Healing Autism via Microbiota Transfer Therapy with Dr. James Adams

Hello everyone, this is your host Lindsey Parsons with The Perfect Stool: Understanding and Healing the Gut Microbiome. Today I'll be talking with Dr. James Adams, who is a president's professor at Arizona State University, and he leads the Autism/Asperger's research program and recently published a study called Long-Term Benefit of Microbiota Transfer Therapy on Autism Symptoms and Gut Microbiota. In the very prestigious journal Nature. And before we get to the conversation, if you would like to support the show, please visit HighDesertHealthCoaching.com and check out the supplements and lab tests area. I have an affiliate relationship with many products and companies that I believe in, so if you order through my links, you can support my work in sharing this great information on gut health with you at no additional cost to you. And also, please subscribe to my email list there, or follow me on Facebook at High Desert Health, or Twitter at @HDesertHealth, or Instagram um, at hi.desert.health. Also, if you like the show and you're on iTunes, please give me a quick rating there. And if you can share it with one person who you know has gut issues, that would be awesome. Or maybe just throw it up on your social media, because 10 to 15% of American adults are believed to have the symptoms of IBS, but many go undiagnosed and they just suffer silently because of the stigma of GI issues. I'm trying to bring these issues to light because, as the book I used to read to my kids is called, everybody poops. Now on to the show, and don't forget to press subscribe.

Hi, Dr. Adams.

Thanks so much for coming on the podcast.

Thanks so much for having me.

Yeah, my pleasure.

So can we start by having you define for our listeners what autism is and what the diagnostic criteria are for autism and maybe how it differs from Asperger's?

Sure.

Autism, it basically involves 3 primary challenges. It involves speech and communication challenges. It involves challenges in social interaction. It involves repetitive behaviors and limited interests. So autism basically involves these 3 core features. Nowadays, we also use the term autism spectrum disorders to describe the broader category of autism. And Asperger's is an older term we don't necessarily still use anymore, but it's basically for people who don't have as much language impairment and are perhaps a bit higher functioning.

But they're essentially the same— same condition on a spectrum.

They're part of the same general category. They share this core issue of social challenges, challenges with understanding social interactions, and also often have these restricted interests and these stereotypic or repetitive behaviors.

Meaning that there's one or several things that interest a person with autism And they tend to focus on those things exclusively?

That's right. So for example, one person I know seems at first to be a person who's relatively high functioning, but you notice after they've spoken to you for 20 minutes about the American flag and the glories of the American flag and how Betsy Ross first made the first American flag, and after they've talked at you for 20 minutes, you realize they don't really understand back and forth social conversation.

Got it.

Okay, and how long have we known about autism spectrum disorders, or have they been named?

Uh, approximately since the 1940s. Leo Kanner was the person who popularized the term back then based on a small number of individuals he identified.

Mm-hmm. And what is thought to be the cause of it?

Well, it's very complex. We know that it's partly genetic and that it's partly environmental. So if a family has a child with autism, there's about a 17% chance that other children they have may also develop autism. In a few cases, there's a single gene that can go wrong, and that accounts for about 10 to 20% of cases. So there are many single gene disorders like Fragile X, which might affect up to 1% of people with autism. Altogether, those single gene disorders account for about 10 to 20% of cases of autism. About 80 to 90% of cases are not related to a single gene but involve a complex interaction of hundreds of genes as well as many complex environmental factors.

And what are the environmental factors?

We're still trying to determine what many of those are. One of the most important ones is low folic acid during the first couple months of pregnancy. If women take folic acid during the first 2 months of pregnancy, they have reduced the risk of autism by about 40%. Another major risk factor is low iron. Many women start their pregnancies with low iron. Iron levels go even lower during pregnancy. If a woman has low iron, they have about twice the chance of developing autism.

Oh, okay.

And is there any relationship between C-sections and autism?

Uh, there's certainly a concern about them. In general, probably not. However, in our research studies looking at gut bacteria in individuals with autism, we found that children with autism who developed gut bacteria were also much more likely to have been born by C-section, and that's important because you receive most of your normal microbiome from the mother during a normal vaginal birth.

And so you said that most of the children who had gut problems had, had been born by C-section.

That's right. In our study, it was— I forget the exact number— it was about 65% had been born by C-section. There were several other factors also that put them at high risk of GI problems. If you like, I can explain those.

Sure.

