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Kiran Krishnan, microbiologist, talks about the benefits and research on Spore-based Probiotics with Dr. Ben Weitz.
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Podcast Highlights
5:49 When Kiran was researching which strains of probiotics are most effective and have the most research, he kept coming back to the spore-based bacillus species. Because these probiotics are encased in a spore, they have the capability to survive through the acid in the stomach and the bile salts and the pancreatic enzymes in the small intestine. This is why most other, non-spore-based probiotics are killed by the time they end up in the colon.
6:59 The difference between soil based and spore-based probiotics is that most of the bacteria in the soil have no benefit for us in our gut as probiotics. Only a few of the bacteria in the soil are bacillus species and have endospores and these are the ones that can survive the trip down our digestive tract and are native to our gut.
9:35 If you do a Google search for spore-based probiotics, mostly negative articles come up that claim that they are new and that there are very few studies on them. This is the opposite of the truth. Some of the spore-based probiotic strains, like bacillus subtilis, have been used in most of the world (in Europe, Asia, and Latin America) as prescription drugs since 1952 and have thousands of studies on them. In fact, if you go to Pub Med you’ll find that some of these bacillus strains are the most well-studied of all probiotics.
15:32 Kiran explained that it is interesting to note that most people think that the strains like lactobacillus and bifido bacteria that you see in most conventional probiotics are the natural strains found in our guts. But this is not true, since the particular strains of lactobacillus acidophilus in the stores are different than the strains found in your gut. Many of these strains were first pulled out from a human volunteer 35 years ago and since then, they’ve been growing in a factory and the strain has completely changed and has adapted to life in the factory. And each of us have a unique set of bacteria strains that we first got from our moms.
18:26 Like conventional probiotics, spore based probiotics do not permanently colonize the gut. They do colonize the gut and adhere to the wall and outcompete bad bacteria, but they only last about 20-21 days. Then they form spores and leave the body through defecation and then find another host through being eaten in some dirt. Our primitive ancestors were consistently eating dirt since they could not wash their food before they ate it, so they were constantly getting exposed to these bacilli. Not only do these bacilli crowd out pathogenic bacteria, but they increase microbial diversity in our gut.
22:15 I asked when we do a stool analysis on our patients, why don’t we see these bacillus strains listed as commensal bacteria? Kiran answered that some of the panels will list bacillus subtilis under dysbiotic flora due to a misunderstanding. The resolution of some of the tests is not good enough to easily pick out the exact species and since we often have over 1000 species in our guts, but the tests usually do not list more than 15 or 20 commensal species, so they are not really a good representation of what’s in our gut. Stool tests that use culture are not very accurate, since 98% of the commensal bacteria are not able to be cultured in vitro outside of the body.
26:51 Bacillus subtilis produces a number of antimicrobial compounds that help get rid of pathogenic bacteria, including H. pylori. During World War II when the German army was in North Africa many of the troops were dying of dysentery. They noticed that when the locals would get sick that they would consume dried camel dung and that would cure them, so they started to do the same thing. After the war, they studied this camel dung and isolated the bacillus subtilis from it and in 1952 a German pharmaceutical company patented it as the first probiotic treatment for dysentery and gut infections. The bacillus gets into the gut, does quorum sensing, which is the ability to read the other bacteria signatures, and and produces more than 20 different antibiotics to precisely kill off specific pathogenic organisms.
30:31 One study has shown the bacillus clausii strain to be effective against IBS/SIBO.
37:03 These bacillus endospore probiotics produce various nutrients in our guts. Bacillus subtilis produces the enzyme nattokinase, vitamin K2-7, methylated B vitamins, and CoQ10. The bacillus indicus produces 12 different carotenoids: alpha carotene, beta carotenene, astaxanthin, zeaxanthin, lutein, lycopene, all at RDA levels and they will be absorbed 100%.
Kiran Krishnan is a microbiologist and researcher on Soil Based (Spore-based) Probiotics and designed the formulation in MegaSporeBiotic from Microbiome Labs. https://microbiomelabs.com/ https://microbiomelabs.com/products/megasporebiotic/
Dr. Ben Weitz is available for nutrition consultations specializing in Functional Gastrointestinal Disorders like IBS/SIBO and Reflux and also specializing in Cardiometabolic Risk Factors like elevated lipids, high blood sugar, and high blood pressure and also weight loss, as well as sports chiropractic work by calling his Santa Monica office 310-395-3111.
