This New Invention Blocks Microplastics

The microplastics bind to the gut. It's like a tug of war, and you actually want to build the microbe to win the tug of war so it can get pooped out. How do you do that?

It's tens of trillions of particles floating through that liter.

What the parent does will affect their grandchildren almost directly.

Everyone has plastic exposure, so there's some level of baseline. The more we learned about it, we couldn't look away.

Your immune cells stepping on a Lego piece and screaming inflammation into your blood vessels.

How can we take plastics and dissolve them away within the human body.

All right everybody, I'm really excited for this interview, but it's a bit of a scary topic and I want to frame it up a little bit with some personal reflection and context, which is for years I've been very concerned about this omnipresent issue of microplastics in the environment. It seems like they're everywhere, you know, not just in our environment but getting into our bodies and really damaging our health. Now it seems like an insurmountable thing to try to avoid microplastics. Basically, it's impossible. When I came across the work of, uh, Dr. Matthew Dunn, which we're going to talk about, I was immediately taken by it. Now I'm going to put the disclosure up front, which is that I'm now involved in his company, Winnow Labs, which we're going to talk about, but it's because I think it's genuinely like an innovative and very cool solution to a big, big problem. So with that, let me introduce our guests. This is Dr. Matthew Dunn. He received his PhD in molecular biology and biochemistry, Arizona State University, and has since worked at the intersection of biotechnology and health for years with a very eclectic background, everything from precision fermentation to modifying ruminant microbiomes and so on. But he's recently turned his attention to this pervasive problem of tiny plastic showing up everywhere— our food, our water, and then in our bodies. So I'm excited to get into this conversation. Welcome, Dr. Dunn.

Yeah, thanks for having me. It's always great to have a conversation with you, Nick.

Yeah, I know we've had a lot of fun conversations behind the scenes, which is what got me taken by you and your team and the work you do. I want to start by talking about just a sample of data that my audience might already be familiar with. It made the rounds, the headlines a lot last year, and I covered it recently, which was this big, big paper in the New England Journal of Medicine. And those who don't know, New England Journal is like the top impact clinical medical journal in the world. And the headlines were running that microplastics are associated with this massive astronomical increase in cardiovascular events, risks. It was like a 350% increase, a hazard ratio of 4.53. And it was really dramatic. Basically what they did is they took patients who were undergoing a procedure already where they were looking inside their arteries so they could look in their arteries with microscopy and see, is there microplastic or no microplastic? And then follow people to see in those with microplastics, which is about 58% of people, what was the increased risk of cardiovascular events? And it was 350%. It was pretty crazy. And then they did other things to kind of parallel those terrifying data. So look at, you know, inflammatory markers, inflammatory cytokines, and then look on like really fine electron microscopy to see the microplastics jammed in immune cells, kind of like irritating them. And the analogy I've used is it's like your immune cells stepping on a Lego piece and screaming inflammation into your blood vessels. So I'm sure you're familiar with this paper. I wanted to get your thoughts on it because I think that's a, where a lot of people got introduced to this idea that microplastics can really damage our health.

I mean, that paper was pretty startling and it, it kind of echoes signals we're seeing in lots of other papers across reproductive health, liver, kidney health, gastrointestinal health, that there are really these, these signals of correlation between microplastic and these disease outcomes like cardiovascular health, stroke, even, even clotting time for some of our major clotting factors goes up in the presence of microplastics. And I think the feedback we always hear from, you know, the field is it's just, it's just correlative, it's not causal yet. But that once again always plays into the, it takes years, years and years to find really correlative data that is very striking. I mean, even today, things like smoking are still more or less just correlative. You know, you can spend your entire life smoking and some people develop cancer, some people don't. And so yeah, it's, it's really these long-term longitudinal studies of data that have to build up over time to bolster a case.

Yeah. You, you nailed two things there that I wanna really emphasize. It having to do with like the existing literature and this idea of just correlation. So I have a pretty scientifically savvy audience, and what comes with that is an understanding of certain things like correlation doesn't equal causation. But I also think that there's a tendency to overgrab onto this and then overlook data based on these catchphrases like correlation doesn't equal causation without a full appreciation of like, well, what do you need to prove causation? So in this paper, I'm going to give my two cents and I want yours. What we have is a massive effect size. It's not like a little blip. It is massive. And then technically it's a correlative analysis because you're not going to do randomized controlled trials where you inject humans with microplastics. That's just not ethical. But you also have other signals that build a biological story. You also have increased inflammatory markers in these people with the microplastics. And if you look on microscopy, you can see how the macro microplastics are like irritating the immune cells. In the plaque. So you have a biological story and a very large effect size correlation in a situation where you can't actually do a randomized controlled trial. What are your thoughts?

