Microbiota Transplant Therapy: What Is It and How Can It Help Autism?

Episode Transcript

Dr. Nicole Beurkens: 

Hi everyone, welcome to the show. I am Dr. Nicole and today, we’re going to talk about a really cutting-edge topic in the world of autism and other neurodevelopmental disorders: Fecal transplant therapy. Some of you may have heard about this, but it wouldn’t surprise me if it’s a new topic for some of you, as it’s a relatively new medically-focused therapy for children and adults, it’s being used for a wide variety of purposes. And basically, what we’re talking about is transplanting the feces of a healthy donor into someone with a compromised or unhealthy gut microbiome with the goal of improving their gut microbiome and overall health and function.

And it may sound a little bizarre if you haven’t heard about it or learned about it before, but I really believe that this is cutting-edge medicine and something that is going to become a really valuable or even more commonly used tool to treat not only many physical disorders but also mental health issues and neurodevelopmental issues that we see in children in the years to come. So to help us understand this therapy better and to discuss his recent research on this topic and autism, I am thrilled to have as my guest today Dr. James Adams. Let me tell you a little bit about him. 

He is the director of the Autism/Asperger’s research program at Arizona State University, his research focuses on the medical causes of autism and how to treat and prevent it, including the areas of nutrition, oxidative stress, gut problems, gut bacteria, toxic metals, and seizures. He has published over 150 peer-reviewed scientific articles, including over 40 related to autism. He’s also the president of the Autism Society of Greater Phoenix, the president of the Autism Nutrition Research Center, the co-leader of the scientific advisory committee of the Autism Research Institute and chair of the Scientific Advisory Board of the Neurological Health Foundation. He also has an adult daughter with autism. Dr. Adams, thanks so much for being here, welcome to the show.

Dr. James Adams:

Thanks so much for having me. 

Dr. Nicole Beurkens: 

So I’m excited to dive into this because I think as I said, this is a new topic for lots of people and you’re on the cutting-edge of this, especially in autism. So let’s start out by just explaining to people who aren’t familiar with this type of therapy: What is it? How is this done? What is this fecal transplant therapy about?

Dr. James Adams:

It’s very much like taking a probiotic, except instead of taking a probiotic of a few strains of bacteria, we’re taking a probiotic developed from the gut of very healthy donors who have typically about a thousand different species of gut bacteria. Most gut bacteria are very good for you, they provide you many benefits, they produce key vitamins, they help digest your food, they help balance your water, they help promote motility and also they help prevent the overgrowth of bad bacteria. 

And so, what we do in our study is we investigated in a very intensive way the transfer of the microbiome from someone who is very healthy to someone with autism who has had chronic GI problems for years. What we do is we first pretreat with vancomycin — an antibiotic that kills off bad bacteria in the gut. We do that for two weeks because a previous study showed it was very beneficial at fighting the specific type of bacteria, and then what we did was we went ahead and then had them fast for half of a day and then did a bowel cleanse, just like you do for a colonoscopy. So really clear them out so there’s very little of their native gut bacteria still there and then we give a high dose of the gut bacteria from healthy donors and then low-maintenance dose every day for 7-8 weeks. What we’re actually giving is not raw stool as they use for some treatments, we actually work with the University of Minnesota, they developed a process to highly purify it and remove all the waste materials so it’s 99%, over 99% just gut bacteria just like a probiotic. 

Dr. Nicole Beurkens: 

So that’s why it’s called in the title of your study, ‘The Microbiota Transplant Therapy’ because really, you’re taking the actual microorganisms themselves and putting them in as compared to maybe the term that I used earlier, some people are familiar with, which is fecal transplant therapy where actually you are taking fecal matter and embedding that, right?

Dr. James Adams:

That’s right, and usually with fecal transplant, the approach if just to do one dose, one time for people with chronic C. Diff infections, which is a really nasty type of diarrhea. It affects half a million people in the US each year, kills 29,000 people. It is incredible. One dose, one time, you have a 90% cure rate for people who were literally dying from severe diarrhea. It can be treated with antibiotics but often it comes back again and again — when you treat it with C. Diff, not only is the cure almost immediate within a few days, it essentially never comes back. But we work with a gastroenterologist in Australia, Tom Borody who is a global expert in FMT, he has treated over 5000 people with FMT and he treated 9 children with autism and he found like with C.Diff, one dose, one time was enough — autism was much, much harder to treat.