Podcast Transcripts
Dr. Weitz: This is Dr. Ben Weitz with the Rational Wellness Podcast, bringing you the cutting edge information on Health and Nutrition from the latest scientific research and by interviewing top experts in the field. Please subscribe to the Rational Wellness podcast on iTunes and YouTube and sign up for my free ebook on my website by going to drweitz.com. Let’s get started on your road to better health. Hello, Rational Wellness Podcastors. Thank you so much for joining me again today. And for those of you who enjoy listening to the Rational Wellness podcast, please go to iTunes and give us a ratings and reviews so more people can find out about our podcasts.
Our topic for today is spore-based probiotics. Probiotics as most of us know are live micro organicisms, usually bacteria, but sometimes also a fungi and other organisms that naturally grow in our colon, the rest of our digestive tracts, and other areas of our body. There’s increasing evidence that the healthy bacteria that live within us are crucial to our health for so many reasons, including for immune function, the production of various vitamins, cardiovascular health, brain health, we can go on and on about all the amazing benefits of probiotics for which the researches is proliferating. Today, we’ll be talking about a particular category of probiotic, known as soil-based probiotics that contains one or more species of bacillus, such as bacillus subtilis. Despite the fact that most of the probiotics on the market contain the more conventional species like lactobacillus acidophilus and bifidobacteria, spore-based or soil-based probiotics have actually been around for a long time, and have actually been studied quite a bit. Today we’re going to be speaking with microbiologist and researcher, Kiran Krishnan, who has been doing a lot of research on these spore, soil-based probiotics. Thank you so much for joining us today, Kiran.
Kiran Krishnan: Thank you for having me. It’s a pleasure to be here and always fun to talk about bugs, and dirt, and probiotics.
Dr. Weitz: Exactly. Tell everybody to eat some dirt, right?
Kiran Krishnan: Exactly. Go back to nature, back to nature.
Dr. Weitz: Exactly. Before we get into some of the technical questions, can you tell us a little bit about your background and how you became interested in soil-based probiotics?
Kiran Krishnan: Yeah. I’m a microbiologist by training and I did a lot of research work. University of Iowa is where I came from. When I was at the University, I focused a lot of my research work on virology, on viruses, studying viruses. In fact, I got to work on HIV vaccine project with using live virus. I worked on some … But then I also ended up working on a project on E. coli. E. coli such a fascinating organism in many ways we know our gut is heavily populated with E. coli. It’s a common commensal bacteria, but we also know that there’s the E. coli that causes disease. And so when people hear about E. coli, they immediately think that, when there’s numerous, very beneficial, healthy E. coli species in your gut. In fact, if you’re trying to eradicate it, it would actually cause way more problems and than any benefit.
This dichotomy of having the species that are typically talked about in a negative way, like E. coli, versus the reality of them being actually really important beneficial is what drew me into the realm of probiotics where I wanted to focus on organisms that theoretically from a microbiologist standpoint would be very beneficial. But the perception in the market was that there’s something bad about them or unknown about them. That brought me to the bacillus endo spores. The bacillus endospores really was a set of probiotic strains that we came across doing probiotic research for a large multinational. I had a research company which I still do have and we still do some research trials through that, but we were hired by a large multinational to study the probiotic industry for them, study the products that are on the market, look at the way products that develop, they’re formulated. Does it make sense to be refrigerated versus non refrigerated? Do we need 100 billion, or 50 billion, or 200 billion? Do we need 17 strains or five strains? And there’s so much variety out there in the marketplace. They wanted us to figure out what is really backed by science and what is really the right approach to probiotic use, and we came back to these spores, because we started looking that … We found that the vast majority of products in the market didn’t really have any scientific substantiation to them. There wasn’t any studies that showed that 100 billion CFUs was better than 50 billion, or that 200 billion was better than 100 billion. There’s no dose dependency in that way. There was also no studies that showed that 15 strains is any better than seven, or five, or three.
As it turned out, it was pretty much all marketing. When we dug deeper into what types of strains could really make a significant difference in the gut with measurable clinical outcomes, we kept coming back to these spores. Because the biggest thing about them is they have the capability to survive through the gastric system, so that passage through the stomach acid, the small bowel with the bile salts, which are very strong antimicrobials, and then even the pancreatic enzymes in the small bowel, that passage kills 99% of the bacteria that are used as probiotics. The vast majority thinks that dying these are getting through and it’s my tendency to always look at evolutionary biology for answers. So in my view, they were designed to be able to get through the system and go and function in the gut. Because of that, my inclination was that they would play a significant role in the gut, and as we’ve been doing our studies and looking at all the other studies that have been done, our inclination was sure that these are significant players in the gut, in the microbiome.
