Dangerous Probiotic Myths, The Probiotic Ben Greenfield Uses, Anti-Aging Effects Of Probiotics, Should Males Vs. Females Take Different Probiotics & Much More

Fermented food, fermented beverage, which is a very different category from a probiotic, is uses the term because it's the fastest growing category in consumer health at the moment. No one's going to put a year and a half into something and say, let's publish a non interesting finding. This is a serious field, and if people want microbiologists to stick around and continue using the term, then companies and even other scientific researchers need to start taking it seriously and need to start respecting the scientific definition.

I have a master's degree in physiology, biomechanics and human nutrition. I've spent the past two decades competing in some of the most masochistic events on the planet. From Sealfit, Kokoro, Spartan Agoji, and the world's toughest mudder to 13 Ironman triathlons, brutal bow hunts, adventure races, spearfishing, plant foraging, free diving, bodybuilding and beyond. I combine this intense time in the trenches with a blend of ancestral wisdom and modern science. Searched the globe for the world's top experts in performance, fat loss recovery, hormones, brain beauty and brawn to deliver deliver you this podcast. Everything you need to know to live an adventurous, joyful and fulfilling life. My name is Ben Greenfield. Enjoy the ride.

Oh.

Ah. I'm pumped up. I just started to record today's introduction for you and I got attacked by a wasp in my office. My heart is beating. I went to battle. I won. I killed the wasp. I killed it with a copy. Was this mega. I had Paleo magazine on my desk and I killed a wasp with Paleo magazine. I felt very ancestral doing that. This podcast today is with Raja Dir of Seed Probiotics. I think they're the smartest, most cutting edge probiotic company. They're doing very cool things, a ton of clinical trials. I was absolutely blown away by this dude. And I think you're really going to love this show. Tackle a lot of myths in the probiotic space and talk a lot about the microbiome as you can imagine, and a lot more. Hey, so Raja, what do you have here that you're taking out of this.

Paper bag here we have some very meaty, very fatty bone marrow. Except for me, these dogs eat better than me.

You give this bone marrow to your dogs?

Yeah, these are wild arctic tundra pups. These are not bred dogs. These are dogs from a lineage which predates modern domesticated dogs from a village in northern Russia where the people have lived the exact same way for thousands of years. And I've domesticated them.

If you tried to give them Dog food. They would, they would literally rebel. They would eat you probably. These are like wolves.

They are docile, they have been domestic. You know, with these animals I've learned the process from wild type to domestication can happen within one generation. I found these puppies from without having any history of domestication. Now granted, having been in proximity to humans means they've probably been pre selected for traits or traits that were advantageous for living in proximity to humans might.

Have propagated not eating your babies.

Like gentleness.

Yeah. Okay, so you got this bone marrow. They just eat this stuff raw, huh?

They just go right for it.

And I like it on sourdough bread with salt.

Yeah. And this is the stuff that keeps them occupied for about an hour and a half. So this, this is a. If I know I'm doing something for an hour and a half and I don't want them bothering me, this is the.

So this is basically going to ensure that they don't chew my arm off while we're recording this podcast and that.

There'S good sound quality and not background.

Wolf noise, hot dogs growling at the tall lanky man.

But I will save some for you too.

Oh, thank you. Sweet. Now I'm going to be salivating during the show watching these dogs eat their bone marrow. By the way, for those of you who are tuning in, the voice of the man who owns the dogs is that of my guest, Raja dear. You pronounce your last name Deer, don't you?

Deer, yeah.

Raja dear. I met Raja a couple years ago at this investment kind of syndicate that we were at because he was doing a lot of research in the field of probiotics. And I don't know if you remember, I was talking to you in the pool and you blew my mind with your knowledge of the gut, the microbiome, probiotics, bacteria. And it was like way back then, like two years ago, I was like, I gotta get this guy on the podcast.

I appreciate you saying that. From someone who I think understands the science and is as friendly with PubMed as myself, it's high praise. So thank you.

Yeah. And quick intro to Raja. He's the co founder and the co CEO of this company called Seed, which is of course a wonderful name for a company that's focused on improving the health of people's guts and their microbiome. He leads the research strategy, academic collaborations, clinical trial design, the product development, the intellectual products or property strategy, all of that for Seed. He's kind of the architect of the Seed platform and he's also the co chair of their scientific advisory board where they focus on solving pretty complex ecological problems like honeybee colony collapse and plastic degradation and soil fertility, but all through the use of bacteria. So he basically spends his time researching microbes, the microbiome bacteria and specifically probiotics. And I actually want to start off right there because yesterday in the Uber here in la, we're recording this in this little, this little ranch that Raja lives at in la. Raja sent me a link to a paper that he had written that delves into why we misunderstand probiotics and especially probiotics research. There's really, really interesting paper that I was reading in the back of that little Toyota Prius Uberx. But by the way, can I link to that for people in the show notes? Is that gonna be published?

Yeah, you got a pre publication draft, but it will be published in the scientific journal Frontiers and it should be out within the next couple weeks. So by the time this goes live, you absolutely can link to it. It's called Probiotics reiterating what they are and what they are not.

And by the way, for people listening, it's going to be BenGreenfieldFitness.com seedpodcast like S E-BenGreenfieldFitness.com seedPodcast I'm gonna put the links to all the research and everything that we talk about. So it's called Probiotics reiterating what they.

Are and what they are not. We went with a really translational title for it. So it's the lead author on the paper is the chief scientist of our company who is a scientist by the name of Dr. Gregor Reed. He's brilliantly charismatic Scotsman who now runs the Canadian RD or the Canadian Microbiome R and D Center. Does he work hilt and he is, he's probably published more papers on probiotics. I know he's published more papers on probiotics than anybody else in the world. Something which when I sent him over my final, I actually sent him over the final version of the drafts and he didn't like one of the edits that I made and it was late and he was very tired and he reminded me that he'd authored 530 more papers than me on the phone before begrudgingly accepting my final edits. But collaboratively we got the paper to a really good place.

I like rubbing your academy face.

It was no all in good fun. I mean we have that dynamic together and we work really well together, so. But we wanted to really take the central thesis of the paper is that we're coming up in a really exciting time in microbiology. And it's a time when novel organisms are being discovered, where we're understanding more and more about the gut on a day to day basis and other aspects of the human body microbiome as well. Skin microbiome, vaginal microbiome, oral microbiome, developing infants microbiome. These life stages are incredibly important. We're finally getting data and getting data back from proper intervention studies showing the effect that microbes can have on all these different organ systems in the body. And the paper kind of wants to clear up this idea that probiotics aren't just anything that's a result of they have a very strict scientific definition. And it's a scientific definition that was defined by an expert panel for the United nations and World Health Organization, which was chaired by Gregory Reed in 2001, which states that basically an organism must show in a human clinical trial for a specific indication that it has an effect in a randomized controlled trial before the term probiotic can be used.

Really?

Yeah. And so does everybody do that?

Like when you see a probiotic on a store shelf, do they all fit that criteria or can people just say probiotic?

The term in the United States is completely unregulated. And so in the scientific literature the term is defined as such. But because there's no regulation, unlike the European Union around using the term every product or every, you know, food, fermented food, fermented beverage, which is a very different category from. From a probiotic by the way, is uses the term because it's the fastest growing category in consumer health at the moment. Gut health is exploding and in many ways consumers are way ahead of the science.

So it needs to technically be, you said live microorganisms, which when administered in adequate amounts, confer a health benefit on the host. That's technically.

That is the scientific definition, what a.

Probiotic needs to do to properly be qualified as a probiotic. Okay, so what else do you get into in this paper?

