Spectrum of gluten related disorders: People shall not live by bread alone

Dr. Blyweiss

Hello, and thank you for taking time out of your busy schedule to join us today. My name is Dr. David Blyweiss, Chief Medical Officer for Cell Science Systems. The purpose of this webinar series is to broaden your understanding of the immunological differences between innate and specific immunity, and how those differences manifest in disorders ranging from gluten and other food sensitivities, to more severe manifestations, such as celiac disease.

And this lecture, titled Spectrum of Gluten related Disorders, Dr. Alessio Fasano, Chief of the Division of Pediatric Gastroenterology and Nutrition for Massachusetts General Hospital and Director of the Center for Celiac Research, will be discussing cutting edge research on celiac disease and gluten-related disorders. Be sure to stick around at the end of the lecture, as I’ll be giving you information on some of Cell Science Systems’ innovative laboratory testing.

Dr. Fasano

Alright. Afternoon, everybody. He took half of my talk. Yes, I can recommend also for olive oil. I sure can do that. So of course, when I was invited by the organizers, I was delighted to come, mostly because I had the opportunity, old friends, speakers, that we cross road once in a while. And I think that this is a very fascinating field. And for somebody like me that learned very recently about the wisdom of complementary alternative medicine, because I’m general on the other side of the fence, I come here with a very unbiased mind to share what is the factual news about not just celiac disease as the program originally mentioned, but what we now call the gluten-related disorders, because we are in a spectrum of conditions they are related to gluten.

And I know that you already enjoyed today many lectures discussing little bit about that. So I think that I want to focus my hour and a half, I think that I have to talk, or one hour forty-five, whatever it is, in three major sections, starting to the question, why gluten is so toxic? And again, my job is going to be facilitated, and has been already facilitated, by other speakers that touched upon this concept. Maybe that we want to go a little bit more on mechanistic details. Folks like to talk in jargon as evidence-based data.

So once upon a time, there was no gluten, and there was no celiac disease. And if we look at the evolution of human kind, from what we know right now, that spanned 2.5 million years, for 99.9% of humankind evolution, our ancestors survived on a gluten-free diet. And matter of fact, biologically speaking, we were not meant to eat gluten. And it’s been already mentioned that gluten came into the picture only 10,000 years ago, so the drop in the bucket of this 2.5 million years.

When there was a revolutionary change in lifestyle, our ancestors that shifted their way of living from nomadic, i.e. moving around, chasing food by going after migration animals and seasonal crops, to settlers, in which they domesticated animals and crops. In doing that, they “invented,” or engineered, whatever you want to call it, this tribe of grass family, the Hordeae, to which wheat, rye, and barley belong to. They are the only grains that contain gluten and similar proteins. They are toxic with people with celiac disease and other gluten-related disorders.

So all this to say, again, that evolutionarily speaking, we were not meant to eat gluten. I have also to say, though, that if you are sitting here and I’m giving the talk today and we are not still jumping from one tree to another, it’s because of the advent of such a versatile commodity. And matter of fact, 8,000, 7,000, 5,000 years ago, wealth was not measured by the number of stocks and bonds that you had in the bank. Rather, by two commodities: oil and wheat.

They were the commodities that make a difference if you were rich or poor. And reason why, because these commodities can do many things. Not only that, they are not perishable. And that’s reason why the advent of wheat that was something in a very limited region, the actual turkey, to use a jargon that our teenagers use nowadays, went viral, because it was so popular, and expanded it. And it’s roughly speed of one kilometer a year from south to north and east to west, so that the rest of the world eventually was exposed to gluten.

So all this to say, again, that we give for granted that this protein and the grains that contain protein’s been around forever, and the matter of fact, it’s not. A matter of fact, if you got a chance to visit Italy, and there are several museums in which there are artifacts, like the Mayan aggression artifacts, or the Romans, that eventually are jars. They were taken from vessels that sink in the Mediterranean Sea. They end up to have grains in there and the grains that you find there are probably these grains here.

