Healthy Worms to Repair the Gut & Immune System with Garin Aglietti

Today we follow up on our recent conversation on helminth therapy, aka intestinal worms.  We speak with Garin Aglietti, who is a worm farmer and works first-hand in helping people rebalance their gut ecology with worms.  As weird as it sounds, intestinal worms used to be the norm and the current day absence of them may open the door for inflammatory and autoimmune conditions.

In This Episode

Prelude …00:00:39
Episode Intro … 00:05:16
Garin’s Own Experimentation … 00:07:45
Ecosystems and History of Eliminating Worms in Humans … 00:11:00
Worms Provide an Anti-inflammatory and Immunomodulatory Impact in Our Bodies … 18:12:00
Malaria … 00:19:30
Example of How Hookworms Work … 00:21:00
Using a Surrogate … 00:23:28
Are Certain Kinds of Worms Ideal? … 00:26:36
Ameobas … 00:31:50
Fecal Transplant and Helminth Therapy … 00:33:15
How to Find the Ideal Dose … 00:36:00
Clinical Trials … 00:41:20
Time Indications for Dosing and Response … 00:44:23
Contraindications … 00:45:36
Episode Wrap-up … 00:49:11

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Prelude

Dr. Michael Ruscio: Hey, everyone. This is Dr. Ruscio. And let’s talk about successfully treating SIBO. Namely, let’s talk about successfully treating SIBO with an herbal protocol.

So here is an understandable mistake that healthcare consumers often make. They view their health or their health problems in the context of whatever health topic is currently in vogue. So if everyone’s talking about SIBO, then the way that people view their health is very SIBO-centric.

Now, in my new book, Healthy Gut, Healthy You, we cover natural treatment options for SIBO, yes. But our antimicrobial or anti-SIBO approach does not stop there. Sometimes, the reason someone can’t “beat SIBO” is because SIBO is not their only problem. So in chapter 24, we will detail a self-help plan that addresses SIBO, but also addresses Candida or fungus biofilm, protozoa, inflammation, motility, and an overzealous immune system. Or said more simply, we will work through a treatment plan that improves the entire gut ecosystem, instead of narrowly focusing on the hot topic of the moment, which is SIBO. And I’m glad SIBO’s receiving all the attention, but we want to make sure we don’t abate on other important health practices, because there’s a lot of emphasis on SIBO right now.

Now, perhaps equally as important, the self-help plan in my book is adaptable, meaning that the amount of treatment one has to do will be directly proportional to their needs. So if your gut imbalances are minor, you have a shorter, simpler program. However, if your gut imbalances are more progressed, the plan evolves with your needs to make sure that you obtain results also.

Now, another item that often comes up when trying to optimize gut health is the use of digestive acid and digestive enzymes. And I think that chapters 16 and 17 of the book, which are on digestive acid and enzymes, will be considered two of the more controversial chapters.

The field of functional medicine is so inundated with claims of the importance of digestive enzymes and acid supplementally that it has created a culture wherein these are considered almost a treatment norm. But what if I were to tell you that some of what we have held dear is not true and that overuse of enzymes and acid can actually damage digestion in a decent amount of people? For example, overuse of acid or enzymes or both can cause diarrhea, bloating, abdominal pain, amongst other things. So certainly, those are symptoms that are fairly common and people are often trying to treat. And it’s really unfortunate if someone is actually causing symptoms that they’re trying to improve by overusing a treatment that they think is supposed to help them.

So the good news here is there is a way to determine if you should supplement with digestive acid and/or enzymes. And it does not require any testing, but rather working through the self-help plan that’s listed in the book. And the best news of all might be that, for many people, once you repair your gut health, you may no longer need supplemental acid or enzymes. So this is one less supplement to take.

Now, again, all this is detailed in my new book, which again, I’m so excited about, Healthy Gut, Healthy You. And you can learn all about the book and or pick up a copy at drruscio.com/GetGutBook. And for our audience only, we’re opening up a presale campaign. It’s open right now, but it’s ending on Friday, February 2nd. So if you want to know how to apply everything that we discussed in the podcast—probiotics, enzymes, elimination diets, elemental diets, motility agents, and probably more importantly, how to sequence them, how to know when to use what, when to stop—then this book is for you, because we will lay all of that out in the self-help plan at the end of the book.

The start of the book will help you understand, in a reasonable fashion, all these different things that we talked about: diets, gut immune system development, what the evidence actually says about things like gluten-free diet or gluten enzymes or adrenal support or probiotics or antimicrobial herbs or what have you. And then, we piece it all together into a personalized self-help plan at the very end. So, again, I’m very excited about this. It’s been a long time coming. You can learn more about it or pick up a copy at drruscio.com/GetGutBook. If you want to get a copy before anybody else, then make sure you head over there and purchase your copy on or before February 2nd. Okay. Now, we will get on to the rest of the show. Thanks.