Well, so we start with a definition clearing the air. We go into a couple areas where over the past three years there's been. The field itself has been gotten a lot of bad press and it's become, you know, discredited in ways that in the paper we discuss as very unscientific. And so the core of this is the idea that taking one single data set or one product or one study that's not causative, that is just even correlative, if that. And then Applying the findings and generalizing them to the entire field is an unscientific practice. And so in the form of shepherding the definition, we go through the two or three case studies of the past year where, you know, the term has been totally demonized. The oppressed cycle ensues, and then everyone is left kind of holding, you know, when the dust clears, not sure what, whether they should stop taking probiotics of those.

One of those demonizations a couple of months ago, it was basically this idea that if you use probiotics after someone has been on an antibiotic regimen, the probiotics could make the microbiome worse or aggravate that person's gut.

That is the third example that we address and respond to in this paper. That was a study that was published in the Wiseman Institute of Israel. The scientists that led that research group are in general doing very interesting work in the field of microbiome science. And so it was a pedigree group. What was really unique about that study was that they got subjects to consent to do invasive small intestinal biopsies or tissue samples to try to see the effect of what's going on in the small intestines rather than just the colon. And so, I mean, just by virtue of publishing that finding and those results, the paper was very novel. The problem is that, yeah, because usually.

You'Re just looking at the large intestines.

Usually you're just looking at the large intestines, you're just looking at the colon, and more importantly, you're not even looking. So if you think about the body as a big donut or a big tube. Right.

Stool.

I mean, a lot of people are. There's a gold rush right now to go into stool and try to find out what you can find from it and glean from it and the activities that that's having in the body. But most people don't realize that you're.

Talking about like, like Viome or Longevity or any of these other companies that are doing stool testing.

Any diagnostic company even, even, even researchers in the lab. So it's not even about companies. But yeah, there are a lot of private companies now that are looking at stool and trying to find pathways or patterns and have implicate that to health effects or to dietary lifestyle choices. But even scientific researchers in the microbiome field that are very obsessed with looking at stool, I can see why it's very attractive because big data people can come in and run bioinformatics on the data set and then look for correlative Patterns and pathways between individuals cluster them very nicely and neatly. And the problem with big data people in biology is that they assume that data, if you get enough of it, will give you an answer. So classical science, or classical biologists think very differently, which is to have a hypothesis, narrow down an intervention and then test it in either animals or humans in a large enough sample size and look for biomarkers or functional endpoints that changed in that host. And so there's a huge uproar when this Israeli paper came out, because all the medical doctors and practitioners and gastroenterologists are saying, well, hey, we've used probiotics in our practice for a very long time and we see dramatic changes in individuals, whether it's they're presenting with constipation, whether it's a constellation of symptoms like ibs, whether it's a cat inflammatory cascade that could result from a barrier, a gut barrier being disintegrous. I mean, the problem, the gut is a very, you know, hard to reach place. And so sometimes mechanisms are a little bit elusive, but you see very clear functional changes in the population that you're studying. Right. So, you know, doctors said, well, hey, this is, let's, let's take a pause here. We can't just make broad assumptions that an entire, any microbe that you ingest is going to be bad for you because a combination of, you know, 10 or 12 organisms delayed normal reconstitution of the gut microbiome. And I mean, we've, there's a lot of reasons to question those findings in the first place. So if you look even deeper into the study over, the group that started with the probiotics had about 20 species less in the gut than the one that started in spontaneous recovery. And so the same rate of recovery occurred, but they just happened to cluster back to a level that had lower species. I mean, that was something that wasn't explained in the paper. Right. At 90 days, everything lost statistical significance whether you got the FMT. So basically for people listening that want to know how the study worked? They took three people. The three groups of people give everybody antibiotics, massive doses of Cipro and metronidazole. Then they gave one group probiotics.

I hope they pay the study participants for that.

Yeah, they gave one group probiotics, they let the other group just recover spontaneously, what they called watchful waiting. And they gave the third group actually FMT of their own stool injected back up inside rectally a fecal microbiota transplant autologous. So their own original community and they wanted to test the hypothesis if, well, could this actually, what's the fastest way of recur of returning back to your normal baseline to the way the exact alpha diversity of your microbiome before you took the antibiotics.

Take a probiotic, don't do anything or shove your crap back.

Shove it right back up in there. Yeah. So first of all, forgetting about the, you know, limitations of shoving your crap back up commercially, look at all three groups. At 90 days, everything lost statistical significance, everything. So that means that the recovery, whether you took probiotics, whether you took an FMT or whether you just did nothing at all at 90 days, all three groups were indistinguishable from one another, meaning.

Indistinguishable that it did. They didn't change their bacterial profile, meaning meaningful.

You couldn't pick which person was in which group after 90 days because the error bars are all overlapping. And so for all intents and purposes, the paper should have said 10 species are delayed for up to 90 days on probiotics, but we don't know by how much. I mean, but that's much less exciting of a paper than saying probiotics delay the gut microbiome recovery.

Are there any other studies that show that if you're on antibiotics and you take probiotics, it's useful?

Absolutely. So we discussed two examples in the paper, in the Frontiers paper. And actually within that same month, two new large scale studies came out showing after antibiotics, a group that was given probiotics and compared to watchful waiting. One was in infants that were given antibiotics and had a C section cesarean born birth. And they showed that probiotics actually improve the composition of the gut microbiome in this very vulnerable infant population. We link to that in the paper.

That's important too. I was, I was at dinner last night with a couple that just had a baby and did a C section and they had, they had no clue about the idea. And I think it's like seven years that it takes for an infant's gut who's born via C section versus vaginal delivery for their gut flora to repopulate the same as if they'd been born vaginally and been able to breathe in mom's, mom's fecal matter and be populated.

We'll jump, we'll jump, we'll jump into that in a second. Because that's a really deep field in microbiome science and there's two kind of arch nemeses in the field that have competing viewpoints. The, the short answer is there's three things that you can do. Have a vaginal birth, not have antibiotics during birth, or give it to a child in the early stages and breastfeed. And if you do two out of three, you dream correctly, you dramatically increase the chance of the baby might the infant's microbiome developing normally now.

So you could have a C section but then also just don't use probiotics and breastfeed.

Don't use antibiotics and do breastfeed. Breastfeed. I think, I think the research now shows that breastfeeding and the human milk oligosaccharides from breast milk are a lot more contributive to a developing infant microbiome than mode of delivery.

Probably the colostrum helps too, right?

Colostrum is. And now we know that there's even communities that are passed down that colonize the mother's areola. So even contact with, with the breast, I mean human skin to skin contact, skin microbiome.

Yeah, that's a good point.

But the second, the second study that came out that same year, or sorry, that same month was a double the intervention period. So instead of four weeks, they did eight weeks, they did 700% the dosage of probiotic when compared to the Israeli study. And they found that there is no change in some cases trending on a higher alpha diversity in the probiotics group than compared to the watchful waiting group. And we linked to that paper as well. But the point is really we try to not be sensationalistic. I mean scientists, science in general shouldn't be a very sensationalistic field. And so one of those studies had really good PR behind them and ended up penetrating into, you know, everybody's phones in the mainstream.

You mean the study that probiotics don't really work if they've been on antibiotics?

That they don't work or could be dangerous because they have a really good, they had a really good proven lab. I mean they spent a year and a half gathering these samples, for God's sake. They put shoved fecal transplants back up the patient's rectum and invasively scrubbed their small intestines. Of course they're going to want to get a meaningful publication out of that, right? So there's human bias in everything and there's human error and people want their work to get of wide reach because no one's going to put a year and a half into something and say, well, let's publish a non interesting finding.

Statistically insignificant. I think one big part of this too is that and correct me if I'm wrong, whatever probiotic strain that they use in that paper or in any other probiotic studies, it's all so different. I mean, how do you even know when you're looking at probiotic research, what strain they use versus the bottle that's in your cabinet?

