Human Milk Oligosaccharides and the Future of Gut-Brain-Immune Therapies with Alex Martinez

Welcome to The Perfect Stool: Understanding and Healing the Gut Microbiome. This is your host, Lindsey Parsons, and today I'll be speaking with Alex Martinez, CEO and co-founder of Intrinsic Medicine, patient, entrepreneur, business advisor, and healthcare industry leader committed to transforming how gut-brain-immune axis disorders like Parkinson's disease juvenile idiopathic arthritis, IBS, IBD, and autism spectrum disorder are diagnosed and treated. Previously, Alex was the director of corporate development of Ionis Pharmaceuticals and associate attorney at Wilson Sonsini. He received his Juris Doctor from the University of Michigan Law School and his Bachelor of Arts in Health and Societies with a public health concentration from the University of Pennsylvania. Before our conversation, if you haven't yet followed or subscribed to the show, be sure to do so. And if you want to get transcripts of the podcast, pop over to my website, HighDesertHealthCoaching.com, and sign up for my newsletter. You'll also get my recently updated free ebooklet, Finding Your Root Cause Through Stool and Organic Acids Testing, when you sign up. And if you haven't yet done my quiz on which stool or functional medicine test would help you get to your root cause, you can find a link in the show notes and take that. Now onto the show. Welcome to the podcast, Alex.

Hey, Lindsey. Thanks for having me.

It's my pleasure.

So you wanna share with us what took you from working in law and pharmaceuticals to co-founding forensic medicine?

Yeah, absolutely. As with everything, it's usually when you realize the position you're in is not the position where you can make the impact that you desire. And I probably started my journey into this even before I began my formal education and professional career. The, the first job I had— I grew up on a farm in central Maryland, and after about 10 years of farm labor. My first position outside of that was working as an instructional assistant for children with special needs, specifically, you know, severe autism, nonverbal children. And so that was an extremely special experience I had. And it was something where firsthand I was able to immerse myself in the needs of children as well as families and see how they were trying to orient themselves and realizing that there's just many different ways to, to create a difference around the different angles that are needed for, you know, cases like autism where, you know, there's a social component. Of course, there's a very profound communication component. I think also that really kind of laid the seed for where I am today, because I also saw the GI issues that these children often had and firsthand got to participate in some of, even some of the early dietary interventions, right? Being like, oh, you know, seeing, of course they're constipated if this is all they eat. Right. But also recognizing the challenges associated with that. So that was really kind of the fundamental inspiration that transcended when I went to UPenn. For school. And that's really where I wanted to understand the overarching ecosystem that I felt was not serving these children. Right. And so that's where I focused on public health. So of course I went to law school 2 weeks after I graduated from college. And then from there I worked in the healthcare system. I was originally going to be a healthcare attorney, realized that in some ways I was perpetuating the dysfunction in the system through that practice. And then Led me to Silicon Valley, practiced at one of the top law firms for, you know, a year or so, and that was boring and terrible. So from my early entrepreneurial experience, I actually started a digital health company before that was an industry class. It was like 2008, it was an MIT spinout. So that was like an important part of my genesis story because one anecdote I'll share from that. Is we were helping patients take care of themselves in the community setting after being discharged from hospitals. And we used teach-back to ensure that they could comprehend why they were hospitalized and what their treatment and follow-up needs were. One of the things we found out was there were patients that were being readmitted with glycemic issues, and we realized that the nurses we're showing them how to inject insulin on an orange. Some of them were actually injecting their insulin in an orange in the community center.

Oh my gosh.

Right. And so that's, that's a gap. It's not something we think about and we can't fault these people. We have to think about education mismatch to the literacy and comprehension of those patients, figure out what their comprehension is. And so that's using teach-back and we actually use virtual avatars And said people are actually exposing where they had comprehension gaps, right? So I've always thought about how do we empower patients with education so they can go through a patient journey and make truly informed consent? Because as I got into the pharmaceutical industry and focused on genetic diseases, I was always concerned about, are patients comprehending what they're doing, joining clinical studies, and they're eventually making pretty major decisions about these, these treatments. And just to kind of wrap up, you know, the final thing that got me here is while I worked on a bunch of transformative drugs for genetic disorders, I realized that all of these chronic conditions, the ones driven by the common causes of dysbiosis and immune dysregulation, the pharma industry really kind of turned its back on. And so my premise was no one's developing new therapies for the things that me and my loved ones are going to suffer from. I'm going to do it and I'm going to take a different approach and versus the approach of which I think has a certain amount of hubris in it. We know better than nature. I'm going to lean in the other side and say, there is a, an intelligence in nature that we can't comprehend. And I'll use evolutionary biology to look for molecules that appear at the most vulnerable junction in human life and then assess those for therapeutic properties in a therapeutic context. And that's what led me to these special oligosaccharides that are found in human milk.