Episode Intro

Hey, everyone. Welcome to Dr. Ruscio Radio. This is Dr. Ruscio. I am here with Garin Aglietti. And today, we’re going to be talking about the creepy crawly world of helminths, which is the polite term used for worms. This is a follow-up to when Dr. William Parker from Duke was on talking about this, which is a fascinating subject. And I’m really excited to have him here to discuss this topic today.

So, Garin, welcome to the show.

Garin Aglietti: Well, thank you for having me.

DrMR: Can you tell people a little bit about your background and how you got involved with this topic? It’s just certainly not something that you just fall into, like, “I want to be an accountant one day when I get older.” So can you tell people kind of how you stumbled in here?

GA: Yeah. Mike, there’s no guidance counselor in high school out there telling people to become worm farmers. It’s not on the radar. I was in graduate school. And in between first and second year of medical school, I did a clinical preceptorship and got introduced to non-ulcer dyspepsia. A very interesting condition that was kind of an impetus for all of my studies because it’s something I was seeing every day. And it’s just this mystery. It’s a diagnosis.

For people who don’t know, it’s a diagnosis that excludes one thing. You have stomach problems, but you don’t have any visible ulceration. And so what was causing that? And I think that if you study that problem long enough, you’ll get to this idea of the gastrointestinal tract being an ecosystem. And if you strip enough life out of any ecosystem, you will make it fragile and self-limiting. And non-ulcer dyspepsia is one of these conditions that could possibly be caused by that fragility.

So in 2005, I got convinced that putting some life or rebiosing the gastrointestinal tract would be a good course of action, an interesting experiment as it were. And so I went to Africa, Kenya, and collected some beef tapeworms and took them. Because as a child, I always had seasonal allergies and food intolerances, and then in my 20s, got some psoriasis. And that was the one that was really scaring me.

Garin’s Own Experimentation

So I had the raw material to run a pretty interesting experiment to see if these problems are coming from my gut and then putting some life in there and see how that all worked for me. And I really had a nice response to it. But the problem with the beef tapeworm is that after 107 days, they become sexually mature. And these little proglottids, these little caterpillar-like segments, start migrating out of your gastrointestinal tract. And for me, it was very unpleasant, just psychologically. There was no peaceful coexistence for me with the beef tapeworm.

So I went back to the literature and I started looking at other worms that maybe had scared me a little bit when I first started considering the idea and settled on hookworm, Necator americanus, the New World hookworm. And then, about a year later, went to Peru and collected some and didn’t have much of a response. I’ve only done six, which seemed like a lot at the time. But it was not enough to really do anything, modulate the immune system or change my gastrointestinal function. So then, I went to Belize, a year later, and did 60. And I got a real nice, clear signal in that experiment. A lot of the beef tapeworm stuff came back. And some other stuff responded really well. So that was it. That was how the ship got launched.

And so for the last 10 years, I’ve been hosting the population of hookworms for the purposes of not just the absence of my conditions but to just be healthy, just to have some life back in the gastrointestinal tract.

DrMR: Are you having to maintain these with repeated administration? Or how does that look?

GA: Exactly. Adaptive management. That’s a principle in ecology for these complex self-organizing systems. You just steer them. You can’t control them. You just keep pointing them at the direction you want to go. So one of the neat things about the hookworms that I’m hosting is that it does not expand its population in your gastrointestinal tract. It makes ova. But those ova have to go through a soil phase. So you’re not expanding your population unless you’re putting the infected larva on your skin. So that is a way to control the population size.

So, for me, it is about a year that I have to freshen up the population. That’s recently changed. Because now, the last three years, I’ve been working real hard on restoring my microbiome, that bacterial lawn the worms live in. And when you get that a little healthier, then the worms live longer. So now, I’m closer to two years between my inoculations.

DrMR: Interesting, interesting. Okay. And we’ve already defined helminths. Helminth is a medical term for worms. And I want to ask you a question. I guess, this is probably going to lead into that question. Some people are loosely saying that worms might be the next or the new probiotic. We used to look at all bacteria as bad. And then, we realized that some bacteria are bad and infectious but some bacteria are very health promoting. And now, we’re taking capsules of bacteria as probiotics. We might soon be doing something similar. Well, I guess some people are. But it might become more mainstream to do the same thing with worms. So, you’ve already hinted at this, but can you expand a little bit on why worms might be the next probiotic?

GA: Yeah. I’m going to borrow something I heard Dr. Razon, from University of Wisconsin, say once. He said, “Things that are unavoidable become necessary.” And so, we have just coevolved with worms for so long that it’s really the absence of them that’s the abnormal condition.

