Microbiome Deep Dive: Probiotics, Prebiotics, Postbiotics, and Psychobiotics

Michael Roesslein:

And this time we are recording. I am Michael, I’m your host. I’m here with Kiran Krishnan, microbiologist and microbiome expert, re-recording a conversation on probiotics, prebiotics, post, para, ghost biotics, which is a term I learned from you last time, and psychobiotics. So all things biotics. First, Kiran, thank you for coming back to record with us again. And second, this was a really interesting topic. I thought I knew a lot about these things and I learned a bunch of stuff last time, so I’m going to ask pretty much the same questions we did on the webinar and we will get through those. And I do have some Q&A we can throw in at the end that we didn’t get to last time, so it’s actually a bonus.

So let’s start with the term out of that list that everybody is most familiar with, which is probiotics. Now, that’s a huge, huge term and it has been for a long time. There’s a lot of products and foods and things and stuff on the market all over the place. They talk about it on the TV, it’s in the newspapers, it’s a buzzword and it has been. Let’s clear up a few things, and if you could just define what is a probiotic and what is not a probiotic.

Kiran Krishnan:

So the assumption is that anything that’s a bacteria that could be beneficial is a probiotic. And that’s a misnomer, because there is a widely accepted scientific definition of what a probiotic is, and that’s a definition that’s been laid out by the World Health Organization in accordance with cooperation from lots of scientists across the world. And the definition is, a probiotic is a living organism, when administered inadequate amounts confers a health benefit to the host. So there’s a few important things to unpack there. The first part is a living organism. So the intent of a probiotic is, it’s an organism that works when it’s alive, and that means working alive in the body or on the body or wherever you want to administer the probiotic. If you can prove that it’s functioning alive in the human or on the human system and it’s conferring a health benefit to the host, then it can be considered a probiotic.

But surprisingly, the vast majority of “probiotics” that are used don’t meet that definition, that very first part of the definition, and we’ll unpack that a little bit more. The second part of the definition, administered in adequate amounts, which implies that there is a dose understanding of the probiotic strains. Where you could show that at half a billion there’s a marginal impact and then 1 or 2 billion the impact gets bigger, and at 5 billion then it’s diminishing returns. So there’s somewhat of a dose response where you can actually demonstrate clinically that there is an adequate amount that you give. And we’ll unpack the dysfunctions in how probiotics misuse that component to it. And then of course, the final part is, conveys a health benefit to the host. So you do have to prove that there is a health benefit to the host. You can’t have a presumption that there is a health benefit to the host just because the strain is this and this is what the supplier says and so on.

So this is where a lot of things go awry. So there’s three parts to the definition that we’ll work on unpacking. The first one is a live part, the second one is the dosing part of it, and then the third part is the health benefit component. So going back to the live one. Number one, if it’s a probiotic that you ingest, for it to meet the probiotic standard you have to prove that it can survive through the gastric system, which is starting all the way in the mouth. In the mouth you’ve got secretory IGA, alpha amylase, and some bactericidal components. So those don’t kill it depending on how you’re consuming it, whether it’s a capsule or food. If it makes it past the mouth, it gets into the stomach, it has to survive stomach acid. If it can survive stomach acid, it gets into the small bowel, it should survive things like bile acids and pancreatic enzymes, all of which kill microbes.

So there’s quite a bit that the microbe has to go through in order to survive to get to the site of action, which typically is either a part of the small intestine or it’s the large intestine, for many microbes. It has to get there alive and function to a certain degree alive in order to meet the definition of a probiotic. Now, in the industry that’s one of the primary parts that gets misused. For example, probiotic foods and probiotics in candy and probiotics, topical products, probiotic lotions, all of these things, all these kitchen sink probiotic products that you just throw together with the assumption that it’s working and it’s surviving. When you test most of those, they don’t really survive. Even if you look at things like kombucha, if you look at things like yogurts and kefirs and all of these fermented foods, the magic of the truly fermented food isn’t in that microbe surviving and getting to your gut and living in your gut. It’s in what it did during the fermentation process and you ingesting the fermented components.

We’ll touch on that deeper when we get to things like postbiotics and so on. But ultimately, for something to be a probiotic it has to meet that first part of the definition. And there’s been a good amount of regulatory and legal action in different countries for companies that don’t meet that criteria. Now, the US is a much looser place than Europe, for example. In Europe, in most countries you cannot use the term probiotic. Probiotic is in itself a health claim. And so none of the probiotic products in Europe are called probiotics. They don’t even use the term. And if you do it, you’d better have substantiation that it meets that first definition at the least. And so now countries are starting to get a little bit looser about how you substantiate it, but probiotic has a very definitive meaning.

