Probiotics: More than expensive poop?
Probiotics are one of the most intriguing natural medicine therapeutics. A probiotic is a live microorganism (usually bacteria) that is taken orally, topically, or rectally in an effort to influence and shift biochemical, microbial, and physiologic state of some system in the body. Since humans are born with a relatively sterile digestive tract and in the first few days it rapidly accumulates flora from mom via breast milk, skin contact, and the environment; we innately understand the pivotal role that gut microbes have on our digestion, nutrient absorption, and survival. And since much of the microbiome research from the American Gut Project pointed that gut microbiota diversity is a key in health and longevity; we have seen a growing interest in figuring out the best way to shift the microbiome. The use of probiotics is rampant with the sales of probiotics globally projected to reach 65.87 billion by the year 2024. We can assume that a fair percentage of people taking probiotics are experiencing noticeable benefit and some may not be benefiting at all from taking probiotics. The illusion that we can take a probiotic and make it grow in our gut has since been dismantled and now we are trying to conceptualize why and how probiotics work and which specific strains are most beneficial for certain diseases. In my practice, I use probiotics for all types of digestive disorders, skin disorders, allergy disorders, and mental health concerns. However, they are chosen artfully and used at specific times and status of a patient’s health status. I have posted on various issues with probiotics as well including the fact that some times probiotics may make people feel worse. I also have growing interest in therapeutic prebiotic use. See, prebiotics are non-digestible fiber components that support our microbiome. Also, an interest in the direction of fecal microbial transplant for more long-term microbiome shifts. Recently I invited an esteemed colleague Dr. Jason Hawrelak (The probiotic advisor) on my podcast.
Below I am sharing a summary of that conversation. To listen to full episode click here. The full transcript of this podcast is at the end of the post.
Jason Hawrelak, PhD, ND , the probiotic advisor on Probiotics
About our guest:
Jason Hawrelak, PhD, is a research scientist, educator, naturopath and Western herbalist with nearly 20 years’ clinical experience. Jason practices at Goulds Natural Medicine, a 138-year-old natural medicine apothecary and clinic located in central Hobart in Tasmania, Austrailia. Dr Hawrelak did his Honours and PhD degrees in the areas of the gastrointestinal microbiota, the causes of dysbiosis, and the clinical applications of pre- and probiotics. He has written extensively in the medical literature on these topics – including 16 textbook chapters – and his research has been cited nearly 1000 times.
Dr Hawrelak has taught health professionals at both the undergraduate and postgraduate level for the past 18 years. He currently coordinates and teaches the Evidence-based Complementary Medicine Programs in the College of Health & Medicine at the University of Tasmania (Hobart, Australia) and teaches natural approaches to Gastroenterology within the University of Western States Master of Science in Human Nutrition and Functional Medicine program (Portland, Oregon). He is also a Visiting Research Fellow at the Australian Research Centre for Complementary and Integrative Medicine (ARCCIM) at the University of Technology Sydney (Sydney, Australia).
Jason 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. He is also Chief Research Officer at ProbioticAdvisor.com, which offers a searchable database that enables easy, evidence-based prescribing of probiotic products and online resources for clinicians, and health-conscious members of the public, to learn more about the human microbiome and how they can positively influence these ecosystems.
Background and interest in probiotics:
Dr. Hawrelak’s interest in probiotic began in his final year of Naturopathic training and he attended 1999 lecture on microbiome and it drew his interest. He was at a research institution and did a research project on a prebiotic, probiotic, herbal combination. He went on to do a PhD with emphasis on this topic and in 2000 did his honor thesis on probiotics. 20 years later is still passionate about his PhD topic.
Definitions of Probiotics:
The strict definition and criteria determining if something qualifies as a probiotic of probiotics is as follows;
○ It must consist of live microbes, when administered in adequate amounts, that have demonstrated therapeutic effects in humans. Human clinical studies done with the exact human strain used in the product.
○ It must have gastric acid stability (be able to survive the stomach pH)
The different types of probiotics include
Food sources of probiotics: typically a yogurt base with a probiotic integrated into the probiotic including Medicinal yogurts and Medicinal Kefir
Human origin strains (a lot of the lactobacillus and bifidobacterium strains found in probiotics are human origin)
Yeast based probiotics : Saccharomyces boulardii (from the skin of Lychee) also Saccharomyces cerevisiae.
Spore based probiotics : Bacillus clausii ( fromphylum firmicutues) .Bacillus clausii, has been found to produce antimicrobial substances that are active against gram positive bacteria including Staphylococcus aureus, Enterococcus faecium, and Clostridium difficile. Bacillus Coagulans which is originally from cow intestinal tracts. Also see Bacillus subtilis, an endospore, gram positive, bacteria found in soil and the gastrointestinal tract of ruminants and humans. Can survive in anaerobic environments. Bacilus subtilis is strongly antimicrobial.
Prebiotics
Dr. Hawrelak states this is a class of agents poorly used by clinicians
● He points out that they do more then feed bacteria
● The definition of a prebiotic is as follows :
○ A substrate that is selectively used by host microbes conferring a health benefit.
○ Must be indigestible
○ They must be a selective substrate for 1 or more commensal bacteria primarily in the large intestine.
○ They shift the ecosystem to a healthier state
○ There is some benefit from the ecosystem shift
● Many fibers do not meet the definition of prebiotics
Most prebiotics will increase bifidobacteria, akkermansia, lactobacilli, faecalibacterium, and butyrate producing bacteria. (hence the importance of prebiotics in the diet)
See my handout on prebiotics here.
Myths and controversy of probiotics
● There is a long standing and hopefully squashed myth that probiotics permanently colonize the GI tract. 95% of the time there is no long-term colonization. Probiotics may stick around for 2 weeks at most and usually cannot be seen on stool testing after you discontinue taking.
● Yet, probiotics are still therapeutic even though probiotics are not inoculating the intestine
● The probiotics have an action while you are taking and you will benefit for that time and a number of days afterwards
● Some probiotics for example decrease cholesterol; they will only benefit you while you are taking the probiotic. Once you stop the benefit stops.