Yeah.

Like, is there any regulation or any standardization at all when it comes to that?

So what I will tell you is that your supermarket probiotics, for the most part are. There's five or so contract manufacturers that just produce these species. In many cases, they're species, not even strains.

Can you describe that for people who aren't familiar with the supplement industry?

Yeah, so a contract manufacturer is just kind of a manufacturing facility which produces comp. I mean, you can basically Google and find a manufacturer that white labels a product for you. Right. And so by that, I mean, like, there's five or six places that in many cases spun out of the dairy industry. And so they found actually the reason why still some of the best fermentation facilities in the world are in southern France and northern Italy. I mean, our whole supply chain is in Europe because they have the best fermentation facilities, because they invested in that infrastructure, because of the role that fermented cheeses and dairy products play in European culture. The big American contract manufacturers that produce probiotic strains here are like Danisco and dupont, like, they're, they're these dairy manufacturers. And it's very interesting to me that food corporations. Well, yeah, these cultures that are used for dairy production, how whole side industry was born that said? Well, we could just turn these into. Turn these into packaged products, or we could turn these into supplements. But it was really bad up until a couple years ago when the microbiome field started. And then we've added a whole new birth of organisms that are being discovered, that are being tested, that are going into trials, that are being properly designed trials. Strains that are very specific and different and are cataloged. But to answer your question, so if you think about kind of dogs as a species, they're all dogs. All domestic dogs are not the same yet at the species level they are.

And so each individual, like a Chihuahua is a dog and a Doberman is a dog.

Yeah. But they're very different strains of dogs, so to speak, if you want to use the example. Right. And so their attributes are very different from one another. Everything from their physiology to their. To their. The way they perform to the metabolic output that they generate. And so bacteria are actually in some cases way more different under the technical definition A strain can be. Some strains of lactobacillus reuteri are 70% genetically different from other strains of the same species. So if you just go. If you just go look at a supermarket probiotic and it just says Lactobacillus reuteri, Lactobacillus is the genus, Reuteri is the species. But that's it. That's where that story ends. And the question is if there can be 70% genetic difference between different strains of that Reuteri. Lactobacillus reuteri species. You need to look for a human trial. You need to look for a strain that has undergone a human efficacy study, and that is the minimum requirement. Otherwise, that product should call itself a microbial product and not a probiotic.

How do you even know if you're looking at the label of your probiotic?

Well, I mean, I think that there's a lot of confusion. I don't think that. I think that companies enjoy there being kind of a sense of consumer confusion in the category.

Yeah. I want to talk later on about what is in some of these strains that you're helping to create. But what's the takeaway from the paper as far as the answer to these flaws in the research on probiotics? Like, what's the answer?

So we lead with a really optimistic view. We think that in the. I mean, we have a table at the end which says these are all the physiological and metabolic processes in the body that can be changed or will be impacted by the human microbiome in the next five years. And so, I mean, a good.

I have that table now pulled up in front of me. It's enzyme pathways, energy metabolism, neurotransmitter production. So I think a lot of people kind of know about bacteria. In your gut make things like serotonin, vitamin absorption, regulation of bile acid synthesis. It's an interesting one. Endocrine and gut hormone regulation, protection against pathogens, cell proliferation, immunity, vascularization, bone mass, appetite signaling, and metabolic transformation of xenobiotics.

Yeah.

So that last one, what's the metabolic transformation?

Those are, for instance, drug. If you take drugs.

Okay. If you take an antidepressant, being able to metabolize drugs.

Absolutely. Or not even just drugs. I mean, even things like heavy metals, dioxins, PCBs, or bacteria provide you a line of defense against environmental contaminants or xenobiotics. And so, you know, and those are just some of the more technical ones. The more, you know, for instance, we have a research track in our company where we're looking at activating a switch in the body which prevents and reverses food allergies. I mean, that's a huge indication to think that knowing that certain microbes can signal TH1, TH2 cells in a pattern that it promotes tolerance to foodborne antigens. That's the type of research where I'm saying, I mean, how are consumers going to take a probiotic which can reverse a life threatening allergic sensitization seriously? How are they going to take that seriously when there's products that are, you know, marketing themselves as supplements or probiotic tortilla chips or.

That's huge. Yeah, that would allow me to eat green beans again. What else? What are the other conclusions from this paper?

We go into the minimum strict requirements. Before anything should call itself a probiotic, you have to be, you have to declare the genus, the species and the strain. You have to have undergo at least one human clinical trial, double blind and randomized and controlled in the population that you're targeting. So here's another, here's another trick a lot of companies use. They'll test that their probiotic is very effective at say antibiotic associated diarrhea. Right. But then market their probiotic as beneficial for a generally healthy population. But they haven't shown that it would have any benefit for a generally healthy population. They've just shown that it only shown.

If you drink bad water in Mexico, it could work.

Yeah, bad water anywhere. But bad water in Mexico is particularly bad stereotype.

Mexicans.

No, I mean, I mean, I'm thinking of, I mean, I know people that come back from Southeast Asia and they, they're shitting for weeks.

Oh yeah. Raising my hand. He's happening to me all the time when I go race triathlons over there in Thailand.

Yeah, yeah. So I mean the field, the fields really serious, the takeaway is that this is a serious field and if, if people want microbiologists to stick around and continue using the term, then people need to start, then companies and the media and even other scientific researchers need to start taking it seriously and need to start respecting the scientific definition. Because you can' it both ways. You can't market and sell, you know, products that are just, you know, have no science behind them at all. And then also have, for instance, I mean, one of our fellows, one of our siege fellows is a researcher in the Department of Genetics at Harvard and he's now looking at probiotic using probiotics to deliver antivirals against HIV in sub Saharan Africa. I mean, how are these researchers going to continue using the Term and shepherding the field. If they're being compared with torti, with probiotic tortilla chips, I think the whole thing is just all wrong. Yeah, that's interesting. Yeah, it's a serious field.

I had an important question I wanted to ask you because I get this a lot and I seem to have a hard time finding good answer for. It's about this whole colonization piece because I think it was the journal Cel that released a paper about how, yeah, probiotics kind of seem to work like they're doing something, but we don't know why because it appears they don't actually even populate the gut. Is that true? Like do probiotics just pass through you?

Yeah. So probiotics for the most part are what you call transient microbes. They don't take up residence long term. Some ways of describing them have been they do their work on the, on the road. But even that, I mean even to be respectful to what I just finished ranting about, we can't put all organisms that could have a benefit or could be probiotic in the future into one category. What we do know is that Lactobacilli and Bifidobacterium tend to be non colonizers and tend to be involved on their work through the production of metabolites, through signaling to toll like receptors and activating molecular pathways in the body which change the composition of the gut barrier, which produce mucin, which create specific metabolites, they produce short chain fatty acids, they swap genes, they deconjugate bile acids. I mean these are all pathways that we have strains that have a stack that we have strains in our product which have gone under, have underwent double blind placebo controlled randomized trials to show these endpoints without. Without having called in the seed profile. Yeah, in our first product.

So, so did, did, did your product actually actually seed, to use the term? It's a good name, I'm telling you. Did it actually seed the gut?

So seeding is the term. Seed actually comes from when in the earliest stages of life when an infant's microbiome is first colonized by microbes is a biological process called seeding. And so it's a little tip of the hat to the origin story of the microbiome when a child gets it from her mother and then it's grown. I think that's a really nice story and it certainly was the basis for our name as a company. But our strains, in all the studies that have been done in our strains, the longest that we've shown persistence is about eight weeks afterwards and around eight weeks after ceasing consumption, you will get a sort of washout. And that's why it's so important to take or to. If you want to experience benefits from organisms. Certainly these signaling and metabolic benefits that occur from the oral consumption of these, of these probiotic strains, it, it you need a daily consumption is very necessary. I mean this isn't something like a drug where you can take it in a defined quantity and that's it, it's done. You know, this isn't. These are.