So there are 5 factors we found to be important for having a high risk of GI problems. You inherit most of your microbiome from the mother. One of the factors was the mothers of kids with autism were on lower fiber diets. Fiber is very important for healthy gut bacteria, and so the mothers had lower fiber intake, hence probably lower quality gut bacteria to begin with. Then being born by C-section, the children inherit less of their mother's gut bacteria. And then mother— the children with autism were nursed for a shorter period of time, and breast milk carries some very special, uh, components which help make a very healthy gut. And then the children with autism had a higher use of oral antibiotics, which again kill off much of your normal gut bacteria. And then they also had a slightly lower fiber intake like their mothers. So all 5 of those factors, um, it's no— not much of a surprise these children with autism developed chronic GI problems.

And as I understand, there are— there's a certain portion of children with autism that have GI problems and then another portion that do not. Is that correct?

Yes, about 30 to 50% of children with autism and adults with autism have chronic GI problems, typically chronic constipation, chronic diarrhea, or often alternating between the two, whereas over half of children with autism and adults with autism don't seem to have those chronic GI problems.

So would you postulate that there maybe are sort of— well, you already did say that there are certain genetic— certain amounts of autism can be explained by genetics. So do you believe there's sort of two different origins then? One is a genetic origin and the other might be a GI origin?

It's more complex than that because it's often a subtle change in your genetics makes you more vulnerable to something in the environment. And so with the role of folic acid, for example, there are certain genetic polymorphisms that if you have those and you— and your mother also has a lower folic acid intake, then you're at greater risk. So it's not one or the other, it's a combination of those.

Can you define a polymorphism?

A polymorphism means just a variant in someone's gene. It's not necessarily a defect, but it might make an enzyme slightly more or less active. And so people with a certain polymorphism may have lesser ability to convert folic acid into the active forms. So either lower level of folic acid, lower intake of folic acid, or a polymorphism that's not as good at converting folic acid into the active form— either of those could be a problem. And both of them together would be more likely to be a problem.

And do, do folic acid and iron interact with the gut microbiome, or are those two separate issues?

Those are somewhat separate issues and somewhat related. So with folic acid, and with many vitamins, your gut bacteria actually make some key vitamins in the gut. So your gut bacteria also can make folic acid to some extent. And so if you have lower intake of folic acid, or if you have fewer of the gut bacteria that help you make folic acid, either of those could be a problem, and together would be worse.

Mm-hmm. I—

iron is a bit different because the main role of iron is to carry oxygen throughout the body, uh, on the red blood cells. And the part of the body that uses the highest amount of oxygen is the brain. So that's why it's so important during pregnancy that women consume enough iron so that their child's developing brain gets the oxygen it needs for proper development. Low iron is one of the leading causes of intellectual disability, and now we know that low iron seems to approximately double the risk of having a child with autism. The child's brain just isn't getting enough oxygen.

So if we're thinking about prevention, probably the single most important thing is having women know as soon as they're pregnant to see the doctor and start getting on those prenatal vitamins, right?

Well, unfortunately it's too late because most women won't know they're pregnant until second month or so of pregnancy, or even— and they really need to be on it at conception. It's the first 2 months that are most important. So about half of pregnancies are planned, half are unplanned, And so we're really trying to encourage women to start a prenatal before they get pregnant so that way they have enough folic acid on board and also enough iron on board.

So it sounds like you give a prescription for birth control, you give a prescription for prenatal vitamins at the same time.

As soon as someone goes off the birth control, we want them on the prenatal.

Right.

Absolutely.

Right. But the implication to be, if they're sexually active, they should just be on the prenatal vitamins since, since half are unplanned, right?

Yes, yes.

Right, okay. So what is going on with the rates of autism? Is it on the rise?

Certainly the reported incidence of autism has been rising for many years. From 40 years ago, it was a few per 10,000, then a few, several per 10,000, and now then rates at 1 in 250, 1 in 100, now rates of 1 in 59. So the rates do seem to be going up. That's partly due to better awareness, better diagnosis, especially for the milder cases. But much of that increase seems to be real as well.

And to what do you attribute the increase?

That's a great question, and we wish we really knew what all the factors were. So we think that certainly folic acid is an issue. We certainly think that poor gut bacteria are an issue. We think Low iron is an issue. Certainly exposure to pesticides also— I didn't mention earlier, but that's also— that can be a significant risk factor. But which of these is primarily accounting for the rise is hard to say.

Any particular pesticide?

There are a number of pesticides that are used for agricultural purposes. Certainly there are concerns about Roundup. I think in general anything, almost any pesticide is probably a concern. So I think it's wise just for women to try to avoid chemical exposures, including pesticide exposures, as much as possible. And that of course also means eating organic foods, since otherwise you're getting your food with pesticides, right?

And, and would you say avoiding GMOs as well then, because they're more likely to have higher levels of Roundup, right?