Yeah, I agree. These signals are pretty startling and they echo once again a lot of the data we're seeing not only in animals but in other human causal studies— or I'm sorry, correlative studies. What we're finding is, yeah, that additional data set like inflammation accumulation, macrophage implantation and, and their lack of breakdown in them are all triangulating on that, that similar mechanism, which is, is pretty startling, starting with oxidative damage, then mechanical abrasion and buildup over time. And then when you start to look at the chemistry of the plastics themselves, how fat-like they are, they're hydrophobic particles. They, it makes sense that they're sticking in very fatty places like plaques and accumulating maybe more readily than they would elsewhere. And so all of that starts to build a picture around the fact that these are signals we should be really paying attention to.

Yeah, for sure. So, you know, that New England Journal paper caught my attention, but you've read a lot of the broader literature, so can you gimme other indications? You referenced like other, you know, health systems where we're seeing microplastics show up and the effects that they are having on human biology.

Some of the most interesting places, I, it actually is interesting, maybe as the wrong word because it's also scary at the same time. Are in the reproductive health space because re reproduction is such a sensitive system based on really intimate and delicate balances of not only hormones, but also interactions between our biology. And so even things like, um, in terms of microplastics being found in the placenta, when they look at women who have what's called intrauterine growth restriction, they find that out of 13 women that they tested for that, they found in all 13 of of those women very meaningful amounts of microplastics in the placenta. And then when they correlated that to, you know, women who had normal pregnancies, only 3 out of those 40 that tested of normal had detectable microplastics in their placenta. And so once again, it's, it's correlative, but the fact that all 13 women with IUGR had detectable amounts of microplastic and very few in the normal is, is startling. But that, compounds into additional studies, even in IVF, they find the fertilization rate drops substantially when tested with microplastics present. Fortunately, the implantation rate doesn't, doesn't change, but at least the fertilization rate does. And same in male studies, it's sperm quality decline and count also seen a drop.

That's really terrifying. I mean, what I hear you saying, just to reiterate, is that there's, An enrichment of microplastics in women with intrauterine growth restriction. So within the uterus, growth restriction, basically the baby doesn't grow. And it scares me for two reasons. One, I mean, one, it's an alarming thing and can impact the health of the, you know, fetus to become the child. But also intrauterine growth restriction, such a gross thing. And when I say gross, I mean like macroscopic, very easy to visualize. Is the baby big? Where's the baby smaller? Like, it's very obvious. In fact, the most obvious thing you possibly could look at. And if we're seeing a strong signal, even if a chordal of 1 there, what could that mean for all the more subtle things? So think about neurodevelopment. You can take an ultrasound probe and like, look at, ah, the baby's this big, but you can't say like, well, how is the brain wiring? Or how are the organs wiring? And how is that gonna set the baby up for life indefinitely? And we even have these examples of natural experiments, like with the, um, sugar rationing in like 1953 in Europe where we see, you know, variations in sugar exposure can— and we find this out decades later, over half a century later, actually massively impact risk of chronic disease. So again, scares me for two reasons. One, it seems like there's a pretty powerful signal. And two, that's just the most gross, obvious thing that we're observing now. What could it portend with respect to development of the next generation?

See, when you think about, like the female developing babies in utero, because once again, they're developing their egg cells in utero. And so throughout my chemical exposure, at least in mouse models, there have been very strong studies, at least with other chemicals showing these transgenerational effects where you're changing the epigenome or the genetics of the egg cells in the developing baby. So then you're seeing 3, 4 generation out effects, which is kind of scary.

No, it's terrifying. That is a difference. So when you're looking at like the epigenetic, you know, effects like in men, spermatogenesis happening all the time. I'm making sperm literally right now. And so if I do something like have sugar or even there's some data on aspartame, like in diet soda, it could potentially affect my sperm quality, which I could pass on. Women are born with all their eggs, but that also means that if you have a female fetus or developing embryo to fetus to, you know, neonate, what the parent does will affect their grandchildren almost directly because that's when you're affecting the development of the, the reproductive cells, the gametes and the, the, the female. So anyway, we can jump off reproduction to not give people an existential crisis, but okay, we got cardiac, reproductive. What's another organ system where we're seeing microplastics potentially cause some severe damage?