● For hyperlipidemia (high cholesterol) the following strains of lactobacillus probiotics (L. plantarum and L. reuteri) have been beneficial in reducing cholesterol
● The other often debated question.When should you take probiotics when on antibiotics? According to Dr. Hawrelak, take them spaced between antibiotic dosage. Don’t wait until after the course is done!
Researched indication for probiotics
● Traditional uses: Irritable bowel syndrome, Inflammatory Bowel Disease, and Antibiotic related gut issues
● Emerging indications: Alzheimer's disease, anxiety, asthma, rheumatoid arthritis, mastitis, chronic fatigue syndrome, cervical dysplasia, celiac disease.
● Endometriosis is being studied with a non-commercially available strain
● We will eventually have a probiotic materia medica to co-exist with herbal materia medica.
● Esschericia Coli Nissle 1917 has good evidence for IBD. Been available since 1920’s. N. America is cautionary because of E. Coli association.(ask me about patients of mine flying through Germany to stalk up on this one!)
● Strains are not available worldwide. This is slowly changing. Europe is leading the way in probiotics.
Shopping for probiotics, how to select a good strain?
● If generally healthy, Dr. Hawrelak says you are better off getting your probiotics from fermented foods such as sauerkraut, kimchi, and yogurt vs. taking probiotics.
● Even though yogurt bacteria will die in the small bowel; there can be some benefit to immunity/natural killer activation related to even dead probiotics.
● For specific use of probiotics, you need to work with a health practitioner.
● Don’t use label claims to make your decisions.
● High CFU and most species/multiple strain does not equal a good selection of a probiotic. For example: Antibiotic associated diarrhea. 60 billion CFU multi strain (4 strains) Vs. 1 strain Lactobacillus reuteri ATCC 55730 200 million strain, single strain . The 200 million did help reduce diarrhea rates and c.difficile rates but the larger multi-strain probiotic did not. See study here on Lactobacillus reuteri https://www.ncbi.nlm.nih.gov/pubmed/21552138
Evaluating microbiome for probiotic selection
● Dr. Harwelak uses lactulose/mannitol for checking intestinal permeability. Arguably the most validated test for gut leakiness. Tells you how severe. (authors note: there are others including stool or serum Zonulin and also panels looking at Actomyosin IgA, Occludin/Zonulin IgG, Occludin/Zonulin IgA, Occludin/Zonulin IgM ,Lipopolysaccharides (LPS) IgGm Lipopolysaccharides (LPS) IgAm and Lipopolysaccharides (LPS) IgM)
● Healing intestinal permeability can be a 3-12-month process.
● Example Chronic Fatigue Syndrome patient. Had intestinal permeability. Was 80% improved after 12 months of gut healing protocol. This was consistent with his improvement in the lactulose/mannitol testing.
He also uses microbiome testing. American Gut Project, Thyrve[1], 16srRNA testing. Is a game changer. He has found that the overall diversity score and number of species on these tests is very helpful. Only $100 follow up testing. Gauges changes and dietary compliance. Example Bilophila wadsworthia (a gram-negative, obligatorily anaerobic, bile resistant bacteria) will be high if someone is on a high fat diet. It only feeds off bile. Bliophila wadsworthia produces hydrogen sulfide gas which is something we want to be careful with it. (authors note Hydrogen Sulfide production has been linked with intestinal inflammation ) Follow up testing helps with motivation and understanding how well treatment recommendations are working. These are now essential tools that have improved the results.
Dangers, contraindications, and warnings in probiotics
● Systematic studies say to be careful with yeast-based probiotics specifically like saccharomyces boulardii in hospitalized immuno-suppressed patients.
Future work and take-home messages from Dr. Hawrelak
● Looking at research for natural agents that will not harm our commensals. He is concerned that some of the herbal medicines we use for sibo and dysbiosis that are being used for long term use may actually harm the microbiome.
● He is continuing to build the Probiotic advisor data base.
● He states to choose probiotic tools wisely. Based on evidence. Not on manufacturer information.
● Prebiotics are undervalued and are the best at shifting microbiome
○ Used for obesity and metabolic issue as well
○ Prebiotics and prebiotic supplements taste good!
Resources
One of my favorite articles on prebiotics by Lauren Glucina, a New Zealand based Naturopath, Medical Herbalist and Nutritionist https://ascensionkitchen.com/health-benefits-of-prebiotics/
Addition comments on the topic...
Plethora of possible mechanisms of Probiotics.
Probiotics have taken a big hit in scientific and lay person circles. Mainly because people think that we are just making expensive “poop” and that since probiotics do not necessarily permanently grow in the gut then they are a waste. Well many research models have continued to show some of the beneficial shifts that might happen while on probiotics. I think the graph below really highlights a few. Probiotics are best viewed like a medicine and once you stop then the benefits will likely taper down. Prebiotics might be looked however more of a longer-term move. For now these are some of the benefits of probiotics proposed.
(Hill et al., 2014)
When I think of this list as a clinician, I would rank the following as most noticeably:
Regulation of intestinal transit (better stool consistency and frequency)
Neurological effects (I will often see less anxiety and depression)
Reduced intestinal permeability ( probiotics help in some cases improve mucus lining, and helps reduce endotoxin levels)
I typically see less gas and bloating
However, do note, in my practice we focus on really specific strains and not mega volume, multi-species probiotics. Also, probiotics are usually introduced at a later stage of health stability in my patients. Hence, the body is usually in a better state to integrate this microbiome shift.
Future directions of probiotics will likely be further exploration of the long-term benefits of spore-based probiotics. I am personally interested in the spore-based probiotic Bacillus subtilis (HU-58) as its ability to live in anaerobic environment and release antimicrobial elements that may be effective in warding of pathobionts make it an attractive option. Also developing a flexible and prebiotic-centric diet
If you are generally well and want increase prebiotics in your diet you may start with something like a prebiotic smoothie bowl. Warning : if you currently on unstable digestively adding prebiotics rapidly like this may lead to more GI-distress temporarily. For the recipe ; Check it out below
Recipe courtesy of www.conciousdietitian.com
Transcript of episdode
Dr. Adam Rinde: What's going on everybody? This is Dr. Adam Rinde and welcome to the next episode of The One Thing Podcast. Today, we're speaking with a probiotic expert, Dr. Jason Hawrelak, all the way from Tasmania, Australia.