It's kind of like coffee. Once you start drinking it, you just have to drink it for the rest of your life.

Yeah. You can't drink coffee on Monday.

Probably testosterone replacement therapy would be a better. Once you start, you feel really good, but you gotta keep doing it repeatedly. So are you saying that's the same for probiotics?

Certainly.

So why wouldn't you just eat a wide variety of fermented foods for the rest of your life? Like just working kimchi and sauerkraut and some kefir and some yogurt and just go that route?

So I'll give you an example. There's a study that was published on kimchi and of the several hundred or so strains that could be found in aggregate across kimchi products, only four or five of those strains have been shown to possibly have probiotic potential. That doesn't mean it's not good. That doesn't mean it's not delicious.

That doesn't mean that by your definition of a probiotic that you laid out in that paper must have some kind of human clinical research behind it, be shown to act on that multitude of ways.

I would love for kombucha companies to do randomized controlled trials. I, I know it sounds crazy, but I would, I. If you. What is the benefit that they're. I mean, you see these vague words like immunity. I mean.

Yeah.

Or anti inflammatory. I mean ginger detox. I hate to break it to you, but there's many cases where you don't want to down regulate the inflammatory response in the human body. That is not a good thing to happen.

Well, what baffles me even more is that the anti inflammatory one has like 120 added calories of cane sugar.

Yeah.

In it.

Yeah.

And yeah. We could go off on kombuchas for a while. By the way, your dog is absolutely enjoying that.

They're going to town.

Yeah. If you guys hear the crunching in the background, that's this giant wolf laying on the floor. Gnawing on this bone marrow bone. So what you're saying with the fermented foods piece, because people are going to say why can't I just eat like my ancestors who didn't take probiotics.

So I mean I think that it's a beautiful store. I think that the idea that living like our ancestors and certainly I know, you know, the Paleolithic era has been really glorified in certain even in modern day health and health and wellness fitness communities. There's certainly very many good things about it. The level of activity, the resilience and exposure to environmental microbes and contaminants.

Being outside in the dirt with lots of animals getting covered in blood, having natural birds, like there's a lot like there's like if you have you, I don't know if you've seen the research when you fill dress an animal, like if you kill a deer for example, while you're hunting, the act of field dressing exposes you to an enormous number of bacteria.

I believe it, I believe it. And, and you know it's the basis of a lot of books. One of our scientific advisors is the author of is it was a professor at NYU and microbiology Marty Blazer and now the the star of an upcoming documentary called Missing Microbes. I mean he's one of the big legends of the field and his whole thesis is around this idea that there are certain microbes in modern society that are missing from our ancestors, from how we evolved or when we lived in the wild. Justin Sonnenberg's group at Stanford has actually shown that when a low fiber diet compounded over multiple generations actually results in irreversible damage and loss to diversity of the microbiome after four generations it doesn't matter if you return the animal to a high fiber diet. Those organisms have gone extinct. They have found that there's extinction in the microbiome in as little as four generations in their animal models from a low fiber diet. And so certainly I think it's very intriguing. I mean it's, it's, it's very interesting to think that we've departed so far from our natural state that our gut microbiome has evolved away from its normal state.

So you could argue that maybe people who are working on farms out in the dirt with animals all day eating a wide variety of fermented foods, like that population might not even need to take a probiotic.

I would argue that if you are living like the Hadza, then I mean I actually think that's a very interesting study. I think that let's design a trial and add a Hadza tribe arm to it and see the effect that it has.

But not living like a Hasda in a westernized society where you're also exposed to glyphosates and jet fuel and all these other things that influence the health of your microbiome. And part of it is that you're fighting an uphill battle.

Yeah, they influence the health of your microbiome, but they also have a lot of functional effects. So I'll give you one example. So we've studied, we five of our strains that we acquired in our strain bank came out of a research partnership with, from the Department of Genetics at Harvard. And there they specialize in building these, these, these models, these predictive models which look at really specific pathways in the body. And so one of the things that really bothers me is when people start talking about detoxification or detox this detox that I think the whole term means nothing because the body has very sophisticated detoxification pathways that are regulated by something called the NRF2 transcription factor, which results in the production of glutathione. And we are very, very good at mitigating oxic and toxic stress in our body and oxidation. And so we, I mean this is really well established, but the problem is that there's, there's a lot of things that are triggers for activations of those pathways. Things like extended, extended exercise, which elevates your heart rate for a prolonged period of time. Things like access to a wide variety of phytonutrients that are extremely diverse that activate those receptors. There are certain things that are bad for you. In a weird twist of events, things that are bad for you are good for you. Sulforaphan is a great example. Sulforaphan is the darling of the health community at the moment. It's found in raw broccoli and actually works the exact same way because it's a defense mechanism that the plant produced against, to avoid against predation. And it activates certain transcription factors in the body which catalyze or begin the detoxification response system. Right. And so we looked at, in these models where you take these C. Elegans, you take these really, these model organisms for looking at gene expression and you knock out some specific genes. And so if you knock out genes that are response or over express certain genes, you can see how exposure to your microbe activates or inactivates very specific defined pathways in the human body. Right. So we thought that was a great target. We screened for strains for probiotic strains, which activate this NRF2 transcription pathway in the human body, which begins the process of detoxification. So for people that, you know, are. Have a lot of. One of the theories for barrier breakdown or. So the biggest theory for when people just refer to gut problems and they implicate it from everything from their autoimmune condition to brain fogginess, is as follows. Their gut barrier is impaired. Compounds that are either produced by microbes or particles from your diet or contaminants from the environment enter into your bloodstream when they shouldn't. The body mounts an immune and inflammatory response to those foreign compounds, which it rightfully should. And then that triggers and trips up the immunological response, and it begins a cascade of events that some people results in arthritis, and other people could, they say, could result in an autoimmune condition. Other people, they say it results in an allergy, allergic sensitization. I mean, there's a number of ways where people believe that their microbiome has been impaired. And so to the extent that that pathway is true, I can't say one way or another, because I don't think those trials have been appropriately designed. But what I can say is specific bacteria do increase the expression of what's called tight junction proteins to tighten up the intracellular space in your gut that's one cell thick and one cell deep. And so I think we need to see exactly what functional effect that has. But certainly one effect that we have tested our strains on are inducing expression of tight junction proteins in the gut barrier. And to go back to your earlier point about how probiotics works, that's a pathway which is totally. Which has no effect on whether an organism colonizes or not. Right. Because in passing through the long tube of your gut, it's signaling to your gut wall, and it's tightening up gut barriers, gut barrier proteins.

So when you're saying that different strains have different effects on more than just the microbiome, you talk about oxidative stress. I'm looking at the label right now of your women's bl. Your women's probiotic blend, and you have a whole bunch of different strains in there, like Bifidobacteria infantis and Lactobacillus rhamnosis.

So those are species.

Okay, so those are species.

And the strain designation is right after that. It's. It's something like.

It's like A. Yeah, BR3 it. Okay, got it. And then you also, in addition to that, have some things like Indian pomegranate Chaga mushroom, Scandinavian pine bark. Why are. Why are things like that mixed in with these different strains?

So we were very curious about a specific endpoint that happens when gut bacteria that are already in your gut, it's called biotransformation of nutrients. They take food particles and they convert them into secondary metabolites that then enter into your body and unlock new nutrients or transform nutrients that you'd get from your food. Food. So bacteria, in some instances, can produce nutrients themselves, micronutrients themselves. So one of the. One of the strains that we have in our product is actually a folate synthesizer. And so it increase. It produces methyltetrahydrofolate as part of its metabolic process, which then passes through the bacteria, does that.