In the US, where you’ve seen action taken is through class action lawsuits. Some of the most prevalent ones are probiotics in food, where people just add bacteria into food products, post-production often, and these bacteria don’t survive the packaging, they don’t survive shelf life. They’re just there. It just says probiotic on the package, it means absolutely nothing. Or in cosmetic or topical products, where they call it probiotic lotions, probiotic skin care. They’re taking gut commensal organisms. Well, they’re supposed to be gut commensals, adding it to things like lotions and all that, with this crazy presumption that somehow those are living and doing something on the skin. And they’re not.

Same thing with pet probiotics. A lot of times pet probiotic products are human strains that are now just being added to pet snacks and foods with zero substantiation that they survive through the digestive tract of the pet, and that even if they survive that they do anything in the pet. So in the US in general, people dramatically abuse the word probiotic. They just call anything that has a bacteria in it a probiotic. When the vast majority, I would estimate at least 99%, of the things out there being called probiotics don’t actually meet that first part of the definition.

Michael Roesslein:

Wow, that is a pretty low success rate of meeting the definition. And I’ve noticed since moving to Europe that the languaging around supplements and the rules around supplements is much more strict and that it’s almost impossible to even get anything shipped from the US to here because of the rules that are in place and everything else.

Kiran Krishnan:

Yeah, you can’t ship a probiotic with a US label that says probiotic on it into Europe. They don’t allow that.

Michael Roesslein:

No, we used to be able to, but we run into a lot of problems now. And then I can’t get things, I have to go through distributors that are in Europe with different labels and different packaging on them. So we’ll talk more about what you mentioned, because it’s really interesting about the kombucha or the yogurt or the different things and that the benefits likely come from the metabolites of the organisms that are in those foods and the byproducts and essentially waste or other things they’re producing. But we’ll talk about that more in a minute.

When we did the webinar, you mentioned the importance of having clinical tests or research on the strains. And not only bifidobacterium or lactobacillus, but it has to be the specific strain of the organism that’s used in the product, in the amount that’s used in the product. And if there’s multiple strains in the product, they need to have been tested together. You can’t just go and look and say, “This has tested to do this. This has tested to do this, this has tested to do this. Let’s throw them all in here together and then they’ll do this.” Right? Is that a good summary?

Kiran Krishnan:

It is, yeah. And again, there’s a lot of presumptions being made. And actually that particular reason alone was the reason we came into the probiotic space. Because I would look at all these products, and I never took a probiotic because none of it made any sense to me from a microbiology perspective. And then I met a clinician, Tom Bain, who was my cofounder at Microbiome Labs, who was running a very successful practice in the north side of Chicago focused 90% on gut health. He worked through almost every chronic issue with his patients, starting with the gut. So he had a big gut practice, and he was not using any probiotics, which was a really surprising discovery to me when I met him. Because I said, “Oh, here’s a clinician. He must know a lot about probiotics, and I want to talk to him about what he uses and so on.”

And as it turns out, he wasn’t using any probiotics because intellectually it didn’t make sense to him either, the approach that we’re taking, and then he would see clinically lots of issues with how people reacted and how these things function. In many cases it made them worse. And so we could talk about why that is as well. So you’re absolutely right, and this goes back to the second part of the probiotic definition, which is that administered in adequate amounts. Because that basically conveys that you have to have some understanding of what the bacteria is doing in the system and at what doses it is effective. Because you can’t just take a strain that is, let’s say it’s shown, a single strain that’s shown to have efficacy at 3 billion CFUs per day. And then you go, “Oh, I really like that research. I’m going to take a hundred million of those, sprinkle it on my yogurt product, and call this a probiotic infused yogurt product.”

It doesn’t meet the definition because now you’re at 1/20th the dose that’s effective, that’s been determined by science. But the only way you would know that is if you did the research to figure out what the effective dose is. In that same vein, the probiotic industry just goes through and mixes things and all that non-specifically. And we have come to find out, we had hypothesized this for years, but we’ve come to find out now through work that’s being done at the University College Cork in Ireland that when you mix a lot of these microbes, they actually can knock each other’s functionality out. Microbes are inherently competitive with each other. They may have genes or genetic elements that cancel other microbes’ functionality out, and in fact, that’s how they live in an ecosystem. When you bring a bunch of microbes together in your gut, they find ways to compete with each other, and that competition actually creates a stability in the ecosystem. So this is very natural for microbes to do that.

So when you bring this bacteria and this bacteria and this bacteria, throw them all together and assuming they survive, they could very well be competing with each other. And we have a really great example of that. We launched a psychobiotic strain, and we’ll tackle what a psychobiotic is, but we launched a strain, 1714. It does amazing things in terms of reducing stress, reducing anxiety, changing brain wave function, reducing cortisol and all the inflammation. So it does all of these wonderful things. All of those functionalities come out of one gene from that microbe. And it’s a very unique bifidobacterium longum that has that gene, and every other bifidobacterium longum does not have that gene. So this is where it also starts to fall apart, because like you said, it’s very strain and subspecies specific. Because you could take all the research from this bifidobacterium longum 1714 and get a generic bifidobacterium longum out of China or somewhere else, and use this research to substantiate this product when it doesn’t do any of the same things because it’s missing that gene.