Ecosystems and History of Eliminating Worms in Humans

I know it’s not familiar. Worms are not familiar to the typical American. We got rid of them almost completely 80, 90 years ago, and then the last pinworm, the last one that was hanging on in the 50s and 60s. So worms are really foreign.

And this is an important point. Cultures are shared fears. And I want to be very clear, I’m not rejecting anyone’s fears. If you don’t like worms, you’re not going to host worms, you don’t want worms to be any part of you or your ecosystem, that’s fine, if that works for you. But for some people, the absence of those worms can be a real problem. Because worms are part of an ecosystem and ecosystems are massively interactive. They’re all interdependent. We go back and read the writings of the environmentalist and naturalist, Aldo Leopold, “When you tug on one thread of nature, you find it all intertwined.”

And so when you collapse what’s known as a trophic level in an ecosystem, and you remove all the large multicellular creatures from the human gastrointestinal tract, that causes these collapsing cascades that don’t just affect that level. It affects the levels underneath it.

So the problem is, is that we got good at killing worms. And then we just killed them all. And maybe we started killing ones that really weren’t even causing any problems. We just got so good at killing. And it was easier to go in and kill everything. And it’s very hard for me as an ecologist not to draw parallels to the work that was done in Africa 50 or 60 years ago. People were trying to save the forest and the grasslands. And they went in and they killed a lot of elephants thinking that they were helping the grasslands and the forests. And it’s just a terrible, terrible mistake.

And so, I think, what’s happening is you’re starting to see doctors and researchers appreciating the nuance of how massively interacting ecosystems are. And realizing that, yeah, you want to take some worms out, but not all of them. You become a victim of your own success. What’s the saying? “Your success sows the seeds of its own destruction.”

So a hundred years ago, yeah, we needed to knock down worm population. There was too much worms. The parasite burden was too high. And so there was a nice clear signal towards health by killing worms. But then, we started to lose this signal. And now, we still do it. And it’s pretty clear that we don’t have a whole lot of health. We have people who live a long time in America. But the health span of those people have gone extremely short.

DrMR: Yeah. And that might be a double-edged sword. And we’ve talked about this in the show before where we’ve done a lot toward healthcare with the hygiene movement, with antibiotics, with improved water sanitation and sewage sanitation, and everything in that regard. And a lot of that has been good. But we may have gone too far. And yes, while we‘ve reduced infant mortality, for example, and improved life span, along with that, there is a fairly high degree of morbidity like autoimmune conditions and inflammatory conditions that accompany that. And so the pendulum, I think, is now swinging back to realize, okay, we’ve gone perhaps a bit too far in that direction. And now we have to try to balance some of this out. And one of the ways we might do that is, like what we’re talking about today, with helminths.

GA: Yeah. So one of the things that you see in the African data is that when you come in with a deworming program, you’ll start to see allergies and asthma start to appear in these populations. And then you stop the deworming program, with the villagers pick-up their worm burdens again, and the allergies and asthma goes away.

Asthma, that’s like the number one emergency room visit in America, besides childbirth. It’s a condition I had as a child. And it is pretty hard to live a full life when you’re always afraid you’re going to be strangled without any warning or notice. That is one of these situations that—I like to chase problems down to fundamental trade-offs. Everything’s a trade-off. There are no free lunches. So what was the free lunch we were supposed to get with these deworming programs that we were only going to get healthier? It hasn’t really worked out. And that kind of made sense with everything I’ve learned in my life journey, is that there’s always some price you’re paying. For me, kind of rolling the clock back a bit and putting the worms back in, it’s just a better deal for me. The trade-offs for having a reactive airway and seasonal allergies, that’s just not something I wanted to do anymore. I tried that for 35 years. And I liked this a lot better.

DrMR: Well, I think there’s definitely something here. Hence, our conversation today. I should just mention briefly for the audience, just to make sure we’re all in the same page, do not do anything without talking with your doctor. Don’t try to find a worm in the backyard and just go at it your own. This is for educational purposes only. Don’t do anything without talking with a clinician first.

GA: That’s an excellent point. There are some very bad worms out there, very bad worms that were gotten rid off for a very good reason or a number of good reasons. And particularly, some of the worms that travel around with the hookworms can be deadly.

DrMR: So, yeah. Don’t go at your own. This is not something that we would say is a DIY. Get the appropriate counsel. But we’re discussing this concept, Garin, of course, of altered gut ecology and how that may impact one’s health. I’m wondering if you’ve noticed, are there certain conditions that people have that might be more or less associated with altered gut ecology?

GA: So the gut ecosystem, a big player in that is the immune system. So depending on who you believe, 70%, 80% of the human immune function occurs in the gastrointestinal tract. And for most of our experience on this planet, going back to our proto-ancestors or depending what you believe of the way God made you, we have been covered in parasites and blood-feeding organisms. And then going back to that saying, “That which is unavoidable becomes necessary.” Your body just evolves around it. It just becomes very efficient.