You treat them every day for 3 months but within that, he was eventually able to greatly improve their GI symptoms, and to his surprise, the parents told him that the autism symptoms began improving too. The children were sleeping better, their language was better, they were better able to pay attention to what the families were saying. With his observations, his treatment, he then guided us in developing our own treatment, we did that phase 1 treatment study. And if you want me to talk about the outcome of that —

Dr. Nicole Beurkens: 

Yeah, I would love for you to. I want people to hear about what the potential benefits of this are. 

Dr. James Adams:

Yeah. So using this very intensive treatment therapy for two weeks of Vanco and the bowel cleanse and 7-8 weeks of a microbiota transplant, what we found is that after about 5 weeks, there was a good improvement in GI symptoms in almost all the patients. 80% reduction of GI symptoms. And these children, ages 7-16 had all had these GI problems since infancy. Chronic constipation, chronic diarrhea, sometimes alternating between the two. So they had these their whole lives and within 5 weeks, they were greatly improved or even cured of it. And then, their autism symptoms began improving a little bit later. So by the end of the study, there was about a 25% reduction in autism symptoms and we thought it was great, so we did an 8-week follow-up, checked to see that the results were stable, that the GI symptoms were stable 8 weeks after we stopped treatment.

The autism symptoms were stable 8 weeks after we stopped treatment. And even the gut diversity at the start of the study, the kids were missing several hundred species of bacteria, at the end of the study, they had a normal amount, a normal number of species of gut bacteria, so it all looked very good. So we stopped there, published our paper. And then a year later, three different families came up to me individually and said, “Professor Adams, my son’s doing better than ever.” After I heard that the third time, I said, “We need to investigate this.” 

And so we did another small study and followed up with all 18 of the families, that was one of the great things about it is that there were very minimal adverse effects, that all of the participants who started the study completed it and all were kind enough to be interviewed again two years later. A professional evaluated them and we found that most of the GI benefits had continued, it was still about a 60% percent reduction compared to before treatment, but really interestingly — Parent after parent said their child had just slowly gradually continued to improve. The evaluator said that on average, it was a 47% reduction in autism symptoms. At the start of the study, over 80% of our participants were severe autism and by the end of it, only — I forget the exact percentage, roughly 15% were severe. 40-something percent were mild to moderate and 40-something percent were below the cutoff for autism. So that was very exciting, this is an open-label study, with no placebo effect, much of the effect is real. When you’re counting the number of days someone has a bowel movement, it’s hard to have a placebo effect that is affecting your number of bowel movements, so it’s pretty hard data, you could say. 

Dr. Nicole Beurkens: 

It’s incredible outcomes and it really speaks to the power of the gut microbiome, right? I mean we talk about that a lot now — about how the gut is really so pivotal in all the symptoms that people experience whether it’s neurological symptoms, physical symptoms, but wow does this really speak to it, right? I mean here you did this treatment where you specifically went in and altered the gut microbiome and all of these changes in all these different aspects of functioning and that they continued over a period of time. 

Dr. James Adams:

Yeah, it was just very, very interesting and our best interpretation is that by improving their gut bacteria, we were now able to indirectly improve brain function. So now the children were able to learn better. So the treatment didn’t necessarily give them new words, we think it gave them a better ability to learn words, to learn social cues, to learn better behavior. Really interesting things about the study is that there had been a study 19 years ago that guided us where they gave vancomycin by itself.

That antibiotic by itself, they gave it for 8 weeks and they found by itself, it was able to greatly reduce GI symptoms over 8 weeks, over 8 weeks substantially improve autism symptoms but the issue was when they stopped treatment, then those benefits were lost in just a few weeks. So we think it was killing off the bad bacteria, but if they didn’t have the good bacteria to prevent the bad bacteria from growing back, they lost the benefits in a few weeks. In that study, they found right at the start that the first day or two of the antibiotic treatment, the kids got a little worse. They had increased activity — usually for just a day, sometimes a few days, then they got better.

In our study, we found the same thing, so the participants in the first few days had slightly worse irritability, slightly worse hyperactivity, usually for just a day or a few days and then they got better. We found out it was in the people who had the worst of those symptoms to begin with, so our interpretation is that they had more of the bacteria that were causing those problems, causing the irritability and hyperactivity. When you kill them off with the antibiotic, then those bacteria release all their toxins all at once, so you have a surge of the symptoms that they were causing. Once those bacteria are dead and gone, then you begin seeing improvements. So I think that’s a very good clue as to a big part of the problem with these pathogenic bacteria. 