Okay. Interesting and winding story.

Yes.

So yeah. Can you tell me about the research around the gut bacteria then and gut-brain-immune axis disorders? And you can take 'em one by one or lump 'em all together, however you wanna do it.

Yeah, absolutely. So I think the first thing is let's define the gut-immune-brain axis disorders. 'Cause probably because you, and I'm sure as your listeners would say, oh, okay. So these guys are They added another letter. We know about the gut-brain axis. Why did you add immune there? And this is an evolving space. And what we realize is the, the, the crosstalk between the immune system, both the innate and the adaptive immune system, it really needs to be called out as its own aspect to modulate this system because they're, they're all, they're all participants in the system. And this is where for a lot of these gut-mediated disorders, we're seeing that at least subsets, there seems to be a, a primary immune drive. So for example, major depressive disorder, about a third of patients will have a very clear cytokine profile and associated dysbiosis. Same thing with autism spectrum disorder. And even disorders like Parkinson's, which based on Brock's hypothesis starts with a disturbed microbiome, both in the oral nasal pharyngeal, but also the gut. And that's typically been approached in pharmaceuticals as a neurodegenerative disease, like brain first, when there's been clear evidence for a long time that the prodromal symptom in many Parkinson's patients is constipation, right? And it's constipation, actually REM sleep disorder, some of the earliest symptoms before the motor manifestations of Parkinson's. And so, then we're thinking about these protein aggregates and say, what are they doing? There must be an adaptive context that for them occurring, that's then become maladaptive and pathogenic in a chronic context. And that's where we see kind of a local immune activation, which drives production. There's a clear dysbiosis. And in fact, it's, it's a dysbiosis, but it's also one where the metabolites, which change how the gut's functioning, what's crossing over. And as many people know, it's like 70% of our immune system's in the gut. And then that immune system is sending out signals that's changing protein synthesis. And there's some speculation that alpha-synuclein may actually be part of an acute immunological response that when chronically activated, you have all these excess proteins. And what, what are proteins? They're unstable molecules, especially in a context of oxidative stress. And then they are able to travel directly from the gut up the vagus nerve, central nervous system, where they essentially activate microglial, the local immune system, and eventually they're overwhelming it as it tries to clear it out. And that creates a lot of collateral damage, namely on, on neuron function. So that's just kind of like one example. So that's why we thought it was so important to add that immune component because we think that we have to essentially look at the gut as an ecosystem, but we actually have to look at the entire human biological system, including the somatic cells as part of that ecosystem. I think they're, they're all connected.

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What are the somatic cells?

Uh, the immune cells, the immune cells, but, but, but even the colonocytes as well, right? They're all, they're all talking. And I think this is one of the other interesting things about this The human milk oligosaccharides. What's, what's fun about these is that they're not ours. They're not intrinsic medicines. They're, they belong to everyone. And we're just kind of, I think of us like Sherpas. We're, we're carrying them up this mountain of sort of the burden of scientific evidence to elucidate their properties. They've been known for a long time. But it's like we need to rigorously elucidate their properties so that then they can be applied in the right context. And I think one of the things that is important, and this is why I think the time is only right now, it's through the work of people like you and your listeners, the practitioners, or helping diffuse out understanding of, of the microbiome. But oligosaccharides are called by a different name. They're called glycans. Some of them are also called siglecs. So all this science has been siloed based on semantics. What are glycans? They are an interspecies language. It's how organisms communicate, especially microorganisms. So what we're looking at is a language from mothers to be able to directly communicate to the microbiome., but also to the developing cells in her baby's body and saying everything's okay. And essentially providing bumper rails for the appropriate development of this union, this symbiotic ecosystem.

You mentioned alpha-synuclein.

Is that, can you explain exactly what that is?

Yeah, that's so that, that is the protein. That is found in people who pass away from Parkinson's. So they find aggregates of it. So like clumps of that in the brain. And they say, oh, this is what causes Parkinson's. They also found clumps of that in the enteric nervous system, the gut nervous system. And so the mechanistic or the sort of the mechanical pharmaceutical approach is, okay, let's take out that protein.