So if these parasites are going to be making these chemicals that modulate our immune system so they can take their blood meals, the body, the way we evolve takes advantage of that. It’s an efficiency there. And so, when we get rid of our ticks, our lice, our fleas, our biting insects, our mosquitoes, our intestinal parasites, we lose this immune modulation that occurs with these biting, blood-feeding organisms. So what they have to do is they have to convince the immune system to leave them alone long enough to get their blood meal. And one of the neat tricks they can do to do that is they can turn attacking immune cells into regulatory immune cells. And it’s like a Jedi mind trick. It’s like, “These aren’t the droids you’re looking for. Nothing to see here.” And they kind of turn around and create this protective barrier so that the blood-feeders can take their meal.

Worms Provide an Anti-inflammatory and Immunomodulatory Impact in Our Bodies

Those regulators don’t die. They’re derived down to the periphery. They last a couple weeks. They circulate around the body. And they keep inflammation turned down where it’s not necessary. When you have a deficiency of regulatory immune cells, you have conditions that deteriorate your immune signal detection, which is a fancy way to saying it makes mistakes.

I’m going to show my age here. But if you ever had an AM radio with an old analog dial on it, the signal would be static on one side signal and then static on the other side. And this regulated immune system makes the same mistake. Instead of picking up the signal and listening to the music, you react to harmless stuff or you ignore stuff you should be paying attention to.

And on either sides of that signal are autoimmunity or allergies. The immune system should be ignoring self-tissue or harmless organisms that live inside of us. Instead, it attacks it like a dangerous invader. Or it attacks a harmless substance that it should be ignoring, like pollen or cat dander.

And so what we’re really trying to do here is get signal optimization in what our immune system is doing. And going back to our proto-ancestors, worms have been involved in helping us optimize that signal detection. Because a lot of these worms live inside of us for a very long time, it’s not in their best interest to hurt us. They want to create a nice environment for themselves, but they also want us to do well.

Malaria

And one of these ancient battles that has been going on is between malaria, the worms, and us. Malaria isn’t familiar to us in America anymore. It’s probably killed a majority of human beings who’ve ever walked on this planet. It’s just a tremendous evolutionary pressure. And we have blood types because of it. We have curly hair because of it. We have changed skin tone. We also have immune functions that’s been shaped and forged by it.

And the worms aren’t really interested in our brains cooking from cerebral malaria. That ruins their whole game. So you have this ancient battle that’s been taking place. And when you get rid of malaria, you’re, ‘all right, no big deal, we can get rid of the worms.’ But the signal detection problems start to reveal themselves. And then what you start to see are all these allergies and autoimmune conditions starting to arise. So you can either put the malaria back in or you can put the worms back in. And for me, I didn’t want malaria. So the worms were the way to go.

Example of How Hookworms Work

DrMR: Yeah. There have even been studies. I know that Moises Velasquez talked about this in his book, The Epidemic of Absence, where even the removal of malaria in the Sardinian population seemed to really stimulate MS. And so, even something like malaria in the right population may actually serve some kind of protective for all. Any thoughts on that?

GA: Yeah. So when you’re using worms, you got to get used to how they work. So the species that I spend a lot of time working with is Necator americanus, the New World hookworm. And you put them on the skin and you get a rash. And then in 19 days, they take this long migration to the gastrointestinal tract. And then at day 19, they take their first blood meal, make a little gastrointestinal thing going on. And then, it builds up to a peak in week six. And then week 6, drops off the peak, 85% of what you’re dealing with in the way gastrointestinal side effects goes away. And then week 11 or week 12, you start to get this immune modulation.

What we see when we use the hookworms in a condition like MS, we get this immune deviation from when they go into the skin. The immune system’s distracted. It’s really got something to go after. And the worms get to the gut where they’re hiding. And then we have these little side effects and things can get worse. But then, we get to week 11 where we get the benefits. And that’s where we’re starting to get a lot of this population of regulatory immune cells circulating out in the periphery and turning down that inappropriate inflammation. And that is pretty much the standard course you see with hookworms and people who have this autoimmune problem.

But what you see in MS is something even better. There’s like this third level effect that occurs in between the immune deviation and the regulatory immune cells. The only thing that makes sense to me is that it’s remodeling the bacterial lawn. And whatever bacteria causes that MS problem, the hookworms just don’t even create the right environment. Either I’ll compete it or select for some other bacteria that don’t allow it to gain a foothold. So you get this enhanced, I don’t want to say response, but there is just this really nice little phenomenon that you see with MS and the hookworms.