Dr. Nicole Beurkens: 

It’s fascinating in that I like that you’re talking about sort of the historical precedent that you went off for this and then what I think is so great about what you’ve done with the two studies is that follow up piece that says, okay — this wasn’t just something that in the short-term, right after the weeks of transplant that we saw these benefits but actually well further down the road and not just that the benefits maintained but that for many of the symptoms that there continued to be improvement along the way, which I think is really that follow up is just great. 

Dr. James Adams:

We would have been just thrilled if the symptoms were stable at that point. To see that improvement was just really exciting. And so that’s one thing we’re very pleased about: There have been very few long-term studies of effects of microbiota transplant. There’s been one other for constipation it showed that benefits mostly remain a year later. It’s different for C. Diff infections, once you treat it, you pretty much never have it again. The hope is that these benefits will be long-term, though they may need a booster down the road, but so far, it looks very good. 

Dr. Nicole Beurkens: 

So this really differentiates this from what people think of with traditional probiotic therapy, where we’re taking a capsule or a powder or those types of things where I think, as you touched on a few minutes ago, there’s a real limit to the amount and the diversity of bacteria that we can get that way, right? I mean even in some of the most powerful probiotic supplements out there, you’re really not looking at being able to fit too many strains of bacteria in those products, whereas you are talking about the thousands of strains that we can populate through this transfer therapy.

So to me, that says why many kids and many people are on the probiotics lifelong. They have to keep taking them in order to have even minor benefit from them, but what you’re saying with the transplant therapy that it really seems to take hold and that the body is able to hold on to that. Is that just because once it gets in there then those good bacteria continue to replicate and because you’ve changed the entire environment of the gut that those good bacteria can thrive. Is that what’s happening there?

Dr. James Adams:

Yeah, so we think that’s a big part of it. Two of the major changes that we saw was that the daffodil Bifidobacterium went up four-fold after treatment, it was low in children with autism at the start, improved a fair bit after treatment. And Bifidobacterium is commonly used as a probiotic. But also, we saw a big increase — 80-200 fold increase in Prevotella, which is seen in healthy fiber-rich diets. And at the start of the study, the kids with autism had virtually none of it and it went up greatly. So other bacteria that probably changed as well — we need a larger study to see.

The bottom line as you say is that commercial probiotics are bacteria that grow in milk, in air, they only have typically 1-10 strains in them, we’re limited to what’s been grandfathered in and what grows in milk. What grows in the gut is very different. Your gut lacks oxygen so most of the bacteria there are anaerobe. So it has of order, about a thousand different species. Kids with autism are missing several hundred. One or two species doesn’t make a big difference when you’re missing several hundred.

And the complication is that one child might be missing this several hundred, this child might be missing this several hundred. What they all seemed to be missing, we found, was Prevotella and it went up 80-200 fold. It’s, I think, a big part of what’s going on — then also because we used very healthy donors. A key part of what we did was we had one donor for the initial high dose and a second donor for the maintenance dose. I think that’s very important because one healthy may have this 1000 healthy species, this healthy person may have this 1000 healthy species, they are somewhat different. When we add them together, we get more like 1300-1400 species. And in fact, when we looked at the kids with autism two years later, at the end of treatment, they had a normal level of bacteria. Two years later, they actually had substantially more bacteria and typically had a healthier level of bacteria. So we think that it looks very promising. It will be stable for years to come. 

Dr. Nicole Beurkens: 

And obviously, donor health is such a critical part of this, right? And you read things online and I see people talking about stuff and doing these kinds of things and finding donors — I know there is stuff out there on the internet, but really I think it’s so critical to stress that if you’re going to do this, the health of the donor, making sure that you’re transplanting from somebody that really has a diverse and healthy gut microbiome is really important, right?

Dr. James Adams:

Yeah, I think that’s extremely important because animal studies have shown a few transplants of bacteria from an unhealthy mouse can make the recipient unhealthy. What we use is a very rigorous screening process, a collaboration with the University of Minnesota. It’s so rigorous, 90% of the general population is screened out.

The American Gastroenterological Society has certain criteria. So just like the American Red Cross has criteria for the blood donors, we use the same criteria and then we have a lot of additional criteria to check for GI problems, GI history, to make sure the person has a normal body weight. They’re not too skinny, they’re not too fat, they’re just right. And so by doing that, using super healthy donors, it seems very safe. FDA regulates it like blood, like drugs, so we’re still cautious and so we certainly don’t recommend people do this on their own, there is probably some degree of risk. That’s why we use this really careful screening process.