Dr. Weitz: Just to clarify. Can you explain what the differences between soil-based and spore-based probiotics?
Kiran Krishnan: Yeah, that’s really important. I’m so glad you mentioned that because a lot of people are familiar with soil-based organism products. There have been a few prominent products on the marketplace in the last decade or more. There is a significant difference between a soil-based product and a spore-based product. Soil-based product is typically a product that has a whole bunch of bacteria from the soil that are typically not very well characterized. They have some genus and species mainstream, but these bacteria aren’t very well characterized, and then they put them in a capsule and utilize them as a probiotic. The problem with that is the vast majority of bacteria that live in the soil really don’t do anything for us in the gut as a probiotic. Their job is in the soil. Their job is to break down plant matter, fix nitrogen for the roots, break down decaying animal matter, and so on. Now, exposure to them can be beneficial, because it up-regulates the immune system as it’s moving through, but those bacteria also die in the stomach, die in the small bowel, and you put them out 12 hours later. Now, spore-based organisms are unique in that you do find them in the soil. But the spore-based organisms actually live in the gut.
The difference is they use the soil as a vector to transfer from host to host, so when they leave the body, when they know they’re going out into the outside environment, they will cover themselves in this spore coat, which is basically a protein calcified coat that protects them from the elements outside the body. That allows them to exist indefinitely in the outside environment until they get swallowed again by a human or another mammal. They pass through the gastric system with this armor-like coating around themselves. The moment they get past it and they get into the small bowel, they will actually break out of this spore coat and become a live functioning probiotic cell. When we were looking at the environment for answers to probiotics, we basically went and refined it and dialed down to the types of bacteria in the environment that can actually survive the journey of being swallowed and then function as a probiotic in the gut. That’s how we came across these spore-based organisms as being more than likely the ones that will do most of the probiotic function.
Dr. Weitz: When you go on the internet and if the average person just does a search on Google for spore-based or soil-based probiotics, even if you put scholar in parentheses, there’s not a lot of good research that tends to come up. I saw several articles including one that looked like it was written by somebody from Scientific American claiming that there’s only one small study and there’s really no research on these things. Then I went to PubMed and you put in some of the specific names of the spore-based probiotics like bacillus subtilis, and you find out there’s thousands and thousands of studies there. What is the story about these spore-based probiotics. How long have they been around, and is there really good research on them?
Kiran Krishnan: Yeah. And I’m glad you bring that up, because I get that question a lot from people, because the vast majority of people, like you said, when they’re researching something, and the word research is a loose term when you use Google, right? When they’re researching something, they will go into Google and they will type it in and see what the first … Usually they’ll read only the first three or four things that come up. One thing that’s important to note about Google is that the first few things that come up aren’t based on their relevance or their accuracy in any way at all. It’s really based on the people who are behind it, doing good search engine optimization, so they’re back linking that link to many different websites and so on, and they’re putting a lot of content on the blog.
What I came to find out when I started looking into what is the market saying about the bacillus spores and finding all of these unfavorable write ups which, and I’ve read through vast majority of them, they’re all blatantly inaccurate in how they describe organisms, how they describe the microbiology of things, how they describe the microbiome and so on. I started digging into why are these out there, where are they coming from, and then you come to find out that many of these things are from companies that sell conventional probiotics and they basically pay people to put up articles about competitive types of probiotics to try to gain market share. And in fact, that was the main reason why we were hired by the large multinational company to do the research on the probiotics because they were looking at going into the soil-based or spore-based area and we’re seeing a lot of this misinformation on the web and wanted us to give them an overall real scientific review.
Now, when you look at the real science, which is like you said in PubMed and places where you can actually find scientific studies and papers, you’ll find thousands of research studies on bacillus subtilis. It is well known in the world of microbiology. They’re two of the most well studied bacteria in the world. We know more about these factor than any other bacteria that’s ever been discovered, and that is E. coli and bacillus subtilis. Bacillus subtilis is one of the most utilized bacteria in microbiology research. We use it in all different ways as bacteria transferring genes to another bacteria or as a way of testing things to grow on and exclusion media, all kinds of stuff that we do in directed evolution we use bacillus subtilis. It’s one of the most well known bacteria that have ever been discovered. The thing about the spores is they have been in the prescription drug market since 1952 in Europe, Asia, and Latin America. In two thirds of the world, the spores have been prescription drugs for well over 60 years. Their use is actually far wider and greater than the vast majority of probiotics that we’re familiar with in the US because they’ve been used in hospitals, clinics, doctors offices and so on as prescription drugs. And when you start looking at the number of studies that are behind the spores, it’s staggering. These are some of the most well studied organisms on the market with respect to their probiotic function in the gut.