Using a Surrogate

DrMR: Does this seem to be consolidated to a particular type of worm? I know for example when William Parker came on, he talked about the TSO worms and the HTC worms, which are kinds of worms that people are using in the States in this underground sort of DIY protocol. But are you noticing that for some of this benefit, is it dependent upon certain species of worm?

GA: Yeah. Like the hookworms can be really obnoxious sometimes. And people are just too fragile to host them. So in ecology, you would use a surrogate. So if you can’t put the elephants back into the forest, then sometimes you’ll manage cattle in a very structured, grazing routine to restore the forest to a healthier state. And then you can put the elephants back in.

I think, one of the people who pioneered this is Allan Savory. He’s an ecologist. And I call it Savory principle or Savory technique. And we use it sometimes ourselves. We’ll use a non-human worm. We won’t do conservation. We’ll do this structured management of a non-resident population. You could use TSL. I don’t work with TSL myself. But there is Hymenolepis diminuta, which is a rodent tapeworm, which is really good at this. And it can help build some stability in the gastrointestinal ecosystem. So that then, you can use it as a stop galv to get you over true conservation and putting the resonant species there.

But sometimes people are just too broken. It’s like the barefoot running movement. People got really excited about running barefoot. But their feet have been in shoes their whole life. And then they went out to try run their mileage barefoot and they hurt their feet. They needed to make that transition. Maybe to a zero-drop shoe, then to a sandal, then some barefoot running. You let callouses get built up. Let the ligaments and the tendons all get strong. Let the feet start to become feet again instead of flippers. And then you can go out, run your miles. And that’s kind of what we do in the gastrointestinal tract.

DrMR: So some people may have to build up with non-human worms first. And then eventually graduate to the human, essentially, is what you’re saying?

GA: Yup. Just stuff that passes through. So you give their immune system an opportunity to take a look at worm protein, let those regulatory pathways get practiced, let there be some remodeling, presumably, to a healthier microbiome. And then you can start to work on building up to a conservation program.

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Are Certain Kinds of Worms Ideal?

So, I guess, with the end in mind of getting to a human type of worm, do you notice that certain species of worms have more benefit for certain ailments or does age or sex make a difference in this?

GA: Well, everybody’s different. That is what is very humbling about working in the gastrointestinal ecosystem. It’s very complex. And everything that you think you know—I can’t remember the name of the bear researcher, but I think he just nailed it. Some reporter asked him, “What does it mean when a bear does this?” And he said, “If you’d ask me 10 years ago, I would’ve told you exactly what it means. But now, I don’t know.” Because it’s just so complex. You see all the exceptions. I’ve had elderly women that I thought on paper would never be able to host. And it was kind of a Hail Mary. They did fantastic. I have otherwise robust men that you would think would have no problem. And they just have a terrible time. It’s so complex in there.

DrMR: When you say that, it brings up something that I, again, read in the book Epidemic of Absence, which was essentially, Velasquez thought he observed two general response types to helminths. One, which would mount a very aggressive immune response and try to eradicate the helminth. The other, one that would mount a much more mild response and seemed to be geared at coexistence. So perhaps, the people that were not able to tolerate these worms were having that response because they were that immune type of very strong, acute responders. Whereas the other people who responded okay were able to do so because they were more of a mild, ‘let’s coexist’ kind of response. Have you seen anything like that in your experience?

GA: I think there’s something to that. There appears to be two attractor basins. All right, so a lot of this stuff is all grounded in complexity theory. That’s the mathematics that helps us understand these complex self-organizing systems. Attractor basins are basically a way to describe how these evolving fitness landscapes—because ecosystems are all interdependent. And one change in one part of the ecosystem can have an action at a distance. And so, the way the mathematicians or physicists lay this out, they do it in fitness landscapes. And so, there appears to be, in the human gastrointestinal tract, two different attractor basins that predict about 80% of human beings. One is roundworm-dominated and the other is amoeba-dominated. So there are some people who think that sometimes putting roundworms into people who need an amoeba-dominated type ecosystem is where we’re getting some of this mismatch. I don’t know if I really buy that.

If you’ve got two really dominant keystone organisms that predict what the bacterial lawn is going to look like, either the roundworm or the amoeba, my suspicion is that we all carry the gene complexes that can be turned on or off to host one or the other. I think what we’re seeing just a lot is the fragility because we have this depleted microbiome. I used to joke a long time ago about the worms being very lucky to find themselves in a Western well-nourished gastrointestinal tract. But I realized I was exactly wrong now. They were doing just fine in the Amazon and in Belize where I found them, because those people that were hosting them had a complete microbiome.

Because when we look at that Western biome compared to fossilized poo or to modern hunters-gatherers, it’s half dead. And that half dead microbiome is, I think, why a lot of people have trouble falling into a balance with the worms. They just don’t have enough life in that bacteria to help them make fully functional regulatory immune cells. And if you don’t have those fully functional, fully suppressive regulatory immune cells, the worms will never be fully invisible. And then you won’t be in complete balance.