You're not taking methyl tetrahydrofolate like you would in a multivitamin. The bacteria is making it for you.

Yep. So vitamins. So B vitamins and K and K vitamins. Most people don't realize that if they're deficient in it, it's because they're very low in a normal diet. Right. In a diet where you don't always have access to some seasons of the year where you don't have access to animal, to meat or to fermented foods, which, I mean, Most of our B12, for example, we get from meat. Right. It's not really just floating around in plants. And that's why vegans and vegetarians are very deficient in vitamin B12. But originally, gut bacteria were who we outsourced that responsibility to. They would produce these B vitamins and these K vitamins, which would then pass through receptors in the gut and enter into serum circulation. And so we have a folate producer, and we think that's a really interesting way to think about. I mean, folate is involved in. Every time a cell replicates, Folate is used as a cofactor in cell replication. So. So folate's an incredibly important micronutrient, and not just during times of pregnancy. Its role in DNA methylation and methylation patterns and cell division is pretty remarkable. It is an essential micronutrient. And so to think that bacteria can introduce a continuous supply over the course. I mean, a near. It's a steady drip of these essential micronutrients to us was very attractive.

It's like you're consuming little. Little soldiers that make their own multivitamins.

Exactly.

Okay.

Yep. But.

But that Scandinavian bark and all that stuff, why is that?

Yeah, so our. Our bark is standardized for these oligomeric pro. Anthocyanidins these are compounds which modulate microbial communities in the gut. Most important in that list is our what we have listed because of from a taxonomy perspective you have to identify the part of the fruit. But that pomegranate is standardized for a compound called Punicalgen. And Punicalgen is a really, really interesting polyphenol which specifically is turned by bacteria that are already in your gut into a metabolite called urolithin A. And urolithin A was a publication came out a couple years ago in the scientific journal Nature and it made a big it's way around the press called the fountain of youth or the golden molecule or you know, a molecule which revert which doubles the lifespan of mice and reduces urolithin. Urolithin A.

He's talking about that in the, they're talking about metformin or rapamycin and nad. Urolithin A. Urolithin A. Interesting.

Yep. And so the, one of the, the only way it's only actually produced, there's no way to get it in nature but you can use precursors from nature and couple it with the right bacteria in your gut to biotransform a nutrient into it. And so this is really interesting. I mean so the way that that metabolite works is it induces a process called mitophagy which clears out decayed or ineffective mitochondria and begins the cycle for mitochondrial regeneration. And so certainly in C. Elegans, which is the model organism and also in mice, we've now shown that urolithin A has tremendous effects in the mice. In the, in the mouse study with urolithin A it was really interesting that older mice, older rodents that were exposed to an intervention of urolithin A A reverse sarcopenia and so they regained their, their muscle function very high in things.

Like, like very, a lot of these berries like blackberries and boysenberries, pomegranate granite, interesting urolithin egg. But if you take a prebiotic like this along with the probiotic, you're making your own, you're getting your own.

So you are.

There's almost like an anti aging benefit.

You to, to be determined. I mean look, we're very cautious to say that's, that's where you have to say that we know the mechanism.

Yeah.

I don't know what, how many years or, or what a functional effect that that's going to have.

But at the very why I respect you because most people would say yes, no, I, I live longer.

We can't go there. I think the research is certainly interesting. I think it's very promising. And most importantly, it fits our thesis. Right? Our thesis is how can we unlock the power of microbes or bacteria to confer benefits to their human hosts?

Are males different than females? I mean, it seems that our biomes would be different, but because of that it would seem the type of probiotic strains that we should have in our guts or be popular in our guts with would be different.

Well, we, so I'll start with women have a slightly longer digestive tract than men. It's why women across the population suffer from digestive issues, cramping, really bloating, indigestion significantly more than men. I don't know if that's because they have a slightly longer GI tract, but that's one theory that's being proposed. In terms of the composition of the microbiome, it's unclear. I think that differences between. I can pick. It's easier to pick someone's microbiome or what their microbiome is based on what they eat rather than based on their gender. So if there is differences, it's very weak, they're non significant. And it actually leads us into a really interesting point which is, look, there is no one healthy microbiome. So this idea that, that, that this is the gold standard or this is what you need to move your microbiome towards is total horseshit. And scientifically I can tell you why. It's because there's microbes are very, have what's called scientifically a high degree of functional redundancy. And so certain microbes within one genus or taxa might perform the same function as ones in another, but be very different on the phylogenetic tree. So you can't just say, well this, because you have this ratio of Bacteroidetes to firmicutes or you have this pathway that's being over overexpressed or under expressed And I mean none of it means. And none of it means anything. And I'll give you another example. So back to. Go back to your earlier point about, well, if we just lived like our ancestors did, would we need to take a probiotic or would we need to modulate our microbiome in some way? I mean, there's no amount of money that you could pay me to transplant a Hadza tribesman's microbiome. I've looked at the sequence data. There's so much junk in there. I mean, yes, it's more diverse, but there's a ton of pathogens, there's a ton of, you know, uncharacterized metabolites that we have no clue what they're doing, what they're performing, which they probably at some point picked up living in the wild, but also probably kills a fur compounded across a population level data set probably has, has harmful effects too. And so I, it's not a neat and easy answer that this is better than that or this is the right way to do this. What we as a, as an organ, as a company try to do is look at, you know, defining the characteristics of the microbes themselves to determine whether they would be beneficial for the human body or not.

So what does that do with the males versus females thing?

Well, because there's. So for instance, I mean, the female females could, during pregnancy could benefit more from a folate producer in their gut. But that doesn't mean that it would be bad for a male to have that same or it would be out of place in a male biome. And more importantly, a female Hadza microbiome is very different than, is more different than a female in New York City's microbiome. And a female in New York City is probably very close to a male in New York City's microbiome. So your environment matters, your diet matters more, that your antibiotic and drug use matters more than your gender, I think.

Okay.

And the research does show that.

Okay, got it. So when you're talking about this idea of you not necessarily being able to just toss any probiotic willy nilly into your body to replace what you think might be missing. I'm curious what your opinion is of this idea that a lot of companies are now proposing where they'll test your microbiome, you know, test ratios like the ones you're just talking about, like bacteria to pharmaceutical ratio, and then spit out which probiotic strains that you should be consuming to fix your deficiencies or your imbalances. What's your take on that?

Without a doubt, I can tell you that there is no science. The field itself hasn't determined what a healthy microbiome is. Or I mean, forget about looking through a pattern from an at home sampling kit and then telling you that you're deficient or could benefit from a specific species or taxa. I mean, it just makes no sense. There's, there's absolutely no evidence to support an intervention from an at home diagnostic kit. Now what I always say is at home diagnostic kits are very interesting to the extent that one's curious about the organisms that are living in their gut, micro in their stool Micro in their colon. Right. You're not getting the small intestinal microbiome from there. It's interesting. I mean, look, all these companies are using, for the most part, the same base technology, right? Everyone at a certain point is looking. Illumina changed the game. Illumina is a company that changed the sequencing game completely. And so everyone's using iterations or applications of Illumina's underlying technology or related technology. I mean, some other groups or organizations, some are looking at RNA, some are looking at the 16s region. That's the least. The least comprehensive. And then some are using whole genome metagenomic shotgun sequencing, which I think is still a very effective tool for understanding the gut more at a population level than anything else. But it's just that it just tells you it'll just spit. It spits out. Depending on how deep you go and depending on how wide you cast and set the parameters, it just looks at the DNA or the RNA and tells you which organisms are there and ranks them in a phylogenetic tree and gives you a nice little distribution of the organisms in your gut. But knowing what those organisms are, do or mean, or even more so, are deficient in, and the most egregious is if they then try to sell you a product or sell you a service based off of those findings. Show me the paper. If people literally just said, show me the paper, show me the study, show me the trial. Yeah.