Yeah, I mean, my favorite system, as you know, is the gastrointestinal one. And that's kind of at least the vision behind Winnow and what we're building together is that once again, plastic is ubiquitous in this world. I don't think there's any chance we're going to get rid of it anytime soon because it requires system-level changes across society, but it is building up over time. And so with the best place, in my opinion, is to try and reduce the exposure rate. How do we lower the amount that we're experiencing. And then by doing so, maybe we can reduce the amount that accumulates within us over time. And so one of those main places is the gut. And so I'm gonna share a couple papers together, which I thought were pretty fun to look at. The first is this paper that took human gastrointestinal cells in culture and then looked at 3 different chemistries of polystyrene, but then also multiple different sizes.. And this is where it gets pretty complicated because not only does—

if we introduce different plastic terms, so it's like polystyrene, it's a plastic, like where that might be found just to help ground people in. Yeah.

Like Styrofoam is the number one.

Okay.

More commonplace. That's how Styrofoam gets its name from polystyrene. Right.

I might pronounce it.

Yeah. And so they, they looked at how do you, how does the chemical surface of that plastic affect its ability to penetrate and interact with those cells? But then also what about its size? And they We found that both matter quite significantly. And so what we're looking at here is 3 different chemistries. The first, amine conjugated surface. That means this plastic particle, this, this 50 nanometer polystyrene plastic has a positive charge on its surface, and that'll be meaningful here in a minute. And then carboxyl modified, mostly negatively charged on the surface, and then non-functionalized. These are bare, bare polystyrene particles, virgin by Um, they do have like a small negative charge to 'em based on how they're made. And what they found is that the positive charge makes a huge difference. You can see here in these confocal microscope images, more or less taking a cross-section of the cell and looking at it. Um, and to really dive in, what they did is they stained each of the nuclei blue. So each one of these blue balls is a nucleus. Of course, they stained the cell membrane red. You can kind of see that as you dilute over that green colored polystyrene particles. And at least the amine conjugated one, you can see they are pervasive throughout the entire cytoplasm of the cells. You can even see them localizing in the nucleus, which is pretty scary in some of these cells. And you can see them kind of blobbing together, which kind of suggests that they're really in these like intracellular vesicles that are being pervasive throughout those cells.

Sorry, did you see what cells these were?

Yeah, these were human gastrointestinal cells.

Okay. All right. So what we see is the negative charge polystyrene, the amine is really accumulating quite richly in these human intestinal cells.

And that makes it, it kind of mechanistically makes a lot of sense because these amine groups, they create a positive charge on the surface of that plastic. And then our cell membranes are negatively charged. That phospholipid membrane has a very strong negative charge to it and, and opposites attract. And so they're more likely to go in just by and be attracted to those cells. And you can see that kind of opposing when you get a negative charge on those, they still penetrate in, but at a much lower rate.

What are some of the consequences in terms of physiology? So we talk about cardiovascular events, potential effects on like intrauterine growth. When you have microplastics getting into the intestinal system, what can that cause?

When you have them, I mean, it's really quite striking. And so now unfortunately we have to go into a mouse model to really start to deduce that.. But here what they did is they fed these mice, um, polystyrene nanoplastics for 32 days, and then they looked at what happened to their guts over time. And so what they did is they dissected out some and put them under the microscope. And for these control cells, you can see, or these control animals that received no plastic in their water over that month period, they have really long villi, they have really tight crypts between those in all 4 of their intestinal sections. And then as you start to add in more and more polystyrene nanoplastics, you can see those villi start to shrink. You see the crypts start to get bigger and you start to see the signs of inflammation and damage over time.

Break this down for people because I remember even from like first year medical school histology, which is what we're seeing here, the stains being intimidating. Each row is a different portion of the intestines. And as we're going left to right, and you can correct me if I make any errors here,, but we're seeing more and more high concentrations. So the controls for our left column up to high concentration for our right column. And you can kind of see very obviously what are very tight and long little extensions of the intestines, which is what you want. They're basically decaying, they're shrinking, they're spacing out. This is bad. Basically how people can interpret these images.

