Nirala Jacobi:

Welcome to another episode of The SIBO Doctor Podcast. I'm your host, Dr. Nirala Jacobi, and with me today in the SIBO Doctor studio, well, not really, but online and recording is Dr. Mark Davis, who I've been trying to get onto the podcast for a long time. He's an expert in helminth therapy and is a naturopathic physician, a 2011 graduate of National University of Naturopathic Medicine, and a fellow of the American College of Naturopathic Gastroenterology. He's on the board of directors of the Gastroenterology Association of Naturopathic Physicians and the editorial board of the Natural Medicine Journal. Dr. Davis teaches the Naturopathic Gastroenterology course at Southwest College of Naturopathic Medicine, and he has focused on patients with inflammatory bowel disease since 2016. Welcome, Mark Davis, I'm so happy to have you on the program.

Mark Davis:

I am so excited to be here. I've learned so much from you, from all your materials over time, and so it's just a delight to be here.

Nirala Jacobi:

Thank you, appreciate that. So I know there's a lot going on in your life. You're basically doing FMT, you're starting all sorts of new things, but talk to us about helminth therapy. And I remember being at the AANP, the American Association of Naturopathic Physicians, I don't know how many years ago, but where you gave a live demonstration of the... I can't remember which helminth it was, but let's start with what helminthic therapy is and how did we get there in terms of therapeutics?

Mark Davis:

Great. So when we talk about helminths, these are tiny, usually microscopic worm-like organisms that live in the guts of every kind of vertebrate on the planet. So all wild populations of fish and birds and mammals of all kinds, any given wild population, usually a little over half of them have helminths in their gut. Most of them are commensal, they're harmless, and there are some that cause very bad harm. And so when we talk about helminthic therapy, it's saying that out of the hundreds of thousands of different species of helminths, there are basically at this time four that we've found to be so safe in humans and able to provide benefit that we'll talk about a lot on this episode, I'm sure.

So safe and able to provide benefit that we can use them as medicines. And the CDC and other health organizations usually classify these as parasites. But I argue with that definition because by definition, a parasite lives in its host and benefits from the host and causes harm. And commensals live in the host and don't cause harm or benefit, and mutualistic organisms live in the host and cause benefit. And even the ones we're talking about today, like my favorite Necator americanus that I gave to a colleague on stage at the AANP years ago.

So Necator americanus, it's true, it can cause harm if you are in a place where there's eggs all over the soil and you maybe have a population of several hundred in your gut or a thousand in your gut, yes, they are technically blood sucking parasites and they do have tiny amounts of your blood. And if there's a thousand, you'll get anemic. And if you're an adult, anemia is bad. And if you're a child, anemia is even worse. Permanent effects on growth and IQ and other things. Yes, in uncontrolled situations, they are parasites, but they can be commensals as well, and there is a lot of evidence to indicate that they are mutualists in certain conditions and for certain people as well. So when we talk about helminthic therapy, that is the bottom line is we're using these tiny worm-like organisms called helminths as medicine for humans.

Nirala Jacobi:

And what would be the circumstances or the conditions where one would consider this? And obviously this is done with a professional, this is not like a probiotic you can buy online or maybe you can, I think...

Mark Davis:

I will say, yeah, they can't see me here, but I kind of shrugged because you kind of can. And there are a lot of other doctors besides myself who have used a lot of helminthic therapy and some way more than me. And there are a lot of great scientific trials, and we'll talk about some today I'm sure. But to be honest, the DIY helminthic therapy community has really moved knowledge forward in a really interesting way. And it's true they're not risk-free in terms of dosing and other things. They're not quite as risk-free as say, probiotics. But when I give them to patients, I don't write a prescription for them. I don't administer them myself. Now, there was a period of time where I was growing them out in an incubator in my lab and giving them to patients, and after maybe two years of that, my lawyer was like, "You cannot do that anymore. You cannot, but it's okay because there are organizations that will just send them to you."

So I tell my patients, get in touch with one of several organizations and we'll talk about them later as well and order them for yourself. And here's the dosing that I recommend. And sometimes the companies that produce and distribute these have differing dosing schedules that they recommend. And I tell my patients, listen to me and listen to them. I've worked with a hundred and changed patients and some of these companies have distributed to thousands of patients, so I have my opinions and they have theirs, and I recommend my patients weigh both of those perspectives.

Nirala Jacobi:

So you said that there are four different types of helminth, but before, actually, let's go way back to 10,000 years ago when we had very different microbiomes. We had a lot more what would be considered parasites on board now and then the agricultural revolution, then the industrial revolution, all that basically made us more hygienic and really affected our microbiomes and affected the presence of helminths. And that some argue was to the detriment of human microbiomes.

Mark Davis:

Like anything humans do, I think it has pluses. Everything you just described has pluses and minuses. And if you look at hunter-gatherer communities in the world today, the Tsimane in Bolivia or certain groups in Sub-Saharan Africa, they're about other mammals who are non domesticated. Oftentimes, little over half of them have helminths living in their gut. And if you look at industrialized countries and our cats and dogs and our cattle, helminthic populations are way lower. And for us in the United States and you in Australia, there's all kinds of reasons for that. You mentioned a bunch of them, industrialized food supplies, wearing shoes, flush toilets, antibiotics and antiparasitic drugs that we take a lot and give to our cattle and our cats and dogs. And that brought prevalence down very, very low. And over that stretch of decades when all those things were occurring, we had the great benefit that suffering from infectious disease dropped a lot and that's great.

