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Podcast: Autism, Autoimmune Disease, and Leaky Gut

By The Paleo Diet Team
February 27, 2014
Podcast: Autism, Autoimmune Disease, and Leaky Gut image

Dr. Loren Cordain: I'm Loren Cordain, founder of the Paleo movement.

Shelley Schlender: I'm Shelley Schlender. This is the Paleo Diet Podcast for May 2014.

Loren Cordain, you have thought for decades that autism is something that's related to low-grade inflammation and leaky gut. Now scientists are saying the same thing in journals like Cell. This is an idea that used to be considered woo-woo.

Dr. Loren Cordain: You know, I was fortunate in that I did not have a traditional medical background, or even a background in immunology. I kind of have been self-taught. I didn't know what I was supposed to know. I kind of approached disease and ill health from a perspective of trying to put together the pieces in the puzzle and not listening to the dogma. Just seeing what kind of came out.

There were symptoms of autoimmunity in autistic children. They had signs and symptoms that I don't think anybody at the time, in 1999 or 2000, or whenever we were digging around with this idea, I don't think anybody at the time would have ever said, and I don't think that most immunologists would consider autism an overt autoimmune disease. It does have components that are highly suggestive of autoimmunity.

Since we really don't know what autoimmunity is, it's a black box, it's difficult to say that a disease is or is not an autoimmune disease. It doesn't have the classic autoantigens.

Shelley Schlender: At least we haven't found them.

Dr. Loren Cordain: We haven't found them but that doesn't mean that they're not there. That's kind of the working hypothesis that we had. That maybe there are autoantigens that the immune system is going after, we just haven't been able to determine precisely what those are.


Shelley Schlender: A lot of autism researchers today will say that there may be different causes of autism. What manifests as symptoms of a child or an adult having trouble in social situations, having trouble with transitions, having trouble with anxieties, and wanting to withdraw away from all of that, there may be all kinds of things like a tough delivery or genetics.

Dr. Loren Cordain: That's right. I think that there are components, particularly when you're looking at a behavioral pathology that, in part, may be physiological. It may also have behavioral components or other environmental triggers. The point that I want to make, and we've made for years, is that when we think about autoimmune disease we typically use an infectious disease model. A bacterium causes typhoid fever. We find something that kills the bacteria.

It's this kind of unidimensional disease. Modern medicine is filled with examples of we find the pathogen and we get rid of it. The notion that autoimmunity also may be a unidimensional disease, or cardiovascular disease, that it's caused by too much cholesterol and saturated fats, is really way too simplistic in nature.

Shelley Schlender: With autism, one fascinating new area of research is that instead of killing microbes to try to get rid of something like autism, there are some studies now which indicate that adding certain healthful microbes in will reduce autism symptoms in mice that were bred for autism. Those studies are fascinating.


A recent study in Cell, which showed that when you breed mice to be prone to these autistic symptoms by kind of messing up their immune systems, if you add in a probiotic, a microbe that tends to heal leaks in the tight junctions of the cells of the intestinal tract, the autism symptoms will go away. At least they'll go down.

Dr. Loren Cordain: I think it's fascinating and it really follows up what our group was saying almost a decade ago. The notion here, of autoimmunity, is it's not a singular disease, it's a moving target. When you look at multiple sclerosis, it's an autoimmune disease. We are looking for a genetic factor and we're looking for an environmental factor that triggers it.

What makes it so difficult, whether it's multiple sclerosis or autism, is that what if, in one genotype, one person that has a specific gene. Let's say tomatoes aggravate their immune system whereas other people it's not tomatoes at all, maybe it's dairy or it's a peptide sequence in the gut coming from bacteria. It causes similar symptoms but it's as if there are multiple environmental and genetic triggers that are causing the symptoms.

That's what makes it so hard to chase down this black box. Autism, in some children, may manifest itself with certain peptides.

Shelley Schlender: That means certain protein molecules in the ...

Dr. Loren Cordain: Protein molecules that interact with the immune system and they seem to operate through the gut. That's the one common denominator that we pointed out and I pointed out in my research 10, 15 years ago. Even before Dr. Fasano, Alessio Fasano, at the University of Maryland, he now has also come out suggesting that a common environmental trigger for most autoimmune disease is leaky gut.

In the early days, 10 years ago, 8 years ago, we compiled a few case studies where they actually look at autistic children.


Low and behold, there seemed to be a fairly high incidence of leaky gut.
Shelley Schlender: Yes, a lot of the autism researchers have said to me, "Not every child has digestive problems and they have autism both but a lot of the kids do." Some of the research indicates that children who don't have a lot of digestive problems, if you look at the microbes in their gut and what's happening with how their gut works, there is evidence that their gut is leaky even if they aren't having indigestion or having trouble with loose stools or something.

