay. And that. And we were doing that to try to counteract some of the impacts of restriction of other fermentable substrates. And what we from stool testing was like, yeah, we were able to feed as bifidobacteria and maybe faecalobacterium, but nothing else. Like diversity didn't improve. You know, like there's a bunch of parameters that we look at from ecosystem health that didn't improve, but we did increase a couple of marker species, which was better than not, but it was limited. And I think with most patients I work with these days, and looking mentally thinking back about the treatment plans I've written the last couple of weeks, I'm often doing three different prebiotics for these patients. Not at once. Generally because the patients I work with, their guts could not tolerate that. We might be starting off with a little bit of PHDG. Some of these patients, it might be a 20th of a teaspoon or 16th of a teaspoon and then slowly working their way up. And then once they're up to therapy dose, you might introduce laxulose. Once they're up therapy dose, we want to introduce glycoligosaccharides. So it's not unusual for me to use two or three prebiotics to ensure that. I think that we're actually feeding a wider range of beneficial species. And we're lucky that we do have things like partial hydrolyzed gorgon that can feed a range of butyrate. Producing species, for example. And then we've got something like lactulose, which can feed faecalobacterium, achromansia and bifidobacteria, none of which probably are that well fed. But from PhD it has a little bit of impact on bifidobacteria, but not really on faecali bacterium or Akkermansia. So between that you can ensure you're feeding maybe, you know, 10 different species, which is not too bad. And at the same time you're trying to slowly enhance the diversity of someone's diet and maybe you're starting off with a bit of polyphenols or supplementations with things like green tea or with dragon fruit powder, you know, some little, little steps. Again, we're talking about more sensitive patients here that we have to go slow and we're trying to increase the diversity because really we know that the best way of increasing diversity of the ecosystem is a diversity of plant foods in one's diet. You know, that that is, you know, yes, getting exercise, adequate exercise is important. Yes, getting seven hours of sleep is important. Yes, modifying our stress. And I'm not trying to belittle any of those things because they're all key things we need to be doing. But we know that just feed, providing a water diversity of food sources results in feeding a wider variety of microbes. It just, it makes total sense and it's true, you know, so at the same time that we might be starting off with prebiotics, we are at the same time trying to slowly or maybe have to delay work on the background stuff to make sure we're nurturing a wider diversity of microbes as well. But perhaps by targeting the bead ray producing species, by targeting bifid bacteria, Akkermansi, we speed up the gut healing process which then facilitates the broadening of the diet afterwards. That's certainly the approach that I work with.

And as you were saying earlier, I guess, you know, the, the whole polyphenol aspect is kind of is prebiotic in nature ultimately as well. So the more from that perspective as.

Well, they tend to be less gassy, you know, so, so we can often get away with polyphenols in some patients that we can't do oligosaccharides or lactulose, that indigestible disaccharide because those tend to be more gas forming. Now, partially hydrolyzed guar gum is a bit of a exception for many patients, but as you would know, not all, you know, but many people tolerate that beautifully. At the therapeutic dose and have a decrease of intestinal gas. But you do get the occasional one where they will get the opposite. Whereas polyphenols generally don't have those same gaslight issues to consider.

Okay, perfect. And on the concept of probiotics and sort of single strain multistrain within that, we also get this kind of query around. My lactobacilli has been shown to be low. Should I not be sort of supplementing a lactobacilli probiotic? This kind of very much. Let's just replace what's lacking concept. So is there anything that you kind of, I guess expand on within these considerations?

Yeah, I mean, I think there's a couple things there. Maybe we'll start off with the latter. I think if you go back and start looking at probiotic research, the 70s, 80s, 90s, beyond, it's a pretty consistent pattern that probiotics given as supplements or as a food source or in yogurt base do not permanently stay. They're temporary colonizers. So they will be there for a week, two weeks max. And some, some research you can look at in two days. Afterwards, it's gone, it's gone, it's gone out of your system that quickly afterwards. So if you are lower lacto sili, you know, really taking our current generation supplements is extremely unlikely to actually permanently colonize. Extremely, extremely unlikely. You know, based on the research data that we have and I could say working with tool analyses over the years too, that that's very true.