He will take us through all the fundamentals of probiotics and we will speak deeply about clinical applications of probiotics, how to know which ones are proper to select, some of the controversies around probiotics and we will walk away with a better understanding of how to utilize probiotics for health and for specific health conditions. Without further ado, welcome our guest, Dr. Jason Hawrelak.
I'm here today with Dr. Jason Hawrelak. Jason, welcome to The One Thing Podcast. It's great to have you here. I thought we could just jump right into the interview and hear a little bit about what brought you into the microbiome space and interest in probiotics.
Dr. Jason Hawrelak: Thanks, Adam. It's a pleasure to be here and chatting about my favorite topics that you couldn't even give me this shut up about even once. What started me was almost like one of those random chance events that I was in my final year of my naturopathic training and there was this just fantastic lecture by one of our senior academics on what the data was around dysbiosis and increased intestinal permeability in these different disease states and this was back in 1999.
Probably 20 years ago now actually is probably at the time of his lecture and it really triggered something me passion drive to learn more and I was lucky that that it was at a research institution and I've trained here in Australia.
Where we have the opportunity to research honors degree which is essentially, we do a research project and we actually end up in the end doing a human clinical trial of a prebiotic-probiotic herbal combination for the treatment of IBS which my literature review started back in 1999 and followed that up with it with a PhD looking at the same topic area.
So, amazingly well timed because you had no idea about the boom that was supposed to happen but this was that area that was immense interest to me and it's always been an area of intense interest for naturopath broadly speaking, but there's some that it just really resonates well with and for me, it wasn't a health issue per se because I would argue that my health issues are mostly lung related but it just something that really captivated me and I just had to learn and delve more.
I'm really lucky that I chose a topic that 20 years on, I still find immensely interesting and I'll still read papers late at night and watch other people lecturing late at night. There's a lot of people do their PhD in a topic that they really found boring and they just did it to get a PhD. Whereas I'm lucky that I chose a topic that I'm passionate about.
Dr. Adam Rinde: It's in the prime time right now. You can't open your browser without seeing a study every day about microbiome, probiotics and you're there at the right time.
Dr. Jason Hawrelak: It's pretty amazing to be from that time point and when I was writing my honors thesis in 2000 like going back and looking at all the probiotic research and all the microbiome research and you can read all of it back from the stuff that was done in the '70s, '80s and '90s.
So there wasn't that much and there's only a few research centers and researchers around the world who really focused on it and who were passionate about it and they were managed to pass on that passion to me, as well.
So, that absolute love and this idea of protecting and being custodian of the microbiota really grew out of that early research that was around that time point and certainly expanded dramatically due to changes in technology, which has allowed us to see so much more.
Now there's 1000s of researchers around the world, many 1000s are working on this area so the level of evidence is just powering more and more space all the time as you said before.
Dr. Adam Rinde: people are familiar with probiotics by now. People can just go to the supermarket, grab some yogurt, and they'll see that there have been customized to have certain probiotic strains in them. There's Kombucha on the shelves. So, it's not this conversation is likely to fall in the ears of someone who hasn't heard of probiotics.
This is likely to be listened to by clinicians but also health consumers and people who are dealing with health challenges, but I thought we could start out with just discussing the different types of probiotics and different categories because it can get quite confusing for people to understand everything from symbiotics to spore based products. If you could walk us through just some descriptions of these different categories.
Dr. Jason Hawrelak: I'll just take a step back to and just look at the definition of probiotics. We've all got a general idea but it's worth teasing out of the most commonly accepted definition at this time point, which is live microbes that when administered in adequate amounts confer a health benefit on the host.
If you take that definition apart, there are three components live microbes number one. Even if you have a therapeutic product that has lovely clinical trials on it, showing it works but it contains dead bacteria, it's actually no longer a probiotic at that time point.
Secondly is the adequate amount and once again, you can often look at some the range of probiotic products on the marketplace and see that many might well contain live microbes and they might contain those that has therapeutic effects shown in human studies, but don't have adequate amounts to actually have a therapeutic effect when we're given in that form that is recommended dosage.
So, that again would not be a probiotic and the third part of that definition is some parts of the world take that component where it confers a health benefit on the host very strictly, where you need human clinical trials done on the exact genetically unique strains found in your product for you to use the term probiotic you describe in your product.
Because if it doesn't have you in clinical trials, you can call it a source of microbes but you can't actually call it a probiotic itself. So, it's worth teasing out those aspects. If you look at how few products out there that claim to be probiotics actually meet that strict definition and a lot of those would be in a category of food and even within that food category.
You'd have what probiotic researchers would call sources of live and active culture which would be typical Kombucha's, Kefir's, Sauerkraut, Kimchi, where you're getting live microbes in generally large amounts.
They're wild ferments, so you really don't know about the potential of the strains that you're consuming. You don't know about the basic details of those strains. Do they have the characteristics that are essentially vital to have a chance of producing therapeutic effects in humans and that would be things like gastric acids stability, bile salts stability.
So that it can survive transit to the upper gut, can adhere to intestinal cells, does it produce the antimicrobial compounds that might have a selective decontaminating effect on the ecosystem or shift the ecosystem into something better.
And then, there's another category of those food sources of microbes that would meet the definition of probiotics where you might have a yogurt base, which would use a nondescript strain of Lactobacillus delbrueckii subspecies bulgaricus and Streptococcus thermophilus.
Those are the two species that always made milk into what we call yogurt today but they limit in their capacity to have any greater therapeutic effect, because in general they don't have the capacity to deal with gastric acid or bile. So, they will generally die in the stomach and small intestine.
This has been known for a long time. So, what some companies will do will actually add well characterized, well researched probiotic strains into that yogurt or kefir or kimchi potentially too.
You're getting fermenting bugs that are in that wild varying amounts of microbes, a whole range of different species and strains might be there but then you're also getting these therapeutic strains on top of that and that would define them as more medicinal yogurts or medicinal kefir.
So, I'd actually separate them quite clearly based on the addition of those human well researched therapeutic strains versus just the wild ferments rather than was there.