Yeah. And when people think like 10 mcg per liter seems like a lot, I mean from an environmental perspective, but I just wanna put that in context, like a grain of a milligram on average. So this is like 10 grains of salt worth of plastic per liter. But when, and so it's really not that much, but when you bring it into a nanoscale size, like a, a 50-nanometer polystyrene piece weighs on average like 55 femtograms. That 10 milligrams is trillions. It's tens of trillions of particles floating through that liter. And so that's, that's a lot compared to our environmental exposure. Like people estimate Based on measuring, like if you drink out of a plastic water bottle, you're averaging thousands per bottle of nanoplastics. And so to get to trillions, you have to drink like, you know, 300, a couple years worth of, I think, plastic water bottles to get to these levels. But that's just like one source of many where you could start to build up. So they are higher than we would typically see. And that's what allows us to see these effects over 30 days rather than many, many, many years worth of studying. And then it gets kind of really interesting. This is one of my favorite papers that came out recently. They re— they were looking at the effect of polystyrene on, on gut environments, but then they started finding these really unique interactions between the expression of some of our tight junction proteins and the gut microbiome. And so to break it down, they started feeding microplast— or polystyrene nanoplastics once again to mice. And they started looking at how does that gut look over time. And so here, what we're looking at is an endothelial-like layer of mouse gut cells. And you can see each one of these nuclei, once again, stained in blue. And now rather than looking at them alone, we are, you know, making these tight junction proteins, in this case ZO1, glow using immunofluorescence antibodies that stick selectively to ZO1 protein.

We're looking at linings of intestinal cells, and the green dots are kind of the proteins that represent tight junctions between the cells, which is what you want. I mean, the opposite of that is quote unquote leaky gut. So my understanding is if you're losing green signal, you're getting more quote unquote leaky gut.

The cells aren't bind bound together as tightly as they should, and it, it's in a dose-dependent manner. And that dose dependency is really interesting cuz it shows, you know, a toxic effect of those plastics over time. Or over concentration. And then they did exactly what you said for leaky gut. And this was really quite clever because they grew these, um, human, in this case, um, intestinal linings on a filter. They wanted to test whether or not that intestinal lining was intact. And so on top they put, um, fluorescent dextrin polysaccharides on, and then they put nanoparticles into that at varying concentrations. And they were looking if that endothelial lining started to become damaged, it would become permeable and/or leaky and more of that fluorescence polysaccharide will pass through to that bottom layer. And so simply by measuring the glow in this bottom chamber, you can measure how leaky that, that lining was. Wow. And they found that when you got to 10 to the 6th particles, you, you started to see a breakdown of that gut lining and a penetration, a leaky signal.

And that is a physiologically possible concentration to get to where you have that big jump. Yeah.

Especially over time because these, these hydrophobic plastics, they tend to attach or absorb onto our cells, onto other hydrophobic things like the plaques and the, that we were talking about earlier. And they don't typically let go. I mean, fat likes fat and so it stays quite stuck into place.

Well, You know, after 20 minutes of scaring people, and I wanna be respectful of your time, why don't we take a step back and then talk a little bit about the solution? I teased what we were gonna talk about, but this idea of probiotics to create an internal shield so that you don't have these scary effects that we talked about. And I'm kind of like, I don't wanna waffle around here because I don't want this to be just like a sales pitch. You're wearing a Winnow like shirt. I have a hat that you guys sent me, like This is a cool company, a cool product, so I don't want to hide that. I want to show it up front. But with that said, I do think this is something, an example of where like a product has been developed to genuinely fit a need and plug a hole, provide a solution to a big problem that needs to be filled. So I now want to go back to maybe the origins of Winnow Labs. When did you come up with a concept of this is problem you really want to solve? Was there like a moment or did it just Dawn on you gradually?

Within the last couple years, my friends and co-founders of the company were talking about microplastics, and the more we learned about it, we couldn't, we couldn't look away. It became just something that was obsessive that we dug into. And then when we started seeing how ubiquitous they are, but growing, the damage that they may be correlated with, we really wanted to apply some more of our background to it. But microplastics in, in essence were kind of like a, a gateway or a reminder that our world, you know, even at, at the cost of all of the beautiful things we've built together as society has come with, with some, some cost, which is, which is pollution in this regard, in this case, microplastics, but there are many others like heavy metals, organophosphate pesticides, and the like. And so we as a company wanted to build tools that could provide people some form of protection against those environmental pollutants, starting with microplastics.