Then on top of that, this single gene gets inactivated by most of the bacteria that you mix it with. So we found that if you took this bifidobacterium longum 1714 and mixed it with a different bifidobacteria or adolescentis or animalis or infantis, for example, it’ll knock out its effect. There are some strains that it mixes well with that it doesn’t knock out its effect, but you only know that if you do the studies. So that’s a perfect example of a highly beneficial strain with lots of research where we know the specific dose, and we were offering that strain as a bulk ingredient in the probiotic industry. And what every company wanted to do who bought the product or who was looking at buying the product, was they wanted to put it in a hodgepodge of 15 other strains. And so we refused to sell it to them.

We said, “It’s not going to work. You’re going to use the research, you’re going to give people false hope, you’re going to throw it in with all these other species, and it’s not going to work because these are going to knock each other out.” So microbes are highly complex. They have thousands of genes, they make all kinds of proteins, so you have no idea what they’re going to do unless you study it. And how much is effective becomes a very important scientific exercise. How much is too much? How much is too little? You have to know all those things, and that’s where the probiotic industry continues to falter.

Michael Roesslein:

That’s really fascinating. I always enjoy the behind the scenes insider industry info we get when we chat with you, and you don’t have to answer this, but I’m curious how many of those companies didn’t care that the probiotic wouldn’t be effective if they added it to the formula.

Kiran Krishnan:

Oh, not a single one. Yeah, they didn’t care at all. They were going to put … Most of the time what they would do is that they would go, “Okay, we love this strain.” We’d meet them at a trade show convention or something like that. We’re there with our booth and we’ve got technologies, we have ideation and all that, and they’ll come to us, and these are big retail probiotic companies. They’ll come to us and go, “We need something for stress and mood. That’s a big thing that our customers are looking for. This is fantastic. You’ve got a psychobiotic with great substantiation.” “Okay, great. How are you going to use it? Let’s talk about formulation, what you can mix it with, what you can’t mix it with.” “Oh, we already have a formula with these 13 strains. We’re going to add it to that.” “Okay, well, that’s not a good idea because it’s not going to work. So we don’t recommend you add it, you use it as a single product.”

“Well, no, we can’t do that. We have to add it in and we want to use the research because it improves the claims on this hodgepodge of nonsense that we put together, because your strain has all these research studies on it.” And we’re like, “You cannot use the research if you mix it with all of this stuff, and you have to add it in the right amount.” And they’re like, “Well, we can’t add it at 2 billion because this mix becomes too expensive, so we’re going to put 500 million in with 10 other strains and use your research to substantiate this product.” And they absolutely don’t care. And so you have to be very wary when you look at any probiotic product out there in the market that has eight, nine, 10, 15, 20 strains in it, and you have to ask the companies, “Have you done at least one study on that finished formulation to show that it does anything?”

99.999% of those companies have not done a single study on that mix. Very few have. There’s a couple, like VSL3 has this crazy hodgepodge of microbes in a few of the products, and they’ve done some studies on it. So there’s a few of them out there, but the vast majority, especially the ones that use a lot of fancy marketing, they do a lot of advertising, they’ve got this really cool look and influencers and all that. It’s just nonsense. And to me, it really irks me because I see people spending their money, $50, $60, $70, hard earned dollars buying this crap, and it’s doing absolutely nothing for them.

Michael Roesslein:

There are some that are way more than that.

Kiran Krishnan:

Well, yeah, it’s absolutely crazy. And this is all disposable income. This is not stuff that’s covered by people’s insurance and so on. So it’s just their hard earned dollars that they’re not using for something else or not saving, and it’s because they need help. And these companies are absolutely taking advantage of people. And then the last part of the definition is confers a health benefit to the host. And it rounds out everything, where you have to prove that your product confers a health benefit to the host. Now, 99.99% of companies, here’s what they do. They throw a bunch of strains together, and the way they decide how many strains and what CFU count they’re going after is because they compare it to the company, the brand that they’re competing with the most in their channel. If it’s a health food store brand, they look at which brands have more shelf space than them, and they’re trying to compete with that brand.