Dr. Loren Cordain: Right, and another point, too, that should be brought up is the way that we traditionally measure leaky gut is very crude. We use two different sugars, lactulose and mannitol. We feed them these two sugars and then we measure, in their urine an hour or two later, or you can measure it in plasma, the ratio of these two sugars.

That actually assumes that the gut is being breached through these tight junctions or cell to cell pathways.

Shelley Schlender: You're not really convinced that that's the major way.

Dr. Loren Cordain: Right. There's at least two other mechanisms by which bacteria in the gut can interact with the immune system. There's actually a number of ways it can happen. We have cells called M cells in our intestines that actually sample what the gut sees. It kind of primes the immune system.

Many scientists believe that M cells are not the gut cell that ultimately cause autoimmunity but rather a cell called a dendritic cell. Dendrite means kind of root or tree-like. It's the same thing. A dendritic cell in the gut is a white blood cell, it's an immune cell. Its function is kind of like a macrophage. A macrophage is like a garbage truck, it goes around and it gobbles things up.
Dendritic cells tend to gobble things up in the gut. That's part of our idea, is that, certainly, dendritic cells can gobble these things up.


Dendritic cells actually reach into the epithelial cells that line the gut. More importantly, what I think is going on ...

Shelley Schlender: You keep making with your hand the hook. You picture this dendritic cell actually grabbing things like a grappling hook.

Dr. Loren Cordain: That's a good way to visualize it. It engulfs these peptides or these proteins that escape the gut that, theoretically, shouldn't get past the gut barrier. The dendritic cells then can set off this whole agitation of the immune system. Normally they don't, they're not susceptible to going nuts.

Shelley Schlender: You think that the proteins from our food can end up being not properly digested and in too big a chunk they can somehow slip into the bloodstream from the digestive tract, which really freaks out our immune system.

Dr. Loren Cordain: Well it doesn't ultimately go to the bloodstream, it goes into the lymph first.

Shelley Schlender: Okay, the lymph is that system that's kind of a clear liquid that goes through a little slower pathway than the bloodstream.

Dr. Loren Cordain: It empties into the liver. The liver is supposed to get rid of this stuff and blah, blah, blah. It doesn't seem to do that. It seems that, ultimately, specialized immune cells called CD4 T lymphocytes are the ones that end up doing the dirty work that starts this autoimmune process.

Think about the dendritic cells, they kind of hand off the alarm to these T cells in a manner saying, "This is a big deal. This is not where the firemen should just relax and have a cup of coffee. We are being attacked."

Shelley Schlender: It starts out with just a little red button that's blinking saying, "Warning, slight warning." Then, if these dendritic cells get activated enough, it goes to a warning buzzer. If they get way activated then all of the alarms in the fire station go off.

Dr. Loren Cordain: That's why autoimmune disease is still a black box.


It's kind of like cancer and heart disease was 35 or 40 years ago when we really were just beginning to understand at the molecular level what's happening.

One of the factors that has just been surprising everybody is that the gut seems to be in the middle of it.

Shelley Schlender: Of autoimmune diseases.

Dr. Loren Cordain: Right.

Shelley Schlender: If your joints ache, it may be something going on in your gut. If you're overly anxious and you wish that you could calm down, which is a symptom of autism quite often, then it sometimes may involve some health problem in your gut.

Dr. Loren Cordain: Not sometimes. I think that that's probably one of the best places we should be looking right now and seeing how food, because clearly the biome, the gut biome, is influenced by food. We can change the type of bacteria that grow in the gut.

Shelley Schlender: Backing up a little bit. You're mentioning the gut biome because a lot of the latest research about the health of the gut involves the billions and trillions of microbes that live there in our gut to help us digest our food, and have been there for eons of time. They've always been there as part of our team. If that team gets sick then something happens to promote leaky gut more.

It's not just the food that we eat, it's the health of the microbes in our gut.

Dr. Loren Cordain: It seems to be a symbiotic relationship. We work together with the bacteria in our gut and vice versa. That's some of the $64,000 question. We used to think that the only people that were really allergic to wheat were celiac patients, which in an autoimmune disease of the gut. It's now turning out that many people tend to have gluten sensitivities.

The best scientists in the world, including Fasano's group and another one from Europe, they now have identified multiple pathologies and syndromes that seem to be associated with gluten sensitivity. As many as 5% or even more of the world's people may have problems with gluten.

Shelley Schlender: A lot of people think, when they hear the term gluten, they just need to go to the gluten free section of the grocery store.


Dr. Loren Cordain: There's three major gluten containing grains, wheat, barley and rye. Oats are thought not to affect some people with celiac but some people, they seem to be affected by it.