These were what the Romans and the Greeks used to eat. Very simple, rudimental grain, had 14 chromosomes, 50,000 genes. Then again, particularly Egyptians, they start really to become sophisticated, to play with these grains, and start to really develop this other series of grains, the T. turgidum. And that’s what we eat right now. That is a mixture of the two. There is a tetraploid, 42 chromosome, 150,000 genes. I want you to pay attention to this number, because we’re going to come back later on about what this number means.

And therefore, you see also how not only aesthetically, but trust me on the word, also organoleptically speaking, these grains changed dramatically in these 3,000, 4,000 years until this modern grain that came about relatively recently, and up to come to on our tables. I love paintings, and this is one of my passion. This is a painting in the 1500s from Belgium. Now pay attention to this fellow here, and this is a wheat field.

Granted, at that time the folks were not 6’2″, 6’3″ right now. Nevertheless, see how tall was wheat compare to humankind. Because at that time, the plant was pretty tall, and the seeds, the part that really are useful for us, were just the 5% top. The rest is just wasted. And in the next century or two, agronomers really play to trying to enrich the seed part so that the yield will be much better, and in doing that, enrich this plant of its own component, including gluten. And that’s pretty much what’s the story in terms of the evolution of the grains that really I shrank in five minutes 2.5 million years of evolution of grains.

But why it’s so special, this gluten? Why it’s such a one of a kind protein? Well, first of all, because it gives characteristics to the grain. They’re containing this stable protein that is unparalleled. And that’s reason why it became so popular. You heard that when we say gluten, actually we mean a mixture of proteins, the two key components being gliadin and glutenin, both toxic for people with celiac disease.

Glutenin are these stretched fiber kind of structure that in this electromicroscopy are these fibers here. And gliadins are little blurb that are accommodated in these chambers. Now, the reason why this is one of a kind, that you can do stuff that you cannot do with any other grains that don’t contain gluten, is because that structure is the one that gives grain containing gluten, that characteristic makes this unique, elasticity.

 

You can’t have that with maize or rice. And if you mix this with water and yeast, so much so that you can produce gas, and this gas is entrapped in these chambers, this puffs, grows, so you can have the beautiful croissant, the smelly baguette, you can make the pizza…stop, okay. If you try this with maize, it’s not going to work, because this is not happen there. But with the beauty comes the beast, because if you now zoom in and look at more, specifically, what this organoleptic characteristic that makes this protein so desirable are based upon, this is also the reason why we got in trouble when we are exposed to this protein.

This is a cartoon of the most studied component in gluten that is called alpha gliadin. Now, I don’t pretend that you can read this, because I can barely read myself here, but one of the characteristics of this protein that is extremely rich, totally unbalanced, I should say, of two amino acids. They are proline and glutamine. The proline are in P, and glutamine in Q. And there are some stretches like this here, for example, almost all Qs. What that means?

Means that we are not able to dismantle completely this protein. We cannot digest completely this protein. Indeed, the destiny of any protein we ingest with the diet is to be completely dismantled in the elemental blocks, they are the amino acids. So if you allow me a parallel, consider this like a pearl necklace in which each amino acid is a pearl. The way that we manage proteins, we break the necklace, and initially we break and open the necklace, and then we cut the necklaces in pieces.

And then we pull one pearl at a time, so that we can make use of it. Regarding gluten in general, so gliadins and glutenins, what we can do, we can break the necklace, we can cut in pieces, but we cannot peel off the amino acids, i.e. the pearls, because we do not have the enzymes that do these tricks, mainly due to this enrichment of the sequence of glutamines. Because the enzymes, they are the scissors that cut these proteins, recognize specific sequences of amino acids. And when they see proline, proline, proline, or glutamine, glutamine, glutamine, they don’t recognize that sequence as a sequence to be cut, and therefore that piece stays undigested.