Right. Sort of like the amyloid plaques with Alzheimer's, right?

Bingo. And what these may be is just a marker of a perturbation of a system. And these, these actually may have been band-aids, right?

Right. Much like amyloid plaques, right?

Yep.

Yep.

They may have been band-aids for what was actually going on, which is, so you, you have activated immune cells causing collateral damage and creating oxidative stress that then damages the cells in the body. And then there, it's basically a sterile inflammatory response that's occurring, right? So these protein aggregates, we're, we're thinking about them a little bit differently cuz we're like, the body produces these for a reason and also has its own clearance mechanism for it. So what we're seeing is an overwhelm of that mechanism. And so we say like, hey, how do we go upstream of this where we can stop whatever's causing this cascade? And then we can send signals to those immune cells where they're able to say, hey, well, actually we've been overexcited here, right? Because you think about immune cells are either kind of like in soldier mode or they're in construction mode. And it's like, that's where we want to change them. And that's the, I think one of the fascinating things that I'd want to remark on here, Lindsey, is this is not, these molecules don't just act in the microbiome. So independent of that, we know some of them enter the bloodstream and we've done our own studies and we've looked at, for example, macrophages, which are kind of the first responders, the innate immune cells. And the phenotype of a macrophage when it's like super active and it's ready to take something out, it's called the M1. So that's the pro-inflammatory phenotype. And then M2 is a regenerative phenotype where it's actually just clearing debris. It's kind of rebuilding tissues. These compounds can actually shift an activated macrophage back to a regenerative phenotype. And this is independent of metabolites or anything from the gut or any signals from the gut microbiome. So that's, that's really kind of the premise here is we're looking for a return to homeostasis. And ultimately that's, that's why these compounds exist in early life because a baby, if you look at their immune system, is totally imbalanced, right? And it's like totally hyp— right. It's totally hyperactive. It's why they, it's why they get rashes. It's why a food allergen can lead to a massive atopic dermatitis and colic and all these other issues. And it's been known for a long time that these compounds can ameliorate all that in babies and change their, change their lifelong trajectory in all of these chronic disorders. And then we just looked at adults. With these different gut-immune-brain axis disorders. And we looked and we said their immune systems, their gut permeability is like an infant. So the simple question is just, does that same biology that benefits babies, does it benefit grownups?

So if you're looking at the human milk oligosaccharides as food for Bifidobacteria in babies, and that then allows them to produce short-chain fatty acids. Would butyrate not be the end result of all of this in either direction?

It's an absolute great question. So it's, it's part of it. Yeah, it's a good part of it. One of the reasons, so I think butyrate actually does have its utility and it's, it's been, it's been shown, but as I said, it's kind of only a portion of the benefit, right? So for example, these compounds are preferential substrates for, for Bifidobacteria. One of the things that they also do, so my lead compound is called 2FL. It actually upregulates adhesion genes in Bifidobacteria. So it actually adheres and colonizes.

Mm-hmm.

It also serves as a soluble receptor decoy. Or invasive E. coli, as well as enterotoxins. So what it's doing is it's advantaging the, the bugs we want, our friends, the bifidos. It's a food source for them, but it's also telling them to bind and it's helping them outcompete pathogens at the same time. The Direct molecule itself is also binding to TLR4, right? So it's blunting the immune response so that the gut can mature and, and heal because it's clearing out all those pathogens that would be activating the, the immune system in a, in a permeable manner. And it's also changing gene expression in those colonocytes. It's upregulating tight juncture proteins, occludins, claudins, right? So that's kind of where we say, I think butyrate's a great compound if you want to like promote instant colonocyte, right? 'Cause that's what colonocytes like, if you wanna like instantly bathe them in that, it has utility there. I think in research it definitely can help mechanistically identify the, some of the, these, these actions. But we also know that you can give the HMOs to, it's been shown in healthy normal adults who are free living on like their own diet, right? Not a standardized diet. And we can increase butyrate levels as well as I think propionate and, and some of the other short-chain fatty acids. So this is, again, it's an upstream approach.

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Right. That's further upstream than butyrate.

Okay.

So we haven't actually done an intro to what human milk oligosaccharides are and I covered 'em a couple other times, but, but let's, let's do that so we don't lose people.