So if brand A has 15 strains and 20 billion CFUs as a claim and they’re trying to compete with that brand, what they would do is they’d create a product with 20 strains and 25 billion CFUs to look more potent. And then they’d try to bring the cost down by a couple dollars to make it more price competitive, which means that their quality has to go down even more. They have to buy even cheaper strains to put more at a cheaper price. And then the basic claim that everyone makes is, “Supports immune health, supports digestive health.” The understanding in the industry is that you could basically get away with that. The regulatory bodies aren’t really going to question that. That’s a very general claim for probiotic bacteria. They’re not really going to question it.

So don’t do any studies. Formulate the product in the lowest cost way to compete with your biggest competitor, throw in as much as you can, and just slap on there, “Supports immune health, supports digestive health,” and then spend all your money marketing. That is the formula, and it’s still the predominant formula today. Microbiome Labs, when we founded it, was founded to fight against that approach.

Michael Roesslein:

And you guys have published tons of studies, so I wish I could say that I’m surprised, but it’s not just the probiotic industry that operates like that. It’s most industries that operate like that that have anything to do with food or supplements or any of that. So thanks for sharing all that, makes a lot of sense, and it makes a lot of sense why so many people have hit us up and been like, “Hey man, I want to try your probiotics that you guys have in your shop, but I’ve tried a bunch of probiotics and they don’t work and I feel sick.” And I had quit, I’ve told this story a million times on recording, so I won’t get into it, but I had quit using probiotics in my practice because the results were so random. Some people would be like, “Oh, I felt great.” I’d give the same thing to another person and they’re like, “Dude, I get bloated if I eat anything.” And it’s like, man, why does this not work?

Kiran Krishnan:

Totally.

Michael Roesslein:

So thank you for sharing all that. Let’s jump into prebiotics. Pre usually means before, but in this instance this is food for bugs. And so prebiotics can be foods, prebiotics can be supplements. A lot of people with digestive issues who are in our audience may shudder at the idea of prebiotics because they’ve eaten the wrong foods or taken the wrong prebiotics. And if they have something like SIBO or some other overgrowths in their gut, this could have caused a very distended belly and problems with digestion. So can we just do a quick, what are prebiotic foods and supplements and why do a lot of people with GI issues have problems with these foods? And then on the flip side of that, the conundrum is that these things are essential for healing the gut from the problem that doesn’t allow them to consume them. So let’s just jump into that.

Kiran Krishnan:

Yeah, exactly. Okay, so a few things there. Number one, so prebiotics, and there is a specific definition for prebiotic as well. There are certain ingredients that have been authorized to be called prebiotics. So things like inulin, oligosaccharides, normally the things that are authorized to be called prebiotics are smaller molecular weight but highly complex structures. So they have all of these really complex carbon bonds in their glucose or fructose monomer structures, which means that every prebiotic and carbohydrate and all that are made up of glucose or fructose or galactose monomers. So these are individual units of sugar that are bound together with complex bonds. So the most basic carbohydrates are the things that we call high glycemic carbohydrates, tend to have very simple structures, so they break down easily and release a lot of sugar. So when you think of simple carbs versus complex carbs, so that’s where the idea of complex came from. It’s referring to the complexity of the bonds that make up the carbohydrate.

And the more complex it is, the harder it is for the human to digest because we are really terrible at breaking down carbohydrates, complex carbohydrates. So we don’t have a lot of enzymes to be able to do it. So any complex carbohydrate or prebiotic basically goes past our small intestine undigested, goes into the huge array of microbes in our large intestine, and inevitably there’s going to be some microbe in there that has the capability of breaking that down because they produce the right enzyme, and then as a result they will metabolize that. But prebiotics and fibers are a little bit different. So prebiotics, as I mentioned, tend to be more complex, smaller molecular weight compounds that are found in very specific types of foods, and then fibers tend to be roughage. And they’re not as complex as prebiotics, but still the human system can’t digest them well.

Fibers are soluble or insoluble, meaning they can either bind water or they don’t bind water. And it’s important to get a mix of soluble and insoluble fiber into your diet. So fiber is something as simple as cilium husk, for example. So cilium husk or the husk of brown rice and so on, those are all fibers. We don’t digest it well. It moves through the bowel, it does help motility in the bowel for most people. And the difference between a fiber and a prebiotic is a fiber can typically be consumed by lots of different types of bacteria in the gut. A prebiotic is normally going to be consumed by only a smaller class of bacteria, and that’s because a prebiotic is even more complex in its structure than the fiber is. So as a human trying to have a healthy digestive system and a healthy microbiome, you do need both.

You need fiber, soluble and insoluble versions, and you do need prebiotics as well. It’s easy to get some of those from food. If you’re good at following your nutrition, monitoring what you’re eating, calculating things, I always think in the case of both of those you should supplement, because they are really important for longevity. They’re really important for your microbiome. They’re really important for building resilience so that your body can handle stress and things like that. And so it’s really hard to really measure that you’re getting adequate amounts of these things. You should always be conscious of eating high fiber, high prebiotic foods. You should try to add those into your diet as much as you can, but I always recommend supplementation.

