Audio Transcription:

Vaish:

Hey listener, parent, teacher. Welcome and welcome back to functional nutrition and learning kids, your one-stop short podcast to learn about the various diets and protocols and research that impact inflammation in children with autism Down syndrome. Children with disabilities are entitled to good gut health as well. In today’s episode, Dr. Jim Adams, author of many, many phenomenon studies on GI symptoms in autism leads us through his pathbreaking study on fecal microbial transplant, specifically MTT, and the huge effect that it has had on nearly everyone enrolled in the trial. Listen on to find if FMT or MTT is legal for you to do in the US, and if there are other things you can do while waiting for your child’s GI symptoms to subside.

Hi, Dr. Adams, I’m really excited that you’re joining us today, you have over 45 publications on the various factors surrounding GI issues, nutritional status, dietary factors, and so much more as relates to symptoms and comorbid conditions that autistic children have an I am personally so grateful for your work, especially for the way that you control for and restrict variables such that there’s a clear conclusion and much less ambiguity than is the case with, with a lot of research that I have seen specifically on nutritional interventions because often I can tell what the aim of the study was your most recent study that I feel like it just shook everybody and everybody’s so excited about I am to is called multivariate analysis of plasma metabolites and children with autism spectrum disorder, and GI symptoms before and after microbiota transfer therapies.

This is a follow-up paper. And since this is a on your earlier study on microbiota transfer therapy, and since this is a short podcast, I was hoping to focus mostly on this study today. Could you start off by explaining to us what microbiota transfer therapy is and what your biggest outcomes or Takeaways were from this study?

Dr. Jim Adams:

Sure. So microbiota transplant therapy is a specific type of fecal transplant, what we do is we first we’re trying to treat gi problems in children with autism. And so we first use two weeks of antibiotic therapy a special antibiotic vancomycin, that only stays in the gut, so it’s very safe, then you do a bowel cleanse, to try to remove any remaining bacteria. And then we re-implant with healthy bacteria from very healthy, carefully screened donors.

Unlike the typical fecal transplant or just one dose, we found the daily dosing for many weeks was necessary. So we dosed every day for eight weeks. And we found great benefit in terms of GI symptoms, that over the course of time was slowly gradually a big improvement in GI symptoms, and also, eventually some substantial improvements in autism symptoms.

Vaish:

The one question that I had, and that I’ve, that comes up quite a bit is that there’s this general fear of antibiotics, but were you doing the antibiotic and the bowel cleanses so that there was less competition for the transplant?

Dr. Jim Adams:

So the reason we use antibiotics, this specific one, vancomycin is there had been a study back in 2000 by Sandler. And they had found in a small study of 11 children with autism who had serious gi problems, that they treated them with vancomycin for a very long time, eight weeks, and they found slow, steady improvement in GI symptoms, and surprisingly, also a substantial improvement in autism symptoms. That was incredibly exciting. But what soon as they stopped treatment, within a few weeks, they lost all of the GI benefits and all of the autism benefits, even though some of them children were taking began taking a standard probiotic. So a simple analogy I’d like to give is that it’s like having a garden filled with weeds.

Vancomycin is like pulling all the weeds getting rid of all the bad bacteria. But if you do nothing else, what’s going to happen in your garden, those weeds are just going to regrow. So we want to do is we want to use the vancomycin to kill all those harmful bacteria, use the bolo cleanse to remove them as well and then replant with beneficial bacteria from very healthy carefully selected donors. And that seems to be a big improvement that we saw, unlike with C. diff infections. So fecal transplant or FMT is primarily used in hundreds of hospitals in the US for treating people with life-threatening C Diff infections that affect half a million Americans a year, killing 29,000 Americans a year. And just one dose one time is enough to save these people’s lives that within a few days 90% Cure, and it essentially never comes back.