But during that same time, suffering from allergic and autoimmune disease rose a lot. Do I think it was all worth it? I mean, I'm glad that we have the options of antibiotics and shoes and industrialized food supply and flush toilets, all of those things, I think they do have benefits, but they often come with some harms, especially for certain people with certain genetic heritages and certain hyper inflammatory tendencies. Sometimes the suffering can outweigh the benefits of being exposed to so much microorganisms, including pathogens and commensals. So yeah, over that 10,000 year period, and actually before our genes had adapted to be in partnership with these microorganisms that were so often living in our gut, we call probiotics like the gut flora and I call helminths the gut fauna. They're larger, they're not single celled, sometimes they are macroscopic and they're wandering around the forest of your gut.

And Necator americanus, it only lives in human beings. Homo sapiens is its only host. There's no intermediate host or anything else. And so it is exquisitely adapted to the environment of the human gut. And when it does latch on, and we can talk more about the lifecycle more in depth if you want, does latch on in the small bowel and it does sort of suck our blood or our blood passes through it and is excreted and what is in our blood, but inflammatory cytokines and so to the helminth, those inflammatory cytokines are a warning flag. Here's how the human immune system is going to start attacking you. And so it has developed ways over millennia to modulate that response.

And part of that modulation comes with inducing a more robust T regulatory response. And Tregs are the whisperer of the immune system. They're what tell our immune systems to calm down after the threat is over. And for most of us around the world with autoimmune and allergic diseases and other hyperinflammatory conditions, a lack of T regulatory cells is a significant part of the problem. So I feel like I'm wandering a little bit in my long response to your question, but yeah, I think as our genes have changed, we've grown to depend on this immune modulating message from our old friends that live as part of our ecosystem.

Nirala Jacobi:

So you've talked about the benefit of it, basically it's downregulating this inflammatory immune response. So you would consider using helminth therapies for autoimmunity or any condition where the immune system is either overstimulated or even understimulated.

Mark Davis:

Well, where it's not properly regulated because there's an abnormality or a lack of T-cells. So I haven't thought about understimulated, that sends my brain thinking all sorts of ways, but really the conditions that are most evidence supported for a helminthic therapy are what I would call hyperinflammatory conditions.

Nirala Jacobi:

So not just connected to the digestive tract. So not just inflammatory bowel disease, but really conditions like just systemic conditions of autoimmunity?

Mark Davis:

Yeah, the most exciting non-GI one. Can I talk about a specific indication? Yeah.

Nirala Jacobi:

Yes, please. Yeah.

Mark Davis:

It's multiple sclerosis, so that data is a little confusing, but I still do recommend helminths for people with multiple sclerosis. So the original trial was around the turn of the century in Argentina, there was a huge economic crash a couple of decades ago, and it got so bad that in urban Argentina, sewage water was getting in the drinking water. And so there were a lot of fecal oral transmission of helminths and protozoans and other microorganisms like that. And previous to this Argentine crash, there had been some data coming out of Southeast Asia and parts of Africa that showed anti-helminthic campaigns, decreasing infectious disease and the harms from helminths, but increasing hyper inflammation. And so this Argentine neurologist, Dr. Correale, knew about this data and he said to his MS patients who were coming in with signs of parasites, he said, "Well, if you want, we could just not get rid of them."

What are those signs? So eosinophilia or elevation of eosinophils in a blood test is the main sign, and then some digestive symptoms for some of them, but mostly just, oh, we see elevated eosinophils in your blood. So all of those patients with MS and elevated eosinophils, Dr. Correale said, "If you want, we can not eliminate them and just keep track of how you do and see how that is." So he took all his patients with MS and hypereosinophilia, and most of them, he did stool tests and found these helminths in their gut, in their stool samples. And he compared those to all of his MS patients who did not have eosinophil or detectable helminths in their stool samples. And he kept track of them for over five years and kept really scrupulous data about it.

And for MS, there's a scale that tracks how far it has progressed. It's called, I think the extended status disability scale or something close to that. And it's just a zero to 10 scale, and zero is you don't have any symptoms and 10 is death. So a lot happens in those 10 points in terms of becoming less able to walk and becoming only unable to move in various ways. So anyway, what he found was a dramatic and statistically significant difference between the two groups of three points on that 10 point scale. And so that's the difference between being able to walk and not being able to walk or being completely wheelchair bound and being close to death. Huge difference in five years. And so that was the first ever data about multiple sclerosis. Questions before I talk about other studies?

Nirala Jacobi:

No, no, it's fascinating.