A good example is my mother received a blood transfusion and she got Hepatitis C from that and my brother received a blood transfusion, caught Hepatitis C from it, almost killed him! The problem then is we pool blood donations from hundreds of donors to make blood products. Here we have one donor for one dose, so we’re not pooling and that helps keep it safer. So far FMT seems extremely safe, we want to keep it that way by using really careful donor selection.  

Dr. Nicole Beurkens: 

That’s helpful to understand that part of the process. I wanted to ask too, just for people who are wondering about this, the logistics of actually how you do this. So you mentioned the initial major dose and then the follow-up maintenance doses. Is that through a capsule? What is the actual process of getting these things into the study participants?

Dr. James Adams:

In our first study, we tried two different ways. One was that we gave the first dose through a rectal enema. The patient just laid calmly on the table, we had a wonderful physician with a wonderful bedside manner and we gave them a deep rectal enema slowly over the course of one hour, then the parents carried them prone to the car, carried them prone into their house and kept them lying down to keep that gut bacteria in them as long as possible. So that was one approach. The other approach was we used — in both cases we used this highly purified form, it was just a liquid — and drank it down mixed with chocolate milk or with juice or whatever they wanted to, they just drank it right down like a probiotic.

In that case, we gave them a stomach acid suppressant because normally your stomach acid kills off most of the bacteria in your food. But here we suppressed the stomach acid so more bacteria would survive. And then all the maintenance doses we gave orally, just like a probiotic, just a little bit mixed in their juice with a stomach acid suppressant. And that worked very well. Both groups did well, 90% of the people had a great improvement in GI symptoms. But it wasn’t a 100% so we want to go back and work on improving that. That first study was the first guess on dosing and first guess on duration, so now if we have this treatment that’s very safe at the dose we’re having and we’re seeing 90% of the kids responding, well now, let’s try a higher dose, let’s try a longer dose and maybe we can get to 100%. 

Dr. Nicole Beurkens: 

Well, that’s one of the things I wanted to ask next is, what do you think the future holds for this? So we see that fecal transplant, microbiota transplant have been used now, sort of several different applications — you mentioned C. Diff. We’re obviously talking about autism and related disorders. What do you see as the future, both from a research standpoint and a practical treatment standpoint? Where do you see this evolving to?

Dr. James Adams:

So the FDA classifies FMT like a drug and so it needs to go through phase 1, phase 2, phase 3 clinical trials. We did the phase 1 study which showed it’s very safe. We’re not doing a phase 2 study for adults, it’s a randomized, double-blind, placebo-controlled study. It’s going well so far, although we’re running short on money for that, so we’re doing fundraising now for that to enroll more people, and then the FDA just announced that microbiota transplant for autism has been granted fast track status.

That means that the FDA recognizes this as a promising treatment based on our research and also feels that it is for an unmet need, that there is no treatment out there for the core symptoms for autism, these core GI symptoms. So this fast track status is very exciting, FDA has been very helpful, but still, we need to go through those phase 2 trials and then larger phase 3 trials, with 500-1000 people, to a $100,000,000 — then we can get it approved for autism, that’s a few years down the road. 

Dr. Nicole Beurkens: 

Amazing. It’s wonderful about the fast track status and now, yeah, you’re running into the resources probably both study participants as well as the money to do it. So how can people get involved with this? I think we’ve definitely piqued the interest of many listeners, many families out there who are listeners to this show, who have children either younger or even adult children who are on the spectrum. Where can people find out more about what you’re doing with this, how can people support the studies that you’re doing? 

Dr. James Adams:

So if they go to our website: autism.asu.edu, then they can go there and if they have someone who is 18 years and older, they can get on the waiting list for a study, they can fill out the application. If they are under 18, they can be added to our contact list. We hope to do another study for children in the future, we just need to fundraise for that, and when we do, we will advertise that to everyone who is on our contact list.  

Dr. Nicole Beurkens: 

Wonderful. So I highly encourage people to go to the website to get more information and also to potentially — if you’re eligible to be able to sign up to participate. Such a need for this research and the potential for so many millions of people to be helped by what is happening with this. So thank you so much for being here today and for doing such a great job of explaining what this is and the research behind it. Really helpful information, I really appreciate it. 

Dr. James Adams:

Thank you very much.

Dr. Nicole Beurkens: 

Alright, everybody, that’s it for this episode of The Better Behavior Show. We will see you here next time.