DrMR: It makes complete sense. Yeah.

GA: I do think there is some mismatch. But I don’t think it’s the primary effect. I think the primary effect is we’re seeing that front edge of all the depleted microbiome. But my own personal experiments, when I restored my microbiome to a more pristine state—I’ve been hosting worms for eight years, before I did those fecal microbial transplants. We got some donors that are living in very primitive conditions. And my ova count’s tripled in days. And that is an indirect measure of how we were measuring the health of the worms. And those numbers then started to reconcile a lot better with the work that is done by the German scientist, around the turn of the century, when they were looking and studying and cataloging hookworms. Because what we have noticed was that the ova counts were depressed and the lifespan was significantly shortened in the Western biome. And then when we get it restored, then we see that. And then we just think you could come into balance a lot better when you have a healthy bacterial lawn.

Amoebas

DrMR: Let me start first with amoebas. I haven’t actually heard anyone make the argument. And I’m very curious to hear a little bit more about this that amoebas may have beneficial impacts. Of course, there are some amoebas that we classify as at least semi-commensal and there are some that are highly pathogenic. But curious if you have any expansion on the amoeba piece?

GA: I don’t remember the name of the authors in the study. I can get that for you. Maybe we can put a bibliography up for you. But there was an 80% predictive effect when they looked at microbiomes in Africa. If they had amoeba, we could say with 80% certainty—if you saw one assay of a bacterial lawn, you can say with 80% certainty that that person had either an amoeba or a roundworm infection. And so, the amoeba that most of them are hosting is a harmless commensal Entamoeba dispar that isn’t associated with any known disease. But it also travels and looks a lot like histolytica, a very pathogenic—

DrMR: I had that one. So I know that guy firsthand. It was not fun.

GA: Right. No peaceful coexistence with histolytica. And most of the time, histolytica is misidentified. It’s actually just dispar. And so the idea is that you might be able to put that amoeba—the problem with using amoebas is that they expand their population. So it’s hard to control the population size if you’re trying to do some structured management.

Fecal Transplant and Helminth Therapy

DrMR: Okay. All right, that makes sense. And then, what’s your take on fecal transplant versus helminths, maybe used together? If so, in what sequence? How would you come in on that?

GA: Yeah. So that, I think, we’re making a mistake by fracturing this ecosystem. I think this work all needs to be done together. I don’t know the exact order. And I’m sure it’s going to be complex and different for everybody. There’s such an incomplete information and just trying to kind of feel around the dark cave.

I would say that if we look at the way the microbiomes start to transition from childhood and when you’re suckling from a milk-digesting microbiome to what starts to look like your adult—this all occurs in an ecological window right around two and three. It’s also the age that children all start putting stuff in their mouth, so that they can catalog the things that their immune system is supposed to react to, what’s in their environment. They’re basically loading the software into the hardware to have proper immune thermostat settings and signal detection.

So it would seem to me that it’s almost simultaneous how this is occurring. You’re weaning from mom. You’re transitioning into your soil base microbiome and the stuff in your environment, not so much what’s on mom’s skin or in her breast milk. And that’s right at the age you’re putting the worms in. What’s the saying, “In the face of sustained scientific uncertainty, turn to nature, see how she does it.” Now, I say it’s probably a simultaneous process.

DrMR: Now, have you worked with anyone or heard anyone make comments with their own experimentation in terms of they did one and then the other? And have you teased out people who maybe have done both? And have you seen more of a positive response if someone does one before the other? I know that would be extremely speculative, but just curious if you’ve caught anything kind of through the grapevine.

GA: Well, I’m the worm guy. So most of the people that I’ve worked with or what I’ve done, we always started with kind of a worm foundation. So I have real bad selection bias when it comes to this. It’s always kind of ‘worms first.’ The thinking being that if the worms help create this population of regulatory immune cells, then that minimizes our risk of putting healthy microbiome and then having the immune system learn to react to healthy stuff. We don’t want any more of that problem. We want tolerance. And so, I think for the foreseeable future, we’ll be working in a worm-first perspective. But if some kid in their garage, tomorrow, discovers that if you put the microbes in first, well we would do that. It’ll be a pretty compelling argument.

How to Find the Ideal Dose

DrMR: There’s a lot to be learned here. So, yeah, I totally get that. What about dose? I’ve heard simple recommendations in terms of start with the lowest end of a tentative dose range and see how you respond and slowly work your way up. It seems like a reasonable vague principle. But are there any tips there that you found to be helpful?