So to make this a little bit more clear in perspective, and again, if somebody heard this, I apologize that I repeating myself, but if you’re so nuts to put the tube in your nose and suck up a little bit of the juices in the stomach, and you put this in a little vial or glass, and put your little finger in there, in a matter of 10, 16 seconds, your meat is gone and you’re going to be gone to the bones. That’s what it takes. You put gliadin in there, and 12 hours later it’s still there, would not go away.

Now it is also important to clarify the notion that in order to induce an immune response from our immune system, the enemy that immune system goes after in general are proteins, or fragment of proteins, i.e. peptides. They don’t go after the amino acids, because the amino acid that we have are very similar as a pool to the amino acid of anything that we ingest: cow’s proteins, the wheat proteins, the fish proteins. What makes a difference is the sequence of these amino acids that makes proteins specific for cows as compared to human beings.

And because the immune system is there to defend us against enemies, they are not belonging to our body. If we are exposed to fragments of proteins, they are not part of our body, what we call nonself, somehow, for example, because we have a leaky gut, then we have an immune response and we generate a collateral damage that we call inflammation. And you heard already concept, there is…inflammation is the heart and soul of what is the disease status, no matter what conditions you talk about, no matter what organ you’re talking about.

I can make an argument that any kind of disease, from cancer to infection to autoimmunity to Alzheimer’s, there is an inflammatory component. So all this to say, if you have proteins that cannot be completely digested and can sit there for hours, and this protein will find a way to sneak through the intestine barrier, that may create problem. And that’s the reason why this can be toxic for many people. I will not say for all, and maybe I’m in disagreement with somebody here, but definitely can create problems.

As matter of fact, as an example, I want to show you here this color-coded fragment, they are not digested, what they do for living. This guy here, this will induce what we call program death to cells, apoptosis. But not just the cells of an individual we see with the disease, anybody. This fellow here is a super antigen, in other words, will induce and have super exaggerated immune response, and therefore an exaggerating inflammatory collateral damage when it’s exposed to the immune system, the host.

 

These two blue guys communicate to the cells to release this protein that you heard a few times today, zonulin, that makes intestinal leak, and therefore create a shortcut, so that more enemies will come through, and will create problem if you’re genetically skewed to do that. And this one here, I’m going to show you in a moment, very interesting fragment they call soldiers, i.e. immune cells on a battlefield, i.e. the intestine, as a requirement to really face this enemy. And when you have the soldiers, these are armed soldiers. And when they got on a battlefield, the intestine, they create collateral damage that is inflammation.

So that’s pretty much what we know in terms of mapping out what this undigested fragment of gluten can do to any of us. Now there are people that may go through this process that would not even know, and people that we get at the other end of the spectrum extremely sick because of that. So because of these two fragments, and because they can communicate the cell to release zonulin, make the intestine leak, anybody that eat gluten will have a situation of a leaky gut. Anybody, not just the people we see the disease of gluten sensitivity, anybody. But the consequence of this, again, can be very different depending who you are.

So what are the steps if you’re genetically skewed that you go through that eventually will put you over the edge and switch from a state of health of a state disease? By the way, before that I keep going, am I losing you guys? Am I talking too technical? You sure? Because we’d start all over again, guys. We stay here until 10 o’clock. I am on a mission. As David was with the brain, I’m on a mission with the guts.

So what are the possible steps that you go through when exposed to gluten that can lead to inflammation? And we will discuss also what we mean for inflammation. First and foremost, the very first thing that happen, you’ll leak. And again, tomorrow we’re going to go in deep details how this all really happened and what are the clinical consequence of that. The second thing that will happen immediately is that as soon as you have this breach in the intestine barrier, and this is uncontrolled passage of this fragment, and God knows what else, the soldiers are called on a battlefield, because there is… Imagine that you have this middle-age city with a wall around, and the only way to get into the city is to have this bridge to come down.