Dr. Adam Rinde: So, once my probiotic has met those particular qualifications and they do fit the probiotic definition, then take us from there. Let's say that they do have live microbes in adequate amounts and have been used in clinical trials. There still is separate categories, correct?
Dr. Jason Hawrelak: There might be ones that are based on lactobacill,i bifidobacteria based. There's a few exceptions to this but it essentially initially isolated from healthy human people. We don't like to think of it that way. My patients like to think of the fact that they're ingesting microbes that were originally isolated from someone else's poo but that's the reality.
So, some people have described it as more human origin strains and the idea has always been that because they came from human guts that they probably like living in a human intestinal tract environment in terms of the pH will be to his liking, the temperature will be to his liking, the food that we eat will be to its liking.
But there are other probiotics that have other origins. They're saccharomyces cerevisiae variety boulardii was isolated from the skin of lychees back in the 1920s. Henri Boulard was a microbiologist, went to Southeast Asia.
There's from memory a cholera epidemic going through and he noticed that that some locals were drinking this tea made from lychee skins and they were one not getting cholera into getting better. Coming from a microbiology background, he obviously assumed there was some microbe on it. So, he isolated a yeast which he then named after himself.
That microbiologists do and that's been used as a probiotic sold around the world since 1950s which is quite fast in terms of the duration of time that's been sold as a probiotic supplement isolated from skin of lychee and there's no other probiotics come from lychee's skin that I'm aware of.
There's a newer class that people have brought into the market in the last 10 or 15 years which is so called soil based probiotics that originally had their origin from microbes standing in dirt.
Dr. Adam Rinde: That's the spore-based probiotics.
Dr. Jason Hawrelak: Many would fit into that category. Taking another step back, there's some like bacillus clausii. It's a spore-based probiotic that has been sold as a probiotic in Italy for decades that does have long history of use. There's another bacillus coagulans that I read about. I can't remember the strain designation but originally came from cow intestinal tract.
So, there are some that have other origins as well and research is certainly clear that it doesn't have to be from humans. It just has to be therapeutic. That's clear thing. If it wasn't a clinical trial showing it works and it came from a cow or came from soil, or it came from somewhere else, then there's no way of knowing it works essentially.
Dr. Adam Rinde: Let's go through prebiotics versus probiotics. Besides the obvious if you could just take us through some of the key elements of what a prebiotic is and comparison to probiotics.
Dr. Jason Hawrelak: Prebiotics are a class of agents that are poorly utilized by clinicians. That's been to change I can see but that's certainly been the case. It's partly due to a lack of clarity around what the definition actually is because people often just assume prebiotics feed bacteria and that's it. It's not quite right because again the strict definition is a substrate that is selectively utilized by host microbes conferring a health benefit.
For a food ingredient or something, et cetera to be classified as prebiotic, they have to meet four criteria, one be indigestible so we can't break them down or absorb them because then they won't reach the lower gut to be therapeutic.
Two, they act as a selective substrate for one or a limited number of what we generally see as beneficial commensal bacteria in the large intestine primarily. Three, they shift the ecosystem to a healthier state and four, there's some health benefit that comes from that shift. When you strictly enforce that definition, there's a lot of things that don't meet that.
There's a whole range of dietary fibers, which are essential for us to be consuming but they don't meet that definition of prebiotic because they might feed 30, 40, 50 different species in the gut and that's not a bad thing.
It's just that they're not prebiotics by definition, whereas the prebiotic really is selective. If you do really good stool testing, you can clearly see this on the before and after results of supplementing with a prebiotic supplement is you'll see exactly what the research tells you. You'll see an increase of most prebiotic supplements that we have access to now will target Bifidobacteria.
There are some there will also feed a bit of Lactobacilli. Some that will feed up the Faecalibacterium and Akkermansia. Those would be probably the four with the best data set and another group called butyrate-producing bacteria, which is a broader group of organisms.
But you can clearly see the shifts and this is where prebiotics are absolutely wonderful. When you have an ecosystem, you assess the ecosystem and say, "The diversity is okay but you're actually really low in Bifidobacteria or potentially below detectable levels of Bifidobacteria. Here, we can introduce a prebiotic into their regime.
You can do a follow-up test in two months and you'll see almost exclusively the Bifidobacteria population goes up. It's pretty clear how selective it is but you also get because of the shift in environment that occurs with that prebiotic ingestion generally a lowering of the pH because you're getting increased short-chain fatty acid production due to feeding Bifidobacteria generally or Faecalibacterium or Akkermansia.
You will get a reduction in potential pathogens as well pathobiont populations. Pathobiology is a term often used in the microbiome literature that's really describing species that when present in the right amounts and the right area are actually helpful and don't cause any harm.
But if they have a chance in the wrong environmental conditions or the wrong numbers causes harm and then most of the research around dysbiosis is around that definition pathobionts rather than single isolated pathogens.
But what I love about prebiotics is you tend to see pathobiont populations go down with their use as well as species that we tend to classify as beneficial like Bifidobacteria, Faecalibacterium. Their populations actually increased. You can see massive shifts with that.
If I've got that same patient to eat more fiber, we're still going have some nice shift to that ecosystem but you're not going to have that same thousandfold potentially increase in Bifidobacteria. There might be a slight increase because they might be enjoying some of the fruits of that fiber too, but they're not going to be selectively fed in the same way as with a prebiotic.
Dr. Adam Rinde: That's a really big point right there and helpful point because a lot of the patients I'm sure that see you would not tolerate just being loaded up with lots of fiber and the fact that you can step back and say, "Here's what I see is, something that's specifically going to help you" versus just taking an aim at the whole ecosystem with increasing fiber in the diet.
Dr. Jason Hawrelak: I agree. We were speaking before this recorded about the different patient sets we see now. I still recall the days I could be much broader with recommendations. They were generally healthier population base, whereas now we're seeing people that are often farther along in the disease process. So, you have to more gentle in targeting with how we approach.
Dr. Adam Rinde: People are looking for answers in their gut now more than ever, so they're coming to us with all chronic conditions not just irritable bowel syndrome or some constipation or diarrhea. This is a complex health condition and they're looking at their gut for answers.