Were you surprised nobody had tried to do this before? Because when, when you described the idea to me for the first time, I'm like, well, this is ambitious, but it actually seems very feasible. Huh. I'm surprised this hasn't been tackled before. Were you surprised?

Yeah. Yeah. I think what you're finding is that that's very typical of like a Western medicine or, or Western ideology, which is treatment for a disease that's already existing, right? The, the preventative side of medicine or the preventative side of consumer health tends to be more ignored. And I think that may have been part of it, but then also, I mean, maybe microplastics is just very new, but the field of environmental protection or defense is, is, is pretty lacking just writ large. And maybe it's a sign of us growing awareness over time of, of the environment and the pollutants within it.

Yeah. All right. Well, let's get to the action items. How did you go about developing this probiotic? And I definitely want to get to that image that really struck me of the microplastic binding and non-binding probiotic. But what was the journey of innovation?

Yeah, the journey of innovation was pretty unique because we started at, in a completely different spot, like typical development cycles. We originally were, were wanting to do a more therapeutic approach. How can we take plastics and dissolve them away within the human body as more of a detoxification system? And, and the more we researched it, the more we thought, yeah, that would be fun. But what happens? Like, to the rest of the chemicals within a plastic after you dissolve away the plastic matrix? Because plastics don't come as this pure ingredient, which is obvi— usually an oversimplification of the field. Rather, like, there are 16,000 different chemicals today known that people can mix and match together to make different types of plastic. And so the question begs, like, when you release those, where do they go? And we didn't want to deal with that outcome. How do we handle every single plastic chemical? That is, that is available to be used. So we thought, is there a way to drag those chemicals and the plastics out of the body along with them? And that's where we got to these more physical mechanisms of probiotics and attachment.

Just to circle back to earlier, we already saw that the chemical nature, not just the material nature, but the chemical nature of a plastic can determine that it binds to a surface, be it a gut cell, but also a microbe. So how do you go about selecting the microbes that will preferentially bind up Microplastics in the gut. Now I'm seeing it as kind of like we saw that image before about the microplastics binding to the gut. It's like a tug of war and you actually want to build the microbe to win the tug of war so it can get pooped out. How do you do that?

Yeah, so we went about it looking in terms of plastic stickiness, and I'm gonna refer to another paper that recently came out this year because they show the process very similar to how, to how we went about it. I'm not identical, but similar.. And so what they did is they did a screen of bacteria and they just used some glowing plastic. And what they did is they mixed a whole bunch of different types of bacteria and simply added them into a centrifuge. Those plastics that stuck to the bacteria were heavier and thus came out more readily than plastics that were not stuck to bacteria. And simply by measuring that residual glow after centrifugation or spinning, you can measure the amount of that plastic capture. By those bacteria. You can see it kind of here where the liquid is slightly more green on top, but also the bacteria down here are slightly more green. Not the most beautiful image to see it whatsoever. We did a very similar thing just in much higher quantities and against many more types of plastic, not just polystyrene, but we did it against the 5 most prevalent polymers found in biological samples today, and then looked not only at what those single bacteria could do, but together, how do they stick to all 5 plastics as a team more readily than they do alone? So these combinatoric analysis of these bacteria, what you can see is that when you find plastic-binding bacteria, which is not a very common trait, they don't all bind the same types of plastic. Like for example, Probiotic A binds to PET and polystyrene really well. Probiotic B binds better to polypropylene. And then when you, when you mix them together, just like we do as people, they come together as a whole better than they do alone, which is pretty amazing and unexpected.

Yeah. So it's just like Herculean effort, brute force processing of a bunch of different thousands. I think it was like 3,000 different bacteria and you see what team performs the best in the plastic binding world series, and then you pop those together into a product effectively. Yeah.

And what's exciting is this paper went a step further and they started looking at the amount of excretion you can get from in a mice model. So now does that mechanism of stickiness actually help drag plastic out of the bowel more readily than it does alone? And so what they did is they fed the bacteria or a control with no bacteria to mice for a week and then challenge them to drink polystyrene. You can see in this control animal, those plastics spreading throughout the gut bowel quite readily, but in this strong binding strain, they found DT88, a really high clustering of that plastic. They're like more or less glued together as a plug transiting through that gut lining.

What does the DT stand for?

They is just an arbitrary name.