Oh sure. Absolutely. Absolutely. I, I always jump ahead. Thanks for keeping me on track, Lindsey Parsons. Okay. So human milk oligosaccharides are class of of oligosaccharides, basically bioactive sugars. They're found in human milk. They're the third largest solid component in human milk after fat and lactose. And what's important about that third runner-up category is they're actually first when it comes to non-caloric molecules in milk, because fat and lactose are used primarily for, for calories. Human milk oligosaccharides are amylase resistant, so we cannot digest them for caloric energies. And to give you an example of how prominent they are in early milk, like, you know, colostrum, they're like 15 grams per liter. And in mature milk, they're still about 5 grams per liter. And there are over 200 distinct structures of them. And this is also important because these compounds require special synthesis. They, they require a lot of energy for a mother to synthesize. And so to have them in such specific diversity and concentration without providing caloric energy means they're really, really important.

Did you say there's 200 different types?

Over 200 different molecular structures of milk oligosaccharides. And what's, what's really interesting about that is like we have data showing that ones that even though they're made of the exact same thing, despite they have a different bond and their activity's completely different. Hmm. So it, it's kind of like a, what I, what I kind of said earlier, when we think about these sugars as a molecular language, glycobiology has always been extremely hard to crack because it changes over time. Honestly, our tools to specifically identify these, it's hard to see them because they all have, they're all made of the same thing. So when the only difference is shape, that's really challenging to see. And so while it's been an exciting field, there's never been like, how many sugar-based drugs are there? Right? That's a trick question. There's only a few. The, the one that most people will know, it's heparin. It's like, and, and then there's some aminoglycoside antibiotics. That's it. There's like, there's nothing. And so when we look at HMOs, those 200 distinct structures, I almost view that as like the Rosetta Stone of glycobiology because that is a mother's repertoire to talk to the cells in the baby's body. Further in that 200, there's basically 3 different broad categories. There's fucosylated, there, there's basically acidic, neutral, and fucosylated ones. And so all of those have different functions and, and that's what we're figuring out right now, what they all, what they all do.

And what are the, I know, you know, I'd heard of 2FL. What are some of the other ones that are, that are commercially available at this point?

So 2FL is absolutely the foundational one of those, and that's why it's been most readily studied. And there's a few different sources. We'll talk a little bit later. We're, we're actually launching a, a clinical grade one and, you know, probably a month or so because I have conversations like this. And then the logical question is, wow, we'd love to try this on ourselves and, you know, patients we work with. And so we're, we're finally working to make that accessible. 2FL is 30% of those 200. So that's certainly the, the base of the pyramid. The other ones that I think have important functionality are the, come from the acidic side. So those are 3-C allyl lactose and 6-C allyl lactose. And these, this is a great example of what I just said because these compounds are exactly the same except they have a different bond, right? They have a 3' and a 6', mm-hmm, different functions. So 3SL, it has benefits in— we actually started Intrinsic Medicine around 3SL, but it didn't have the same commercial availability. So we were always trying to balance, you know, access, availability with, you know, the scientific rationale for something. So 3SL is the primary anti-inflammatory, primary direct anti-inflammatory oligosaccharide in human milk. And it's shown to be capable of really promoting like joint and bone development, as well as having that for things like rheumatoid arthritis, juvenile idiopathic arthritis. It can have positive effects that look like today's immunosuppressive drugs.

Mm-hmm.

But it's extremely safe.. And so the question is, how is it working differently? So the immunosuppressive drugs, they say, hey, you know what we're going to do? The immune system's causing all this problem. We'll take it out. We'll eliminate it. We'll suppress it. Right. And then, and then you have a bunch of side effects, which includes severe infections. So how does 3SL exert similar benefits on cartilage healing? Systemic inflammation going down, it's because it activates resolution pathway, right? There's acute phase of inflammation and then there's a resolution side where it resolves and you're taking all those immune cells and you're saying, okay, it's time to rebuild and stop destroying things. And so that's what it activates. So that's a really cool mechanism. And then 6-acetyl is interesting because it's implicated in neurological development. And so one of the neat things, and I think this is one of like the important talking points with HMOs, is that there's probably not a one-size-fits-all. And I think that's what's hampered commercialization has been. It's the same, it's like the thing with nutraceuticals. They're always like, here's our proprietary blend. That's perfect for you. But then when we look at nature, right, we always have to get the Cliff Notes from nature here. This is a completely dynamic system. Like moms are producing different levels of HMOs based on the different, her environmental context as well as her babies. So it completely changes. And so we can look at human epidemiology and so we can look at the levels of these compounds in milk for different babies. And some moms are producing low for whatever reason, others are producing higher levels. 6SL is one that is like 2FL associated with better development of executive function long-term. And it also, 3SL is operating on connective tissue and bone. 6SL is operating on muscle as well. And so it, it upregulates something called PGC-1α. And what's kind of neat about PGC-1α is all of us can upregulate this. And if you upregulate this, it promotes muscular growth. And what is it? It's exercise, right? And so we think a little bit about this and say, wait, okay, so what's this 6-SSL thing doing in milk? And you're like, well, how do babies grow? And like, you know, babies are strong. You know, I remember like, you know, holding my son and being like, wow, How are you getting stronger? You just lay around all day.