Dr. Jason Hawrelak: That's been again brilliant looking at the research out there really looking at dysbiosis as a driver of primarily gut conditions to what we see now. Dysbiosis is a driver of anxiety, depression, obesity, type 2 diabetes, nonalcoholic fatty liver disease. There's very few Western diseases that I would argue that there isn't a degree, if not a lot of research that's built up around dysbiosis as a potent driver of that disease state.
Dr. Adam Rinde: You've already talked a little bit about this but I want to go deeper into certain controversies about probiotics. One of them I'm just going to put out there because a lot of people think that if you're deficient in certain microbiota or a certain genera in the microbiome that you could take a probiotic and it will fix it.
And so, I want to talk a little bit about your thoughts about that because there's some misconception or gray area around that and then just any other controversies that you like to bring up about probiotics.
Dr. Jason Hawrelak: That's a great starting point and that's what I would call the permanent colonization myth. I was taught this too as part of my naturopath training. That myth probably goes back to himself who believed that when we ate yogurt, the yogurt producing bacteria would take up residence in our gut.
This is going back to the early 1900s. So, there's a lot of history behind that mythology. It's sadly not of course based on research but you can look at the last 30, 40 years of clinical trials on probiotics and 95% of the time, there's no long term connotation with their use. If they stick around for a week to two weeks after cessation of these people that's very good and they do this follow-up test, you can see that it's there.
When they take it two days later, it's completely gone from that ecosystem and there's a tremendous body of evidence showing that same thing. So for probiotic researchers, this idea of colonization has been a myth for long time ago. It has been slow for this myth that you get out there so they do get people to do a test.
But actually here, I can just pop a supplement and I'll be colonized forever from this time point and that's not the reality of it. There's very few strains of Bifidobacteria and Lactobacilli that has been shown in research to stick around for any duration of time, and even then, it's been only a relatively small proportion of people that occurs that just might be the right environmental conditions but there's something unique about those potential strains as well.
So, we have to put paid to that one and that really shift your consideration in view of the microbiome too, because if you've got this idea that you can just hammer it, take tons of antibiotics and not worry about the consequences you can just pop up a high potency multi strain high CFU probiotics supplement that will recolonize your gut, then it cheapens. There's no appreciation for the complexity of that ecosystem and the fact that's not real. You're a custodian of that and it's not that simple.
You could do a fecal transplant but that's a whole new ballgame in terms of getting your head around if someone getting other people's poo in your system and that does have the capacity to recolonize in a much different way than current generation of probiotics. It's just that Lactobacilli and Bifidobacteria in current versions of something to form don't have great capacity to colonize the gut for any length of time so it's a myth one.
Dr. Adam Rinde: Just to follow up that, what are they doing? Where are they living when they're going through your gut transit?
Dr. Jason Hawrelak: This would depend on your gut transit time too and that you would know too Adam that there are some people whose bowel transit time is like two weeks. So, they probably will be doing this test for two weeks unlike someone else who've got a 16-hour transit time, it's probably going to be gone in 24 or 48 hours.
But they are temporarily taking it residence and that doesn't mean they're not therapeutic. We've got hundreds of clinical trials showing that these agents are therapeutic despite the fact they're not growing and reproducing in any great amount in your gut.
Just like some patients taking their medicine, I'm not expecting them to be permanently fixed necessarily from taking that herb but the herb is going to have an action that will manifest while they take that herb and that's exactly how the research on probiotics is gone. While you take that probiotic, they will produce a certain action and you will benefit from that action whilst you take it and for a number of days afterwards.
All you need to do is take it for six weeks to get the full benefit of that and that might be for the prevention of antibiotic associated side effects and in helping to prevent like C. diff overgrowth post-antibiotics.
Six weeks is totally enough for that action, but then times where there are some probiotic strains that can decrease cholesterol levels. Whilst you take it, it will break down cholesterol in the gut and you won't absorb it and your cholesterol levels will go down, but if you stop taking it, the cholesterol levels will go up.
There's another strain that's used in Europe that produces an ACE inhibitor and while you drink that fermented milk, you get this ACE inhibitor and your blood pressure goes down. You cease drinking that milk and cease ingesting that strain, your blood pressure goes back up.
You haven't treated any of the underlying issues obviously. You're just taking something that has a therapeutic effect. Just like if I just give a patient my favorite herb for hypertension is Rosella and after two weeks, almost everyone has a decrease in blood pressure.
But if they stopped taking it, it stops working and if we haven't fixed the reason why they have high blood pressure, it's going to go back up. It's clearly just looking at probiotics as therapeutic agents that have specific actions. We just need to match the action of the probiotic strain to the condition or physiology we want to change.
Dr. Adam Rinde: That makes a lot of sense to me and it will ground us in knowing how to work with them better so busting that myth.
Dr. Jason Hawrelak: Yeah, for sure. If you look at the probiotic trials showing the probiotic has in like cervical dysplasia, mastitis, anxiety, depression, all these things aren't related to the lack of Bifidobacteria populations in the gut.
There is for some of those conditions, but it's true to the action of that particular probiotic strain and the some strains of Bifidobacteria that speed up that transit time and that's been very helpful for a slow bowel transit timer, your constipated patients. But again, if they stopped taking it, if you haven't fixed the underlying issue, it's going to cease working.
Dr. Adam Rinde: Any other controversies that come to mind you about probiotics?
Dr. Jason Hawrelak: The ones that is I've been trying to bust for nearly 20 years, I want to see the antibiotic issue about when you take the probiotic along with antibiotics, do you take it afterwards, you do it during and I can say conclusively based on meta-analytic data, top grade data that you take the probiotic during the course of antibiotics, you don't wait till afterwards, not the same mouthful. Ideally, you want to space it out by a couple hours if you can but if you can't, same mouthful will have to suffice.
But we know from dozens of studies that we actually get less side effects and other studies with other strains show less damage to the ecosystem if you take it concurrently. So, there's absolutely no benefit to waiting till afterwards. In fact, you're arguably causing a patient harm if you're telling them to wait until after antibiotics are over before they start ingesting their probiotics.