Now back to your analogy with dogs. You know how you have a strain which is the dog, but then there's all these different species, like the Chihuahua versus the Rhodesian Ridgeback versus the Dilbern Finch or whatever. When a company like that is testing and then making recommendations on a probiotic, are they making species recommendations or strain recommendations?

Yeah, well, they're making species level recommendations, and sometimes they're even just making genus level recommendations. They're saying, you need more Lactobacilli. The whole thing just baffles me. It makes absolutely no sense. Forget mentioning that these companies look at what's called relative abundance. So they look at the percentage of Lactobacilli compared against the rest of the organisms in the gut. Relative abundance means nothing. If you really want to start finding some information from these data sets, look at absolute abundance. You want to find the microbial load, you want to find the amount of organisms of that genus that are there in your gut. And then maybe you can start looking at enough data and saying, well, once Lactobacilli falls below a certain microbial payload, some issues begin. But just comparing it relativistically amongst other communities in the gut. I mean it's a very, what you call in science an unclean data set.

So are you saying a better approach would be to take the different strains in the species that have been identified in peer reviewed double blinded clinical research, have specific effects on whatever skin health, immune health, anti inflammatory activity and to simply say okay, well you know, regardless of what my gut test, whether my viome test or longevity Test or Day 2 or any of these other companies, regardless of what those numbers are telling me, which are interesting and may prove useful in the future to have that data, I should instead take the route of just taking a probiotic that has the strains and the species that actually have human clinical research behind.

So, so in our paper we discuss personalization. It, it's, it's really sexy in the, in media and in the health and wellness community. But in science it's very, it's, it's kind of, there's nothing new about it. It's called stratification. If you can't show your intervention works in what's called a heterogeneous population, so it works across a wide range of people, not based, not just on one individual, then that's generally a bad thing, right? That means that like, like some anti, some depression medications will only work in stratified populations. Some IBS medications only work in a stratified population. But in general the gold standard is always can you find a microbe or an intervention that works across a human population and has reproducible effects. So I would go even further than say that. I mean if most of these things work not just amongst all humans, but they work amongst all mammals too. So even you'll find that they'll work in dogs and they'll work in horses and rodents. Right now I think for gut microbiome research, animal models are very poor approximations of the gut microbiome because I think that human immune system co evolved with microbes much differently than other mammals. So I don't think animal, I think human studies do need to be conducted. But the answer is if a personalization company publishes a paper that says, well, we recommended, we placebo controlled a study and we recommended that these strains work for people that have this condition and these are their findings and the results. But it only worked in people that had this starting gut microbiome, then I'd be the first to say, well that that sounds fantastic. So as long as you test in the target population that you're marketing or selling to, there's nothing Wrong with personalization. There's nothing wrong with stratification. It's just biologically not what you would expect from a microbe that has powerful modulatory effects. You'd expect it to modulate, have effects agnostic of an individual starting microbiome. Right. So in many ways it's kind of settling for second if you, if you have to find something that's customized or that only works with you, or that only stratified to you.

Do you think there's any way that personalized microbiome testing is going to change in a way that would allow people to really target a probiotic species to their specific gut profile?

Yes, but it's not going to be your, it's not going to be anything like the probiotics that are available in the market today. It'll be like you don't have organisms that are butyrate producers that are within the Clostridia cluster 14A and so, but you can't culture those. I mean, trust me, my whole career has been in translational development and including biofermentation. And I know what it takes to make facultive anaerobes, which means organisms that, that sometimes are okay with oxygen grow. But to make strict anaerobes grow is one of the most magical feats in microbiology. I mean, some organisms in your gut in fact won't forget about oxygen, right. They won't even grow if other organisms that they like to hang out with aren't in the mixed community, if they're not in that same extracellular biofilm like exopolysaccharides matrix that they like to be in that complex community. I mean, that's what people forget. Your gut is an ecosystem and ecosystems theory comes into play. And so this idea that one organism or one bug, I mean, so my answer to your question is no. I never think that one organism from an at home test is gonna, we're gonna find that you're deficient and that you should take it. But there are some cool party tricks you can do. For example, if you have Noxelobacter, right, Then that means that you should probably avoid eating raw greens that are high in oxalates because your body doesn't. Because your gut microbiome doesn't have an efficient means of converting those oxalates or detoxifying those oxalates so they don't accumulate in your kidney.

Okay? So you could do useful things with the data that you get from one of these biome testing services. You just may want to avoid the Part that says test take this probiotic because you're deficient in xyz.

Yeah, the only. Well, in fact, I can list on one hand all the useful things that you can find. So Axelobacter is one of them. You can find if someone has low or high butyrate production. If you have low. But then the intervention is take more to eat more fiber. Right, or eat more.

Or butter in your coffee.

No, I think that the research is pretty clear that high fat is very high fat diets modulate. I mean, a recent paper just came out in Gen Ed News showing the effect that high fat in particular has on modulating cancer stem cells related to colon cancer. And so the point is that no one in the keto community is looking at that type of mechanism stuff. All they're seeing is that if you have a high fat diet over a six week period of time, you lose a lot of weight.

Right?

So weight loss, we as a society need to decide if weight loss is sufficient as an endpoint or is the only endpoint or if it's worth exploring other areas. I mean, carnitine, you know, high red meat consumption is in multiple mechanisms, whether it's tmao, whether it's quarantine production that produces, that increases risk of carcinogenesis and cancer in colon cell lines. I mean, there's a lot of mechanistic work that shows again, a diet that is high in fiber is probably more important than red meat consumption. But I'd be very nervous. So my point is by having high fiber you can mitigate or eliminate any of these risks that are found only in these mechanistic studies. But we do know that, that these mechanisms are clear. And I'd be very nervous for people on the carnivore diet because we don't have long term data to show what eating that consumption of meat has. But a gut micro, to go back to your point, a gut microbiome test isn't going to tell you whether your gut is better for eating high fat or eating high meat. I mean, you can't, you can't tell that.

But you said there were five things, you said butyrate. What was the one before that?

So axila back, you can tell.

And the trick for that would be if you're low on it, if you.

Don'T have Axelobacter, then you should cook your greens. Okay, but again, and I bring that up to say we don't know if there's other organisms in the gut which have that oxalate degradation pathway. I use axelobacter as an example. But that's an example of a function of one functional endpoint. Right. Another thing you can tell from at home gut testing kit, for example is whether you have the pathways to break down certain drugs.

Right.

But if you're not taking a lot of, you know, you're not, you're not undergoing chemotherapy or you're not taking antidepressants, then that's kind of an irrelevant point for you. You can look at drug, drug xenobiotic breakdown pathway if you have the metabolism for certain drugs.

Okay. And then what would, what would the.

Other ones Butyrate production? You can look, you can look to see if you have organisms in a particular cluster that produce butyrate urolithin A. So what we prime for in our community in our product with the punicalgen you can actually test for and it's the dominant species which produces and converts punicalagen to urolithin A as Gordonobacter. And so that's an organism that you'd want to look for that could be very beneficial. And the last one is we are now starting to. None of the at home testing companies are offering this because it's very new research. But in the future you would be able to also add on your predisposition for type 2 diabetes.

So interesting.

We now know that there's certain.

That's some actionable data.

It's not actionable because the action, it'll tell you whether you have a higher risk of type 2 diabetes or not. But the action is the same. The action is don't have high quantities of simple sugars.

Yeah, that's what I mean. Actionable it is.

That is not the action is this. The point I'm making is regardless of whether you took the test or not, the prescription of how you should, what you should eat or how you should live your life is the exact same. Right?

Right.