Mark Davis:

Okay. So that one, I'm obsessed with and I've read many times and so I know off the top of my head in detail, and the follow-up studies, I don't have right in front of me, but I can tell you none of them are as exciting as that. None of them. There are some that have showed statistical significance in some parameters versus placebo, and that's cool. But what I want is a three point difference in my patients with MS. I want to say, "Wow, this made a big difference in your life." Of course, maybe it is helpful if it's statistically significant, but a small clinical difference but not as exciting. And so what were they doing? Well, there were a few differences. Usually, they were only following for six months because running a clinical trial is expensive and you can only run it for so long. And then also they were just giving a single helminth all by itself. And honestly, that's usually what I do too.

But I have had it in my mind for a while that if I or someone very close to me got multiple sclerosis, and these were all patients with relapsing-remitting multiple sclerosis in the Correale study, anyway, at least got relapsing-remitting, I would want to do helminthic therapy with FMT at the same time, because the truth is these people are being exposed to sewage water. They were getting a dose of fecal oral, and some of them just happen to have helminths in that as well. Some deep burning part of me really wants to know if that could be what made the huge difference instead of the small differences that we've seen in these clinical trials or some have no difference over placebo. The more carefully done trials were not that exciting. And I don't think it's because they were more carefully done, I think it's because they were cleaner perhaps.

Nirala Jacobi:

So besides Necator, you mentioned four organisms. Let's talk about what each one is sort of indicated for and also what you're most exciting clinical outcomes have been so far using these organisms.

Mark Davis:

Yeah, great. So Necator americanus is by far my favorite and all of the super exciting clinical outcomes I've seen have been associated with that, most of them, I'll talk about some others. So, that's Necator americanus or the new world human hookworm, Necator americanus is Latin for American killer, but it's usually not much of a killer. It's definitely less of a burden than the other human hookworm, which is Ancylostoma duodenale, and Necator americanus not only is it not really a killer, it's not really American, it's native to Africa. And really, it was African immigrants and usually forced immigrants in the slave trade who brought it to the Americas. And that's where it was first discovered and named. And of the form I'm going to mention, it is the only one that has a dermal application. So you contract it in the wild, and I will let you know this. Here's how we have so much great safety data about these things.

Probably 500 million people have Necator americanus around the world by accident. So we have a lot of information about what harms it could cause, who it's safe in, what it's like in pregnant women, things like that. So anyway, it's given dermally, and in the wild, it's from sitting down. I had a patient who actually got Necator americanus through her buttocks while sitting on a beach in Hawaii or through just walking or putting any unprotected skin on the ground where this microscopic stage three larvae are crawling around. So that's the only one given dermally. The next one and the other one of the two that only lives in humans is Trichuris trichiura, that's the human whipworm. If you look at it under a microscope, it looks like it has a very flared whip like tail. And I'll say about, to backtrack a little bit, Necator americanus, the first one lives in the small bowel and it provides a hyperinflammatory benefit locally and globally for sure.

And Trichuris trichiura, that's the human whipworm, only host is humans that lives in the large bowel, and in my experience mostly just provides local benefit. So I use the first one, Necator americanus, for anyone with any hyperinflammatory condition like MS. Trichuris trichiura, I use with my patients with ulcerative colitis and Crohn's colitis. That's where I use it. And it's great in that regard. And I have seen some great stories there, and I can talk about those. The other two that are commonly used are not native to humans, and one is Trichuris suis, that's the pig whipworm. Once data from human whipworms started to come out, this German company got this idea, they would call themselves Ovamed, and they said, "Maybe we could have one that's not native to humans." And so people that have to dose more frequently, it could be a decent pharmaceutical if it downregulates inflammation.

And so they contracted with a company from Thailand called Tanawisa to create a pig farm where there are germ-free pigs that the only microorganism inside their gut is Trichuris suis, which is the pig whipworm. And so they harvest them and they package them and they distribute them. And Ovamed ended up going out of business, but Tanawisa is still alive and well and distributing Trichuris suis all around the world, and they're the only source of that as far as I know. Actually, no, yeah, yeah, they're the only source of that one that I know of. And then the fourth one is also not a human helminth, it's Hymenolepis diminuta. And in this one, you don't give a larva or an egg, you give a form that's in between called a cysticercoid. And for that reason, people call it HDC, which stands for hymenolepis diminuta cysticercoid. It's a mouthful.

Nirala Jacobi:

It is.

Mark Davis:

Yeah. So HDC, its lifecycle takes it back and forth between beetles and rodents. That's its natural lifecycle. And so there's a medical doctor who I've seen lecture at IFM, Sid Baker, he, I think, has a lab where he just lets it go back and forth between beetles and rodents, and he just crushes up the beetles and gives them to people.

Nirala Jacobi:

So that one, that HDC, I think that I remember when that came out a little while ago, 10 years or so ago, that I was aware of it. And it was more marketed towards things like food allergies and sensitivities and things like that rather than systemic inflammation. Is that correct?