Shelley Schlender: Okay, so somebody who says, "I am avoiding bread because I've got a gluten sensitivity so I'm eating oatmeal," it may not be the best thing for some of the people.

Dr. Loren Cordain: The same thing with maize or corn. It also has been shown to adversely affect the GI tract so it flattens these villi, these finger-like structures in the gut. High corn diets seem to do that as well.

I guess the question that really comes up is why do you want to eat such a second rate food. Humans don't have a grain requirement. We can get everything we need from our vegetable garden and some meat. Humans have no grain requirement and there's no elements in grains that are so nutrient dense that we can't get elsewhere.

Shelley Schlender: That's been a premise of your paleo diet for a long time. It's an interesting moment because right now autism scientists who are looking at the human microbe biome, the gut microbes, are starting to say that there's strong evidence that a condition like autism has some links to a leaky gut. They don't always see that food is as significant as just adding in the microbes again or getting rid of the antibiotics that tend to kill off all the good guys.

Dr. Loren Cordain: It goes beyond this. We talk about paleo diets, and that's really what I've been known for. Paleo diets are characterized by you want to try to stay away from dairy products, you want to stay away from legumes and whole grains, or even refined grains for the most part. Eat fresh, real foods.

There are studies in the scientific literature called meta-analyses. With meta-analyses scientists combine the results of multiple studies.


There's been one meta-analysis involving autistic children in which researchers either took dairy out of their diet, or took wheat or gluten containing grains out of their diet, or both.

Not all researchers do both, they do one, and not all take all grains out. The results of that meta-analysis, which was published in 2008 or 9 or something, I can't remember off the top of my head, it is suggestive, the preliminary meta-analyses, are suggestive that grain and dairy free products are therapeutic for some autistic children.

It's not a cure-all. If we could cure autism with just grain and dairy free diets we would have done that years ago. People would have found out about it. It can be therapeutic and I think that's really the point. Humans don't have either a wheat or a grain or a dairy food requirement.

Shelley Schlender: The USDA says that we do.

Dr. Loren Cordain: The USDA has arbitrarily put foods into five categories. Dairy is one of those categories. I don't understand how they can make across the board population recommendations when 65% of the world's people lack the enzyme to break down the major sugar in milk. 65%, that's not a small number, particularly in a mixing pot country like the United States, where we have all kinds of people. Not necessarily Caucasians.

Typically American Indians and blacks, and people from other parts of the world that aren't northern Europeans, have a very high incidence of lactose intolerance. To make those kind of across the board recommendations to the population is bordering on very bad medicine.

Shelley Schlender: As far as medicine for a child with autism, there are enough warning signs that dairy could be increasing the chance of leaky gut that you've got concerns for that.


Dr. Loren Cordain: That's right. Milk contains a number of compounds that tends to allow these large peptides, or protein molecules, to get across the gut.

Shelley Schlender: Into the lymph system, into the body's part that's supposed to be totally safe from big complicated protein molecules.

Dr. Loren Cordain: Mammalian milk does that, it has those compounds. Think about it, milk is a substance that is designed to take a young suckling animal and give it mother's head start in life. One of the head starts is to prime its immune system. In order to do that, to get mother's immune system past the gut, it has to get past this gut barrier.

Young mammals have kind of a leaky gut to start with anyway. There are compounds in milk that facilitate that process. We know, from pretty good studies, that milk is associated with multiple autoimmune diseases. We're right on the trail of it right now with type one diabetes. Children that have early exposure to milk seem to have a very much increased risk to type one diabetes.

Shelley Schlender: That's another autoimmune disease. On the autism front there's always been the Defeat Autism Now Diet, which is reduce gluten products and reduce dairy products and see if that helps. There's some other things that the autism researchers have told me recently about they're wondering a lot about antibiotics.

When the microbes that help the whole body get hit hard by antibiotics, say a child who has round after round of antibiotics as a little kid, they're wondering whether that may do some subtle changes to the microbes in the gut. It may be microbes we can't even track yet because it might be like a wolf in Yellowstone really affects how the elk move and how much areas get overgrazed.

Dr. Loren Cordain: That's right.

Shelley Schlender: There may be some little subtle microbe that gets killed off by a lot of antibiotics that's a little hard to bring back. I'm curious, on a paleo diet, do you have concerns about people taking antibiotics?


Dr. Loren Cordain: I think so. I think that that has kind of been the knee-jerk response of western medicine. If you bring your child in and the child has an inner ear infection, what do you do? Whether they require it or not, they're given antibiotics. Typically many of these upper respiratory and inner ear infections are not bacterial in nature but are viral in nature.
Antibiotics have very little effect on viruses. It's kind of doing it more for the placebo effect, for the parents. It's like, "I can't really do anything, I suspect that you've got a viral," so we give these antibiotics and what do they do? The antibiotics seem to alter gut physiology.