Dr. Weitz: That’s really amazing, mind blowing. I don’t think most people are even aware of that. To just clarify, these spore-based probiotics are typically forms of bacillus bacteria including bacillus subtilis, bacillus indicus, bacillus coagulans, bacillus clausii, whereas the conventional probiotics are species like lactobacillus acidophilus, bifido, Saccharomyces boulardii, these are the conventional probiotics.
Kiran Krishnan: Yeah, and I would actually put Saccharomyces more in the bacillus subtilis category, closer to that. Saccharomyces is a fungal probiotic, but when you look at the environment we would actually naturally pick up Saccharomyces from the environment, because you naturally find it on the outer skins of fruits and things like that, that our ancestors and early humans would have just consumed on a regular basis. Same thing with the spores. Our ancestors got huge amounts of exposure of the spores just by living on the earth, eating dirt, not sterilizing their environment, drinking water out of rivers and streams. These are ubiquitous organisms in the outside environment. So as humans, we naturally gain a huge amount of exposure to them.
It’s interesting to note from a microbiology standpoint, the things that we consider to be conventional strains like lactobacillus acidophilus, reuteri, bifidobacterium, and all of these that you see in 99% of probiotics. Out there, people say, well, those are the natural strains. The difference is the versions of lacto and bifido strains that you see in products are not the native strains in the gut. Even though they have the same name lactobacillus acidophilus, your lactobacillus acidophilus that you have in your gut, my lactobacillus acidophilus I have my gut are completely different than the ones that you find in the products in the stores. Those are not native strains to the gut. Not to say that they don’t have any benefit of the gut, some of them do, some of them do up-regulate the immune system, can control diarrhea, and things like that. But this concept that those are native commensals strains is totally erroneous, because they’re not. The moment you pull out a strain like that from a human volunteer, 35 years ago, whenever they first isolated the strain, and since then they’ve been growing it in a factory, the strain has completely changed. It’s adapted to life in the factory than life in the gut. And as it is, we all have a unique set of lactobacillus and bifidobacteria in our microbiome anyway, right? No two individuals have the same distribution of those types of bacteria and our type, our version of the bacteria we got from our mom, and she got from her mom, and she got from her mom, and so on. Even identical twins born in the same mother will have up to 50% difference in their microbiome. All our strains in our gut are completely unique. And so to think that the lacto bifido stuff you see at the store on the shelf are natural native bacteria, they’re not out there. They’re outside bacteria just as much as any of the bacteria are.
Dr. Weitz: Interesting. Now, we’ve learned that despite the fact that a lot of people don’t necessarily understand this, is probiotics don’t typically colonize the gut. They’re just temporary visitors there. Even though sometimes functional medicine practitioners will do a stool analysis and see that the person is low in a particular type of probiotic and may have the person ingest a product that has that particular species and even strain, those that you ingest actually are just there for a short period of time. Now, we know that they help with developing a healthier microbiota, but they don’t permanently colonize our gut. What about sport based probiotics? How do they work?
Kiran Krishnan: Yeah, and you’re right that they don’t permanently colonize. Most of them just kind of move through like food does. Spore-based probiotics are interesting because they are designed by nature to leave the body, spend some time outside, and then come back in through the oral route, so through being consumed. They are perfectly adapted for that type of cycle, leaving through defecation and then re entering through oral consumption. Now, they do survive through the gastric system. They do get in the gut, and they do colonize, but as it turns out, they are transient in a way that they only colonize and stay within the gut for about 20 to 21 days. And when we initially discovered that, through some of the research we were doing, we were actually surprised, but then when you think about it, it makes complete sense.