Mark Davis:

Yes, I have used it with maybe a dozen or two patients. I don't think it has as strong of a benefit, but I do think it has benefit. I call it my gateway helminth, because it lasts for the least amount of time, and it's the least expensive. I don't have an affiliation with any helminthic therapy companies, so I'm just naming them. The one I ordered from, and I think this may be the only one, is biomerestoration.com. They're in England. I've spoken extensively with a microbiologist who runs the lab and as well as the owner, very, very good-hearted people trying to do good in the world, and they keep the prices very low, ship them all over the world. So the prices are low, and you do have to take them frequently, but if you don't want them in your gut anymore, well, you just stop taking them and they're gone. Versus Necator americanus has a three to five year lifespan, so if you don't want it, you have to take a dose of mebendazole or albendazole or something. So that's my gateway.

Nirala Jacobi:

Yeah. So what would you use the HDC for then?

Mark Davis:

So I use it in people that I want to take a stronger helminth, but they're leery of it. They're nervous about worm-like organism living in their gut, or they're not sure they'll have the money. The other helminths used to be much more expensive, and competition has brought down the price. So now, that's not as much of a concern, but you can pay $50 a month and get HDC like a good dose. And so for people who budget as a concern or the IIC factor is a concern, and for people with allergic disease, that's I've seen maybe a little more benefit with environmental allergies, asthma, that type of thing, that variety of inflammation benefit from HDC. And I should mention too, where I use Trichuris suis, and there's really just one place because I am compelled by a fascinating trial, and that is for autism, so I think it is still up. There was a website blog, that was autismtso.com, and it was really one dad's story of working with his autistic son, his severely autistic son.

And he and his wife cared for their son. And once a year, they had a break because they brought him to camp, to autism camp, and he got to hang out with counselors and whatever, and they got to do grownup stuff. And this year, one year, the counselors called him and said, "Did you do something with your son and his protocols, because he's so much improved in a few different domains?" And he said, "No, we didn't do anything different." And they went and picked him up and he had chigger bites all over his legs. And he said he went to pick him up from camp and his son gave him a hug. And he said, son had never given him a hug before. He was very touch averse and he was having a much easier time conversing without getting very distracted. They stopped in a restaurant and had a meal in a restaurant, which was generally unattainable for this young man.

And this guy said, "Whatever is going on with my son, I have to know what is happening." And started to contact various university researchers, and they ended up saying, "Okay, we think this mechanism of action could be replicated with a helminth." And for that kid, he did get great benefit from this particular helminth, from TSO, Trichuris suis ova. And there was a clinical trial, which is fascinating because it showed benefit in certain domains. And I'm trying to remember. I think it was just the domains of obsessive repetitive behavior. Don't quote me on that though. I'm not remembering the trial well enough. So anyway, yeah, HDC people who are averse to it or want a really affordable product or have allergies, TSO, autism, TTO, Trichuris trichiura ova really for patients with inflammatory bowel disease in their colon in the large intestine, and Necator americanus, everything else.

Nirala Jacobi:

Okay. So moving into what you alluded to when we first started talking about how these people, their drinking water was mixed with sewage water, and you sidetracked into the FMT route and FMT for the listeners who are unfamiliar with that is fecal microbiota transplants. That's sort of fecal donation into the large intestine of recipients for various digestive conditions, and also, oral is coming.

Mark Davis:

And non-digestive conditions.

Nirala Jacobi:

Yes. But I think yes, it did, it started out with... Anyways, different kinds of applications.

Mark Davis:

Different, yeah.

Nirala Jacobi:

And I would like to move into that in a moment because you're definitely an expert and you're about to start your practice in Panama?

Mark Davis:

Panama, yep.

Nirala Jacobi:

So that's super exciting. But how do you assess, I mean, besides the condition that somebody presents with, but what kind of microbiome workup do you do and how do you then add the helminths to the mix, so to speak?

Mark Davis:

So basically nothing, nothing. I look at a lot of microbiomes and there is nothing that I can see in a stool microbiome that is going to tell me helminths are more or less indicated except maybe if alpha diversity is very low, then I could think, well, helminths do, they're in the literature for increasing diversity, but there's a lot of things that increase diversity. I'm not going to just see a stool test that is low in alpha diversity and say, "Oh, we're going to give you helminths." I would think of other things. I would think of diet, and I would think of probiotics, and I would think of FMT and other things. So really it's about the condition. It's about you have an autoimmune or other hyperinflammatory condition, you're open to this. And especially if it's something in the literature that is really evidence informed, then I'm going to really jump on it and say, "Look, this isn't just theoretical. We've got some data out there indicating this could benefit you."

Nirala Jacobi:

Okay. So let's move more into the microbiome then, because this is something that I think we both share this super fascination, longtime super fascination with the microbiome.

Mark Davis:

But before we do, I just want to make sure because I talked about indications and for the other ones, but I'd love to just mention some of the stronger indications for Necator americanus.

Nirala Jacobi:

Please. Yes.

Mark Davis:

Okay. So I just always have to mention, well, okay, so on my practice, my own clinical practice, I focus on inflammatory bowel disease, ulcerative colitis and Crohn's and that's the majority of my patient base, probably 75%. And it can be very helpful, very helpful. So you mentioned being interested in anecdotes, and I remember I had a patient who he'd had ulcerative colitis and had not been in remission for 20 years, 20 years. And usually, I'm a naturopathic doctor, I'm not doing one thing. I'm looking at the whole person and saying, "Oh, let's give a nudge here, a nudge there, what can we do?" And so it could be hard to tease out what is helping and what is not helping.