Eat more than 30. A diversity of 30 fruits and vegetables in any given week that was implicated with the highest diversity microbiome across an 8,000 person cohort in the HMP part two. Second was people that had less than eight different fruits and vegetables per week had an inverse relationship with diversity. So the two most dominant dietary related factors were actually causative and inverse causation. That's so powerful. When you see that in a study that means that you're onto something. It's a smoking gun. So diversity of plant phytonutrients and fibrous foods. And if you're a creature of habit every morning you Just eat blueberries, switch it up, have blackberries, have raspberries, try different types. There's a bunch of nutrients you're getting from a lot of, from a wide variety of different fruits and vegetables. If you only like one different type of vegetable, if you meal, meal prep, just try to switch it up. Diversity is good.

Diversity, diet and seasonality. Yeah. Hello, pharmaceutical market.

Yeah.

Okay, so I, I have a few other important questions I want to make sure I get the time to ask you. One is like there, there's one probiotic strain I know a lot of doctors Talk about it, VSL3 and one of the things they say about it's got like 10 times the, the number of bacteria in it and I think they call it cfu. Colony forming, forming units.

Yup.

Yeah. How important is that to have a really, really high cfu? Because that's like the bragging point for a lot of probiotics.

Well, it depends on the indication. I mean there I, it depends on the study and the trial. So we have two of our strains were tested in a 300 person randomized double blind control trial at a, at a potency as low as 12 billion CFU in aggregate and had.

So 12 billion would be considered low.

It would be considered low.

What would be considered high?

I mean you'll see products that are in the hundred billion.

Okay.

100 to 3. VSL3 is about 120. Their consumer dose is 125 to 150 billion CFU and their therapeutic dose goes up to 400 or 450.

Okay.

I mean we call that and microbiome researchers call that the shotgun approach where you just barrel the gut with high density of organisms hoping that it works but without having established the mechanism. So VSL3 actually doesn't disclose their strains. They are an eight species blend that has a very high dose and they have a lot of clinical data which is effective on conditions like pouchitis. I don't think they have anything on colitis or ibd, but pouchitis was the original condition that they looked and studied. The answer is I know the organization, the pharma company in northern Italy that makes it and there's nothing particularly special about their strains. They weren't isolated or derived from a special microbiome. They weren't screened or identified on any interesting technology. They're probably pre selected if I were to guess because they are very what in the biofermentation industry we call hardy growers. And so you can get a high yield with reproducibly and very limited amount of nutrients. So they're very good commercial strains. And then you put a really high quantity in there. And for some people it works. And if you have pouched out, what.

You'Re saying is you got to return to human studies, the best dose, the best strain is what's been shown for whatever you're going after in actual clinical human studies.

Ask before you take any probiotic, ask the company. Show me the studies on your strains. Have your strains been studied in a human population and for what endpoints? Because another trick that a lot of people use is so for instance, VSL3 is very good at pouchitis, but that doesn't mean that you would expect it to have any effect on having any immune modulating properties or having any effect on your cholesterol. Right, but these are all areas that we've shown that different microbes can have an effect on. I wouldn't use VS Cell 3 for barrier integrity because they've never published a study that shows that it has this effect on LPS binding protein that's found in serum. And so you know, it sounds technical if someone has a non scientific background trying to make sort their way through the biomarkers and the words and the company messaging. But at the end of the day, if a company can't explain to you clearly and simply what their product, what their strains are and what they were tested in and for what endpoints and why that matters, I mean it's that responsibility falls on a company to do right, to clearly articulate what their strains are and what they've been tested in.

Got it. Another question, delivery mechanism.

Yes.

Right. That's another thing people say, oh, probiotics don't survive the assistance acidic nature of the human stomach. They never wind up in your large intestine. Is there, is that true? Like when you take a probiotic, is it actually just useless because it gets beat up by your acid?

We do see that microbes die off in PH in prolonged exposure to pH below 2.5. And the gut ranges from 1.8 to 2. Or sorry, the stomach, your stomach acid ranges from 1.8 to 2.0 point. The, the less exciting answer is that that was, that's been solved. That problem's been solved for like 10 years with delayed release capsules or acid resistant capsules which don't release organisms until they've entered into your small intestines. So okay, it's, it's kind of like.

What about the, you were talking to me about algae, how you somehow like wrap a bacterial.

Well, so we took, we took we took three strains of ours that were notorious for had the highest die off rates and we wrapped them, we basically embedded them inside of a matrix using biopolymers that are derived from macroalgae. So in this case we wanted to have a polymer which was very dense and was very tight, but also had these pockets inside of it that microbes could nest. And so we did it, we did it on three strains. For all of our other strains are an acid resistant. And we've tested this in a technology which is the simulator of the human gut to we can tell you exactly what die off there is at what stage in the gut for every organism. Right. And an acid resistant capsule solves the majority of viability concerns.

So it's acid resistant because it's actually been enveloped in microalgae.

Yeah. So you embed it inside of a polymer which constricts, which constricts upon exposure to low ph conditions. And then as a counter expansion to that restriction, it opens up in the gut. But I don't want to, I mean I don't want to sit here and say that like that's the most radical or revolutionary breakthrough thing. In fact, I'm trying to say the opposite which is everyone solved. I mean acid resistant capsules and acid resistant technologies. As long as something has one of many acid resistant technologies for the most part, and it can company has data that shows that those organisms could survive prolonged exposure to low ph. That's sufficient to check that box. But it brings up a very important point. Two important points. The first is some organisms don't actually die off in low acid conditions because they're acid producers themselves and so they're very tolerant of low acidic conditions only some strains are very vulnerable. Bifidobacterium species and strains within Bifidobacterium genus are very sensitive to it. And the second is fermented is that's why food, there's such high die off of microbes in foods because the system, there is no protection system. It's not in an acid resistant capsule, it's not processed in some biopolymer matrix. You don't have any technology or any delivery system that that makes it more viable. And so you, and oftentimes you'll find in free form microbes, you find a high amount of die off. And remember, at the end of the day that's a good thing. I mean stomach acid is your first line of defense against environmental microbes, not all of them, which would be good for you. Right. So you would think that the human body would evolve a defense system to the ingestion to protect ingested microbes from just entering into your microbial community willy nilly. So it's. Overall that's a good thing. It's spoken about a lot like it's a bad thing. But it's actually a highly protective mechanism that very few strains that, you know, co evolved with us have the ability to withstand those conditions.

Got it. What are the most exciting things you guys are doing right now with seed? Like, like what, what, what's the company up to right now? Because I know you've been, you've actually, you've produced some of these probiotic strains and people can go buy them.

Yeah.

So they're actually available as a supplement out there. Yeah.

So we, well, we launched our first product which is a very interesting concept. It's an aggregate of strain of powerhouse strains that we found in with academic collaborations. We either developed them with an academic collaboration or we identified an academic partner that met our requirements for double blind randomized controlled trials. Or we conducted, you know, we conducted that work ourselves. And so our thesis was, let's just raise the bar with strains that have human clinical efficacy data for a, most importantly for a wide range of indications. And so we have folate producers, we have strains which down regulate the inflammatory response in the gut. We have strains which mitigate oxidative stress, we have strains which deconjugate bile acids to increase cholesterol reabsorption. We have strains which work on the gut barrier integrity, which strengthen the epithelial barrier. You know, so this aggregate of strains. And then of course we have our functional strains that on multiple markers of digestive health, things like stool consistency, regularity, bloating, ease of expulsion, anal itching. I know that's a funny one, but it happens. And we built a strain bank.

So you've basically got this bank of different strains that you've got all the academic research behind. And you can simply draw on each of these, mix them with the stuff like the pomegranate and the pine bark and the chaga, the things that improve their abilities to be able to grow. And then you simply package those and if I'm not mistaken, you've got one for males and one for females, with the female one being more focused on like the folate production.