And so it, I think baby pushups.

Yeah, exactly. Tiny baby. Yeah, exactly. Baby calisthenics when I'm not looking. And it would make sense that milk would contain a bolus of effectively an exercise mimetic that would enable babies to grow healthy functional muscle. And it actually makes sense that it would be there'd be neurological, right? Neuromuscular strength, right? You need that connection, that functional muscle. So it totally would make sense for this compound. So I think these are probably the most mature ones. LNT is another one that I think is widely available. That one is primarily one of these like biphitogenic substrates. It really is designed to enhance the, the fermentation. And that one I think is, it makes, it makes sense in the context of cross-feeding, right? Because we, the, the Bifidobacterium are kind of like a keystone species. They're like the bison or buffalo, right? And then they cross-feed all these other adjacent microbes and that's part of what creates the community. And then there's one more which people may know of. It's LNNT. Does that ring a bell?

Um, not really, but—

Oh, okay. Okay. Well, that's another one that's commercially viable and it lets me talk about something that's also a little bit nerdy, but should be interesting, hopefully. So, and also I think it illustrates the point about thinking of these as interspecies communication molecules. So while we call them human milk oligosaccharides, it also makes sense to call them milk oligosaccharides, right? And that's one of the things that actually gives me a lot of hope, especially because I want to eventually move off of anything based on animal studies and making the argument that we could do this in human organoids and like mice also their milk contains 2'-FL, you know, 3'-SL, 6'-SL, right? And these are not genetically engineered mice. These are just normal mice. And so what we're able to do is actually look at what it does in a mouse with an organic disease, chronic condition, see how one of these oligosaccharides can benefit it, and then show that the same exact biology is occurring in human cells, right? So it's really there's a real close translational point. And that was actually part of the thesis of developing this because there, there's a reproduction issue in today's science, right? Like 40 or 50% can't be reproduced. So I think there's a good translational basis. But anyway, going back to L and N T, it goes beyond human milk. These oligosaccharides may predate mammalian evolution. They go way back. And the reason I'm saying this is that there is a— are you familiar with helminths?

Yes.

Because helminths can be used medicinally even though— and so how, why, how, how, you know, how can they do that? They, how can, how can this outside organism modulate the immune system? Well, helminths produce LNT. And it enables them to move through the tissue without eliciting crazy immune responses. And importantly, it enables them to move through tissue without inducing fibrosis, right? Which would, which could harm the host. And so a team actually looked at this and they use LNNT and burn-in scarring dynamics and lo and behold, it helps in normal non-fibrotic healing.

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Just for people who don't know what Helminths are, they're worms that people take to actually deal with like severe allergies, migraines, things like that. And they, let 'em pass through their system for a couple months and then I think they take anti-worm medicine to get rid of them so they don't go outta control. And then they reintroduce them when they need them. Something like that, roughly.

Yeah. It's crazy when I first heard it and then I, I dove in and I made this connection and I say like, this is really, how does that same sugar in a helminth to human milk? Again, that's like the intelligence of this magnificence of nature. It finds something that works and then make sure whoever needs it gets access to it.

Yeah, no, I, I tried for the longest time to get somebody on here to talk about helmets and there was a guy who was selling them and his method had been to go somewhere in Africa. I can't recall where, walk around a dirty latrine area in his bare feet until he knew he was gonna get those worms. And then go home and culture them from his stool and clean 'em off and sell 'em.

That is amazing.

So suffice it to say that he did not want to attract too much attention to himself.

Yes. And actually I may know somebody if, if you ever wanna revisit that, but, but, oh yeah.

Yeah.

'Cause I, yeah, no, I, yeah, but I, I, I think, yeah, so it's, that's amazing. And that's actually, again, it reinforces the point, which is I think we're kind of on our own. It's, it's a grassroots effort, right?

And that is for sure. Yeah. We're all, we're all, uh, end of one trying to figure out what the heck's going on. Right. Yeah.

Okay.