We don't know for sure that the GMO itself is a problem, but because the genetic modifications are often to make the plants more resistant to pesticides, those GMOs often have more pesticides on them, and hence that's a concern by itself.

Right. Okay, so tell me what got you interested in researching autism in the first place.

Uh, it's very simple. I had a daughter who developed autism. I was diagnosed with autism at age 2 and a half, and I became very frustrated at the lack of understanding of the causes of autism, how to treat it, how to prevent it. And so I began just doing research on it and eventually switched all my research to focus on autism.

And what were you studying or what was your profession at that time?

I was a materials engineer. I was doing computational quantum chemistry. Oh. And so it was a very, very different area, but a lot of my background in chemistry and just the general engineering approach I think has helped me in guiding a lot of the research that we do. So we've certainly looked at exposures to toxic metals. That's certainly a concern. The exposures to lead, mercury, other toxic metals, certainly a concern for autism.

And so did you have to go back to school in order to study this?

I've certainly had to read many different articles, and, uh, so I'd say I was largely self-taught, but also attended many different conferences, worked with many colleagues, and then just began conducting studies and working with collaborators. And by now we've published over 40 papers on our research. Wow.

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Okay, so tell me about how you arrived at the idea of using fecal microbiota transplants as an intervention for autism.

Sure. There are many different factors that led to it. One of the most stunning papers is one in 2000, which found that if you gave children with autism a special antibiotic called vancomycin, which only acts in the gut, it's not absorbed into the rest of the body, when they took that for a long period, 8 weeks— these are children with autism who also had severe GI problems— soon cleared their GI problems and also greatly reduced their autism symptoms. But the tragedy was that when they stopped treating, within a few weeks those benefits were lost. And so that made me very interested in trying to figure out how could we better develop a longer-term treatment and really had us focus on looking at gut bacteria at that point. Then we did another study in which we sampled gut bacteria and also looked at gut severity at the same time and looked at autism severity. We were surprised to find that the children who had GI problems also had significantly worse autism symptoms across the board. They had worse language, worse social interaction, worse behaviors, and worse cognitive problems, more sensory problems. This is very, very stunning because it suggested that if we could treat those GI problems, we might be able to reduce those autism symptoms. So then I worked with a collaborator at ASU. We worked with a new technology, a DNA-based technology, where we could measure levels of hundreds of different bacteria. And as we suspected, we found that there's a normal person might have about 1,000 different species of gut bacteria. Kids with autism were missing about 25% of types of gut bacteria. They were missing hundreds of species. And so this, in general, we know that the— when you have fewer species of gut bacteria, then that's generally a sign of a less healthy gut. And so that was what got us thinking maybe what was happening was that this, the vancomycin I mentioned, was able to kill off harmful bacteria, but then there weren't enough healthy bacteria left to keep the bad bacteria from returning. A good analogy is having a garden filled with weeds. If you, if you just pull all the weeds but don't do anything, those weeds are going to come back. So we wanted to pull all the weeds by giving the antibiotic to kill off the bad bacteria and then replant with beneficial bacteria.

And were there certain phyla that were missing or notable species that you think are important?

We analyzed levels of hundreds of different species, and there's really one that stood out, and that's Prevotella. And what was very interesting about Prevotella, it's a bacteria that primarily— it's one of the major fiber consumers in the gut. So it helps the body digest fiber. We discovered that in people on healthy Aboriginal diets, very high fiber diets, very healthy diets with minimal GI problems, half of these people's bacteria were Prevotella. Whereas when we looked in the same study, they looked at Western Europeans, less than 1/10 of 1% of their gut bacteria was Prevotella. They, they had 500 times lower levels of Prevotella than the Western Europeans, and also we found in the Americans. And kids with autism had even lower levels than the typical Americans, about 10 times lower. So this just seems like a very important bacteria because consuming fiber makes short-chain fatty acids that are the main food for the colon, that without fiber, the cells that line your colon will become sick and will begin consuming themselves and just dying.

And is this a particular kind of fiber, or is any kind of fiber equally good?

We don't know for sure which types of fiber are most important, so in general we just recommend the sort of fiber you get from whole foods and whole vegetables. So for example, eating an orange you get lots of fiber. Drinking a glass of orange juice, you get very little or none if you remove the pulp.

Okay. And so tell me about the first study where you used FMT as an intervention.