But this guy came to see me and he said, "Look, I read an article you wrote about helminths. I want to try helminths." He wasn't interested in any of my other stuff, which is fine. And so we did. Now, for him, we gave him Necator americanus and Trichuris trichiura. Well, I love that combo actually. So we didn't have that to tease out because he got both at once, but six months later, he came to me and he said, "I feel like I want to cry because I'm just completely better. And if I just known about this 20 years ago, I would've had such a different life maybe at this point." But he was very, very thrilled to finally, finally be in remission for the first time in decades. So that was great. Brief mention also with Necator americanus in particular, because it's the only one dermally administered, the other ones are orally administered.

You do get an itch at the site of administration that lasts about a day. The more of them you give, the more of the itches, and you usually give anywhere between five and 25 at a time. And then, typically about four to six weeks later, you get what's called the worm flu. The worm flu is nausea, dyspepsia, sometimes vomiting, can be abdominal pain. I've given myself Necator americanus twice. And so I experienced it both times. And every time you give Necator americanus, the itch gets a little worse and the worm flu gets a little better. So I only really experienced it the first time. Why did I do Necator americanus you might ask? Well, the first time was just because I had been telling my patients, "Look, I think this is safe and it's really part of the natural microbiome." So I didn't do it to really benefit a pathology. I just wanted to say, I've done this myself to help people get over the gross factor. I get a little fall sinusitis I thought might benefit, that didn't benefit.

So that was the first time, and then it was a few years, three, four or five years, and I was like, "Oh, they're probably dead. I should do it again." So I did it again, and I'll talk about why, actually, maybe there is an indication, but it's a preventive medicine indication, and that is, there's a certain genetic combination that I identified in myself in 23 and me that makes you more likely to get late onset Alzheimer's about five times more likely. And I am homozygous for that. And there's some fascinating data from the Tsimane in Bolivia who have helminths versus the ones who don't that those with the same genetics, if they have helminths, they're less likely to experience cognitive decline in old age. And if they don't have helminths, they're just like people without helminths in the United States or Australia, that they're five times more likely to experience cognitive decline.

So I may have a reason actually to have helminths in my gut. So that was my experience. But a couple other things that I've got to mention with Necator americanus. One is an Australian researcher named Croese, I think is how you pronounce it, C-R-O-E-S-E, did a trial that I did a writeup on where he gave Necator americanus to people with biopsy proven celiac disease. And then he slowly microdosed gluten and gave them more and more and looked at their tTg, tissue transglutaminase, and their DGP, their deamidated gluten peptidase, the two big blood markers for celiac disease.

And he did biopsies of their small bowel over time and kept giving them more and more until they were literally, I think eight out of 11 of them were literally eating a bowl of spaghetti a day, a literal bowl of spaghetti a day as part of this study, people with biopsy proven celiac disease. And of those eight who finished the trial, three dropped out. I think one just moved and two experienced symptoms or something like that. But the eight out of 11 who finished the trial said they had no symptoms, no increase in tTg or DGP, and their marsh scores on their biopsies looked fine. Nothing does that.

Nirala Jacobi:

Wow. So is that only been one study of 11 patients?

Mark Davis:

That was the one that got everyone excited. And then maybe two years ago, the same research group, Croese et al, did a follow-up study, which was way messier, way messier, and more confusing and hard to interpret. It was in Australia and New Zealand and the New Zealand group had way worse outcomes. Maybe there was something in the mailing process that damaged them, but we don't know. So they took the whole group as a whole, and there was not statistical significance between the Necator americanus group and the placebo group, but all sorts of bizarre things happened. Like a substantial number of people in the placebo group started to eat gluten and had no symptoms and no elevated tTg or DGP, and their marsh scores looked fine. What? Then how do you interpret that? Oh my gosh.

Nirala Jacobi:

Yeah, let's not talk about that study.

Mark Davis:

Oh, it's messy. It's messy.

Nirala Jacobi:

But I know that a lot of people that are listening are going to ask or wonder in their mind, what is this transdermal application? What are you actually applying? How does it getting to the gut? Can you talk us through that?

Mark Davis:

Sure. Sure. Yep. So the lifecycle, so they're stage three microscopic larvae. And so what you get is a vial, it just looks like a vial of water, and it comes with a little pipette and you squirt it onto the little bandage that comes with it. And then there's an extra vial of water that really is water to squirt into the pipette and into the vial just to capture any stragglers. And you squirt that little one milliliter of water on the bandage too. And then you put your bandage on your shoulder, any clean hairless patch of skin. And then these stage three larvae secrete some enzymes that allow them to move through the dermis and deeper, and that's what the itching comes from until they actually reach the blood supply and then they get into your blood supply, into the heart, pop through the alveoli into the lungs, and then the cilia of your lungs migrate them upwards until they're in your oropharynx, the back of the throat.