The question I had in my mind is okay, if they’re so good at colonizing, meaning they’re really good at attaching and out competing bad bacteria and kind of changing the environment that they exist in. Why is it that they don’t just stay? Why do they leave? Well, two reasons. Number one, it’s we’ve developed this long term symbiotic relationship with them where we provide them a home and then they basically clean up the home for us. And in order for them to get transferred from host to host, to propagate themselves, they actually have to go out into the environment because they use the environment as a vector to transfer from host to host. And when you look at epidemiological studies and other types of environmental studies, they find that these bacillus spores are found in every corner of the earth and have been for millions of years.
Glacial ice core studies, for example, where they put long pieces of cores of ice out of glacial ice that measure few million years back into the Earth’s atmosphere, they found these spores in high abundance in the Tibetan plateaus in the South Pole in the North Pole. They’re virtually everywhere. And the way they get around is they use the environment, the air, the wind, the water to transfer to all of these regions. They need the environment as a vector to move, and so that’s one of their motivations coming out. The second thing is our ancestors if you imagine, would have gotten huge exposure levels to them on a regular basis. And if they never left at some point, they may be too many of them in the gut. What we want to do is promote the diversity within the gut and not have too many of any one species and so they’ve designed their own threshold level in the gut that they will not exceed. If any given area of the gut exceeds a certain threshold level of these spores, they will sporulate and they will leave.
Once they achieve what they think is their healthy balance, they will just continue to leave at the same rate that they’re coming in. And that’s very interesting, because as it turns out, once they get into the gut, one of the big effects of having these spores in the gut is a dramatic increase in diversity of the rest of the microbiome, and that’s never been shown with other probiotics. No one has ever published a research study showing that when you add any of these other conventional probiotic products, that it actually has any impact on the diversity or the population of the microbiota. We are submitting a paper for publication this year, showing that when you add the spores, in some cases, that almost doubles the diversity of the rest of the organisms.
Dr. Weitz: Wow.
Kiran Krishnan: Yeah. They get in there, and they affect change so much that they increase the growth of all of these underrepresented beneficial organisms.
Dr. Weitz: Interesting. How come when I get a stool sample back, that functional medicine based stool analysis that looks at the range of commensal bacteria, I don’t typically see these bacillus strains listed among them?
Kiran Krishnan: Now, some of the tests will, but some of the tests will list them under dysbiotic flora. When you look under the dysbiotic flora category, they’ll show bacillus subtilis, which again is just kind of misinformation and inaccuracy. And they don’t look for any of the other bacillus species. They just don’t know enough about them. There’s a lot of issues with stool testing. The ability to be very accurate with stool testing is really poor. Recently, the head of the American microbiome research which is based out of University of California in Davis, University of California, Davis, Rob Knight, he heads up American gut project. He’s a top microbiome researcher in the US. He came out with the papers and findings that the type of sequencing that’s used in pretty much all of the commercial stool testing systems is incredibly inaccurate.
The resolution is really poor is the problem. You can get down to this genius level, but you really can’t get down to the species level that accurately, so it’s very hard for those tests to identify all of the different species that could exist in the gut. And then their relative abundance as well. That’s another problem because you could have 1000 different species or 1500 species in your gut, you don’t get a stool test report back listing 1500 different species bacteria. You might get 15 or 20 that show pluses and minuses. It’s not a great representation of what’s actually going on in the bowel to begin with, and so certainly it doesn’t pick up on the vast majority things that actually in the bowel.
Dr. Weitz: Does it matter if we ordered a stool test that’s culture based versus PCR based?
Kiran Krishnan: No, it doesn’t matter because the culture based ones are severely limited because 98, 99% of the commensal good bacteria in your gut are not culturable in vitro outside of the body. They’re really hard to grow them because they’re strict anaerobes. The moment you pull them out, they start to die being exposed to oxygen. The PCR DNA based ones still use something called 16 S sequencing, which is low resolution and you can get a lot of false negatives. Just because it doesn’t show it on the test doesn’t mean it’s not there.
The other issue with the stool sample is the bacteria in the stool is not homogeneously distributed, right? That 15, 20, 25 grams sample that you’re taking is not a representative sample of the rest of the microbiome because you’re just looking at what’s in that sample. If you had taken a sample from a few inches away, it could look completely different. And you’re also looking at bacteria that’s being shed. Not necessarily bacteria that’s sitting in the mucosal well attached proliferating. The other thing is if you look at the manual for the stool testing, you’ll see that even in their manuals, they say that stool tests are representative of the micro flora and the distal colon. So it’s really a distal colon sample and it’s a snapshot in time of the distal colon. It doesn’t tell you anything about the ascending and transverse colon, it doesn’t tell you anything about the small bowel and so on.
