Mapping Probiotics with Dr. Jason Hawrelak #118 | 15 Minute Matrix

Hello, this is Dr. Jason Horlack and today we'll be mapping probiotics on the 15 Minute Matrix.

Welcome to the 15 Minute Matrix. I'm Andrea Nakayama, functional medicine nutritionist and your host. This is the podcast that brings you bite sized insights and lessons on how to use the most important tool in functional medicine and functional nutrition. Today on the 15 Minute Matrix, I'm pleased to be speaking with one of my very own teachers along the way, Dr. Jason Horolak. Dr. Horolak is a research scientist, educator, naturopath and western herbalist with nearly 20 years clinical experience. He did his PhD examining the capacity of probiotics, prebiotics and herbal medicines to modify the GIT microbiota and has written extensively in Australian and international textbooks and journals on these topics. He is on the Medical Nutrition Council of the American Society for Nutrition and is a fellow of both the American College of Nutrition and the Naturopaths and Herbalists association of Australia. Dr. Hall Relak is currently the Senior Lecturer in Complementary and Alternative Medicines at the University of Tasmania's School School of Medicine in Australia where he coordinates the evidence based complementary medicine programs. I can't wait to get started talking about one of my favorite topics, probiotics. Doctor Horlack, welcome to the 15 Minute Matrix.

Thanks Andrea. It's a pleasure to be here.

I, I am super excited to talk about probiotics. It's something that we all have a fascination about and I think a lot of confusion around as well. And I want to talk to you about species but the first thing I want to do is just ground on a definition. How would you define probiotics?

Probiotics are live microbes that when administered in adequate amounts confer a health benefit. But that's probably the most concise, clear definition that we're using currently.

And then when we start to look at what they are. Are there certain species that are commonly used in the supplementation area? There are things we should be looking.

For, Yeah, I mean, I think definitely and perhaps it's a matter of chance in some ways that the species that really dominate our supplements at this point are Lactobacilli and Bifidobacteria. Those two genera make up the vast majority of the the species that make up probiotic supplements at this time point. Now this is changing and that I think in 10 years time we're going to have probiotics that are derived from Faecalobacterium, from Akkermansia, from Roseburia, a whole range of other gut species that we now know play very pivotal roles in the gut and arguably far greater roles than what indigenous Lactobacilli do, for example. It's just a matter of time while we make that shift. And this has really got to do with technology. And also, as I said, sort of chance that some of the work that Metchnikoff did back in the early 1900s, he just happened to isolate Lactobacilli primarily from fermented food. And that started the ball rolling on the importance of Lactobacilli.

And when we look at the nomenclature to use, there's a lot of confusion around species and strains. Can you talk into that a little bit?

For sure. And I think that you're spot on there in that I think you often read stuff and even authors and research articles get species and strain completely confused. So it's not that surprising that clinicians get a bit tied up around this too. But let's look for example at that. You know, the prototypical probiotic species was Lactobacillus acidophilus. But then after that you'll generally have some sort of strain code which could be the LA5, LA14NCFM are all three examples of the strain coding. And we now know from research in the last essentially 25 to 30 years that the strain details are immensely important in terms of determining, I suppose, extrapolation from, from research studies and the way that you can often think about this, think of E. Coli as one species, but you've got the Nissl 1917 strain that has sort of got anti inflammatory properties, treats diarrhea and then you've got the EO157 strain that causes bloody diarrhea, kidney failure and death. They're both the same species, but they're different strains and they have different genes turned off or on. Now, thankfully, when we're working with lactobacilli or bifidobacteria, we don't have such an extreme end of things, but we certainly have, I suppose the extreme end we are working with is not functional, have no medicinal benefit. They die when they transit to the stomach and small intestine, to the other extreme of being extremely therapeutic. And that really depends not on species, but on strains. For most applications that we're working with.

As clinicians just to ground on this, there's these buckets of species and within the species there are these strains. And we might go to that realm of strain specificity when we're working with a patient with a certain condition.

Definitely, because we know that the characteristics that we want from probiotics in order to facilitate them having a therapeutic effect or the chance of having a therapeutic effect are what we call strain specific. So like gastric acid tolerance, bile salt tolerance. So will they survive transit to the stomach and small intestine? Not all types of lacroixyls acidophilus, not all strains have those characteristics, but some do. And the ones that do obviously have a chance of reaching the lower gut and interacting with our immune system and interacting with the microbiome in a different way than the ones that die in the upper gut.

Talk a little bit more about that because that's a question. I know that comes up a lot as we start to learn about how acidic the stomach should be, that there is this question of, well, what gets through there? So which are the strains that do get through the gastric acid?

Lots, just not all. That's the challenge.

Lots, but not all.