So the DT88 is the strong binder. And we're seeing just a concentration of the, the heat bar on the—

DT66 is an another strain of plastic binding bacteria that works pretty well as well. And DT22, another strain, these are strain numbers I should say. And DT22 barely binds to plastic whatsoever. So you can see it doesn't really cluster that plastic in the gut very effectively.

Right. So we are seeing more of a spread in the control, DT22, DT66, and then a real foci in the DT88, suggesting that it's been collected and then can be excreted. This is after how long? Because I would hope that that then bolus gets pooped out and you wouldn't actually see it in the intestine.

Yeah. So that gets into the next panel C, which is quite interesting, where only about 40% of that high dose of plastic came out of that control mouse. That's a little scary because where'd the rest of that 60% go? This strain, at least with one, either DT66 or 88, they were able to increase that to nearly 60%. So 1.5. A half X increase, which was pretty startling.

That's a single strain. So that's not representative of the actual like combination of the team. It's just one player on the team.

It's just one player on the team. That's right. And then they went even a step further and they started looking at inflammation markers. And so they looked at 3 pro-inflammatory markers, IL-1 beta, TNF alpha, and IL-6. And what you can see is there in the, when you treat with plastic, each and every one of those inflammatory markers increased in those gut cells of those mice. And then the probiotics did help return that to baseline, which was pretty striking. But the same in terms of the anti-inflammatory IL-10, once again, a return to baseline, which shows a little bit of a protective effect of those.

If you're looking at the, the dark blue bar for 3 of them except for IL-10, it should go down. That's a decrease in inflammation. The one standout, the IL-10 is actually anti-inflammatory signal. So the other 3 are inflammatory. IL-10's anti-inflammatory.. So what you wanna see is those 3 go down and the IL-10 go up, which is exactly what you see again, just for this one bacterial player. So it's a proof of principle, if I may, that this can work. And then what you wanna do is optimize by saying we are not gonna just take one, but a collection of bacteria that work well together. Yeah, right. Exactly.

And then like if you just start looking through the, the gut microbiome effects, you really see these like adjustments or changes in key bacterial families within the gut. And I'm bringing this up because we might talk about this question later, which is what can you do if you can't take a probiotic like Winnow? Like for example, you see a re— a stark and consistent reduction in Bacteroides, Akkermansia, Lactobacillus, and Bifidobacterium. These are key bacteria, not only involved in fiber degradation, butyrate production, gut lining protection. They start to decrease in the presence of plastics where the— you see then biology hates a void. You know, there's no emptiness in biology. It'll be filled by something that gets filled by these opportunistic inflammatory bacteria like Enterobacter and the like. And so, you know, when we think about what Winnow is and what we designed it to be, we first and foremost wanted to have an exceptional probiotic, something that helps people with their gut health just generally. Because if you're gonna pay for a feature like plastic protection or plastic defense, or at least in our case, plastic binding, it should come with, you know, added benefit on top of that. Second, we wanted to be able to replenish some of these bacterial families that are typically, um, reduced in plastic exposure systems so that you, we can at least combat that reduction that you're seeing. And then third, we added that plastic binding feature, the ability to stick to plastic in these preclinical models and mouse models that show, show strong reductions in passage.

I have a few high-level questions that have been very popular among my audience since I started talking about this. And the first has to do with, you know, what the state of the human evidence is. So we went over human correlational data like in the New England Journal and then testing the theory behind this product in animal models. Is it fair to say though, we don't have like human randomized controlled trials showing that say Winno probiotic or anything like it actually works?

Works. That's a, that's a fair call out because that's exactly true. We, you know, have made Onscan a great probiotic that's built and packed with bacteria that have been preclinically shown to help stick to plastic. That is a very different call than clinically proven in humans to reduce plastic exposure and accumulation. We are not there yet as a company. And I think that data is gonna be exceptionally difficult to test because first and foremost, when we think about, you know, a human trial to start, it's not as simple as just measure before and after because first there's no posi— negative control anymore. Everyone has plastic exposure, so there's some level of baseline in every single sample no matter what. And so you're looking at a reduction from an already noisy place and a very small effect down to something noisy and small. And then it varies as people eat, you know, I, I drink out of a plastic bottle or I have a coffee from Starbucks in a plastic-lined cup and it, and my plastic levels are gonna change throughout the day and over, you know, the weeks and how I eat and what I'm doing. And so without being able to, once again, as you said very keenly in the beginning, which is dose people with a detectable amount of plastic, it's hard to see these without very long-term longitudinal studies and high sample sizes that can really start to look past that noise.