It can be a tool to use. I in particular like the functional side of the stool test when you can look at things like short chain fatty acid production, secretory IgA, fatty acid degradation products, protein degradation products, that gives you a little bit more insight into what’s actually happening in the bowel. The microbiota component, what backers there, and what’s at high level, what’s at low level. That stuff is still very much in its infancy, and it’s almost never used in clinical trials for that reason, because it’s really hard to make any sense of it.
Dr. Weitz: Wow, interesting. Interesting. In some of the reading I did, I understand that bacillus subtilis strains can produce a variety of antibiotic, anti microbial compounds that can help crowd out potential pathogens in our gut including H. pylori. Can you talk about that?
Kiran Krishnan: Yeah, actually there’s an interesting story behind that, and the way this was discovered is actually, that’s where the interesting story comes from. During World War II when the German army was in North Africa and they had a whole campaign in North Africa, the vast majority of German soldiers were dying of dysentery because of the food and water in that part and their bodies weren’t used to it, their guts weren’t used to it. But they also noticed that the locals when they would start to get sick, what they would do is they would look for dried camel dung and they would consume the dried camel dung, and that would basically heal them of the gut infection. They took a bunch of this dry camel dung back and started studying it in Europe to figure out what is it within the dried camel dung that was curing the dysentery and they isolated the bacillus subtilis strain.
The bacillus subtilis strain from further research that they did was shown to have this capability of getting into the gut and then doing something called quorum sensing, which is the ability of bacteria to read other bacteria signatures, and they can find pathogenic or unfavorable organisms. They’ll sit next to them, and they’ll produce upwards of 20 different antibiotics to kill off that organism. But it does it in such a precise position manner versus when you think about taking an antibiotic prescription, which is like an atom bomb for your microbiome, right? It basically kills everything and it kills everything very quickly. And so, this is like a precision SEAL Team Six type of attack to those pathogenic bacteria. From that very research in the late 1940s, by 1952 a big German pharmaceutical company launched the first probiotic treatment for dysentery and gut infections from that work and that product is still in the market today. It’s been over 60 years and it’s still prescribed and used because it’s so effective.
Dr. Weitz: That’s amazing, and you just hear all these spore-based probiotics, they’re new, they just came on the scene, we hardly know anything about them. It’s pretty much the opposite.
Kiran Krishnan: Absolutely. They’re the most widely used probiotics in the rest of the world, and they’re using it in the medical setting, not even so much in health food stores and things like that. Their use has been very well documented because they’ve all been prescription drugs, and as prescription drugs, we know that there’s something called post market monitoring where all the adverse events and all of the negative issues that could about when a product is in a health food store, you might never know about it. But when it’s a prescription drug and doctors managing it, those are all reported and it’s all made public. The fact that these strains have been used as prescription drugs for over 60 years and there’s so few adverse events or reports to them is really fascinating. It means that their level of safety and efficacy is unparalleled.
Dr. Weitz: I understand that there is at least one study using these spore-based probiotics for IBS/SIBO.
Kiran Krishnan: Exactly, yeah. In fact, bacillus clausii, one of the species that we work with in our product MegaSpore has a great published study showing that the bacillus clausii can reduce the overgrowth of organisms in the small bowel just as well as any antibiotic can, but it does so in a way that doesn’t disrupt the rest of the microbiome.
Dr. Weitz: I understand that you helped design and formulate the strains in the MegaSporeBiotic?
Kiran Krishnan: Yeah, exactly. When we came across these bacillus endospores and started to really understand their value in probiotic therapy and also manipulation of the microbiome for favorable outcomes, we saw that on the market in the US there was really only one strain that was marketed and used widely and that was bacillus coagulans. And then bacillus coagulans strain and product had actually been in the retail market for 10 years or so at that point. It was the one and only used one, but then there’s so many other useful spores that we went ahead and created the first multi spore probiotic product on the market and that’s the MegaSporeBiotic product.
We made that available only through physicians and health practitioners because it requires education. The product is really powerful. It has a lot of therapeutic benefit. It’s really stuff that only healthcare practitioners, physicians, can understand and convey to their patients. And so we made it available only through physicians. Now, we’ve engaged in a significant amount of research because in our view, when you have a multi spore product, and assuming you have the right spores, and they are in spore form, and they can survive through the gastric system and do colonize. And that’s something important to talk about because there are differences among spores as well. I’ll mention that after this part. But what we saw was there could be significant therapeutic benefit to having a multi spore product. And as it turns out, we published our first study on the multi spore product in August of last year.