GA: Absolutely. So adaptive management, the principle being of disturb and observe. And so you put a little bit in and you see how they respond. And you put a little bit more in, and then you see how you respond. Now, one of the tricky things about the hookworm is you don’t want to get to a trickle dosing, where you’re just doing a couple at a time because you can kind of keep the immune system in this hyperstimulated space. You do need some rest in there to let things settle down or come into a balance. Yeah, it’s adaptive management. So you’re just trying to pick up the signal.

And then when somebody starts reporting to you that they’re noticing some improvements in gastrointestinal function or overall global health metrics, then you start to optimize around that signal. Maybe you try to go up a little bit. Maybe you let it rest a little bit. Maybe you do a wash out. Maybe you add a species of worm just so the immune system can see more worm protein. And it’s this tinkering. And this is where I know a lot of people get frustrated, because the human mind craves certainty. Aren’t I supposed to take 25 every two months? It’s too complicated for that kind of stuff. You have to be tolerant to a little bit of messiness in these complex biological systems.

And there’s just so much stuff in the modern world that goes along with this that makes it hard to do a real clean type of experiment. We have stuff in our food supply that is not healthy for us or for worms. And if your diet isn’t dialed in, we have lifestyles that aren’t healthy for us or for worms. If you’re going to be reordering your—because that’s what this therapy really is, it’s reordering your interaction with nature. On one end of this spectrum, there’s the village existence or hunter-gatherer existence. And then at the other end of the spectrum is the New York/Los Angeles experience. And everybody has a health maximum that exists in between, or maybe a couple that exist in between these two ends of the spectrum.

So if you’re going to go rewild and start to move towards the more village from where you are in your modern world, lifestyle, and diet, you got to kind of do those things along with it too. You can’t eat antibiotics every day or sit on the couch drinking Mountain Dew and eating Cheetos and expect the worms to do everything. They’re not going to do well in that environment either. So if you rewild and get the lifestyle changes working with it, then that’s how you pick up the signal. And then you can find just where that sweet spot is for you in there.

And for some people, it may be 25, 30—so if you do a fecal audit of villagers who live with a species of hookworms and different places of the planet, the males carry around 40 some, the women about 35, somewhere in there. So some people will do really well with just that 35, 40. Other people who have a lot of immune scarring and problems with their lifestyle and diet, because they’re not healthy, they may be 75 to 80. You just don’t know until you start to tinker in their gastrointestinal ecosystem, where their signal will take you.

DrMR: Got you. And so I’m assuming that dose frequency follows that same kind of trajectory, which is very individual, except for maybe that one note that you made where you don’t want to be taking these too frequently.

GA: No trickle dosing. So then, the trick for us is to find a sustainable population. We want to find a schedule of inoculation or boosters that is sustainable. Because in ecology, you don’t want to just building up until you fall over the carrying capacity of the ecosystem and cause a collapse. And so, if you have worms who are living a year, and our species with Necator americanus, you want to stay below 110 if you can, because that’s the boundary between a mild and a moderate infection. That’s when, in moderate regime, you’ll start to develop anemia. You’ll start to have some vitamin deficiencies that you see in long-term chronic host infections. So when you can stay in that mild regime for decades, that is a sustainable population.

So we’re doing like 30 in one year. And, now, a year and a half later, we do another 30, and then another 30. You see that we’re never really building up above 60 or 90. We don’t move into that next threshold. Not everyone can do that. Sometimes, one species of worm living in one segment of the small intestines isn’t enough to give them the proper immune modulation. So you kind of have to push hard. But most of the time, we can stay in that mild regime. And that’s the goal, a sustainable population.

Clinical Trials

DrMR: Got you. Before we started the recording, we were talking about clinical trials. Is there anything that you have found particularly compelling from looking at the clinical trials with helminths?

GA: Well, it’s hard. Ecosystems don’t lend themselves to reductionist thinking. And I just see so many of these clinical trials that are done in a damaged Western biome with no lifestyle instruction, no diet instruction. And they’re just throwing worms into a desert and hoping to pick up a signal. That’s not the way nature works. And if you’re going to study nature, you have to be… It’s very subtle.

So, for me, what I see a lot of times are worm researchers who have never even hosted worms, just studying trials. And they just don’t even have beginner insights into how to do this for a couple years. And then, maybe after a couple years, you start to have something interesting to say. And then, after a couple of years, maybe after a decade or two, you could really do this.

I don’t know, Allan Savory speaks to this a lot better, that ecologist that I was talking about. He was talking about how the scientist would come along in ecosystem restorations and they wanted to test this hypothesis about cattle being managed in a structured way to replace the large grazing animals like the hippos and the lions. And they came up with this diesel engine thing that was on a trailer. And it shot poop out the back end out of a little tube. And it had these pistons that drove hooves-like things into the ground. And they drove it around the field for a couple months. And they said that it didn’t work. And of course it didn’t work, because that thing was big and stupid and it crushed bird nests and it didn’t help with the soil regulation and the poop wasn’t right.