So what we did is we treated 18 children with autism. These were children we discovered who had all had chronic GI problems since infancy, and they were now between the ages of 7 and 16 years old. And we treated them with this antibiotic vancomycin to first kill off harmful bacteria. And then we gave them a bowel cleanse, just like you'd have for a colonoscopy, to really remove any remaining stool or bacteria in their gut. And then we gave them a very high dose of microbiota from very healthy, carefully screened donors, and then a low maintenance dose every day for 8 weeks. This is very extreme case of fecal transplant, much more intensive than is normally done, but it slowly, gradually worked. It took about 5 weeks, but after about 5 weeks, GI problems began improving, and by 10 weeks, autism symptoms had significantly improved as well. So by the end of treatment, 80% reduction in GI symptoms, 25% reduction in autism symptoms. I think this is an open-label study, so there's some placebo effect. But we were just thrilled. This was just huge and very exciting to us.

Yeah.

So we celebrated then. We published our first paper. We thought we were done. And then a year later, family came up to me and said, Professor Adams, my son's doing better than ever. So that's very interesting. And then a second family and a third family came up and said the same thing. And so then we decided to do something that's very unusual in science, and that's to do a long-term follow-up. So we followed up with every one of the 18 families who had been in our original study, and 2 years later we asked them how they were doing, and we evaluated them with our professional evaluators. We found most of the GI improvements remained. There'd been a little loss of benefit, but not much. But the autism symptoms— family after family just said their child had slowly, steadily began learning new language, new social interactions, and was beginning to catch up to their peers. And our professional evaluator said that now there was about a 47% decrease in autism symptoms compared to the start of the study, which is huge.

That's amazing. And what— can you talk a little bit about the connection between the gut and the brain?

It's a very, very complex interaction between the gut and the brain. Part of it is just, we think, that removing the great pain and discomfort that many of these children had had. Imagine if you'd been constipated and unable to poop for a week, and then imagine that had been the case for many years, that there's just a lot of bloating, gas, discomfort. And so just relieving that alone, leaving that pain and discomfort, is going to make it a lot easier for you to learn. You're going to be a lot less irritable. You're going to have a lot less anxiety. And some of these kids at age 15 were in diapers. And so, you know, having control over your bowels is such a great improvement in gut health. And we think that alone has some benefit. The children concentrate better, learn better. They want to be more social. They're just happier. But part of it too is that we know that the normal gut bacteria produce key vitamins that can help benefit. But also, we— there are now 5 studies showing that there's a particular class of bad bacteria that are very common in kids with autism that produce some nasty toxins. So by removing those toxins— and these toxins affect both the gut, but they also go to the brain and disrupt brain function. So by eliminating these bad bacteria, we're able to reduce the toxins getting to the brain. So we think that's important as well. And yet another issue is that many studies have shown kids with autism often have what's called a leaky gut. The cells that line their gut are so damaged, there's not a very tight seal. So what's in the gut, the partly digested food and the waste, can leak out into the rest of the body. And that makes the immune system go after it. It recognizes these partly digested foods shouldn't be in the body, and so it launches an immune attack against it. So we think that's disrupting the immune system, and we think by normalizing gut health, we are helping to normalize the immune system as well. So it's very complex. The gut bacteria also make neurotransmitters that can play an important role. So many different avenues of effect.

Okay. And so you mentioned a bad bacteria that was a problem. What was that?

Um, there are 5 studies that show that there's a class of bacteria called Clostridia. Some of these are beneficial, but some of them are very harmful. One example of a very harmful one is C. difficile. It affects half a million Americans a year. Causes life-threatening explosive diarrhea, actually kills 29,000 Americans a year. So it's one example of the types of bad gut bacteria that kids with autism can have in their gut for many years.

So I was under the impression that if you had low levels of C. difficile, it was not a— it was not an issue. But you're saying that even at low levels, it was doing some damage?

That, yeah, these children did not have the level of a C. diff infection causing life-threatening explosive diarrhea, but they had increased levels compared to the general population. So it seems it's not just one bacteria, it seems it's just a plethora of bad bacteria, several different types of C. diff depending on the person, probably depending on the food they're eating and what they're exposed to.

And what are some of the beneficial Clostridia?

There are quite a range of different beneficial Clostridia, and I, I think the simplest thing to say is that they don't produce these toxins, and hence they can help prevent the overgrowth of the pathogenic Clostridia. So they can help with digesting food, etc.

And tell me a little bit more about the material that— for the fecal transplants.

So we worked originally with a group out of University of Minnesota. They developed a method to take raw stool from humans because raw stool, 50% of it roughly, is live gut bacteria. And so they developed a method to purify that, to remove all the waste material. So it's 99% plus just gut bacteria, like a probiotic pill. And then also test it and test the donors very carefully, just like you would for an American Red Cross blood donor. They use that testing criteria and a lot more, checking that the person is in good GI health, etc., testing for any presence of any bad infectious bacteria, and then they purify it and then freeze-dried it, and then we're able to use that for a treatment study.