We have completed five other studies this year, which are all being written up right now and submitted for publication. And we have five or six other studies going on at the same time. In total, we’ve got 12 clinical trials either completed or ongoing on the multi spore product. From what we’re seeing so far, it’s quite fascinating, and our goal has been the moment we formulated this product, was to quickly become the most well researched probiotic formulation on the market because we want to dispel these myths. We want to dispel these nonsensical assumptions that are being made out there and we want to show through research that these spores have such important and significant functions within the gut. One thing I want to mention, so then, now we’ve seen other spores coming out and we’ve been testing them, so other companies are saying, “Hey, we want to do a spore product too and they’ve been coming out. What we find is that there’s a couple of issues with the types of spores that they’re selecting. Number one, their spores are not completely in spore form in the product, right? That’s part of the technology that it took us almost seven years to develop was, when you grow these bacteria, they’re not in spore form. When they’re in spore form, it means that they’re metabolically inactive. They’re not multiplying, they’re not doing anything really, they’re just kind of sitting there inertly waiting to be consumed, to come out of this spore state, to becoming a live, functional, vegetative bacteria. When we were growing them in a fermentation tank to multiply them, we are growing them as a vegetative bacteria not as spore bacteria. They go into the spore form under conditions of stress and duress. That’s their way of protecting themselves.
What we found is that we’ve developed a way to be able to take this big 15,000 liter tank growing with trillions and trillions of spores in there, and then add a stress to that environment so we can get them all to go into the spore state, and then extract them in the spore state, and we were able to extract them 100% as in a spore state. What we see in other spore-based products is that about 50% of the strains in there are not in spore state, they’re in vegetative cells state. Now the problem with that is when spore forming bacteria is not in its spore state, it’s in its vegetative state. It’ll also die in the gastric system, like any other bacteria will. Only the spore state protects it. So some of these other products coming out, we’re seeing that they’re dying in the stomach, like any other probiotic product would and they’re not necessarily selecting spores that have shown the ability to colonize. Because there are spores that you can find out in the environment that will also move right through because they don’t express the right proteins in order to adhere to the mucosal layer and actually colonize. Those are two very important things that one needs to look at when they’re trying to find and develop a spore for product for use as a probiotic.
Dr. Weitz: Interesting, interesting. How do you create stress in a spore-based probiotics? Do you show them clips of the News or something?
Kiran Krishnan: Exactly, yeah. That’s all you have to do, right? Just show them two or three News sources.
Dr. Weitz: Just show a loop of Rudy Giuliani.
Kiran Krishnan: Right. Let them go on Facebook for 10 minutes and they get stressed out. We do it through manipulation of the nutrients that are in there because the thing is you don’t want to stress them too much too fast or you will kill some of them. You want to create a really calculated stress where you give them a chance to go into their spore state and then you can extract them out into that spore state.
Dr. Weitz: A couple of other things I saw in some of the reading I did it that I thought was particularly interesting is bacillus subtilis helps to produce natto, which is one of the best sources of vitamin K2, particularly MK7 version, which is so important in reducing arterial calcification.
Kiran Krishnan: Yeah. In fact, one of the things that’s really interesting about the spores to me, which some of my earlier work, I was the first guy to bring nattokinase, if you remember that enzyme, to the US back in 2000. I was working with the Japanese company to make nattokinase from bacillus subtilis, actually, the natural fermenting bacteria and then develop ways to extract the nattokinase and then bring it into the US as a fibrinolytic enzyme. One of the fascinating thing about the spores is that they are nutrient factories as well. When they get into the gut, they basically sit there, like the bacillus subtilis does, and when food comes in, they start fermenting and breaking down the food and converting them to things like vitamin K2-7 like you mentioned, but also methylated B vitamins. They produce ubiquinol. They produce CoQ10. And one of our strains, which is a unique strain called bacillus indicus, produces 12 different carotenoid antioxidants in the gut for you, which is fascinating. It produces alpha carotene, beta carotene, astaxanthin, zeaxanthin, lutein, lycopene, all at RDA levels. Right at the site of absorption, right? They are the most bioavailable antioxidant, carotenoids that you can get into your diet, and they’re produced by bacteria sitting in your gut. It’s a fascinating role that these bacteria play and the mutualistic relationship we have with them with this in this regard is really fascinating to me as a microbiologist because somehow we have created this communication with them that, “Hey, go into our gut. We’ll give you a home. Our immune system recognizes you as a normal part of the flora.” Our body is not trying to attack them, and so we give them a residency and in turn, of course, they kill the bad bacteria and get rid of them. They increase the growth of the good bacteria. They seem to be sealing up leaky gut, which is the study we published last year, and then at the same time, they produce the all of these nutrients for us that are directly absorbed into our intestinal lining, so it’s a really fascinating relationship we have with these bacteria.