That.

Yes, well, they're taking it. It shows up in this tool analysis. You stop it for two weeks beforehand, it's not there. If it was, it didn't have indigenous populations. So for me, I'm always trying to work with enhancing indigenous populations as much as I can rather than focusing on replacing lack of bifidobacteria. Because I don't think that's really what would occur if you were even trying that. Yes, we can temporarily have microbes come and take that ecological niche, but they don't stay, you know. So I think it is important to keep that in mind. Single strain, multi strain. I think the reality is that the vast majority of researchers use single strains and it works. They work for a whole wide range of conditions. Now are there conditions or are there probiotic supplements where they combine product formulations that have multiple strains that work in a range of clinical conditions too? There are, but I would say there's no hard and fast rule about multi strain being superior to single strain. This was one example. I can think of let's look at antibiotic associated diarrhea. There's a study, it was actually done in the UK where they gave 60 billion CFU per day of four strains of bacteria, two bifidobacteria, two lactozilli to an older patient group in hospital to see if it would prevent and ruckus Fisher diarrhea didn't work. You know, no change. And yet we have another study that used 100 million bacteria of one strain, lactopilis reuteride. DSM17938. Yeah. 300 times less bacteria, single strain, similar population, older age, people in hospital taking antibiotics and it worked amazingly well for preventing antibiotic associated side effects. You have this examples like that where the right strain with the right attributes gives us the effect we're after. But if we don't match the attributes of what we're after from a probiotic strain perspective to what the action we're after, we're not going to get the result that we want. That combination that didn't work for antibiotics. Fish and diarrhea does have some research for irritable bowel syndrome. It doesn't mean it's not useful at all, it just means it's not useful for that task yet. We know that the DSM 17938 is great for a wide range of things, but there'll still be a condition that it's not helpful for as well because it doesn't have the right traits, qualities or actions to help with that. So for me it's, there's never going to be clear answer of multi strain versus single strain. It's like what are, what strain has the right action to help in this case. And sometimes I do want to give people multiple strains, but to be honest, I will often give it a separate supplement to be, okay, well, I'll take this strain with breakfast and take this one at, at lunch. And the reason why I generally tend to try to separate them when I can is to prevent any chance of antagonism. And you might go, well, truly they're going to be synergistic. We can't make that assumption because there is research showing they're not always synergistic. When we put them all together into a single formula and if we're using a preparation that hasn't been clinically trialed and shown to work in that combination, even if you have strains that worked individually, there is the potential for synergy and there's the unknown potential for antagonism there. But we don't know. And our Patients work as a guinea pigs in that case, but because we're doing so many other things, it's hard to go for sure to see one way or the other. In general, I prefer to give single strains or listen, I might give VSL number three or I'll use Bio Cult or something where it's a clearly trialed combination that's been trialed in that exact formula. And then we give that we know what the results are going to be versus going, okay, well, I'm going to give a range of different random things putting into a supplement that's never been trialed before and hope that it does something. And it's like, I think hope is the best you could do in that case. So I really rely on the research when it comes to that. And as I said before, so there'll be good research for specific combinations, good research, specific singular strains. And for me, I want to err on the side of caution because we know the effects are definitively there when given separately is I will dose them separately.

Yeah, okay, that makes complete sense. So because at HealthPath, what we do is we've got a couple of symptom surveys for our clients around the severity of specific symptoms and we ask them open questions around just their health medical history and things like this. And then obviously we've got the more objective data from stool testing or SIBO testing, et cetera, and we're using both sets of data to then make health programs and recommendations. And I appreciate nothing black or white in this world, but as a general concept, would you, based on what you're saying there, and the way that we've kind of thought about this is we can often recommend probiotics when we're thinking about the outcome that we're after or the symptom that we're looking to improve. And prebiotics might be more recommended based on test data if we've got populations that we're looking to actually increase. Would you say there's some truth to this?