And you mentioned that it was oral. I assume children, young children, can't take pills, so how were you administering that?

Oral?

So in our first study, the first dose, the children— families were given a choice. They could either do it via a rectal enema, or they could just swallow it and mixed in a drink. And some of them, 12 of them, chose to drink it. 6 of them chose to take it as a rectal enema. And then the maintenance dose that we gave them every day was a much lower dose. They just took in a liquid. They just drank it straight down. It was perfectly odorless and tasteless.

Okay, so quite purified.

Very purified.

Okay.

And we also had to give them a stomach acid suppressant because otherwise the stomach acid would kill off all these beneficial bacteria.

Okay. So did you have them take it like at night when they had finished eating or?

We had them take it— it was up to them when during the day they wanted to take it. That was a matter of convenience for them, but we just always had them take it with a stomach acid suppressant so that way the bacteria could survive the stomach acid.

Okay. And do you think that there were other factors involved in the improvements with the subjects during those 2 years? For example, were there diet changes? Were there medications they took?

Yeah, so during the first 10 weeks of our study, the families were very good. They knew not to make any changes in diets, medications, supplements— not in any of those. After the study stopped, it was up to them, and some of them did make changes over the next 2 years. And so in our paper, we list what are the families— and some families did make some changes, mostly minor, but in almost all cases, the families felt that the changes they observed over those 2 years were due to the original microbiota therapy and not due to other treatments that they were doing. Can't say for sure, but that was what the parents felt, was our impression from talking with them.

So in the paper, I noticed that there was one family that put their child on a ketogenic diet, and they marked that as the highest level of, of impact that they felt. Have you looked at that as an intervention?

We're certainly aware of the ketogenic diet and have done some research on it. It's certainly an interesting diet. It's been used for many years primarily for treating epilepsy. Uh, there is one study of it being used for children with autism, and certainly I know many children with autism who are using it. The challenge with the ketogenic diet is a very difficult diet to maintain. You're eating just very high levels of fat things like a stick of butter, and, and we worry very much about the low amounts of fruits and vegetables that are allowed on it. So short-term, very clearly helps with seizure issues in many, not all cases, but very hard to maintain long-term.

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So thinking about the FMT material that you were using, What is, what is going on with that in terms of its availability, you know, in terms of future studies and getting it available to the general public?

Right. The FDA has classified FMT as a drug, just like it's classified blood as a drug. And so it needs to go through Phase 1, Phase 2, Phase 3 trials before it can be approved and available to the general public. So right now, the FDA is only allowing FMT to be FMT to be done for people with life-threatening C. diff infections that are resistant to standard treatment. So it's very restrictive. So we completed our Phase 1 study showing it was safe and seemingly effective. The FDA, based on that, awarded us fast-track status, and now we're doing a Phase 2 study, randomized double-blind placebo-controlled. If that goes well, then we can do a Phase 3, which is just a much larger study, maybe 10 to 20 sites, 500 to 1,000 people. And then if that goes well, then we can apply for FDA approval, and then it could become available to the general public. But it will take quite a few years and probably $50 to $100 million.

And so what is— you said you're already on that second study?

That's right.

Are you enrolling for it, or is it already underway?

It's already underway. We've already treated 18 adults and we're scheduled to treat a total of 84. And so we have still a number of slots left. We have about— we have a number of children, number of adults who are waiting for the next batch, and then we've received about 300 applications for the remaining 50 slots.

Okay, so is it still open for people to apply, or at this point it's—

technically yes, but because we're going to review applications in chronological order It's unlikely that we'll be admitting anyone who applies past today.

Okay, so that's a study of adults though, not children.

That's a study for adults, that's right. We are hoping to do another study for children. We've received many requests from families to do that. We thought previously we had funding to do that. That funding source fell through. So now, based on families' requests, probably in a week from now, we're going to launch a GoFundMe campaign. Because many families have asked to donate to help us just start the study.

Great. Well, if you want to send me that website, I'll— when this is published, I'll get it up on the show notes.

Thank you very much.

Yeah, I'm sure that many of our listeners would love to support your work.

We would appreciate that very much.

And so I had heard that there was a death from FMT involving E. coli and that the FDA had halted studies using FMT. Can you tell me if that's impacted your work at all?