And then they're naturally swallowed and they hit stomach acid, which tells them, because the human host is their only host for millennia, tells them, okay, we're about to be home where we want to be in the small bowel, we can start maturing. And they get into the duodenum and they latch on the duodenum or in the jejunum and start living the rest of their lifecycle. So it's a whole very-

Nirala Jacobi:

So fascinating.

Mark Davis:

... weird, complicated process. Yeah.

Nirala Jacobi:

Yeah. You read about that. Just as a side note, before we go into FMT, I do want to talk to you about that because of your passion around FMT and maybe not hidden, but the promise, it is promising, the microbiome restoration that it has as sort of the capacity of.

Mark Davis:

Yes.

Nirala Jacobi:

I do want to talk about that, but I want to wrap up the helminth thing and want to hear if you've read that case where a roundworm was found in the woman's brain here in Australia, and this is actually a woman who lived in our area where I live, and she got this roundworm from pythons. We have coastal pythons, lots of them. And in fact, the day that this made the news, I had four of them on the roof, and we collect our rainwater for drinking water. And I'm assured that the lifecycle, it's not a human helminth, but I wondered if you had heard of this case that basically women became very cognitively changed and lots of depression and some other visual stuff, and the neurologist found a mass and went in and actually pulled a live worm out of her brain, live roundworm.

Mark Davis:

Wow. That's not the only one, unfortunately. There are a lot of bad guys in the helminthic category, elephantiasis like the elephant man that's caused by a helminth that destroys the one-way valves in your veins. And so tissues have fluid buildup. There's other helminths besides that particular one from pythons that can get into the human central nervous system or ones that can destroy your liver or your kidneys or they're Strongyloides that can live inside your gut for a while. And then if you become immune compromised with a long course of steroids, they can start multiplying inside your gut and lead to full body paralysis. So there are a lot of bad guys. I haven't heard of that case. It sounds horrible.

Nirala Jacobi:

Well, she completely recovered the moment she woke up, she was just like, "Wow, I'm all better now."

Mark Davis:

I'm glad you told me.

Nirala Jacobi:

But they actually showed this live worm, the neurologist, she was all freaked out. But anyways, let's end on a good note with the helminth-

Mark Davis:

Great. Yeah.

Nirala Jacobi:

... that these four organisms that you mentioned really have some benefit-

Mark Davis:

Very safe.

Nirala Jacobi:

... and are very safe to use in these different conditions.

Mark Davis:

Yes.

Nirala Jacobi:

Now, let's veer into what you alluded in terms of what you suspect is that maybe, or maybe I'm just paraphrasing for you, but what I heard is that potentially the people that get more benefit from helminthic therapy are those that may have more of a robust sort of microbiome or perhaps more diversity or more interactions, more things happening that potentiate the effects of these helminths. Is that correct?

Mark Davis:

Yes, at least in certain circumstances. Yeah, I've used helminthic therapy and fecal microbiota transplantation together in the same patients, one and then the other, the other and then one or both at the same time a number of times. And I've definitely seen, I have three cases of inflammatory bowel disease who would get better with helminths and then relapse some months later, 4, 6, 8 months later. And that would happen multiple times. We'd give helminths again and they'd get better again. Oh, I'm sorry, wrong way, wrong way. People would give FMT too, and they would get better in last 4, 6, 8 months, and then they would relapse. And that's not that long.

But then we would give helminths and they would be the master controllers of the ecosystem, and the helminths would create an overall environment that would allow the fecal bacteria, the healthy ones we were giving with FMT to linger for a much longer time. And then they were essentially in remission as long as I followed them for years. So that's a case of helminths making FMT more effective. And I also have other cases of the reverse of FMT making helminthic therapy more effective. So they can be a great combination and also each used individually.

Nirala Jacobi:

I mean, you're an IBD specialist, what other conditions would you consider FMT for? Because I get that question a lot from my patients that I see and many of my practitioners that are listening see a lot of patients that have a lot of reactions, a lot of MCAS out there, a lot of intolerances, and it's beyond SIBO. SIBO is not something that I would necessarily say is in that category where I would say, all right, we're going to consider FMT, but more people that really have these severe sensitivities.

Mark Davis:

Okay, yeah. So it is pretty... Well, so of course, the most evidence supported indication is C. diff colitis. It's basically a magic bullet. And C. diff kills tens of thousands of people every year just in the United States, and FMT can reverse it pretty much every time. So I mostly work like most naturopathic doctors with chronic disease, not acute emergent disease, so I often am very proud when I can restore somebody's quality of life. But it's not usual that I'm saying, oh, I saved someone's life. But there have been people with elderly people with very severe C. diff colitis who was completely antibiotic resistant that I have turned around with FMT, and I think I may have seen some lies with that. So I cannot be remiss and not mention that indication because it is amazing. And also, you don't need a superstar donor to have an amazing, perfect microbiome to do it.