Yeah, I reckon, definitely. So. And I hadn't really thought of it that way, but I'm pretty sure that's how I tend to use the probiotics, not really based because their impact on the ecosystem in the Savage Ecosystem is pretty minor. There's some little tweaks to an ecosystem with some probiotic strains, but compared to the impact you get from changing diet, compared to the impact you get from taking a prebiotic supplement, the impact is extremely minor. Now, that doesn't say, doesn't mean it doesn't in a Very disrupted ecosystem. Post antibiotics or post chemotherapy, post radiotherapy, probiotics can play a very useful role for helping to reestablish a sense of balance in that situation. But their impact on the ecosystem. Yeah, so I tend to use them much more targeted based on symptoms or disease label. And I'm using prebiotics to alter the ecosystem and dietary tweaks and polyphenols, etc. To alter that ecosystem to more optimal levels within all the flow and effects that come from that.

Okay. A question that came up earlier was you've mentioned that the studies clearly show us that probiotics from two days to two weeks after we stop the course aren't detected anymore within stool testing. Is there any data that's looked at like systemic markers? So I know there are studies that have seen crp, so inflammatory markers come down with the use of certain probiotics. Do we know whether, although they don't colonize in the gut, that the actual kind of more systemic impact they're having is something that remains, if that makes sense.

My take on the literature would be no. You might get some longer lasting impact like a week, two weeks after cessation of use if you've been on it for a while. But if you haven't treated the underlying issue of why that's occurred. And now maybe the probiotic has like, listen, like, maybe if you've got, I don't know, let's say you've got an overgrowth of a particular strain of E. Coli or something and that's increasing your, through the release of lipopolysaccharide has increased your systemic inflammation. Your CRP goes up. All right, and, and that specific probiotic you ingested decreases E. Coli and, and maybe to the point where the ecosystem consider doing other things that come into balance and it keeps it low and you're like, oh yeah, it's fixed it. But I would see in general that they would be, I see them a bit like her medicines, listen, that they work when you take it and they stop working when you stop. Now I sometimes when I'm treating patients for depression or anxiety, the impact doesn't stop the next day. They stop taking herbs. You know, like sometimes it will take three weeks before their symptoms will start surfacing again. Then we'll go back on that Hormix knowing it's still needed at that time point. So you still have this sort of effect. And I think with probiotics it's often they might be working for so many different mechanisms, one of which is decreasing inflammation and Then it's going to take a while inflation levels to come back up. We know bacterial populations might stick around for that strain for seven, 10 days, two weeks, closer to two weeks before it goes down. And then whatever it was suppressing will start coming up. But I think that there have actions where we take them and they stop and we stop taking them in general unless we're using it to. You know, I can always think of these exceptions here too. We're thinking of the high methane and we've got again, research on lactose reuteride, DSM17938 can help decrease methane production. Now, if that's all you did, I'm pretty sure that when you for four weeks and you stopped it, methane would probably come back up. Now maybe if you're on it for six months like I do, think the ecosystem can recalibrate.

Yeah.

And settle into a new pattern and then you can stop it after six months and you wouldn't get that resultant bloom, come up with methane back to the original point. Now, hopefully as a clinician are doing other things to help address that hiding thing besides giving that one thing, in which case you stop the probiotic. Again, it might stay low. But I would say in general you're better off thinking of probiotics working in that way.