Yeah, so about 3 weeks ago, the FDA made an announcement, and we received a letter directly from them also, reporting on this very sad case of 2 people who became very ill and one of whom actually died. These were 2 people who were— both had a compromised immune system. We don't know the details, but their immune system was weakened, and they both received a fecal transplant from the same donor. And that donor had a type of bacteria that's resistant to multiple drugs. It's a very dangerous bacteria. Apparently it wasn't affecting the donor. They presumably had a healthy, normal immune system. But the recipients of that donation, unfortunately, both became very ill and one died from it. And so we already— so the FDA issued a warning letter to everyone doing these types of treatments, warning them, requiring them to institute testing for these drug-resistant bacteria and to confirm that with them. Turns out that our collaborators had already test for that and actually already exceed the requirements that the FDA is now asking other groups to impose. So it just took us to write a letter, which we sent off to the FDA, explaining that we already meet these criteria, but then we're changing our consent forms just to inform families about this very sad incident and letting them know that there is some risk.

Now, when you compare this to other treatment options and, and risks, how would you, how would you rate this kind of risk versus, you know, other clinical trials?

It's probably complicated to ask because it depends so much on the type of study that's been done. But I'd say in general, aside from these two cases, all the other cases I'm aware of have been generally very minor, mild reactions. We had no reactions to the microbiota transplant in our study. Children all tolerated it very well. And so because we're just restoring the body's normal gut bacteria, you, you wouldn't expect, and we didn't observe, any changes in liver or kidney kidney function, whereas a lot of drugs that you give, that's one of the first things you check for, is can the body tolerate them, can the liver and kidneys detoxify and excrete these drugs. So in that sense, I think it's certainly safer.

And were all of your recipients getting, uh, donations from the same donor?

That's something special that we did in our study. We used one donor for the initial dose and one donor for the maintenance dose. And the reason for that is that one donor may have this thousand species of beneficial— species of beneficial bacteria, another donor may have this thousand species. Together, uh, you may have, for example, maybe 1,300 beneficial species. So when we looked at the children with autism at the start of the study, they had lower numbers of species of gut bacteria. At the end of treatment, it had normalized. 2 years later, it was better than normal. Their gut bacteria was better than that of typical children. So it was very, very encouraging and makes us think the treatment's going to be very long-lasting.

Wonderful. And who is the commercial entity that's, that's creating these, these samples?

So we worked with— I mentioned a group, University of Minnesota which then licensed their patents to a company called Finch Therapeutics. And so we've worked closely with Finch on our study.

And I think I just noticed an article about the CEO of Finch Therapeutics that he has some relationship with OpenBiome as well.

That's right, that he actually started OpenBiome, which is a nonprofit which works on distributing stool donations to donors. It's like a blood bank. They collect stool donations and use them for C. diff— for treating people with C. Infections. But in order to get this classified as a drug by the FDA, in order to get it approved as a drug by the FDA, they had to start a for-profit arm, which is Finch Therapeutics, so they could then attract venture capital. They can get the money invested in them. They can then do these major research studies to really prove that the treatment works and to bring it to the general public.

But what OpenBiome is supplying for FMT used for C. diff is actual fecal material. It's not the purified drug essentially that you were using.

That's right.

Okay. Do you know if they're moving towards everything towards this one product then and phasing out the fecal donation samples essentially?

I'm going to have to say no comment because I have signed nondisclosure agreements with them.

Okay.

Fair enough.

So thinking about your future study with children, I'm sure we have a lot of listeners who might be interested in trying to enroll their child in that study. What would they— how would they go about doing that?

So on our website, which is autism.asu.edu, we have a contact list. So if people want to be contacted about a future child study when we're able to officially advertise it, they can go there and just give us their email address and and then we will contact them when the study is open. We hope we'll have FDA approval for it in a few months, but really it will just be a question of raising the funding for us to do it. It's very expensive to do these types of studies. It'll probably cost us about $1 million to treat 50 children, but that's the sort of investment that has to be made to get a drug past FDA approval.

Okay, so in the meantime I'm sure there's a lot of parents out there who are just anxious to, to intervene for their children right now. What would you recommend for those people?

Well, we recommend that they wait. Again, there was this very sad case of two children who became— two individuals who became very sick, with one dying because the donor wasn't properly tested. And so I think it's important to wait. This is a very promising treatment, But we still have a lot to learn about how to make it better and how to make it safer. And so I know it's frustrating to have to wait for several years or more for FDA approval, but in the meantime, there are other treatments that are available. We did a study on nutritional interventions for autism, and we found many of the same types of benefits as we found for a microbiota transplant study. It's not as effective, so it was only about a 30% reduction in GI problems. But those treatments are available today. And so at least there's something to start with that may help some children, and I think we just need to wait for the research studies to become available.

And they can find that study on your website?