Dr. Adam Rinde: We're seeing a good trend with even conventional providers making this recommendation now. I don't know how it is in Australia, but are you seeing that trend as well?
Dr. Jason Hawrelak: It's happening more so but I'm still surprised when I'm in clinical practice, infrequently people get told that when they're stuck in the course of antibiotics. I'm just surprised despite that because the evidence has been there for a long time. It's not new 2019 research. It's been there for a long time. It takes a long time for research to filter out and change practice sadly for our patients.
Dr. Adam Rinde: One of the top aspects of your website, the probiotic advisor is that you go through and you have a ranking of research on probiotics, which clinical conditions are most likely to benefit from probiotic use in specific strains.
So, that is a really helpful resource for anybody listening out there and I just wanted to mention that, but I wanted to go into just a few of these clinical applications of probiotics, some of the most noteworthy that you can think of that but that's emerging and some that have just been solid for a long time.
Dr. Jason Hawrelak: That is interesting because you go back and I'd say what are considered to be more traditional uses of probiotics, which are generally around the gut stuff. I remember looking at one of my literature review finding studies of probiotics in IBS, going back to the 1950s. That's been known for a long time. Inflammatory bowel disease, antibiotic associated issues generally were given afterwards.
Thrush issues, I'd say those would make up the bulk of probiotic use for a long time, but what's been fascinating is just seeing that shift from. Now, we're seeing research of probiotics for Alzheimer's disease, for anxiety, for rheumatoid arthritis, for asthma prevention, for prevention of recurring mastitis, for treating the cervical dysplasia, celiac disease and chronic fatigue syndrome.
The list goes on. In fact, there's a whole larger list in my database that you can just look by conditions and these are human clinical trials on strains that are currently available and sometimes there's a number of other strains.
There's some research on probiotics on endometriosis for example. It's just that these strains aren't commercially available at this time point that has shown great efficacy for that condition. Over the coming years, we'll get access to more of these tools in our clinical practice.
Because that's already happening at a quick pace but we'll just start having this huge essentially what I would call a probiotic materia medica to coexist beside our herbal materia medica and then our normal vitamins and minerals in our dispensary to help our patients.
Because soon we have 30 or 40 different probiotic strains you could potentially recommend for different health conditions. So, it's an exciting time to be clinician really in our field.
Dr. Adam Rinde: I'm really glad you brought up the point of availability is one of the strains that has jumped out in the research for IBD. Specifically, ulcerative colitis is the E. coli Nissle 1917. It seems like it has really great evidence behind it, but we can't get it here in North America. I know some patients have traveled to Germany to get it. It's a really good point that we just don't have access to all these strains.
Dr. Jason Hawrelak: We don't. I'm lucky that we do have access to the Nissle 1917 strain in Australia. But I must say I was at a microbiome probiotic conference that’s three years ago now and it was like a kid in a candy shop for me when I went to the pharmacy there.
I was like, "You've got the strain" and I end up with this huge shopping bags full of probiotic products to take them because I was so excited to actually have access to the ones that I've read about in the research, but they're just not available here.
That is slowly changing. Europe is actually quite ahead of the game when it comes to probiotic research and answering the probiotic product availability, but that is seeping through here and seeping through to North American market. So, we've got that to look forward to, but the E. coli one is a different scenario because it's been available.
There's a probiotic in Germany since the 1920s, long time in the marketplace, great safety profile but because it's an E. coli, North American regulatory authorities are extremely cautious about its use despite its long, long history of safe use. We're probably talking many dozens, if not over 100 clinical trials showing a great safety profile.
Dr. Adam Rinde: That's really a good point. It will be interesting to see over the course of the next few years if we're going to see increased access throughout the world for various strains hopefully. Imagine there's some various forces at play like marketing and essentially business agreements that are required to bring strains to various other regions.
Dr. Jason Hawrelak: Sometimes that means there's exclusivity as well like by culture in L. rhamnosus GG for example. They had an exclusivity agreement on the US market for a long time that just lapsed or something like that because there's now more products with that strain in it for example.
Dr. Adam Rinde: If someone is going to shop for a probiotic and let's say they don't have a healthcare provider helping them make this decision, what are some general criteria that you would mention?
Dr. Jason Hawrelak: That's a tricky question. To be honest, you need a healthcare provider to adequately work your way through the probiotic literature and to find the best one to help you. If you're just generally healthy and wanting some microbial exposure, you're better off just having fermented foods like Sauerkraut and Kimchi or even some nondescript yogurt.
They're all fine if you're just after some microbial interaction going on. We know that even those yogurt bacteria that die in the stomach and small bowel, people that eat yogurt, their immune system is ramped up a bit more than less likely their natural killer cell activity et cetera tends to be a bit ramped up.
Even exposure to dead microbes which is the worst case scenario of eating sauerkraut, kimchi for example will tend to improve your general immunity so you get sick less often. That's a good thing.
But if you're trying to target specific health conditions, you're really better off either becoming really research savvy yourself but you're better off working with health professional who already is very research savvy and has clinical experience that can bring to the equation because it's a challenging area to navigate based on label claims.
If that's what you're relying on is somebody who's not trained in healthcare professional to read the label and then decide whether to take something or not, you'll be lost and you definitely won't end up except for random chance of finding the product that's going be best suited to help you and essentially, you could arguably be wasting your resources doing that.
You're better off really working with a clinician who is well read and knowledgeable to fuel the probiotics and has experience in helping people with similar condition in what you've got.
Dr. Adam Rinde: I'm just going to put this out there. So, going out and selecting the probiotic with the most different species and the highest CFU count is not necessarily, meaning you're making a good decision.
Dr. Jason Hawrelak: Definitely not. You're right though it's a great comment because there are so many people out there in the blogosphere who thinks that all it matters is getting multi-strain and high CFU. That's not what the research tells us at all.
Great example of antibiotic associated diarrhea specifically and look at the results of two different studies. One study use 60 billion CFU per day. CFU is colony forming units. Single bacterium is a colony forming unit. 60 billion of four different strains, two types of Lactobacilli and two types of Bifidobacteria and they gave it to him alongside antibiotics to try to decrease the incidence of an antibiotic associated diarrhea and C. diff infection.