Now, let’s talk about when these things go wrong. So with someone with SIBO, for example, they have small intestinal bacterial overgrowth. So they have two issues. Really they have three issues that are really significant. They have, number one, too many microbes in the small intestine. So the small intestine is supposed to have a relatively low number of microbes. And this number may not mean much to people, but it’s like 10 to the four CFUs per gram. And that can be as little as the number of microbes you might have on your desk, for example. So it’s not a very microbially rich environment, even though it’s a great place for microbes to grow. The reason it’s not microbially rich is because your body has a number of ways of combating against overgrowth in that space. And when those things start to falter, you start to get overgrowth. We’ve talked about SIBO in the past that people can refer to. So problem number one, they have too many microbes.

Problem number two, they have the wrong microbes. Normally you end up with gram-negative bacteria versus gram-positive bacteria. And problem number three, when you have too many and too much of the wrong microbes in the small bowel, you also end up with leaky gut. So that’s a triple whammy for them, and this is why fibers and prebiotics can often cause a negative reaction. So what happens with those individuals is they consume these carbohydrates, the fibers, the prebiotics, and instead of passing through the small bowel where there’s a very low number of microbes, not a lot of complexity, and making its way to large bowel, it does start to get fermented and digested in the small bowel, because there’s lots of microbes and there’s different microbes than normal. As a result, you start getting gas and bloating, and many of the microbes that are dysbiotic don’t produce the beneficial items from digesting carbohydrates, they produce things like gas, like hydrogen gas, methane gas, and so on, instead of things like short chain fatty acids and enzymes and peptides and so on that they’re supposed to be making.

So here’s a problem with that entire concept, though. So then the solution tends to be, let’s avoid the carbohydrates completely because we don’t tolerate them well. Well, when you avoid them, the microbes in the large bowel, which is the predominance of microbes that live in your gut, that predominantly eat these kind of compounds, are getting starved out. So you’re losing a lot of keystone species in all that. So then to me the real approach is to use competitive microbes that will compete against overgrowing bacteria in the small bowel. So things like the spores and saccharomyces boulardii and certain strains of lactobacillus uteri, for example. There’s some studies showing that it can compete against microbes in the small bowel. So those things start competing against those microbes to bring their numbers down, but continue to add in very small amounts throughout the day of prebiotics and fibers as well.

Because you have to feed the microbes in the large bowel, because that’s where you get butyrate, that’s where you get propane and acetate and short chain fatty acids, which are then important to heal the lining of the gut that’s now leaky because of your overgrowth. So the tolerance issue may need to be dealt with from a perspective of simply tolerating small amounts of these fibers and prebiotics. Yes, it’s uncomfortable. Yes, you get bloating, but if it’s not posing a significant health risk, you’re not anaphylactic, you’re not getting a big allergic reaction, all that. You’re bloated and distended and cosmetically that doesn’t look good, you don’t feel good, but you may have to deal with that for a period of time to get some of those fibers and prebiotics into the large bowel, which is where they’re really needed. And if you go for prolonged periods of time with not feeding those microbes with fibers and prebiotics, you’ll have far more complicated health problems than just the SIBO and overgrowth.

Michael Roesslein:

Makes sense. To get to where it needs to go, it’s got to go through the place that’s disrupted, and the competing organisms can help lessen the impact there a little bit. And the enzyme that Microbiome Labs made, the Fodmate can help with that. So there’s things that can help with the symptom management there. And you mentioned the saccharomyces boulardii, that’s in the Microbiome Labs Restore Flora formula. That’s a beneficial yeast. And when I try to teach people about it, because it’s used when people have candida overgrowth or SIBO or antibiotics, and when I use the word yeast everyone freaks out. They’re like, “You’re intentionally taking a yeast?” And I’m like, “Yes,” but can you just, like 30 seconds, qualm some fears about that strain? It’s very, very widely used and well-researched, that’s not a secret. It’s not only the Microbiome Labs product that has that. It’s a longstanding strain of yeast, right?

Kiran Krishnan:

It is, it’s been used for 40, 45 years as a therapeutic probiotic. In many parts of the world it’s a prescription drug. There are, I would estimate, at least 300 published clinical trials on saccharomyces boulardii. It’s a phenomenal tool for a healthy gut. And keep in mind, your body and your gut has yeast all over it all the time. Candida is a problem when it’s allowed to overgrow, like anything else. You always have candida in and on your system. Candida is a commensal organism that’s always there. Same with lots of different yeast and fungus as well. So don’t be afraid of these categories. You can absolutely utilize it in a dramatic way to help the gut microbiome.