You basically just have to not have C. diff for the most part, or be hugely susceptible to it. I've had people say, "Oh, I want to use my sibling as my donor or my parent." And it's someone who eats a standard American diet and is not particularly healthy, and it still cures C. diff, really great. Ulcerative colitis and Crohn's disease, especially Crohn's colitis, I won't dive too deep into the numbers and get all wonky, but basically the trials we have indicate that it is more effective at inducing clinical remission than the biologic drugs that costs upwards of $10,000 a month and have small but real risks of serious adverse events. So very, very effective and helpful for many people with ulcerative colitis and Crohn's disease. Fascinatingly, for a long time, so you can do... I've done FMT largely through enemas, but also through capsules.

I've worked with hundreds of people doing FMT capsules, and for a long time I said, "Look, if you have a risk of SIBO or we currently find SIBO in you, we shouldn't give FMT because we're just adding to the overgrowth burden in the small bowel because some of those capsules do open up in the small bowel." And I said that for years and years, even though it was only a theoretical risk, I had it in my informed consent form, would verbally warn people against it and say, "It's just my opinion based on theory." Well, then there was a Chinese trial sometime in the last five years where they intentionally gave FMT via the upper GI to people with IBS and breath test showing SIBO, hydrogen and/or methane SIBO.

And there was statistically significant improvement in the symptom picture and in the SIBO from giving upper GI administered FMT. So I also don't rush to give it to people with SIBO and say, "Oh, let's do FMT," but really my big delight is it didn't make them worse, which I was afraid of for a long time. So it's still in my written informed consent, and I have to really remind myself that we have some published data now and I shouldn't scare people off of it, even though I sometimes forget FMT. So, that's an interesting one.

Nirala Jacobi:

Yeah, that's still doing my head in a little bit.

Mark Davis:

Blew my mind to hear that. Yeah, and I can send you all these references. I don't know if you post references for your listeners.

Nirala Jacobi:

Yeah.

Mark Davis:

Great.

Nirala Jacobi:

We can put references also the labs that you mentioned, if you want to share that information where people can get more information about helminthic therapy.

Mark Davis:

Great. Great. Yeah, I didn't even mention...

Nirala Jacobi:

[inaudible 00:48:03] of a massive spider.

Mark Davis:

Oh, dear.

Nirala Jacobi:

Just crawling around. That's okay. You get used to it in the countryside. I have to just put my feet up.

Mark Davis:

Hashtag awesome life.

Nirala Jacobi:

Yeah, for sure, for sure.

Mark Davis:

Yeah. Yeah. I didn't even mention my favorite company, symmbio.com, S like Sam, Y-M-M-B-I-O.com. Not affiliated with them either, but that's who I send people to for Necator americanus. So what else? So FMT, there has been one trial published and one trial that's pre-publication awaiting peer review, and a third one that's being conducted on children and adults with autism spectrum disorder and digestive complaints. And what both of the trials so far that have collected all the data have found is statistically significant improvements in the neuropsychosocial aspects of autism as well as the digestive complaints that these subjects in the studies experienced. And there was an initial trial in kids with, I think, it was a two-year follow-up that basically found the benefits they'd gotten had not only remained, but actually continued to improve.

And they haven't done a long follow-up with the adults, but similar results with the adults. So that is amazing. Blows my mind. There's fascinating data in mice and there's ways to make mice alcoholic, I guess, and they can press a lever for water or for alcohol, and the alcoholic mice will press the one for alcohol a lot, and you give them FMT from non-alcoholic mice, and they start pressing the water one more. And there have been two or three trials now in humans with acute hepatitis induced by ethanol over consumption by alcoholism, and acute hepatitis can kill you. So they found statistically significant decreases in mortality rates from acute hepatitis. That's how much it can help the liver. I've been obsessed with this lately. If you're familiar with hepatic encephalopathy, that is the process where damage to the liver from alcohol or viral hepatitis or other things makes the liver less able to filter out and detoxify ammonia.

Ammonia comes from the microbiome, especially a dysbiotic microbiome. And so if you have a dysbiotic microbiome and an impaired liver, then ammonia gets into circulation, goes through the blood-brain barrier and causes encephalopathy or brain problems, which can be irritability and mood disorders, it can be insomnia, it can be seizures and tremors and all sorts of huge variety of neurological problems. And a great trial randomized 10 20 men with hepatitis, they were in the VA to either get standard of care, which is rifaximin and lactulose, which themselves are affecting the microbiome, or standard of care plus FMT, and dramatic, dramatic differences and statistically significant differences in cognitive improvement and lack of occurrence and other things like that.

And I get so excited about that in part because I think a lot of us are dealing with patients who have a somewhat dysbiotic microbiome and a somewhat impaired liver and some degree of brain fog or mild cognitive impairment or other neurological things. And it's all mild dysbiosis, mild hepatic impairment, mild cognitive impairment. But I think there is often a connection and restoring the microbiome through probiotics and diet. And yes, sometimes in my patient base, even FMT can provide real great boost to liver function and central nervous system function. Thoughts about that one?

Nirala Jacobi:

Fascinating. Yeah, I mean, I think FMT, the way it's going, it is really I think a whole new frontier of microbiome restoration that in a few years time I think will be much bigger than it is now. Which one of what was starting here in Australia, of course, was the centers of digestive diseases in Sydney. And Dr. Borody was a pioneer of this work. And what they do is they do three months of complete annihilation of everything before they put the donor feces in the FMT. Is that what you do as well, or is that what you're planning to do?