Yeah, we have two things, we have two products. The female product is different in that it has a consortia of strains which down regulated the inflammatory response in the skin and so it decreased inflammatory response expressions in atopic dermatitis. And eczema, which is a shared inflammatory response for a lot of skin conditions and pathologies. And the female strain, the strain bank. The strains in the female formulation also are folate. We included our folate producer because of its role in fertility and pregnancy. Our first product was meant to say for anybody that is currently taking a probiotic, there's no reason why there's no better combination of strains with human clinical support than what we developed in our first product.

When do you take it? Empty stomach with food, does it matter?

Ideally an hour before a meal that contains some fat.

Yeah. Okay, that's what I think. I think on your label it says empty stomach space before a meal, something like that. But I've been using it for about a month. I quit using other probiotics, just switched to the seed. You washed out male formula. Yeah. So I'm, I'm four weeks into regular use, meaning I'm taking three capsules a day. So it sounds to me like I need to wait like eight weeks to really notice differences in terms of either dermatological health or gut health or anti inflammation or things like that.

Eight, wait eight weeks. Wait. If not eight, wait. Take 12 and pay very close attention to stool consistency, ease of expulsion, elimination. The color. Most people don't realize that stool is brown because of microbial communities are responsible for that pigmentation. If you have inactive microbial communities, your stool will be discolored and it'll be resembled closer to the color of the food that you ate. So stool in many respects is a, is a very interesting biomarker. But let me give you a peak preview of some stuff that's, that's coming out this year. We're actually going to do a trial where we're using a very new technology that was published in Nature, which is a gas sensing capsule which actually goes through the gut and picks up metabolites and gases that are produced by organisms through the entire gastrointestinal tract. And so we're gonna get a closer look at the effect that our consortia of strains has on metabolite production and modulation of the microbiome. That's a trial that we're doing.

Would that be something you could use for like sibo?

Yeah, that's exactly right. So anything that right now people are looking at breath tests or these proxy markers, but we want to get a closer look at every step of the way. How are the oral consumption of our strains is modulating microbial communities through the entire gastrointestinal tract. I mean this, we, we are announcing this shortly but we'll be the first group that ever uses this in a clinical trial. We're doing it with Harvard. We're running our trial there. We have another a paper and a draft that's going to be coming out on a two straight combination that was a 560 person trial and it looked at allergic response, allergic sensitization, including seasonal allergies. And so this would be data that shows that the consumption of two specific strains of bacteria systemically modulate the response resulting in allergic sensitization. And we're going to work and publish a paper on that.

Wow. Well, what I'm going to do is link to. You'll send me this other page paper reiterating what they are and what they are not.

They'll be out in a couple of weeks.

So I'm gonna put that in the show notes over@BenGreenfieldFitness.com seedpodcast I'll link to that documentary too that you mentioned, missing microbes, because I think that's gonna be very interesting for folks. And then also you've got the male probiotic formula, the female probiotic formula. I'm sure that at the time of this podcast gets released. This other formula that you're talking about might not have come out yet. But I'll link to your website. We are also have a discount code for those of you listening in. I'll put links to all this stuff@BenGreenfieldFitness.com seedpodcast but if you go to BenGreenfieldFitness.com seed there's a 15% discount code GREEN15 that you can use over there at BenGreenfulFitness.com seed if you want to try this out. And again, I see a lot of probiotics companies. I talk to a lot of people in the this sector and Raj and what they're doing, as you can tell, they're basing it all in clinical research. It's very interesting, it's very unique and your website's actually pretty cool. It's a very cool design. It's fun to explore. There's a lot of really cool information in there. We only scratch the surface of what you guys have on your website in terms of really cool probiotic information.

I appreciate you saying that education is a really big deal for us. So we think that if someone learn, if you can teach somebody the fundamentals, people are a lot smarter than companies treat them and you know, it's educated consumers move the market. So yeah, we're really big on that. And the last thing Is. Well, I'd be remiss if I didn't say, you know, as a company, we're not as. I mean, we have a lot of research tracks that are looking at every single ecosystem on the body. We have a whole women's health track that's looking at modulating the vaginal microbiome for applications and fertility and preventing urinary tract infections. We have a skin research track where we're looking to modulate the skin microbiome to dampen the inflammatory response. And on the next time we talk, I can give you more details on this breakthrough research that we're in the process of acquiring from ucla where actually they look at the methylation patterns of any individual cell and they can predict your, your age of that tissue within 2.4 years. And so it becomes this really interesting way if some people are, they are 10 years older than what your methylation patterns predict, and some people are aging 10 years quicker and most people are somewhere in between. But the idea that the choices that you make and the products that you use and the interventions you have, you can actually look at the epigenetic level is something that, that's, it's very attractive. And certainly microbes and microbial communities have a big effect on that. There's just never been a system like this ever of quantifying it. This is, this is really deep science. But, you know, so we're researching a lot of oral, the oral microbiome where there's. We have several research tracks in our company, all of which over the next couple of years we're going to be making some really big announcements. And the last thing is for people that since your community probably is outdoors, fitness oriented, environmentally leaning, I think that they'd enjoy it. You know, we have a division of our company called Seed Labs where we look at environmental projects. And our first one that we announced that Fast Company covered last year was a probiotic for honeybees which increases their resilience to neonicotinoid pesticides, which are commonly used by farmers in conventional farming. It's a huge problem. The EU just banned them. American farmers still, of course, use them. And it's the leading predictor or cause that people believe for honeybee colony collapse disorder, the decline of the honeybee population. I'm sure, you know, living where you do, if the honeybee goes, a lot of the crops that we are used to, a lot of the pollination goes. And so we found that actually by isolating microbes from the hindgut of the honeybee, characterizing them and Reintroducing them back into young bees. We increase their resiliency to those pesticides, but also we protect them from a very dangerous a nasty pathogen called penobacillus larvae, which kills off baby bees.

Wow.

And so, I mean, the field is incredibly exciting. I don't want to get too bogged down into what a particular. You know, I mean, as a whole, if you. Microbiology is going to impact every decision that we make in the coming years, from the choices we make for our food, from what types of medications we take, to how we cleanse ourselves, to how we treat and prevent and treat diseases, childcare, fertility, how you brush your teeth, how hygiene. I mean, you name it. There's a microbial component to all these different categories, and microbes are going to fundamentally disrupt all these different categories.

I'm glad I know you, man, because I can text you anytime. I have a question about bacteria.

Yeah, you can.

Or saving the bees. You've got the answer. You live this shit. I can tell. Okay, folks, so I'm gonna put a link to all this stuff over at BenGreenfieldFitness.com seedpodcast where you can also jump in if you have comments or questions. You can ask them. Either Raja or I will jump in and reply to any questions that you have. The probiotic we talked about, that's the seed probiotic. That's@BenGreenfieldFitness.com seed. You get a 15 discount on that with Green 15. If anything, check out their website. Like I said, it's pretty cool. Raja, thanks for coming on the show, man. Thanks for keeping your. Your giant wolves quiet with bone marrow to make podcasting magic today. All right, folks, until next time, I'm Ben Greenfield, along with raj deer of seed, signing out from BenGreenfieldFitness.com have an amazing week. Well, thanks for listening to today's show. You can grab all the show notes, the resources, pretty much everything that I mentioned over@BenGreenfieldFitness.com along with plenty of other goodies from me, including the highly helpful Ben Recommends page, which is a list of pretty much everything that I've ever recommended for hormones, sleep, digestion, fat loss, performance, and plenty more. Please also know that all the links, all the promo codes that I mentioned during this and every episode help to make this podcast happen and to generate income that enables me to keep bringing you this content every single week. So when you listen in, be sure to use the links in the show notes. Use the promo codes that I generate because that helps to.