I take saccharomyces in the Restore Flora product on a regular basis. When I use probiotics, I use either a combination of the A258, which is a subtilis, because subtilis is just the quintessential probiotic. It survives, we know the dosing, we have so many clinical studies and evidence of all the things it does. It continuously competes against dysfunctional bacteria, and it’s one of the most powerful competitors against dysfunctional bacteria. It dramatically increases the growth of beneficial bacteria and it produces all these things for you, like nattokinase and vitamin K and enzymes and all these wonderful things. So I take that at high doses, and of course MegaSpore, which has the subtilis as well, but I use the Restore Flora on a regular basis, especially when I’m traveling.

Michael Roesslein:

Yeah, that’s when I usually use it too, or if I … I haven’t taken antibiotics in years, but if I did, that would be part of the approach there. So thanks for clearing up the fear. People just panic when they hear the word yeast. The last two aren’t quite as robust of a topic, but we’re going to jump into them. Well, one of them’s kind of getting there. The post biotic, para probiotic, ghost biotic, I used that term in a couple of the emails the last handful of days to talk about what we’re going to talk about because I loved hearing it, and people are interested because it sounds really cool. But you mentioned earlier with the sauerkraut and the kombucha and the yogurt, things like that, a lot of the benefits that come from those things, if people see benefits, is from what’s being produced by the organisms that fermented the food.

And so that is one. I know that in the webinar you said there’s a more strict definition on this postbiotic, para probiotic, but that’s one thing that’s usually lumped into this category, is a substrate that is made up of metabolites of organisms that the substrate itself is made up of minerals or vitamins or different kinds of things that the organisms made. And then you can ingest those things. We have a product in our shop called Supernatant Symbiotic by bioimmersion, and their Supernatant is this, she calls it a slurry of this post metabolism microbe food that it makes for your gut. And loosely that’s categorized in this topic, but what is the actual definition of this category of thing? I don’t know what to use the right word there.

Kiran Krishnan:

Right. So postbiotic is the most commonly used term, but you do hear ghost probiotic, para probiotic, and so on. So years ago we used to refer to postbiotics as anything that a microbe makes during fermentation that has a benefit to the host, so metabolites of fermentation. So if you take a bunch of fruit or sauerkraut or something and you add a microbe, you allow it to ferment, basically, what the microbe is doing is it’s consuming the substrate. The substrate is the food that we use, the fruit, sauerkraut, whatever it may be. And in its process of consuming it it’s producing these byproducts that all have all kinds of amazing benefits. So now when you consume that, not only do you get some of the original benefits of the sauerkraut, there’s the simple nutrient benefit, but it’s taken that because of the fermentation and enhanced it 1,000 fold in terms of its nutrient density and value.

And so that’s where fermented foods come in. They’re basically predigested enhanced foods because the microbes are breaking it down and adding and creating all kinds of amazing substances. So we used to refer to that whole slurry, which also includes the microbe, which is not going to function in a live form, that microbe will die when you digest it, but there may be some components of that dead microbe that could still be beneficial. So that whole thing used to be referred to as a postbiotic. Now I think it’s the International Association of Probiotics or some organization has come up with a definition that says that a postbiotic is a dead microorganism that has benefit. So it’s basically not a probiotic because it’s not live, but it’s still a bacterial therapy, a therapeutic bacteria, and when it’s dead it still has functionality. So when you see postbiotics moving forward, that’s really what they’re referring to, dead microorganisms that have benefit.

And that can absolutely be true. There’s lots of good, well-documented strains that when they’re dead, in fact their benefit is higher compared to when they’re alive, or at the least when they’re dead the benefit is the same as when they’re alive. Now, some people wonder why that is. Well, because the benefit from those organisms come from unique things that they have on their outer membrane. So they don’t need to colonize and multiply and do all their metabolism. They just need to be present, and your body responds to something that’s on the outer membrane of that microbe in a favorable way. We launched one that I think is one of the coolest probiotic, or not probiotic, postbiotic bacterial products, and that’s the PyloGuard. So this is a lactobacillus strain. It is a lactobacillus strain that binds to helicobacter pylori in the stomach or in the small bowel, wherever it may be, conjugates with it, and takes it out of the system.

It’s a dead bacteria. It doesn’t colonize, you can’t grow it. It doesn’t live in the gut, but it’s intact. And there’s something about its outer membrane that has a high affinity for helicobacter pylori. So if you’ve got h. pylori sitting there in your stomach causing infection and all kinds of issues, this microbe comes in and two or three of them surround the h. pylori, binds it up, and then takes it out through defecation. It’s not alive, you don’t have to worry about maintaining its stability, any of that. It’s dead and it’s functioning great. Now, again, with postbiotics, more often than not the functionality is based on one or two small compounds that are present on the outer membrane, which means, again, it becomes very, very species specific.