So, so that's the different types of HMOs. You mentioned a couple of 'em had the word lactose in them. So I am curious because there's a lot of people who do not do well with lactose who are adults.

Yes.

So I'm curious, do they have lactose in them? Like if you're gonna take them and you're lactose intolerant, you need to take your lactose pills too?

It's a great question. This is interesting. I always urge caution. My overarching philosophy in gut health is it needs to be, everything needs to be pro empowerment, right? This is our opportunity to say like, okay, we know our bodies, we're going to listen to them. And by the way, I had severe IBSD for since I was like 11. And when I had finally obtained consistent supply of 2'FL, I have constructively cured it. Again, 95% reduction in symptoms that were crippling and debilitating. And so that was part of a long titration. And I also thought I had a lactose intolerance component as well. Didn't have that. I actually drink milk every single day now. My chief medical officer is severely lactose intolerant and is able to take these daily at our high therapeutic doses. They have, while they have lactose in the backbone, it's never free, if that makes sense, in, in the gut. So it's not recognized or metabolized as such. The issue is that the substrates for producing 2'-FL are lactose and glucose. So there always probably is gonna be a trace amount in there. And that's where I think on a basic precautionary level, if you're taking 2FL, just take a lactose pill with it.

Yeah. But I've taken 2FL and I've never had any problems and I am severely lactose intolerant.

Exactly. Right. We have those anecdotes. It's just something that, and that's kind of also part of what we're trying to do at Intrinsic is we're trying to run the RCTs, the randomized controlled trials where we can show the benefit, where we can also map all the adverse events, and then we can really have a discussion. We can actually inform it versus where we are today where it's like we're largely anecdotal and people have, they say, have their concerns and then we're able to say, well, Actually, no one's had an issue with this, but until I can prove that, I'm not gonna say that. I'm gonna say trust your own body. It's gonna be a very trace amount. 2FL by itself, part of the beautiful things it does is it actually reduces food allergies and that's fantastic. So it'll actually, you know, reduce the reactivity. You know, one of, again, another anecdote and this was part of my philosophy. I said, imagine how amazing the drugs we'd have today would be if every CEO was required to take theirs, be patient zero. And so I, I've led with that philosophy. I've also been on 3SL for several years and it's on that time period I've had no flares of my lesion atopic dermatitis. And this is another area where it has benefit, right? Skin is also part of the connective tissue. And so after I've had these great, fantastic results, you know, my son had crazy atopic dermatitis. He, when he was born, he had severe food allergies. It turns out my wife had a bunch of food allergies that were then basically IgE antibodies are like being passed through the milk. And when we did allergy testing, he was EpiPen allergic to the top 21 allergens.

Oh my gosh.

It was, that's scary. It was really, it's scary. And you have this like little teeny creature, human being, and they're in distress and you're like, what, what is he gonna eat? And I went into the literature and I saw the food allergy data with 2'-FL and it's generally recognized as safe. For infant formula or as a supplement for infants and toddlers. So I was like, I can do this. Why is this not available? And so I started administering it to him. I, I know how important milk is. We literally had to go off breast milk. And so anyone who's donated milk, you are an angel. You are, you are an absolute hero because that was really important. And then we actually had to import buy the gray market formula from Europe as well, because the allergenic formulas in the US are pro-inflammatory, right? They're corn-based. And so then I was mixing up his formula with 2FL and we did sublingual immunotherapy and he can now eat every single one of those 21 allergens. He could eat a peanut butter sandwich. And doesn't need to carry around an EpiPen. And it was like all part of taking what's out there, taking this molecule, knowing that it would provide the context for his immune system to balance itself while recognizing these antigens. And we got him completely off. So, yeah.

So the immunotherapy you did, was that through like an allergist? Are you talking about like the low-dose immunotherapy that people do?

It, it was, yeah, it was through a, through an allergist. Okay. And it was just really just titrated allergens.

Right.

But yeah, we, we mapped it out cuz normally you do it singly and I think with the background of 2FL, we felt comfortable going and doing all of them.

Mm-hmm.

In this. So it was like just a linear course and I mean, it was amazing. It was like amazing to see that.

Okay. I see we're already getting sort of low on time and I'm, and I feel like we maybe haven't hit the juice of what we're supposed to be hitting. But, but couple quick questions. So do you derive HMOs from cow's milk? Is that where they're ultimately coming from?

No. And is a great question. I'll, I'll try to be brief with this one. So cows are bred for volume.

Mm-hmm.