Autism is much harder to treat than this life-threatening, deadly GI infections. So we found we had to treat the children every day. And it was about five weeks into treatment that we began seeing that we saw most of the improvements in GI symptoms. And then, when we stopped treatment at the end of 10 weeks by then we’d also seen some improvement in autism symptoms. And then we waited.

We waited eight weeks, just like in the original vancomycin study with a big question, would we lose benefit after treatment. And unlike Vanco, where all the benefits were lost within a few weeks, we found it eight weeks, all the benefits remained. So we were delighted, we published the results, and we thought we were done. So there was about a 80% reduction in GI problems about a 25% reduction in autism symptoms. Now it’s an open-label study, there’s some placebo effect, but much of the effects seem to be real. But then a year later, three different families came up to me and said, Professor Adams, my son’s doing better than ever.

By the third time, I heard that I finally listened. And so we did a follow-up study, very rarely done in science. And so we did a follow-up with everyone two years after treatment had stopped. And almost all the families recorded their child had just had slow, steady continued improvement in autism symptoms, that it just seemed like they were suddenly better able to learn. So the treatment didn’t give them a new language overnight, it seemed to improve their ability to learn a new language, new skills, better behaviors. And so it was very exciting. And so our autism evaluator, reported in two years instead of a 24% reduction in symptoms was about a 47% reduction in symptoms. So just huge. So at the start of our study, 80% of the children were classified as having severe autism. At the end of the study, less than 20% were severe, 40%, mild to moderate, and 40%.

Were below the cutoff for autism still had symptoms. But the longer that the cuts off or even mild autism.

Vaish:

And wow, that so that’s super significant. And these children when you evaluated them after about 18 months or so they weren’t actually on any protocol, or they were just, it was just a follow up of the

Dr. Jim Adams:

just to the follow-up, they had not done any they will they had stopped the MTT treatment two years ago. Now a few of them had made some other changes and supplements and such. But our understanding is that those were generally not significant changes. And the families generally felt that almost all the improvements were due to the MTT we did have a few children who lost some of the GI benefits, primarily one child who took an antibiotic for strep infection, right at the end of treatment, they lost all their GI benefits. But the autism benefits were stable.

They didn’t lose them but didn’t make as much gain as some of the other people. So overall, very promising. And but again, it’s an open-label study. So you have to be cautious.

Vaish:

And study Doctor, what does that open-label

Dr. Jim Adams:

means everyone gets the treatment and knows they get it. So there’s no it’s not a double-blind study with placebo control. So some of the improvement is just due to parents’ hope. It’s what we call a placebo effect. We also measured the gut bacteria. Until the start of the study, kids with autism are missing several 100 species of gut bacteria, so missing about 25% of their normal bacteria. At the end of treatment, it had normalized it normal levels of gut bacteria, two years after treatment.

They have even higher diversity, more species of bacteria than typical children, and more species associated with better gut health. And I think that’s because you didn’t give them just donors from typical people. We chose the top 10% of the very healthiest donors to donate bacteria.

Vaish:

This brings me to the question, is there a certain type of child that is a better candidate for microbial transplant? Or are there some habits that make this a better outcome in some children? Did you notice anything like that?

Dr. Jim Adams:

It’s almost every child improved. So 16 of 18 children had huge improvements in GI symptoms, right? And then also various Sub them had substantial improvements in the autism symptoms as well, almost all of them. So we can’t all we can say is this group of children who had mild-moderate, excuse me, moderate to severe GI symptoms. And they also mostly had severe autism at the start, had very major improvements.

That didn’t age didn’t seem to be a factor, or participants were ages seven to 16 years. And the age didn’t seem to matter, that perhaps younger children might have done better, we’ll see. But the other, we did find five major clues in their history as to why they had these gi problems to begin with. So the We Can these 18 Children, we asked what was unusual about the medical history, Item one was lower fiber intake by their mothers. So fiber intake from primarily from whole foods, whole vegetables, and the fiber is converted into your duck by your, by your gut bacteria into butyrate is the main food that lives the cells of the colon. So average American women consume only half the amount of fiber that’s recommended. And these mothers of kids with autism had even less, that’s important because you inherit most of your microbiome from your mother. And so, therefore, that’s an issue. The second issue is that they were born, most of them were born by C section. So about two-thirds of the children. In our study, were born by C section, when you’re born by the C section, don’t go through the birth canal, get less exposure to crucial gut bacteria. And it’s actually very important.