The strain of probiotic that we use to bind h. pylori is a lactobacillus plantarum, I think, if I’m not mistaken. But it’s a very specific subspecies of plantarum, you can’t take any other plantarum and expect it to do the same thing. So even with postbiotics, when you start seeing those in the market, the true postbiotics that have been studied for its effect can be really beneficial. But normally they have a very narrow effect, they do very specific things, and it has to be that subspecies or it’s not going to do it. So if you’re hearing about postbiotics, they can do this, they can do that, you need to make sure you’re getting the strain of the subspecies that has been in the studies.

Michael Roesslein:

Fascinating the dead bacteria are, this is where the term ghost biotic probably comes in, but it’s where the dead bacteria is having an effect. And we carry a holoimmune from Healthy Gut, Steve Wright formulated, and that’s got some freeze dried or heat, I don’t remember how he said, they’re killed in a very specific way, and then they do have an effect in the gut. He mixed that with some beta glucans, which have some pretty nice beneficial effects to them too.

Kiran Krishnan:

Yeah, it’s probably lyophilized. Lyophilized is the fancy word for freeze dried.

Michael Roesslein:

Yes.

Kiran Krishnan:

And the benefit of freeze drying is that it preserves the structure of the microbe. It doesn’t blow up the microbe. And in most cases with postbiotics, you need to preserve the structure of the microbe because the outer membrane is what really conveys the benefit.

Michael Roesslein:

Okay. And if you blast the membrane apart, it’s not going to work.

Kiran Krishnan:

Yep.

Michael Roesslein:

So it has to be very specific, just like the probiotics. Don’t go eating spoonfuls of dead organisms and expect some miraculous occurrence in your belly because we told you that ghost biotics are a thing. And then finally we have psychobiotics, which you’ve mentioned a couple times. You guys at Microbiome Labs back about probably three years ago now formulated Zen Biome, which is two products that have to do with stress management basically, and mood, and then another one for sleep. And then there’s a newer one that came out recently that was called Zen Biome Dual that combines the psychobiotic, which we’ll define in a second, with an organism that has been clinically demonstrated, that exact strain, to lessen IBS symptoms. So it’s a gut-brain dual approach. But psychobiotics are a hot topic right now, taking the gut-brain connection to another level.

So what is a psychobiotic? Because you mentioned in the webinar, people should be careful when choosing these or looking at these or considering one of these. I’m guessing the other areas that we’ve talked about, there might be some shenanigans or dishonest marketing going on, but what would you like to share about psychobiotics?

Kiran Krishnan:

Yeah, so psychobiotics, again, are quite specific. So we work very closely with the doctor and the professor Ted Dinan, who coined the term psychobiotic, and he wrote the book The Psychobiotic Revolution a number of years ago. So we work with him because it’s absolutely important to have the right type of scientific integrity when you’re working with psychobiotics, because they have really important place in your therapeutic regimen. The reason why they’re really important is because they finally speak to a root cause driver of a very, very prevalent condition, which is depression and anxiety. Even in our whole functional medicine, holistic world, which is supposed to focus on root causes, we haven’t really been focusing on root cause when it comes to anxiety and depression. If you think about what most clinicians do, they use magnesium, they use ashwagandha, they use holy basil, they use a few of those kinds of things to help to deal with the patient’s issues around anxiety and depression.

But anxiety and depression are not a deficiency of ashwagandha, it’s not a deficiency of holy basil, it’s not even a deficiency of magnesium. There’s something else going on there. And the reason why they haven’t been able to focus on the root cause is because the root cause of anxiety and depression hasn’t been elucidated until we started to understand the gut-brain connection. The gut is absolutely the root cause driver of anxiety and depression that occurs in the brain. And then it also is a root cause driver of long-term neurodegeneration that occurs in the brain.

And so now that we understand this, then we go, “Okay, how do you modulate this?” If it’s this gut-brain issue, what in the body naturally modulates a gut-brain response to provide stability in the brain? And as it turns out from the research that Ted Dinan and other people have done, that there are microbes in the gut that specifically affect the central nervous system in the brain. And so these are neurologically active microbes. That’s when you get the term psychobiotics, right? So biotic meaning for life, and then psycho meaning for the brain. And so these are microbes that affect the brain, and you have to be able to prove that they affect the brain to be able to be called a psychobiotic. They have to have research on anxiety, they have to have research on depression, they have to have some research on brain wave activity and neurotransmitter activity and immunological activity as it relates to the central nervous system.

Michael Roesslein:

The nuisance of providing proof.