Dr. Weitz: Wow, amazing. Are you going to consider looking at the relationship between the indicus and macular degeneration because all those carotenoids have been well studied as helping to reduce the risk of chronic macular degeneration, which is one of the most common degenerative eye diseases.
Kiran Krishnan: Yeah. In fact, the rates of them are increasing the US and there is some talk that all of this blue light exposure that we get on a regular basis from screens and things like that are accelerating some of that and those are all theoretical, as I understand them right now, and not proven yet, but kind of makes sense when you think about it. But we are working with a neuro-ophthalmologist and we are looking at designing some studies around that. Because when you study carotenoids as a supplement, what you find is that the bio-availability of carotenoids as a supplement is less than 10%. It’s really hard to absorb carotenoids that are trying to pass through the gastric system, the small intestines, and actually gain exposure to the intestinal lining for absorption. Studies have been done on pure beta carotene, and they find that pure beta carotene by availability is a little less than 10%. When you compare beta carotene from the spores, it’s 100% bio available, because it’s produced right at the site absorption, past the gastric system. I really believe that they are the most important sources of these carotenoids and antioxidants that we’re supposed to be getting in our diet.
Dr. Weitz: Wow, really amazing.
Kiran Krishnan: Yeah. Is that fascinating? And here’s what’s interesting. This indicus, that strain, one of the ways it was discovered was a huge European consortium study called The Color Spore Consortium. There was, I think, 14 different research institutes involved. They spent about five and a half million euros on funding this and what they were looking for are bacillus strains that produce carotenoids in the gut. And the reason they even thought of that is when you look at certain animals in the animal kingdom that express a lot of carotenoids on their skin, like flamingos are pink on their feathers because of a carotenoid. Salmon skin is pink because it’s of carotenoid stream, with the orange bands, those are carotenoids that they’re expressing. The question is where do they get their carotenoids from, because they don’t eat colored fruits and vegetables, right? The investigation showed that these animals all have a probiotic bacteria in their gut that produces such high levels of carotenoids for them that it shows up on their skin. And then they said, “Okay, if those animals have those bacteria, there’s a good chance that humans have similar bacteria and are humans supposed to get our carotenoids from bacteria or we’re supposed to get it from the diet?” So they started looking at dietary carotenoids both from foods and supplements, and the bio availability of them had found that those were dramatically lower than we thought, and then they started looking, are there strains in the gut that produce carotenoids? And they found indicus in a couple of the strains that actually do.
Dr. Weitz: Fascinating. Really, really interesting information. Well, it’s been a great podcast, Kiran. Thank you so much for bringing us such great information. Anything you want to say about the products you’re working on and the availability?
Kiran Krishnan: Yeah, absolutely. And then again, thank you so much for having me. I love any opportunity to try to dispel myths and clarify rumors and things like that. I think accurate information in our world today is a rare thing as we know in every facet of our lives, and especially when it comes to your health and wellness, having the right information is really empowering. The product that we work with healthcare practitioners and physicians with is called MegaSporeBiotic. You can find a lot of information about it and also about our research and webinars and all that stuff if you go to our website at microbiomelabs.com. That’s labs with an S at the end of it, and microbiomelabs.com. And of course people can get the mega spore product through their physician, through their practitioners such as yourself. We believe you should always be working with a health professional with your supplements anyway. Because they have the capability of vetting the nonsense from the stuff that really makes sense, and so you’ll get your best bang for your buck. You will get your right nutritional therapy from your health practitioner. We thank you for this opportunity and the ability to talk to you about this product.
Dr. Weitz: Awesome. This has been great. I’d love to catch up with you again sometime in the future.
Kiran Krishnan: Yeah, let’s do it again. I look forward to it.
Dr. Weitz: Sounds good. Keep up the good research. Talk to you soon.
Kiran Krishnan: Thank you.
Dr. Weitz: Okay.