Now, the study used one strain Lactobacillus reuteri DSM 17938 at a dose of 200 million CFU per day so 600 times less single strain. Look at the results of those study studies and you'll find that the four strains in that 60 billion CFU did not help reduce the incidence of antibiotic associated side effects or C. diff whereas the 200 million CFU per day of the single strain of L. reuteri did significantly decrease diarrhea rates and reduced C. diff incidence as well from them.
That's a classic example showing that a single strain with the right action has the right quality for that task was the best job.
It did the work that we want to do, but the other strains that might be good for something else. In fact, there are some research on those same four strains that failed in antibiotic associated diarrhea that they're helpful in IBS. They might have some, for example, anti-inflammatory activity in the gut that could be helpful for IBS.
But they were completely useless for preventing antibiotic associated diarrhea and that is an example that clearly shows that just choosing high CFU multi-strain over strains that have the actions that you're after will generally result in far less therapeutic outcomes or worse therapeutic outcomes.
Dr. Adam Rinde: You have a very eloquent and scientific way of looking at the microbiome based on some of the classes I've seen you teach through your methodology. Can you just share a little bit about some of the testing you do and where you see that going?
Dr. Jason Hawrelak: These days because of the affordability tend to check the microbiome composition for new every patient and this has been a great breakthrough for someone that's been reading about microbiomes for nearly 20 years but not having access to tools to properly assess until probably the last five or six years where the cost point made it actually more doable.
The technology has come down in terms of getting a proper view of the microbiome because previous stool tests had some degree and certainty healthfulness in clinical practice but they're lacking the capacity to give you a full complete picture of the microbiome unlike today's ones really do a good job with that aspect.
So for me, I would often do intestinal permeability tests for many of my patients because that again leaky gut is a common driver and rather than making the assumption that patients have it, I find it more useful to actually assess and I use the lactulose mannitol test which I know is uncool in some circles but it's arguably the most valid test for assessing for gut leakiness.
And then, you get that lovely baseline of not only do you have leaky gut but how severe is your leaky gut as well. For me, that is immensely helpful because it motivates patients because healing leaky gut is something that I find and I do lots of follow-up testing after pretreatment testing is generally a three, six, nine, 12-month process that you can see how severe it is, that gives you an idea of what the timeframe will be.
Also, they may not feel much different from taking a leaky gut healing protocol for three months or six months and you're asking them to spend fair bit of money but their energy and timing to fit this into the routine to take their mega doses of glutamine or what else it might actually be.
I find it's much better compliance-wise if they have a definitive diagnosis of what's going on and then we also have the capacity to do follow-up tests. I can think of one patient chronic fatigue syndrome. We did a microbiome assessment and leaky gut assessment and gut was definitely leaky and definitely dysbiotic state.
We address those two things and working with them and touching based in 12 months later. He was about 80% better and pretty across the board which is not a bad outcome and we're both happy with that. We're obviously not totally content with sticking it being 80% better. So, we did a follow-up gut permeability test and lo and behold, his gut permeability had improved by around 80%. I'm not even joking, but it still hadn't normalized yet.
For me, this was like, "This is a perfect example because if I just would have done that single test at the 12-month time point, I would have gone your gut is leaky but we'd had no idea of going. It actually improved a lot. It means that what we're doing is working. It's just going take more time in your case."
And this was a case where it took longer than what most patients would for whatever reason, but during that initial testing was extremely important in that case first to get an idea where we're at and how long much longer we would take to get to where we both want that patient to go.
Dr. Adam Rinde: Such a great example. Thank you.
Dr. Jason Hawrelak: Microbiome assessment you can get particularly when you're US based access labs that are offering that testing in American gut project. Previously, Ubiome up until two weeks ago or potentially Thrive where you can get 16S rRNA technology to look at the main genera and the proportion of that ecosystem for around $100 mark and that is a game changer.
I certainly found it to be so. Before that, I was using some functional tests. Look at inflammatory markers in the gut and immune markers, short-chain fatty acids, which I love that use that stuff too but you might get a look at 12 species or 20 species that are in the gut and the more advanced ones.
That's nothing if you get the 100 some species that might actually be there and getting the overall diversity score and those tests might have been for some of my patients, we were paying $800 for the test or $600 for the test. That's a whopping big investment and this one offer initial screen sure but I was not going there for follow-ups. But when it's around the $100 mark for follow-up tests, it's been brilliant to actually be able to do frequent follow-ups, have my interventions and I'm recommending made the changes we want it and it helps you to gauge dietary compliance as well.
Now, I suggest that based on their initial microbiome, you can see clearly what species are being fed and what are not. There are other factors that have to be considered too in terms of antibiotic use and probably initial seeding from the family too, but you can clearly see your bile phyla was worthy as high and that species only eats bile really that comes from us eating saturated fats primarily.
So, you can clearly see relationship going. If you bile phyla is like five times higher than normal amounts, you're generally feeding it very well in your diet and what you're eating that's feeding that species.
That's one of the core species in your gut that produces hydrogen sulfide gas. Obviously, I want to know about that population and any test that you do that just as culturing in the side will never tell you about that because they can't find that species, they can't grow it. You need to use molecular based tests to do so. But it allows you to look at that and go, "This is a dietary change we have to make.
This is what you're feeding inadvertently." I find it really has been immensely helpful for compliance with dietary interventions because they can see clearly what impact their current diet regime is having on their microbiome but the motivation that's different when it's healing and growing their inner garden. That's different than when it might be just looking after themselves.
This is a funny concept but it's like they're looking after a garden that they're quite willing to do other interventions with and be more diligent because they don't want to feed the weeds and kill off their good bacteria in a different way than they're looking after themselves even though they're obviously all connected but they see it a little bit differently most of my patients.
So, it really helps with motivation for patients to make the right dietary changes and take the right supplements, et cetera and they find it fascinating to see the change so they're super excited by follow-up tests. They'll go, "What do we change? I've been eating 45 foods per week. I've been these red polyphenols. I've been taking my prebiotics. What's changed?"
It's absolutely fantastic as a clinician to look at that and go, "I can see you've been compliant." We've had the recommended changes. What you would view to be the normal changes in the ecosystem based on what you're doing or not and that also gets bring up talking point.