Kiran Krishnan:

I know, that real inconvenience to sales, right? It’s a real hindrance to sales, this whole investment in science thing. And so most companies forego it. And so my caution to people is that psychobiotics can be extremely beneficial. I’ve seen it absolutely change people’s lives, because now you’re finally addressing the root cause of something they’ve been dealing with for decades. The problem with the industry, again, is because it’s a hot thing, they’re going to start throwing together a bunch of stuff, calling it a psychobiotic. There’s really only two, maybe three studied psychobiotic strains. One very well studied psychobiotic strain, which is the 1714 strain that we work with.

So there’s very, very few strains that have actually been studied as psychobiotics. So you could feel very confident that if you start to see all over the internet and Instagram and all that people marketing psychobiotics, the likelihood is that they’re using stuff that doesn’t have any psychobiotic effect and they’re just throwing strains together and using the label. And so be very careful. A true psychobiotic can be extremely powerful. You have to have clinical studies showing that it affects the brain, affects anxiety, mood disorders, and so on.

Michael Roesslein:

Great, thank you so much.

Kiran Krishnan:

Psychobiotics, another aside on that, psychobiotics can function like probiotics, meaning it can be a living organism that goes and lives in your gut and does things, or it can function as a postbiotic or a ghost probiotic. It doesn’t matter. Within the definition of psychobiotic, it doesn’t say that it has to be a probiotic or a ghost biotic. It can be either one as long as you prove that it has an effect on the brain, then it becomes.

Michael Roesslein:

Ah, interesting. It doesn’t matter if it’s alive, if it’s dead, if it’s anything, as long as it has the measurable effect.

Kiran Krishnan:

Yep.

Michael Roesslein:

Okay. Do you have to go, do you got a minute for questions or are you late to something else, how are we on time?

Kiran Krishnan:

I’m three minutes late to something, but let’s take two minutes and hit questions. I’ll do rapid [inaudible].

Michael Roesslein:

All right. Most of the questions have to do with antibiotics. We send out or will be sending out with this video the Microbiome Labs protocol for antibiotic and gut recovery. So most of the questions have to do with that. All right, one. Consequences, long-term consequences of the carnivore diet on the human microbiome since this is lacking any fiber. What do you think?

Kiran Krishnan:

I think some people, depending on who you are, may see some benefit short-term, may lose some weight, may feel more energy and so on, but it will absolutely reduce the diversity and reduce the keystone species over time. That is to me the big issue with most of these diets, including the carnivore. It doesn’t matter how nice the six-pack of the person is that’s running around on the beach saying that they eat nothing but steak. Maybe for them that’s good, but the long-term consequence is going to be that it’s going to reduce your diversity, it’s going to reduce your keystone species, which makes you far more susceptible for lots of conditions down the road. So it may be six months, eight months, 10 months, or a year down the road, it starts to reduce it. And maybe in the short term you start to feel benefits because your microbiome is very disoriented or dysbiotic, which means that normal carbohydrates and plant-based foods aren’t agreeing with you.

It doesn’t mean that those foods are bad and that the rule is to eliminate them. That’s not a solution to fixing it. It’s no different than, “I work out and I’m sore from working out,” so, “Oh, I’m so sore, I can barely … Working out is bad for me, so I’m not going to work out, I’m going to avoid it because it makes me feel sore.” So we have to get over this idea of a negative response to foods, especially healthy foods that are well-established to be healthy and good for your microbiome, if you have an adverse reaction outside of an anaphylactic allergic reaction, if you get bloating, gas, you don’t feel good, it doesn’t mean those foods are bad. It means your system is dysfunctional and it should be agreeing with those foods. And so what you really have to do is not completely avoid those and eat nothing but steak. You should be working to get your system back to tolerating those.

Michael Roesslein:

Perfect. And a lot of the questions have to do with, and thanks for that thorough answer on carnivore, I have the same opinion. A lot of the questions have to do with antibiotics, recovering from antibiotics, what to do while taking antibiotics. And then also, “I wasn’t breastfed, or, “I took a lot of antibiotics as a kid.” And in the webinar originally we went over, and we’ve done this, we have it on recordings many times before, how the microbiomes form with breastfeeding in our environment and skin to skin in the house and getting dirty.

So we are sending out the antibiotic resilience protocol and then also a gut restoration, pretty comprehensive protocol, all from Microbiome Labs, in the email. So that should cover all the rest of the questions. Thank you for making the time to come back on and record this again. I really, really appreciate it, and there’s great stuff here. And the next time we have you on a webinar, we’re going to be talking about something very different than the gut and the microbiome. So I’m not going to say anything to anybody else, but Kiran’s got something new in the works and you guys will be finding out about it soon. So thanks a lot, Kiran. Sorry to make you late.

Kiran Krishnan:

No problem.

Michael Roesslein:

We’ll talk again soon.

Kiran Krishnan:

Thank you, everyone.

Michael Roesslein:

Bye.

Kiran Krishnan:

Bye-bye.