Yeah.

Of daily life.

No, I think everybody wants the perfect data and part of the art of applied science, which is medicine, is making educated guesses with imperfect science. So not perfect science. I would love, so that New England Journal trial, I would love a 20-year randomized controlled trial with winnow versus a control for cardiovascular outcome. It's never gonna have that trial. Just not gonna happen. It's not feasible to ask for. So, you know, you're left with a little bit of a knowledge void, um, which is just something we have to contend with all the time. But what would you see as the next step for research in which you'd like to invest to, like, forward the scientific field?

Very, very science-backed company. That's one of the reasons we love having you on as an advisor. Um, the next test we're running is a collaboration with a company called Altis Biosystems, and what they do is they do grow human organ gut linings on a chip. They take stem cells, they differentiate them in the gut epithelium, and they're able to measure the penetrations of plastics through that, but also the inflammatory response and stress response of those in the presence of plastic with and without intervention. So that's our immediate next step in terms of testing, but then continuing to work, we're partnering with a company, Aero Labs, which has developed the first microplastic blood test to see if we can measure a long-term reduction in blood plastics in people through a study. And so that'll be, you know, probably years worth of effort, but something we're really wanting to do and start.

I haven't actually gotten that Arrow Labs test. I definitely wanna get it. Do you recommend people who are potentially trying Winnow get a baseline themself? And if you do, cuz this is the question I was getting, can I measure my microplastics before potentially investing in a, Microplastic binding probiotic. What like testing frequency based on your expert judgment do you think is sensible? I can make my own guess, but.

That's a question I'm gonna caveat the test because I think it's great and you can buy it from Blueprint, you can buy it from Keyspan. I'll, I'll send you the links so you can add that in if people want and definitely recommend if people are interested to, to take the test. What, what it's able to do is measure microplastics in your blood and you can do saliva now as well. With them, but it can only measure plastics between 1 and 70 micron in diameter. It's completely blind to nanoplastics. And as we showed before, nanoplastics are the most pervasive. They're the easiest to get in. And so this test shows you what the bottom is, not what your actual is, unfortunately.

Yeah. The tip of the iceberg, which is great.

I mean, it's nice to know. The second caveat to that is no one knows what the safe limit of plastic is. If you get 20 particles or 30 particles or 10, what, what does that actually mean today for humans? We're, we're still too early to make a determination. But if you wanted to look at plastic reduction over time, maybe through lifestyle adjustments or use of dietary interventions or a product like Winnow, it may be a good place to start. And we're wanting to explore that.

Well, let's get into some practicals. So let's start off with the obvious. What are two of the most high-yield ways people can reduce their exposure to microplastics that are unexpected? So I think people know plastic water bottles, plastic takeout containers, but what are like sneaky sources of microplastics?

Those hot plastics are definitely the known ones. I think a lot of people look at like metal bottles and what you'll find is like you go to the store and you get a metal bottle. Often those are actually plastic lined as well, you know. Sparkling water, metal bottles, cans, and, and they're plastic-lined because they're made typically out of aluminum and aluminum tastes horrible when you mix it with, with food. And so they line the plastic in the center to keep it from aluminum, from leaching into the food or beverage.

Love that. Do you have rep brands of metal water bottles that you can recommend?

Clean Canteen, you know, LifeStraws water bottles, those all have, are like really great. Any stainless steel water bottle rather than like an aluminum bottle would be a pla— great place to start.

I didn't know that. This is not a sponsored message for those bottles, by the way, but yeah, exactly.

They're just great brands that I like recommending. The next, you know, most practical is, is where you, in your diet, right after you've already tried to reduce microplastic exposure, you can feed that beneficial microbiota that are tending to be depleted, those protective bacteria like lactobacillus and bifido. You could get that through high probiotic diets like, yogurts, kombuchas, and the like. They may not be strains that stick to back, stick to plastic themselves because they weren't selected for it, but, but they help build back up that population of good gut beneficial bacteria that may be being lost at high plastic levels. And then the second is just a high fiber diet, not necessarily because it sticks to plastic, but because at least non-fermentable insoluble fibers make your bowels move faster, so plastics will move faster with them. Like transit time increases. But then secondly, fermentable fibers form like a gel in our gut and can help trap plastic particles and push them along.