Okay. No, that makes complete sense. That idea of that to me comes back to this idea of kind of resilience and thresholds that sometimes, as you say, we can recalibrate physiology to that new kind of set point. I'm putting you on the spot a little bit here, but you've kind of brought up methanobrevibacter and methane. And I've been trying to get my head around this a little bit recently, especially with the context of redox status. So I've seen studies in severely malnourished children in Africa, for example, whereby they have undetectable levels of methane brevibacta and sort of there's been a shift in the microbiome as a result. And that's one of the kind of consequences. But I'm wondering if you, if you've seen or what your thoughts are in regards to elevated methane levels. Because it seems to me, at least there isn't necessarily an obvious underlying explanation sometimes and there's been this bloom in methanogens for some reason. But do you have evidence or do you have your own kind of, I guess, thoughts based on what you've read around some of the things that might contribute to these blooms? When we're seeing methane and breath testing sometimes at 180, 190, 200 plus.

Yeah, great question. And I think it's. It is a paucity of research studies in this area to help fill in gaps. And I think this is where your clinical aspects come in and going take. You take enough case histories, hear people's stories enough, and you correlate with, with test results, you start looking for seeing patterns. And for me, in terms of high methane, I've seen it is as we know, associated with slow transit time.

Yeah.

And it's like, okay, well what was there initiated event for that? So for me it's like opiate use is one of those things that was often triggered. Food poisoning, travelers, diarrhea, again, not surprisingly, takes that box. And I think again, that caused a dismotility which then allowed the methane that was already there. And I think best research suggests that methane producing species are there in 96% of us. It's just that for a good portion of us, there's in the right amount that, you know, again, it's a microbe. You don't want. You don't not want. You want to have some methane being produced. You just want to have a lot of methane produce. Is really my, my take on it. Somebody, even hydrogen sulfide is that our body can detox a little bit of it. A little bit probably. Okay. But to us, you go above a point, it's problematic. Methane, I think there's probably a wider, potentially wider range there, but alcohol use as well. And again, alcohol slows transit time in larger, larger amounts. Yeah. So those are things. And even antibiotics, I would say are things that I've seen as turning points where someone would be like, okay, my gut was going along fine, maybe I got occasional constipation, you know, and then this event occurred and then my gut's never been well since. And I can't help but see that dysmotility running as a theme through that and maybe an inflammatory event in some of those cases that then, you know, maybe damaged nerves within again initially caused a disposal which then allowed, you know, maybe methane methanobreviracular was on the cusp of being too high. And then it's like, oh, great work, you know, slower transit time ph because more, more neutral to alkaline. It's like starts blooming, produces more methane, which then slows down the gut even more. And you get that sort of cycle that many of our patients are in.

Okay, interesting.

Not sure if you've seen similar things with your patients in terms of patient stories. And anything.

There's one that kind of aligns with research in regards to eating disorders. So I've definitely seen a fair few people with a history of an eating disorder and we're seeing pretty high methane in breath testing or stool testing. And that's one that really stands out for me. And then I had a theory because obviously people talk about food poisoning and hydrogen dominant SIBO with the intestinal cells of Cajal and that kind of whole thing. But the research around sort of competitive elite cyclists compared to amateur cyclists, and the competitive cyclists had high levels of methane in breath and stool, but weren't competing compared to the amateur cyclists. And the authors kind of theorized that this was partly related to the fact that these archaea can extract a greater amount of nutrients or energy from the food. So is it kind of a metabolic adaptive response that has happened? And then you've got the, obviously the obesity and the eating disorder like anorexia nervosa, both have been found in some studies with elevated methane. Different authors who theorized similar things, certainly with those with anorexia, this is obviously just because they're not eating enough, is there? And it's this sort of metabolic response to try and get as much nutrition as possible. So then I, if you've got anything which is creating a sort of an energy deficit, could there be this kind of adaptive response over time that starts to occur and then obviously about a food poisoning causing significant issues with transit malnourishment, maldigestion, could then that feed in somehow in some people.

Interesting thought. Yeah. Yeah, I like where you're going with that one. Yeah, makes sense.

And then I think that those are kind of the main trends that I've seen, but certainly I think just a lack of eating is a big one. So maybe sort of undiagnosed eating disorders as well, or people who have had digestive issues have got onto such a restrictive diet over time trying to fix it, and now we're potentially seeing really high methane.