Yeah. And I would say from 1992, there's a pretty pivotal paper published where they first isolated at what we now call lactic pulse. And the researchers on this paper were golden and Gorbach. GG is where it came from. And they were the first ones, I think, who applied a much more scientific methodology about isolating and doing initial testing on probiotic strains before doing further research. So they got a healthy person's poo sample. They may have isolated, I think it was 100 and some lactobacilli strains from that healthy person's poo. Then they put them through an obstacle course. Which of these hundred strains could tolerate gastric acid, which could tolerate bile salts, which could adhere to the gut, which produced selectively acting antimicrobial compound, and which had good shelf life stability, that they could live at 20 degrees Celsius, which I couldn't tell you what Fahrenheit that is, but 70 something Fahrenheit without dying. And out of those hundred that they started with, there's one that ticked all the right boxes, which they named after themselves, gg. And now is the best research probiotic on earth. But from that time point, many probiotic researchers obviously notice that and go, ah, okay, we shouldn't just randomly take some lactobacillin that we find. We should do this initial testing first to make sure that they've got the greatest chance of surviving through the upper gut and the greatest chance of having a therapeutic effect when people consume them. So most well researched strains used in many probiotic supplements certainly meet the criteria of the basic criteria of survival through the upper gut. That's so true. You'd argue that some of the cheaper end of things don't necessarily have that data set because you can't see that all lactose do or all bifidobacteria do. Again, it's a strain specific trait. But if the company's done their homework properly, those traits will be assumed. Essentially.

Yeah. I think it's such a good thing to know and I think when we're looking at the left side of the matrix, what I call the story, it's pretty common to us these days that there are a number of things that would impact somebody having low microbial diversity from the get go. Certainly what their mom passes down. Even now we know more what dad might be involved with, whether they're born vaginally breastfed. All of these factors, I think we know impact how we come into the world with that diversity. Is there anything else that you have found that's quite novel that impacts us from the get go?

I mean, I think you touched on the main ones and I agree wholeheartedly. The import of that and the role that we as clinicians can play to alter that initial passing on and initial seeding and really, I mean the research around breast milk and its capacity to almost work as a seeding and feeding tool that can even get around some of the stuff that we'd expect from C section I think is pretty amazing and perhaps wasn't known so well before and flowing on from that to also the role of antibiotics around the birth process for that last trimester is huge. And obviously there's a time and place for them where they save lives that they need to be used. But I think there has to be a degree of caution with some consideration of long term consequences which I think has been missing in conventional medicine practice.

We're more and more aware of it now and I think we know that the antibiotics also become a triggering event throughout the lifespan as well as other pharmaceuticals, antibiotics in our meat and our water, which you may not be as subject to as we are here in the States. I don't know how bad it is in Australia. But what other triggering events should we be thinking about in relation to low microbial diversity?

I think you're right. It's proton pop inhibitor use and chemotherapy, radiotherapy and antibiotics I think are the core ones. And there's more research coming out looking at pharmaceuticals and their impact on the microbiota every single month. So this will get. Our list will undoubtedly expand from that. And I think there's even some, I think people who are on fiber restricted diets thinking about that range of plant foods that can also be a triggering factor for loss of microbial diversity, lowering levels of beneficial bacteria in the gut, and eventual extinction if they follow that dietary approach long enough. So I think we also need to be aware of that too. So there's a number of patients that I see further on in their health journey who have gone through some extreme dietary approaches and their microbiome has deteriorated the longer they've been on that dietary approach. And it wasn't necessarily in great state to begin with, but it's actually gotten worse from what they were doing in an attempt to get themselves better.

Yeah, it's so interesting that you bring that up, because we need the prebiotics to feed the probiotics, and people who are eating diets that are low in fiber are missing those opportunities to feed the microbiome. And there's a lot of things we can do, whether it's probiotic foods or polyphenols, all the things we do to feed the good bacteria when absent from the diet, deplete those stores as well. And like you, we see so many patients in our clinic that are depleting their diets because they're trying to get some control. These tend to be people with more severe GI issues. The ibs, ibd. Undiagnosed ibd. Constipation diagnosed, leaky gut or a perception of leaky gut. But probiotics are used now more and more for other health concerns. Where's the research showing us that we can be turning to the gut for, let's say, brain health, but a whole bunch of other things as well?

Yeah, this has been phenomenal. As someone that's been a probiotic researcher for nearly 20 years, we've really shifted from that very much gut focus that it was back in the late 90s, early 2000s, when I started to. You're looking now at this great human research showing probiotics can be useful for the prevention of gestational diabetes, prevention of postpartum obesity. The study that came out in 99 looking at probiotics to prevent eczema, and that was published in the Lancet, was groundbreaking at the time because it was probably the first well done clinical trial showing probiotics were useful clearly outside that sort of gut realm. And that really did open up the door. Probiotics for anxiety, for depression, Alzheimer's disease, food allergies, allergic rhinitis, obesity, type 2 diabetes. I mean, the list is ever growing and expanding. And I think it's just fantastic that we have this whole range of Tools that I think are often underutilized and certainly not utilized to their utmost, I'd say by many, many clinicians due to the lack of the fine knowledge around their use and the breadth of applications that probiotics actually have. I think sometimes we get really. Patients get stuck going, I only use this for people who have got dysbiosis or only use them post atomotics rather than going, okay, no, you've got a whole range of tools, a whole new materia medica open to us as clinicians and you look deep into that research. It's like, oh, I've got a whole new toolkit I can use that I wasn't aware of before.