The third major factor is the nursed for a much shorter period of time. Mother’s Milk contains a very special sugar in it, which doesn’t help the infant and doesn’t help any bacteria, except a very few species, the infant is named after the infant and a few others, and that one bacteria thrives on the special sugar and mother’s milk of competing for all other bacteria. So breastfed infant has a lot of these very healthy being scientists helping prevent bad bacteria from growing. But if you’re not on mother’s milk, then you’re exposed to whatever’s in the environment.

The next major factor was high antibiotic use, we found in this study, as we have found in several other studies, children with autism just had much higher antibiotic use during the first few years of life. And finally, the children with autism had slightly lower fiber intake, although it was more a factor for their mothers. So just to summarize, the mothers had been probably worse bacteria to begin with, less of it got to their children, that took what few bacteria made it to the children were wiped out by antibiotics. They weren’t fed as much by the key ingredients and mother’s milk, every key factor we looked at. And these are the key ones that would make it very reasonable that these are the reasons why these gut bacteria are so abnormal.

A very important clue to is we did a study with our collaborators at Caltech. And so they raised mice that were germ-free, they had no bacteria in their gut. And they took gut bacteria from kids with autism, they fed it to those mice, and those mice had babies. And if the baby mice had received gut bacteria from a child with autism, they developed autistic-like symptoms. But if their mother had received gut bacteria from a healthy person, they develop normally. So it tells us there are some abnormal bacteria in the guts to children with autism, then cause autistic-like symptoms in the off in their offspring. In an animal model, so that’s why we think it’s a very, very important clue.

Vaish:

And as one of the quotes that I’ve underlined from your paper in 2006, is that you studied 51 children with autism. And they were compared to 40, typical healthy controls. And he found that 63% of children with autism had moderate or severe chronic diarrhea and constipation. So basically gut issues versus 2% of the control children. And, and you quote other studies in your paper, so there’s like, there seems to be so much evidence of severe GI symptoms in children with autism.

I wanted to ask if it feels like a no-brainer that they should be accepted in the mainstream by now is it and if it isn’t something that when a child is diagnosed with autism, it should be? You should go through a GI evaluation with your PCP right away. So is this something that’s accepted? Can parents take papers with them to their PCP and ask for an evaluation?

Dr. Jim Adams:

I think that it’s become more accepted that children with autism do have GI issues. And good studies generally show that they have higher levels. There are a few studies that don’t when you ask a question like, has your child ever had a GI symptom? And if you ask that 90% of kids with autism would say yes. And 90% of typical kids would say, yes, it’s not a good question. So that’s why rates of GI symptoms range from 5% to 90%, depending on what study you do, but when to look at a study like we did where we have a specific question, and we asked kids with autism and of controls.

Study after study shows much higher rates of primary constipation, diarrhea, and abdominal pain. In kids with autism, it’s usually not as severe as Crohn’s disease or ulcerative colitis. But it is a chronic problem. And we were surprised to see that every one of the 18 children in our study reported they had had these GI symptoms since infancy. And prior to our study, I don’t think anyone had ever looked at the duration.

I don’t think anyone really realized these GI symptoms, at least in our subgroup started in infancy in every case we looked at. And then we’re seeing that also in other studies as well. So I think that’s very compelling data.

Vaish:

And I’m going to link to some of your studies, but especially those papers, I feel like this is definitely something that parents can take to their PCB, even if they’re not working with a functional doctor to get a GI evaluation.