We're now honing in on gut physiology. A better way, and as it relates to the paleo diet, is why do we get inner ear infections in the first place? Because we're eating high glycemic load carbohydrates and sugars and whatever. Inner ear infections in indigenous populations before they were westernized basically didn't exist. We have real good information with the Inuit showing that they didn't get ... what is it, otitia media?

Shelley Schlender: Otitis media.

Dr. Loren Cordain: Yeah, they didn't get it. That's the medical term for that inner ear infection. They didn't get it. Once they became westernized, it was as common up there as it is down here.

Shelley Schlender: Okay, so instead of eating their Inuit diet of a lot of fat and a lot of wild meats that they collected from the sea, they started eating the bread that the missionaries brought them.

Dr. Loren Cordain: The sugar, yeah.

Shelley Schlender: They brought the sugar that the US government brought in as their rations.

Dr. Loren Cordain: Yeah.

Shelley Schlender: Their ears started having just as many infections as people in the United States.

Dr. Loren Cordain: Yeah, and then, like you said, it's this cascading series of events. What do we do? Now we give them antibiotics. We give them antibiotics and now suddenly we start to see autism showing up. I'm not saying it's cause and effect. It's just enormous cascade of things that are starting to change as we adopt western diets and leave our traditional diets behind.


Shelley Schlender: It is something to wonder about because the rate of autism has gone up exponentially in the last 50 years. There's a lot higher incidence of autism than there used to be. It's not just because of better diagnosis. The estimate right now is one out of 88 children born today will be diagnosed with an autism spectrum disorder. That's a lot.

Dr. Loren Cordain: My wife is a special-ed teacher in the public school district. She deals with these kind of folks all the time. The cost to benefit ratio of doing paleo with children is minimal.

Shelley Schlender: We've talked about the cascade of things that may set a child up for being more vulnerable to autoimmune diseases or earaches. What about a child or an adult who has ended up on a lot of antibiotics and is trying to get their body back together again? The autism research from the microbiome community that's looking at the gut microbes is indicating that they're not so sure that diet alone can make enough difference to restore and heal a leaky gut.

They're starting to think that it may take a good strong load of probiotics, meaning the right microbes. The trick is that it's hard to know which one is the right microbe to add.

Dr. Loren Cordain: Yeah. What I think is so fascinating is that these are some of the best scientists in the world now that are honing in on this, publishing in Cell and in many of these high impact factor journals. Yet, a decade ago, when we first were making these outrageous statements, that we think it was gut related and it may have to do with diet, and even the gut biome, that was not seemingly an issue.

Now it is seemingly an issue and we are seeing these fascinating experiments. We got involved early on and I'm retired now so you hand the baton off to a younger generation. It's just so gratifying to see this kind of stuff taken seriously.


Shelley Schlender: It is being taken seriously and, at the same time, it's a bit of one set of researchers maybe not knowing about some of the research in another area. It's my sense that some of the microbiome researchers, they haven't had the opportunity to see a really strong study of what people eat to know how much that can affect what happens too.

Dr. Loren Cordain: Yeah.

Shelley Schlender: It could be, also, that sometimes a system is so unhealthy, and needs so much help, that maybe some microbial support would make a difference for somebody on a good diet. Not just eating yogurt, not that kind of thing, or taking in kefir or raw kraut.

Dr. Loren Cordain: Exactly. That's a knee-jerk response. The assumption has been that lactobacillus, and some of the other probiotics that people take that come from dairy products, the assumption has always been that those are good bacteria and that everything else, maybe, is bad bacteria. Now that we're doing genome studies of the gut, what is in there with DNA, is that it's probably surprising. It's not necessarily lactobacillus and some of the other common bacteria that are found in fermented milk that are necessarily healthy.

We really need to consult the evolutionary paradigm to find out what is and what is not normal. That's really what our research group has done over the two decades or so that I've been studying this. Taking that organizational template and then applying it to complex health related questions.

When you do that it provides insight that cannot be gained through other ways or mechanisms. We're talking now about autism and autoimmune dysfunction. When we look at the evolutionary template, that seems to provide us with this very helpful insight.


pThat's all for this edition of The Paleo Diet Podcast. Visit my website,, for past episodes and for hot links to the experts and studies that we talked about today.

Shelley Schlender: Our theme music is by Chapman Stick soloist Bob Culbertson.

Dr. Loren Cordain: If you want to send me questions or comments, the place to go is

Shelley Schlender: For The Paleo Diet Podcast, I'm Shelly Schlender.

Dr. Loren Cordain: I'm Loren Cordain.

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