That's right. That's right. I guess I should also clarify that fecal transplant is not legal to do in the US, except for people with recurrent life-threatening C. diff infection. So this isn't something you can go to your doctor and ask to be treated for. They won't— they aren't legally allowed to treat children with autism until we get FDA approval.

But back to the, the other interventions, there is a summary on your website for parents. Is that, is that right?

Oh yes, I'm sorry. So, um, we formed a nonprofit called the Autism Nutrition Research Center, and if you go there, we have a protocol there for families that recomm— that describes in great detail 4 major nutritional interventions we recommend. And that website is autismn4nutritionr4researchc4center.org.

Oh, great. And can you summarize briefly what those interventions are?

We, in our research study, we looked at 6 interventions. The 4 that we think are the most important, the first one is the vitamin mineral supplement we developed for children with autism. Second is fish oil. Third is carnitine. And then fourth is a healthy, allergen-free diet. And so we think that those four interventions are going to help most children with autism, children and adults with autism. For example, in our study, 12-month study, over 12 months, the treatment group gained 7 points of IQ, the non-treatment group, their IQ didn't change. So that alone is huge. Over 12 months of development, the non-treatment group gained 4 months of development. They're developmentally delayed, so they're making progress, just slower rate. The treatment group gained 18 months of development over 12 months. They began catching up to their peers.

Wow.

So we think these nutritional interventions are very important And again, vitamin mineral supplement includes some of the vitamins that your gut bacteria would normally be making. And so until we can get fecal transplant, it's again a great option for people.

And you mentioned an allergen-free diet. Which allergens?

The allergens that are the biggest problem for people with autism seem to be dairy products and gluten-based products— wheat, rye, barley, oats. And then also soy is a concern since 80 to 90% of soy in the U.S. is GMO.

So in a way you're pulling out pesticides, in fact, by pulling out allergens.

Certainly by going after soy and corn, that helps. But going on an organic diet would certainly be recommended, but some families feel they can't afford that.

Right, right.

But yes, we certainly believe in trying to reduce pesticide exposure as much as possible.

And the fish oil, is there— does it need to be like super high in DHA or in EPA?

Yeah, DHA and EPA, the most important ones, the omega-3s, because most people get plenty of omega-6. And so for developing brain, for a mother who's pregnant, it's very important to have a fish oil that's rich in DHA. But for children and adults, EPA is more important, so we used an EPA-rich fish oil. Most people are underdosing— most of the research studies were underdosing, we believe, on the amount of fish oil, and they found only slight benefit. We used a higher dosage and seemed to get greater benefit.

So what dosage of EPA were you shooting for?

It depended on the age of the person, but of order 1 to 2 grams.

Okay. So a lot. Okay, great.

Yes.

Well, this has all been really interesting and exciting stuff, and I so look forward to seeing these future trials go forward into this becoming a drug and us maybe beginning to find a cure for autism in our generation.

Well, we certainly hope. We don't think it's necessarily going to be a cure, but it seems to greatly reduce GI and autism symptoms. So that alone, we're very hopeful. Helpful for.

Well, I imagine if, if the intervention starts early, then you can really impact a lot of developmental delays.

And it's very possible. We— our children in our study were age 7 to 16. We've asked the FDA to go to younger ages in future studies. And because, as you say, we think we may see even more benefit if we start at younger ages. Also, to realize this first study was our first guess about dosing and duration. It's kind of like if I told you to take aspirin, but I didn't know if you should take a quarter of an aspirin or 10 aspirin. We don't know how much to take for a headache. The same way, we don't know how much to take to treat GI problems. So we made a guess in our first study, it worked well, but as we now know more, we think we may be able to have even better results in our first study by having better dosing.

So do you think you'll have the— continue the, the oral FMT for longer, the maintenance dose?

We want to use both a higher dose and a longer dose, and we hope that that will be, be more effective. Think of it this way: since we saw zero adverse effects from the microbiota transplant itself, and we saw some good benefit, why not go to a higher dose? We're just giving more of the normal gut bacteria that should be in there to begin with.

And so if you were giving advice to someone who, you know, they heard they just had a baby and they think they can sense some risk factors based on what you just said, what recommendation would you make for that newly born baby?

Well, certainly some of the things to help them are nursing. That mother's milk contains a very special ingredient in it that really helps the gut bacteria in the infant stabilize and grow. So breastfeeding for as long as possible, up to a year or more, we think is very, very helpful. Secondly, trying to minimize use of oral antibiotics, especially for ear infections, where they're primarily used and they have very, very little benefit for ear infection. So only try using them for the most severe ear infections, um, I think would also be very helpful. So And again, that's consistent with general medical recommendations about overuse of antibiotics for children.