High lactose. So cow milk is actually extremely low in milk oligosaccharides. It's only 0.5 grams per liter. It's, it's extremely low. We don't derive it from cow's milk originally. Some of the research ones were, but we didn't wanna do that. And, and some mammals have different sialic acids, for example. So, so these are produced with precision fermentation. Oh, so the human gene is in a microbe that then is fermented with lactose and sugar, and then it produces 2'FL, which is then processed and you remove like endotoxins and all the other stuff, and then you're able to have a purified human identical milk oligosaccharide. And that's important in making them cheap as well.

Oh, and then I assume that would mean there's no dairy proteins in them.

So it depends on what the lactose source is.

Okay.

But it is minimal and, and that's part of the downstream processing, but.

Okay.

Yeah.

So have you guys already gotten to the level of doing RCTs or prior to that, like what kind of research have you done and on what conditions? Yeah.

So we've actually done a lot of transcriptomics work, which is looking at how milk oligosaccharides impact gene expression on different cells. And so that's where we're some of the first to actually look at the direct effects and, and the systemic effects, right? Because 1 to 4% of these with oral dosing up to 4% enter the bloodstream. And their bioactivity. So we really wanted to understand that. And then through some of our partners, there are actually ongoing RCTs. So for example, you know, we're developing for inflammatory bowel disease. Cincinnati Children's Hospital currently has 200 young adult and pediatric patients with ulcerative colitis and Crohn's enrolled in a 2FL study that's been going for about 52 weeks and And most importantly, the safety component was completed and they were able to step down to younger children. So I'll actually be catching up with them pretty soon, but I actually expect us to have some results later this year. And then we also are running our own studies. So we received Australian regulatory approval to initiate a Parkinson's disease study. In patients with mild and moderate Parkinson's disease and a history of constipation. So that'll be our first RAN as a sponsor study. And I think that one's going to be really important because we're going to assess both the GI aspects, right? So we're, we're going to be doing irritable bowel syndrome, constipation type endpoints, but then as key secondaries, we're going to have the motor and non-motor symptoms as well as cognitive function. And that'll be 6 months of dosing. And then we'll also be doing full multiomics profiling. So that's this gut microbiome, the metabolites, and then looking at the blood of these patients for a whole host of different markers. And then paralleling that with like objective clinical things, balance, physical therapy, motor function assessments. So that's gonna be a great dataset that we will offer to the community after that study.

And what about any studies related to autism and HMOs?

Yeah, so we're, we're actually currently working, we're, we're engaging with a bunch of different autism experts. We have our own anecdotes with, with the compounds. And we'll be meeting with FDA in the second half of this year to discuss kind of what those studies are. And I think what's notable about that is each one of 2FL, 3SL, and 6SL each have a distinct mechanism that could benefit patients with autism. And so we'll initially start with the GI aspects, and then we'll use that as kind of a foundation we do have some pretty compelling anecdotes also supported by preclinical data on Thuria cells' ability to reduce that irritability and self-harm activity. So, I mean, those are really exciting things and I know we're, we're at time, but I think one of the other important aspects when we think about HMOs as therapies or even nutraceuticals is there's no live bacteria in them. And this is really important for the autism community. Because there's a lot of aspiration and there are a lot of special dietary needs. So these don't need any flavor masking. 2FL actually tastes delicious. I don't know about, but it tastes pretty good.

Yeah.

Yeah. And so you can, you can mix it into different things. But one of the things that is, I think, always important to remember if you're trying to do use probiotics in a vulnerable population is that's a live bacteria that can thrive and colonize the human body. And so infections have been seen in immunocompromised patients, and that's certainly not something that we would want aspirated as well.

Yeah. So I interviewed Beau Berman from Layer Origin back in episode 38, a good while ago, and I know they've got both pure HMO powder that's 2 FL. They have the Super HMO prebiotic mix that has the 5 HMOs you mentioned.

Yeah.

So I'm wondering how, if at all, your products are gonna be different from theirs. And also, is, does colostrum have all of these things inside it, including like anything?

Yeah.

So it's a, yeah, cuz I know, I know there's other components in colostrum like IgG and lactoferrin. So I'm just wondering if, if colostrum kind of covers all your bases.