Dr. Jim Adams:

I think the bottom line is I think every child with autism should have a GI workup by a gastroenterologist if they have chronic GI symptoms, and not every child with autism do, but many do so if they have chronic constipation, chronic diarrhea, and it’s not responding to standard treatments, and we’ve heard from many families, standard treatments often have little or no benefit, then they really should have a full gi workup, especially in children who can’t communicate. studies by cat pop gastroenterologists like Kimberlee, Arthur Krigsman have shown that often, in nonverbal children, they might just have very odd behaviors, they may be clutching their belly, they may be twisting their body in strange ways. abnormal behavior without a reason for it.

You want to suspect pain in the body. Pain in the GI tract is especially common. So I think a lot of cases of irritability. Several studies have shown that increased irritability and related symptoms, behavioral problems are just higher in children with GI symptoms. And if you’re in pain, you’re going to be more irritable, you’re more likely to be aggressive to someone else, more aggressive, more likely to hurt yourself.

Vaish:

And I have seen been horrific situations of children that are in pain and screaming and acting out in weird ways. Going to behavioral therapy when this is not a behavioral issue. It’s communication.

Dr. Jim Adams:

Exactly, that behavior is communication that there’s a problem. And often, hidden gi problems are likely, but it could be a migraine headache, it could be infected tooth, there are other sources of pain, but gi pain seems to be one of the most common that’s under-recognized because you can’t see what’s going on in there. Unless you do an endoscopy.

Vaish:

I had one uh, one question that kept coming up in my mind, because I’ve heard different stories about the relevance of specific strains. And you have mentioned today and in several of your papers, that the strains and diversity of bacteria and the guts of artistic kits are statistically different from your typical controls. Is it your knowledge that specific strains are important? Or do the strains not matter as much as genetic diversity?

Dr. Jim Adams:

The honest answer is we don’t really know. In general, it’s assumed that higher diversity, many studies find that higher diversity more species is associated with better gut health in general. Our studies have all have consistently shown so we’re one of the few groups that have repeated our studies and found the same thing. And we repeatedly find much lower diversity in children with autism. So they’re missing several 100 species.

The challenge is this child is missing D several 100. Child B is missing these other several 100. So it’s very different from child to child. The one exception is that we see in most children with autism, very low levels. prepatellar we found this in three different studies. And after we treat with MTT, we see Prevotella levels go up to 100 fold. So I think Prevotella is very important. prepatellar is associated with high fiber diets. So there are some studies showing the people on Aboriginal, very healthy, high fiber diets, lots of beans, and very healthy foods and no gut problems. Half of their gut bacteria is prepatellar.

Americans and Europeans, it’s less than 1%. Oh, wow. Okay, huge difference. In children with autism, it’s 10 times lower than that. So you could say, children with autism are hyper westernized, they have almost no prepatellar. And so we think that’s very important, at least as a biomarker, and we patented as a treatment. But unfortunately, for legal reasons, we can’t invest easily investigate that treatment. So the bottom line is, if you’re missing hundreds of species, let’s say you wanted to have a garden, and you want to play up to 100, several 100 different types of plants, and you only have seeds for corn, you are going to be very likely to get hundreds of other species growing. And that’s what’s going on with probiotics standard Probiotics have typically one to 10 strains. And they’re strains that grow in milk. They’re not the strains that normally exist in the human gut, at least not in high amounts.

When you stop taking probiotics, they usually disappear within a week or two from your body. Probiotics are generally aerobic bacteria, they grow in the air, most of the bacteria in your gut are anaerobic bacteria, they are killed by oxygen, and they grow in the presence of no oxygen. So probiotics, in principle, make some concepts make sense. The problem is, you’re not giving the right ones. So that’s why our microbiota transplant therapies, essentially super probiotic 1000 Plus species in just the right ratios, is found in the very healthiest humans.

Vaish:

That’s a lot of really interesting information there. And I feel like anybody listening to this or having read your papers would want to go out and get their version of MTT. I signed a specific article called microbiota transplant therapy and autism lessons for the clinic. Is this something I haven’t actually read it though, is this something that practitioners can use as a guideline for people that are already offering fmt? Is it can they use it?