And what about probiotics for, for infants, especially born by a C-section?

Yeah, so when infants are born by C-section, there's a 50/50 chance they never get exposed to a crucial gut bacteria called B. infantis, named after the fact that it's the primary gut bacteria in infants. And that one bacteria is different from the hundreds of other gut bacteria. It's the only one that can consume this special ingredient in mother's milk. The infant can't consume it. No other bacteria can consume it, only B. infantis. And so when B. infantis is exposed to mother's milk, then it can grow and flourish, outcompete any bad bacteria, and establish a very healthy gut. And then when they are nursed, when they're weaned and no longer consuming mother's milk, then that gut bacteria normally just naturally decreases and other gut bacteria replace it. And soon, hopefully, you have a healthy near-adult-like microbiome.

So probiotics with B. infantis for a child born by C-section?

Yes, we think that would be very helpful.

And for how long?

As long as they are nursing, but especially important right after they're born.

Okay. And is there any danger?

I should say longer than that, because one of the issues that one— a woman, an infant is born by C-section, remember that means the mother has had surgery and is on antibiotics. So those antibiotics travel through mother's breast milk into the infant. And disrupt their gut bacteria. So you'd want to be taking B. infantis until well after the mother stops taking the antibiotics.

Right, so from birth through, through nursing, essentially, through— for time, like a year old, basically, if they're nursing that long.

I, I think that would make good sense. We don't have a research study to prove that that's beneficial, but based on all the, all the science that we've seen, it makes a lot of sense.

Okay, great. Well, this has been incredibly useful and interesting information, and I'm so glad I was able to talk with you. Thank you for coming on the show. Sure.

Thank you very much for having me.

Wow, that was a great conversation. So you can look in the show notes for all the links that we mentioned, including the articles that Dr. Adams has published on this topic. And before I let you go, I wanted to share a listener comment from Reddit on the show that I did with Saffron Cassidy, the filmmaker who is coming out with a documentary on FMT called Designer S-H-I-T. Don't wanna say it and have to label this episode explicit. The listener was called Sal Mo Nella and wrote, I really enjoy this episode. What I can't seem to marry up is the supposed success of Dr. Borody and the rest of the medical community. If his claims are accurate, why aren't we seeing this as first-line treatment? I really can't wait to see her interview with him. Are there any medical professionals that would comment on this? If the dude is literally putting people into remission for multiple chronic diseases, we should be building statues for him. But I don't know, from outside the medical community, it seems like they are snoozing on him. Also, having ongoing FMTs for years sounds like overkill, but maybe it must be an ongoing treatment if your genes cause functional issues that mean you'll continually regress into dysbiosis. I very much enjoy the podcast. Please keep it up. Well, thank you so much, Salmonella. Yeah, in the pre-interview conversation that I had with Saffron, we did talk about all the different people who she talked to and interviewed for the film, and different MDs, different researchers. And she said, you know, some of them were all hesitant, said, you know, this is very experimental, we can't make any definitive statements about its efficacy, don't try it at home, versus Dr. Baroti, who was much more helpful and open to experimentation. And I think it just comes down to some combination of of liability and personality. Some people and some doctors are just more cautious and are willing to take a, a 1 in 100 or 1 in 1,000 or 1 in 5,000 chance of potential harm given something that has a high possibility of working and turning your life around. And, and you know, as I've mentioned, some people are so desperate with their health that they're willing to do that. My hypothesis of why this isn't the first-line treatment in the US, FMT that is, is because of the yuck factor. You know, it's just, it's hard to, for a doctor probably to say to people, would you like to consider a fecal transplant? Also the lack of control over donors and the difficulty finding donors and fecal material, although now that's changed with OpenBiome and access to those samples and such. And then also once FD, the FDA classified FMT as a drug and limited its use, that pretty much hamstrung doctors in terms of using it for anything other than recurrent C. diff that wasn't treated by antibiotics. But that's not the case in Australia and the UK and Canada and the Bahamas and Argentina and many other places where you can go to clinics and get FMT. And so, you know, I think just in the US, we're such a litigious society, so I'm not surprised that, that people take a more cautious approach here. But I'm more of a health risk taker if I think something might make me better, which is one of the reasons that I share about FMT with you in this podcast. But anyway, if you have any questions about my interviews or gut health, please feel free to write me at Lindsey@highdeserthealthcoaching.com and be sure to include whether I can read your letter on the air. I love hearing from my listeners, so it'd be awesome to hear from some of you. And also don't forget about supporting the show through my affiliations. And thanks for listening. And here's wishing you all the perfect stool.