So, well, I'll answer the colostrum one. So colostrum will have a full stack of pooled HMOs, but it's not gonna be at a therapeutic concentration. Yeah. And then I think with Layer Origin, I mean, they've been doing it for a long time and I've actually used the product then. And so I don't have my 2FL out yet. So if, if somebody's like, Hank, can you do it? I'm like, yeah, try, try the Layer Origin. I know where they get it. It's not where I would get mine. Calling something high purity is great, but what are the impurities? Because these are extremely bioactive compounds. And if downstream processing is not done right, you actually do have impurities. And I've, unfortunately I have received batches where it doesn't work. And so quality control is extremely important. For what Intrinsic Medicine is doing is we're actually doing pharmaceutical CGMP-grade material. So it's a very strict process. It's a heightened standard on any food-grade GMP grade. And I think the benefit of then us having kind of like a wellness component from that is we're using that same, same clinical standard material, which has also a standardized impurity profile. I think that's gonna be one of those important things in the next step as the HMO market's unlocked where, you know, I encourage people to be responsible and I actually think Layered Origin has improved their quality control. So I don't want to disparage them, but the characterization of those residual 2% or so is so important. If somebody's getting it and they're not doing downstream processing, it can have endotoxin in it. These are produced in E. coli, right? So it's like, yeah.

So people, people could ask for a, a certificate of analysis if they want to look at what's, what's in any batch, I'm sure.

Yeah. Basically we need to move to a hyper-transparent paradigm. With these compounds. And my hope is that they don't become the next probiotic where everyone's putting them in everything.

Mm-hmm.

And because there is a, there's basically a target you need to hit and it's gonna be different for everyone. And if you take more, which especially in America, we're always thinking more is better, you actually diminish the effect.

Oh, okay. Interesting.

Yeah, we're gonna have clinical basis for everything we do. And then we've also developed a, a novel titration because that's also really important because most efficacious doses are ones that people will actually have tolerability issues in the early weeks as their microbiome transfers. And as you get this huge bolus of short-chain fatty acid production, and when you're going into people that have background of IBS, of GI sensitivity, that's just not right for, and they'll, they'll lose something that if they had just taken a different way would get them to their goal, their, their health and wellness goal. So, okay.

So tell me where people can find you and you're selling these, you're gonna be selling these products over the counter, correct?

Yes. Yeah. So that's gonna be launched through a distinct company called Intrinsic Wellness and You know, I probably expect that to come out sometime next month.

Yeah. So before this will publish, so it'll have been out by the time this publishes.

Yeah. So, so I'll, I'll basically be sending you the link and everything.

Okay.

So I'll put a link in the show notes. I think there'll be an affiliate link at that point so people can use that if they want to try something out. Any final thoughts before we get off?

Yes, there are. There always is something. One of the things I've been thinking about recently is a lot of people have taken that Quantified Self approach and are thinking about biomarkers and are, they're, everyone's tracking everything, right? And, and they're doing it where folks wake up in the morning and say, let me check my sleep score to determine how darn straight every morning. I I feel, right, right. And so I fully honor that and I think it's a great tool, but I always want to remind people, use the tool to rediscover that, that body awareness. And I think with GI issues, it's the Bristol Stool Form Scale is absolutely your friend. And, you know, it is a lagging indicator, right? And it's going to be individualized for everyone. And so our premise is we want to deliver the, the best standardized HMOs to people. We want to give them a really easy to comprehend self-titration protocol to minimize any tolerability issues and help them get to their goal, which is going to be unique for everyone. And, and that's why we're also giving the most HMOs in each bag so that they can get to full currently being clinically tested doses and really never have to worry about running out. So we want it to be a consumer-friendly product. And basically I'm developing this as my own supply, right? I said, if I get anything out of this, I want to, I want to supply the best 2FL for me and my family. And this is exactly what we're gonna deliver on and, and hope to share with with all of you.

Okay, great. Well, thanks for sharing about all this. This is interesting stuff.

Absolutely. My pleasure. Thanks for having me, Lindsey Parsons.

So do check out the show notes for a link to their products that will support the podcast. You can also support the podcast by buying supplements at a discount from my Fullscript dispensary, ordering tests at a discount from my Rupa Health Lab Store, or using my affiliate links to iHerb, which is available worldwide, or Amazon. And just a note that you can use my Amazon link to buy anything, so I'd appreciate it if you'd bookmark my link and use it not just for supplements, but for gifts and everyday items to support the podcast. If you'd like to connect with me online, you can follow my High Desert Health Facebook page, join my Gut Healing Facebook group, or join my newsletter list at highdeserthealthcoaching.com, as well as follow me on Instagram, TikTok, Pinterest, Mastodon, and X. Links for those are in the show notes. Thanks for joining me today, and here's wishing you all the perfect stool.