Dr. Jim Adams:

And so that’s a paper that we wrote to give general recommendations to summarize the state of research and to give recommendations for both clinicians and future researchers.

The problem is that the FDA has decided that microbiota from stool is classified as a drug. And therefore, it’s not allowed for a physician to use the cold transplant of microbiota therapy, except as part of it part of an investigational research study, like we’re doing. So far as I know, we’re still the only group in the US doing research on microbiota transplants for autism. So you can it would be illegal for a physician to provide that therapy in the US. Okay, I didn’t know that. So that’s why we’re doing our research. So the FDA was very excited by our pilot study, they granted us what’s called Fast Track status means they recognize that our MTT is a promising, but not proven treatment for an unmet need, meaning that we don’t have a treatment for the core symptoms of autism or for the GI symptoms in autism. And this treatment seems to address both. So we’re now doing phase two studies, which are randomized, double-blind, placebo-controlled studies, or adult studies underway A CHILD Study we’ve recruited for we hope to start soon.

We’ve had a bit delayed by COVID-19. But we’re working through that. And so we have high hopes, if these two studies are promising, then we’ll be able to ask the FDA for approval to do a much even larger phase three study. These are very expensive studies to do and it’s probably aborted five years before we can get approval from the FDA.

Vaish:

So it’s many more years before people can expect to see this as a clinical option for them, but

Dr. Jim Adams:

very, very expensive to meet the FDA standards, typical cost to bring a new drug to market. It’s about $1 billion, right. So we hope Do it for a mere 100 million or so. But we have to raise that money. And that’s not easy.

Vaish:

Dr. Adams, this was incredible information, can you? Can you talk to the listeners a little bit about what they can do right now?

Dr. Jim Adams:

Sure. So a treatment that we found that had many of the same types of benefits, just not to the same degree, is we did a comprehensive treatment study, comprehensive nutritional treatment studies. So we combined six different nutritional treatments, vitamins and minerals, fish oil, a healthy diet, and some other things. And over the course of 12 months, we found a seven-point gain and IQ in the treatment group versus no change in the non-treatment group.

Over 12 months, the non-treatment group gained only four months of development, the treatment group gains 18 months of development, and they began catching up to their peers. So we’ve now made a simplified version of this protocol and put it on their website. So we call it the NRC protocol. And it’s available from our website, www dot autism and for nutrition for research see for center.org. And that website is our nonprofit, I don’t get any royalties from it. But it has there the vitamin-mineral supplement that we created for children and adults with autism that previously we see good benefits.

The top three treatments we found from our 12-month study were vitamin-mineral supplements and fish oil many children with autism also benefit from omega-three fatty acids. But usually, they’re under dosing so we’re recommending a relatively high dose and that seems to be beneficial. And then finally, a healthy allergen-free diet. Want to emphasize healthy foods, you’re not going from Oreos to gluten-free Oreos, but you’re going from Oreos to whole foods, whole vegetables. And we found that very helpful.

This combination treatments didn’t help everyone. But it seemed to help well over 80% of people and very rare adverse effects, but slow nutritional interventions take time. It took about three months to see most of the benefits.

Vaish:

That’s fantastic. Oh, well said, and thank you so much for all the work you’re doing, Doctor. Thanks for listening to this podcast. Now for years, we’ve been pushing severe pain experienced by autistic children, non-speaking children, children, maybe with other disabilities.

We’ve been pushing this under the rug and labeling the symptoms as behaviors. This should be criminal on our part. Let’s help people around us wake up so our kids can get the help they need today. Share this podcast with your PCB printer Dr. Adams research studies take them asked to see a GI doctor if your child has GI symptoms, ask for him. Thanks for listening today. Music on as always is by Maitri Gosh and I’m your host Dr. Vaishnavi Sarathy. See you next Friday.