Mark Davis:

No. No. So I started out everything I learned about FMT initially, I learned from reading Dr. Borody's 2004, 2005, I forget the exact years publications where he treated patients with IBD. He treated patients with IBS, and he treated patients with chronic fatigue, and he had had great outcomes. And I said, "I want outcomes like that too. I'm going to copy what he did." And this was when I was a student. And I would email his office in Sydney and try calling. And he was always too busy to talk. And then I was a young grad, a newly practicing naturopathic doctor, and I was writing an article for one of our naturopathic journals, and I called the office and I said, "Hey, I'm writing an article about FMT, could I have a word with Dr. Borody?" And that got them interested, and they did get him on the phone and we chatted.

And after that, we would email from time to time. And he even sent some patients who were from the US to me for aftercare, and I would manage them. So at the time I said, "Well, Dr. Borody, in your papers, you give big doses of Flagyl and Vancomycin and Rifampin orally to all your patients. What about the patients in your practice who decline those antibiotics? Do any of them ever have good outcomes?" And he said, "Oh, by the time they get to me, they're so desperate they'll do anything I tell them to, I've never had somebody refuse the antibiotics." So I thought, okay, we don't know then if they're very important, somewhat important or not important at all. And so then I started experimenting around and I would give his exact pre FMT antibiotic protocol to many people. I would give variations of it based on their own histories and their reactions to different antibiotics.

And sometimes I would give no antibiotics at all. And over the years, I gravitated towards, I use pre FMT antibiotics with almost no one. And I saw Dr. Borody at a conference in Chicago maybe five years ago or so, and I was giving a talk, and I asked the burning question. I said, "Look, I've been doing FMT with no antibiotics beforehand. I'm seeing some really great results. What do you think? What are you doing?" And he said, "Well, they probably aren't necessary, but I still give them to every patient before FMT." So he's a medical doctor. He probably barely knows my name, but he's really been a mentor to me, or in that, his work has really influenced me. And he was kind enough to reach out and support me when I had some questions. So I'm really, really, really grateful for his work. And at the same time, I disagree with him a little bit on that point.

Nirala Jacobi:

That's great. I'm really glad to hear that because that's, I think, the sticking point for a lot of people that I see. And there are cases that I've seen that have failed FMT and are still... So it's not the panacea for every possible thing.

Mark Davis:

Oh, no. No.

Nirala Jacobi:

But I do think it offers some great possibilities for people that have nowhere else to turn. So tell us, in closing, I want to hear all about your new ventures in Panama, this new clinic that you're opening up.

Mark Davis:

Yeah. So the website is biomebridge.com. My partner in Panama is a medical doctor, a pediatrician, and he's Panamanian and he says, "Panama is like a bridge between the worlds." It's between North and South America, and people fly there for different... It's like a bridge. And we wanted to be a bridge between essentially an unhealthy microbiome and a healthy one. So it's biomebridge.com, and we're trying to make it an available treatment in a hospital setting in Panama. There's a fair amount of medical tourism in Panama and great, great hospitals there. I've been there several times now and toured some of the excellent hospitals there. And I'm very, very impressed. And I'm looking forward to a time when we can work with people, for example, who might need sedation or colonic administration or other things that collaborating in a hospital environment can provide even what I've done with enemas and capsules over the past decade.

If we could just do that, I would be so happy. But we're moving towards this other opportunity. People can find out more at biomebridge.com. And I, in my obsession with the microbiome, am doing another project too, working with a naturopathic doctor and midwife, women's health expert colleague of mine, Dr. Ashley Long in Portland, Oregon. We are starting a vaginal microbiota transplantation lab where we have vaginal microbiome donors who we have screened very carefully, and we're collecting the microbe rich vaginal fluid that's normally produced overnight and processing that with a centrifusion concentrating it. And we will hopefully in 2024 be administering that to women with bacterial vaginosis and endometriosis and other conditions. So my microbiome obsession continues beyond just stool.

Nirala Jacobi:

Wow. I'm so impressed, Mark. It's so wonderful that you still have that passion that you've always had for the microbiome. And even after a year of sabbatical, you've come off newly reinvigorated. So that's really wonderful. I really look forward to seeing what successes you have with these two ventures.

Mark Davis:

Thank you. And of course, I am off sabbatical now, I should mention that too. The clinic where I work is Capital Integrative Health, and we're at cihealth.org, and I do visits with people in the four states where I'm licensed, California, Oregon, Maryland, and Washington DC, and then remote educational consults with people around the world, so people can book appointments there, too.

Nirala Jacobi:

Fabulous. And we're going to have that all in the show notes for people that want to get in touch with Dr. Davis, and yeah, FMT, I think keep us posted with all the amazing things that you come up with that. Thank you so much for your time.

Mark Davis:

Thank you.

Nirala Jacobi:

This has been fabulous. And I'm sure people, their minds are blown by all the possibilities that the microbiome work can offer.

Mark Davis:

It's a lot. Yes, and so happy to be here. Thank you so much for having me.