So soluble fibers, my understanding is tend to slow gastric transit. They're the ones that did gel. That's cool. So they're slowing gastric transit. Wouldn't that cause microplastic quote unquote retention, at least in terms of transit time?

Like why it's, I mean, the fiber field is really quite challenging. I think you had a recent video just on this topic, which was amazing.

I had a recent popular fiber video about a paper that really blew my mind about inulin fiber, which is a soluble fiber, helping to adapt the microbiome to basically immunize the liver against fructose. So it can change the carbons in fructose into proteins. But then if that wasn't, I'm not like a more fiber is better kind of guy, but that was very cool. And then I read another paper, it was Lancaster et al., 2022, the Snyder Lab outta Stanford, 'cause I was talking to Professor Michael Snyder. And then it showed that that same fiber inulin in a human controlled trial at high doses could cause inflammation and increases in ALT, a liver damage marker. They actually had to terminate the trial for some patients because it was such an ALT rise. So I bring this up because I think there's a lot of platitudes about fiber, some of it can be incredibly cool and potentially beneficial, but it's like about the specific fiber and the dose and the host. So it becomes very cool.

The host and the microbiome, because even shifting between your bacteroides and your Firmicutes, they can change how fiber's digested. And then, I mean, that's just at a family level. It gets way more complicated as you get down into the strain levels. Of course.

Have to collaborate on like a microbiome, uh, buildup protocol. I, I took a, just to kind of like a, a chop at one and put it on the Substack. It was very popular, but I would love a microbiome expert, so maybe we can work on that. One thing that came up in comments on the newsletter and other video was, and I hadn't heard about this, people were saying sulforaphane is rumored to help mobilize microplastics. Myth or not?

Yeah, great question because I never like to call anything a myth until it's been tested. I haven't seen any data. On it yet showing that it's able to deal with microplastics in any way. You'll, you'll find that with a lot of other common detox agents like zeolites, charcoal, chelators, and these that, you know, suggest that they may be able to help with plastics. And what I'd say is those are amazing detox chemicals, right? They can bind the toxins, they can help and fortify your own personal detox pathways in your body. And plastics once again are not pure. There are lots of chemicals within them that those might help with. And so just because they haven't been shown yet today to help with microplastics doesn't mean they're not helpful in general. So it's just not necessarily one or the other.

Absence of evidence isn't evidence of absence. You have some broccoli, you tolerate it great, but it's not necessarily gonna save you from, uh, chug out.

Maybe not from the microplastic particle itself, maybe from the chemicals or the oxidative effects of them.

I'm so seeing in my mind an Instagram reel of somebody with like a plastic takeout container is like, but it's broccoli with my chicken teriyaki.

Great reel.

Somebody's gonna do that. Um, are there any final things that I should have asked in this first conversation that I didn't that you want to hit?

It gets just back to what can we really do in the world of microplastic pollution? And, and the number one answer is not to stress out about about it because as you know, stress really does affect our health probably more so than microplastics at this point in time. But it really does come when we think of environmental pollution as this constant pressure from all of these different sources that can lead to changes that build up over time. And so being able to take steps, even if they're small and actionable ones, like, you know, replacing some plastic or increasing our probiotic use or or that it's, it's worth starting to take some of those small actions as, as people to make a difference. And then of course, let's try and reduce our plastic use for single uses we can, because the more we can lower that burden over time, the lower the toxicological dose becomes over your time. For, you know, that's pathology in its own right, for sure.

All right. Well, thank you for your time. I want to encourage everybody to drop further comments and questions because this will be an ongoing discussion. And if you'll indulge me in one final moment of reflection, kind of as I finished up my professional degrees, and maybe you went through a similar journey, you start as a scientist, very idealistic, like, I just want to solve problems, want to write papers, just do the science. And then you realize to really make an impact, you need to figure out a business model around something and effectively sometimes make something commercial, a product you can offer to people. It's something that, especially as a scientific communicator, I grapple with because I understand as soon as you say, hey, here's a product, people understandably have reason to doubt your authenticity. So, and I, I wanna see genuinely how people respond to this conversation because part of the reason I really wanted to have it, and like we've had conversations like this behind the scenes, is, you know, transparency, authenticity. I'm learning as I get to know you, Winnow Labs, the science as it evolves, and I just think we need a little bit more of that. Hopefully people can see that, but I want to get everybody's responses, questions, and I know this will be an ongoing discussion. So thank you for joining me.

Thank you.