Yeah, I think there's more and more awareness that we have to go back to the gut for some. So many foundational issues and especially, you know, for me as somebody who is in the realm of functional nutrition, we have to always think about where the food meets the physiology and it's in the gut. So we need that to be in optimal health and function. Let's get into the realm of mediators, what we do as clinicians. I know that you are a fan of strain specificity and finding the right strain for the job. And oftentimes I find we have to build diversity and get that fiber in and get like the environment or the terrain going. What's your take on that from a clinical perspective? How do you kind of get in there and do the job?

And I think you're spot on that I do strain specific probiotics for certain applications and actions that I'm after. But if my, if a patient comes to me with a very ecosystem that's lacking diversity, lacking levels of what we generally consider to be beneficial anti inflammatory species like Bifidobacteria akkermans, if you Callobacteria probiotics don't have a huge role there. In all honesty, in my experience and based on the research that we have, it is really about diversifying the diet with broader ranges of plant foods. So we tend to get. Sometimes we think of fiber as fiber as fiber and it's like no. Comes in all different shapes and sizes, which feeds different bacteria. So the wider variety of diversity of foods that we eat, plant foods, whole plant foods, the wider diversity of microbes we have the capacity of feeding and same with polyphenols, you're going with purple carrots and purple potatoes and you're trying to get as much color as you can and as many polyphenol rich foods as possible because again, 95% of ingested polyphenols reach the colon where they interact with the microbiota. Essentially they're worked as food sources. So I think that's the other key aspect of diversifying their diet from a color perspective from a broad variety of foods. And then I'll also use prebiotics to have a much more targeted impact on that ecosystem. So if someone's low in bifidobacteria, low in Akkermansia, essentially I'll use a prebiotic like fructoligosaccharides or lactulose, which will specifically target those species and their populations will increase with their use, as well as nurturing the broader ecosystem with dietary approaches. And we mustn't forget lifestyle things too about exercise, adequate sleep, stress reduction, all of which we know that when out of balance, negatively impacts the gut ecosystem as well.

Yeah, there's some more recent research on sleep and how that impacts the microbiome and I think it's great to see these studies being done like we were talking about. Two more questions before I let you go onto your day. Start low, go slow tends to be my approach because I think a lot of people go too fast with strains that they don't know work for their system. What do you think about that and how do you work with dosing with probiotics?

It really depends on the population that I'm working with and that I recall in my for nearly 20 years and in the earlier days I didn't really have to go slow with probiotics and go with very tiny doses. But the population I work with now are often on the extreme end of sensitivity, who've tried lots of things before they get in to see me. So I concur with that. And certainly in the realm of prebiotic dosing these days, pretty much all my patients are in the go low and go slow camp that we start with very low doses and slowly build up. But it's amazing to see where we can get to even in some extremely sensitive patients with prebiotics, with patients and care around dosing and how much we can impact that ecosystem. Because I do lots of initial microbiome assessments and I do lots of follow ups, we can actually see how populations are shifting. And I think for patients it's wonderful for them to see too because it's like, okay, sometimes they'll feel better too. And that's obviously the thing we're really after. But it's nice for them, they want to see that objective change as that goes alongside the subjective changes in their Quality of life and symptoms.

Yeah, I love that. You know, it has to be bio individual. We have to work with who we're talking to and see what their body responds to. And the last question, and this is a biggie, but the whole topic is a biggie really. But because I have such a passion about working with people with autoimmunity, can we touch just real quickly on the interaction between probiotics and the use of probiotics and the immune cells and immune function?

Yeah. And I think probiotics can play a pretty important role in autoimmune conditions. And I think there's a few ways in which they can do so. We know that it's a leaky gut perspective. We can start there that imbalanced ecosystem or something else. Many things can cause that initial gut leakiness. And then we can use certain probiotics to help speed up the regeneration restoration of the small bowel, for example. And I think sometimes again thinking clinically, that slow gut transit time and that reabsorption of compounds from the colon because they've got maybe it's 10 days for things to get through rather than 24 hours or 16 hours. Using probiotics to speed that along can also be helpful. And then we have perhaps arguably more direct effects of having direct anti inflammatory effects in the system and then even arguably indirect anti inflammatory effects by altering the ecosystem. So if you have high levels of lipopolysaccharide containing bacteria in the gut, high levels of Proteobacteria bacteroidetes, but we certainly know protobacteria have got far more potent pro inflammatory endotoxin that using the right probiotic can actually help reduce the load of endotoxin containing bacteria in the gut, which then takes the level of inflammation away systemically. And I think really we're looking at what's driving inflammation in this patient. And there's probably a few things coming from the gut, from gut integrity, slow gut transit time and a dysbiotic environment. And we can certainly use probiotics as part of our approach to help with all those areas as well as directly impacting inflammation systemically via how they can interact with tolac receptors, for example, and actually can interact with our immune system to increase the secretion of anti inflammatory cytokines and downregulate the production of pro inflammatory cytokines.

Beautifully stated. Dr. Hawerlich. Thank you so much for joining us on the podcast.

Hi, you're very welcome. I loved it.

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