Yeah, I reckon that occurs for sure.

Yeah. Which takes us on to maybe, I'm mindful of times the kind of a final thing just to maybe finish with, which is. Although I guess we were talking, thinking about the new nomenclature around intestinal methanogen overgrowth, returning to kind of true sibo where we're seeing maybe high hydrogen levels within the breath test. What's your thoughts on probiotics within the use of sibo? Because again, another common question we get from our customers is if I've already got a bacterial overgrowth, why Am I. Why should I take bacteria to deal with this?

Yeah, this is an interesting area and I think because of my background, which was I did my PhD looking at irritable bowel syndrome and the role of dysbiosis in irritable bowel syndrome. This was back in early 2000s. I started my research studies. Essentially 2000 honors for PhD was a subsequent number of years after that. I was looking at all the literature around dysbiosis, irritable bowel syndrome, and also looking at tools we could use to help patients with ibs, which were probiotics. Even back then there was positive studies of IBS going back to the 1950s, positive clinical trials showing probiotics to be helpful for treatment of ibs. Yeah. So when this first, this concept of SIBO being the cause of IBS came out, it was like, okay, well, if it is, if 80% of people with IBS have got SIBO, then we already know probiotics work in ibs, then obviously probiotics are going to work in sibo. That's certainly the mindset I had when I came to it. And also because probiotics don't just sit there like, there's some probiotics that produce antimicrobial compounds that will target things that are growing, others that actually help with motility. So I think again, when you look a bit deeper about the actions that certain probiotics have, of course they're going to be helpful. Yeah. I think if all you do think is they do is just sit there and then produce gas. Well, if that's all they did, then they would be harmful, I'm sure. But that's generally not what they're doing there. But again, I think it's choosing the right ones that are targeted is. It's the way I certainly looked at it. And, and if you look at the research data around probiotics and ibs, consistently positive, you know, a number of meta analyses over the last 15 years. So this essentially found similar things. The number needed to treat of like four or something like that. Whereas looking at even, even I think refaxment for IBS, for memory number, need to treat of 11. You know, you need to treat a lot more people with Fraxman versus probiotics. So it was already superior to rifaximin there. But then if you look at probiotics in the treatment of Sibo, again, the clinical trials are consistently positive. Now, does every single probiotic strain work? No, of course not. If a strain doesn't have the actions that you're after, it's not going to be helpful, but the data suggests pretty consistently and there was a systematic review in meta analysis that got every single study the impact of probiotics in sibo, it's called combine the data together and I think it was like a 54% cure rate in terms of normalization of breath values with probiotic administration. And then they looked at drop of hydrogen. I think it was like 36 parts per million drop of hydrogen gas production with probiotic administration. I think the research data certainly suggests that probiotics are helpful. And I think when you start delving in more deeply into the specifics, you might see which strains are more helpful because I do think there's some that are better for methane, some that are better for hydrogen. And for me, those are the things that I kind of certainly look at because we're often differentiating between methane overproduction versus hydrogen overproduction that are there. But from an evidence standpoint, it's very clear they're helpful. Now, does that mean that every single patient you have will tolerate any probiotic.

That you give them? No.

And I think this has been part of the issue too. And I think you could trace this back to potentially a few issues. One would be potential of some probiotics containing inulin phos, for example, as a filler or as intensely put there that might increase gas and cause acute symptoms when you ingest it. So I think there are some people who might react to that amount of inulin faucets in that particular supplement. And I think for others it could be potentially. We know when we do market basket, market basket surveys of probiotic products, there's a number on the marketplace that don't meet label claims and some are even spiked, so accidentally contain pathogenic species as well. And it's like, okay, well if you're using no strain detailed probiotics from a random supplier, well, you're not sure what you're getting and maybe you're going to get some enterococci or something that's actually more problematic and pro inflammatory versus strains that we know are clinically helpful and useful and not harmful. So I think there might be some that are reacting to things like that and I think others it might be more complicated, complex. And I think I'm just going to tease out the odd people that do react to probiotics who've got sibo. And I do think sometimes their hypothesis might be around leaky gut being quite leaky and you know, bacterial bits entering the system or even bacterial metabolites like potentially Lactic acid. And I don't want to harp on too much about lactic acid because I think in some circles it's blamed too much for things that I don't think is relevant for. But, but I think for some people, a small percentage that might be an issue as well. And I think those, what I call outliers often change the narrative.