He apparently haven't been as compliant as he had on certain aspects of things so what can we tease out about this as well. To me, there are essential tools in my toolkit now. Ten years ago, I would have practiced without them but I could not practice without those tools now nor get the results that you tend to see rusty now compared it too.
Dr. Adam Rinde: I agree. They just have really helped crystallize some of these concepts and helped us be more personalized in our recommendations.
Dr. Jason Hawrelak: Yes, definitely.
Dr. Adam Rinde: Back to probiotics. We're going to close our interview here in just a bit but I wanted to just get a few comments about dangerous warnings and contraindications in probiotic use.
Dr. Jason Hawrelak: If you look at the research data around probiotics and there's been a couple of systematic reviews that have been essentially safety reviews and they've generally found that there's one systematic review that included data from 620 odd probiotic studies finding that there was like no increased risk of any adverse events in the probiotic group versus placebo groups.
So, no increased risk of GI side effects or infections or serious adverse events and there was another review done in pediatric populations showing the kid that took probiotics had less side effects than those on the placebo. So I'd say that in general, they are very well tolerated class of agents.
That said, for me that the main caution is around the use of saccharomyces-based probiotics in immunocompromised patients. Those are severely immunocompromised and the data tells us those that are essentially in hospital bed, they've got an IV drip going into their system because those are the ones that have the incidence of fungemia and have been very extremely unwell from that.
And then, the research tells us that the saccharomyces actually got in not from oral use but from staff that were handling the capsules and then handling the IV fluid equipment then it got directly into the bloodstream that way. So, there's a major caveat around there.
There are certainly research in HIV/AIDS populations in the '90s and early 2000s using saccharomyces with good results without any incidence of side effects. So, it's just certain types of immunocompromised patients where you'd be extremely cautious and try to weigh up the benefits versus drawbacks in regard to C. diff probably primarily.
Dr. Adam Rinde: I'd like a take home message from you but first, could you just give us a little bit of a summary of some of the things you're working on right now, how people could learn more about your work and follow you and highlights of some of the things you're up to today?
Dr. Jason Hawrelak: One of the areas that I'm super keen on and this goes back to actually when I first started too was looking at the impact of herbs on the microbiome. I was really fascinated after my honors research was like, "What?" We know that herbs can be antibacterial against pathogens and pathobiont, but can they potentially negatively impact beneficial bacterial populations and got it as well.
So, that to me is an area of keen interest I'm really keeping an eye on and really trying to choose agents that can work selectively that can work on to target pathogens and passive biomes but don't harm our benefit for bacterial populations.
Because there is a capacity of some of our agents that we have access to as clinicians to actually cause harm to those populations and if used for a longer period of time result in similar impact that you would from courses of antibiotics and so, we needed to have that on our radar.
So, that's an area that I'm avidly delving into. I do obviously have the probiotic advisor database that you find before which is really designed to make evidence based prescribing of probiotics easy for clinicians because we're busy.
I get that. I'm busy too and trying to go look up in Medline what studies might be available on different probiotics to help this bigger patient. Great, you can do that but we've got a database to try to make that far simpler. For me, this database started from bits of paper I used to give my students because I've been teaching about probiotics and their uses to naturopathic students from 2000 onwards.
They start off as researchers as far less of it, you have a few pieces of paper and over five or 10 years, there was a quite a few pieces of paper and eventually, five years ago was like, "I need to shove this into a database." It's searchable.
You don't have to search through five different documents and multiple pages of trying to align the strain with the research and the condition and where you find that strain and all these different products.
So, we put that into database to make that far easier. I've also got a range of courses that are designed primarily for clinicians to upskill around gut microbiome and its relationship to overall health and vaginal microbiome too and this is another area that is very much under considered in women's health around fertility but more broadly what women's health endometriosis is the importance of a healthy vaginal ecosystem.
That's not dysbiotic because you can have dysbiotic vaginal ecosystem and be completely asymptomatic and this dysbiosis is driving inflammation locally in the area but even systemically that we need to have in our radar.
One of my goals is to obviously as a clinician treating patients but I really like sharing what I can with clinicians to upskill them so they've got a better dataset and more tools at hand to better help their patients.
Dr. Adam Rinde: That's great. I feel upskilled right now just talking with you for the last hour, so thank you very much. Any closing thoughts, just take home messages for today's visit?
Dr. Jason Hawrelak: I would say probably big things were choose your probiotic tools wisely and base that on independent evidence on the strains that are contained in on supplements not on manufacturer industry information. Secondly, probiotics as I mentioned before are very undervalued, a class of agents.
They have a great therapeutic potential and nothing shifts the gut ecosystem in the same way as prebiotics. So, I'd say if you're not familiar with the class of tools, look at the research and start using them on your patients. It's not just gut patients but there's this decent research showing up for prebiotics and they're used for modifying the stress response for helping with anxiety, obesity, type 2 diabetes.
There's a whole toolkit there that you probably don't know about that you should because they're generally inexpensive and compliance is easy. Most of the things I prescribe are foul tasting herbal liquids.
These tastes like sugar, so it's fairly easy to get patients to take these long termsand then I can't imagine my practice without them. If you are practicing without them, you're really missing out on a wide range of therapy tools that can transform how you treat not just gut conditions but systemic conditions.
Dr. Adam Rinde: That's great and I'll put some links in the show notes to more information about prebiotics and the different types of prebiotics so that we can pack in some of that learning for the premise episode.
Thank you so much, Jason, for being with us today. This was really great. You took us through a journey about probiotics and prebiotics and various testing. It was very helpful and I learned a lot and thank you for sharing this time with us.
Dr. Jason Hawrelak: You're very welcome, Adam. I've enjoyed it thoroughly as you can tell. I'm going keep going for hours, but we can't.
Dr. Adam Rinde: Thank you and I hope to catch up with you sometime.
Dr. Jason Hawrelak: You're welcome.
[1] "Thryve Personalize." https://www.thryveinside.com/products/thryve-gut-health-microbiome-testing-personalized-probiotics. Accessed 29 Oct. 2019.