I think, maybe, we don’t need a whole lot of scientists in white coats studying this problem. And what we really need are people regaining their respect for nature and the complexity of nature. Some of the Indians that we work with for our fecal microbial restorations, they have a concept of a broken soul. And if you break your soul, you become disrespectful of nature. And I’m not saying that we all need to go back and live in a village. But we haven’t been particularly great stewards of our planet so far. We’re not terrible, but there’s a lot of room for improvement. And those mistakes that we’ve made in the planet, we made it for ourselves.

And I think that this N of 1 where people who experiment and citizen scientists go out and the plurality of their stories, I think, is a better way to attack this problem. Because it’s just messy. And it doesn’t lend itself to a reductionist placebo controlled, double-blinded, crossover study. It’s messier than that.

Time Indications for Dosing and Response

DrMR: A couple of other questions for you here, as we kind of start drawing towards a close, are there any time indications for, okay, this person is not responding and we should potentially look into some confounding factor or kind of move them somewhere else? Is there a time window where someone should at least be seeing the initial indications of a response? Or if not, in that time, then they should be thinking about something else?

GA: It really depends on the organism and the condition. If you you’re using something like the Hymenolepis diminuta, you can see immune modulation in weeks. The hookworms have a more tortuous journey. And then they hide for a while. So you’re looking at months to see it. I think that you really want to have at least a six-month window before you’re making any big therapeutic decisions.

Contraindications

DrMR: Okay. And then, are there any clear contraindications, meaning, if someone’s got x, y, or z going on, do not do this?

GA: Well, yeah. If you have a bleeding disorder, you don’t want blood-feeding organisms living in your gastrointestinal tract. That’s a real obvious one. Some people, psychologically, just can’t get over this idea. It triggers them. And you have to respect that. It all works together. And if they’re chronically obsessed and not sleeping because they have this unease that the idea of worms living inside of them, they won’t get healthy. There’s a psychological makeup for doing this biological therapy. And then, there is a theoretical risk. Some solid mass tumors like to surround themselves with regulatory immune cells. So you want to be real careful about increasing the regulatory immune cell population if you have a history of solid mass tumors. That could be adding gasoline to a smouldering.

DrMR: Got you. What about constipation? I’ve heard some people remark that constipation can be a contraindication to this, but I’m wondering what you think on that.

GA: It depends on the organism. Like Hymenolepis diminuta would not be a good choice. It causes constipation. Usually, when we see that constipation, that travels with other stuff. And what I would look at is the fecal microbial transplant to your constipation people. Serotonin, the neurotransmitters, these are derived down in the colon, between interaction of those specialized interchromatin immune cells and the endospores that reside in the colon. They’re responsible for maybe a third of the body’s serotonin. And if you don’t have that right, you’re going to have fibromyalgia, depression, constipation. That all travels together that just tells you—and probably some visceral fat too, that’s usually a pretty good marker of having depleted colonic micro biodiversity.

DrMR: Okay. For someone that’s significantly constipated, you’d say, starting with FMT might be a better consideration?

GA: Yeah. Get the river flowing well. And then when the river’s flowing well, then you can start putting the large multicellular creatures in.

DrMR: Got you. All right. That runs through pretty much everything I wanted to ask. Is there anything else you wanted to leave people with?

GA: I don’t want to be a Debbie Downer but I do think—I’m basically an optimistic person. And I think that we just had an over-correction. A hundred years ago, there was too much interaction with nature. And then, now, we kind of over-corrected and it just needs to come back a bit. This is another responsibility. And I know that we’ve fallen in love with the idea of pills to solve problems in America. But I don’t think that this problem is a good one to be looking for a pill. So when you hear people talking about, we’ll just make a pill out of the worms, I would not put too much investment in that idea.

Nature is incredibly complex and it doesn’t lend itself to single molecule solutions. Nobody would tell you that we don’t have to practice conservation for polar bears because somebody’s going to make a polar bear pill. And that’s the kind of skepticism that you should have when a scientist says, “We’re going to make a pill out of the worms.”

With that said, if we all get pointed in the right direction, and we start looking at the option of peaceful coexistence with those things that we can peacefully coexist with, I think we’ll improve not only the planet, but ourselves. That’s my optimistic opinion.

Episode Wrap-Up

DrMR: It’s a great, great note to end on. Well, thank you, Garin, for taking the time. I really appreciate you sharing some of what you’ve seen, some of your views, taking us a little bit deeper into this concept of gut ecology. And I think that we’ll resonate very deeply with our audience. So thank you, again, for taking the time.

GA: Hey, it’s my pleasure. Thank you.