Yeah.

Because they're posting on, on all the forums. Ah, probiotics made my symptoms heaps worse. And maybe the 50 or you know, the other 18 out of 20 who took probiotics and these are better don't. Aren't posting because they're feeling better. There's no need for them to be on that forum. You know, things like that that I think sometimes we can get a skewed interpretation of the. How common some of these more what I would say uncommon consequences or side effects of taking supplements are, which can kind of skew our narrative more broadly speaking as well as well to me as a lack of understanding and I think even goes back like if you read through so the original book like the IBS solution by Dr. Pimentol, it's like he was, he was so anti probiotic in that book, you know, and this is probably the time when I was like, I'm read all the probiotic studies, like all of them, and it's like you're not representing the data remotely accurately here and you're promoting Rifaxim, which actually has less data and less efficacy rates as something superior. So, you know, for me it was like things like that that came out at that time. That again also helps skew the narrative around it that I think sometimes it's hard for those stories that come out initially to get properly busted because they get repeated again and again. Then it's gospel, like don't use probiotics for sibo. And it's like, what's that based on? Certainly not research.

Okay. And you've answered my. What was going to be my final, final question around sort of these reactions. But just to expand on this, because a common narrative that we see is, and I'm not quite sure where it's come from, but it's histamine. And people reacting to probiotics might be having sort of some sort of histamine issue. I'm not sure what your thoughts are on that.

I think you're right. I think it does happen with some people. And again, I think leaky gut is certainly is very much the case with most of these people, if not all. And I also think they Often have very slow transit time too, which I think is perhaps adding to the reabsorption of of compounds. And the more further breakdown of histamine precursors to histamine and then greater absorption because the transit time is slow, that I think both those things are playing a role with that. And I think one of the issues that there is around this area about probiotics and histamine is that there's not much good research there that most research has been done in like wine going, okay, what probiotic can we add to wine to make less histamine? And then people go, oh look, L. Plantarum makes histamine or El Castilla doesn't make histamine based on this wine study. Then extrapolate that gut and there's a few issues there. One is around the strain specificity that even if that strain of Lacto plantarum in that study does or doesn't make histamine has got nothing to do with the one, that you're getting in another strain even within that same species. And I think people often extrapolate that across too much. And two, that also means that really in terms of the strains that we're consuming often don't have the research done on to know whether that specific strain has the capacity to produce histamine or not, because it is very much a strain specific trait rather than species specific trait. When you again, you dig into the probiotic research in greater detail and as I said, most of the research is around what can we add to wine to make less histamine in that wine rather than how can we use this therapeutically in some way or how can we limit the harm of histamine overproduction from acidic probiotic strain. They're not. Researchers aren't looking, haven't been looking at that so far.

Okay, interesting. Yeah, I must admit I'm glad you said that because sort of trying to do a little bit of research around sort of histamine probiotics is there. I certainly didn't come across much quickly.

No, it's mostly around that truly it's like around balcony make wine more tolerable participant reactions. Will it affect the flavor of the wine? You know.

Brilliant. Dr. Horlack, thank you so much for sparing some time to come and speak with me. I think, I think this episode will be incredibly popular and hopefully really helpful for a lot of our listeners as well. So thank you very much.

You're welcome, Alex. Great. Touching base. Again, good chat.

Likewise.