Now somebody blew off the walls and enemies, these attackers, are coming in. The soldiers need to come and protect the city, and that’s exactly what happen. If the soldiers do their job, everything stops here, and again, you would not have any consequences. But if the army they’re attacking the city, overwhelms the soldiers, then you go to the next step that is restructuring intestinal mucosa. When I say restructuring, doesn’t mean necessarily there is damage, but is reorganized so that eventually, functionally, change is characteristic.

And then, again, if beside to have that kind of genetic predisposition you have yet an even more complex genetic predisposition, i.e. that eventually you can lose the war, because its enemies will overwhelm you, you’ve got an intestine inflammation. And intestine inflammation can go all the way to utter destruction, that is the classical outcome of celiac disease. So you’re not going to see anything there because I don’t think that…particularly people in the back. So you’ve got to trust me on this.

So what you’re seeing here are these finger-like protrusions that we call villi. These are the complex machinery that we have in the intestine that really helps to optimize digestion, absorption foodstuff. And these villi now are decorated with antibodies to look at the specific gates in between cells. They are technical tie junctions that dictate how leaky is the gut, or how permeable is the intestine, either way.

So this is a blowup of what we see in a normal situation. Typically, what you see is the decoration of these antibodies at the edge of neighboring cells. And when you see these chicken wire characteristics, that means these doors are closed, these tight junctions are competent, and therefore we are tightly control the trafficking of antigens from the environment into our body.

This happened to be a mouse. And eventually, the same mouse later on was gavaged with only one milligram of gliadin, that’s all. And in a matter of 20 minutes, these gates from closed became to totally open. Totally open. So there is a completely open up of these gates, and therefore these enemies now, they are in the environment. Then gluten can come through. So the bottom line is, what you just saw, and what we just discussed, are three steps that are now well-known and thank God accepted by the scientific community.

Gliadin is only partially digested, some of these fragments communicate with the cell to release zonulin, zonulin is released, is the one responsible for that phenomenon I just showed you, i.e. from door closed to door open, and that makes the intestine to leak, so the fragment of gluten and what else will come in. And now, the enemy is in the wall of the city. It’s within the city, and now the war is moving from outside to inside. And here, where all the immune system will eventually dictate the destiny of if this is going to be clinically evident with disease, or the mess will be cleaned up and we will not even know what’s going on.

The step number two, once you’ve got to this situation, is that the soldiers are called on the battlefields. Now I’m going to show you a movie. I don’t know how much we’re going to be able to see this, but we’re going to give it a try. So let me explain first what you’re seeing here. First of all, the guy in the back there, do you see anything? No. Well, we’ll let you know later on. You do? Maybe if we can bring the lights slightly down, that will help, maybe. But anyhow.

So look at the cartoon underneath first, so we can understand what we’re looking at. These are these finger-like protrusions, the villi that I was telling you about. Imagine that now you cut the villi in a transversive way, now you have a cross-section. So you have this finger-like protrusion, you cut them, and now you look from the top, okay? So what you see now is the cross-section of the villi in which the core here is the core of the villus.

The single layer of the cells are the epithelial cells that cover the intestine, and this is the environment outside the intestine. Okay? What you see here is the cross-section of this core of the villus. This black stuff here are the capillaries. And these green dots that you will see a little bit better are the soldiers, i.e. neutrophils. They are particularly treated in these transgenic animals with a fly gene that makes them to be fluorescent. Okay?

So what you’re going to see now is, on the left, these are the villi of a mouse that has been exposed to another protein, BSA. This is the mouse that has been gavaged with gluten. And this is pretty much what you’re going to see there. See how many of these soldiers are stuck on the wall of the capillaries here, and then eventually start to move out, and get out, and got into the external part, what we call the lamina propria, while these guys here, they keep traveling, and they stay in the lumen.

So in the animals that was exposed to gluten, gluten is attracting the soldiers outside of the capillary, and they start to really get on the battlefield, where gluten and God knows, again, what else, is sitting in there, because it’s been absorbed through this breach in the barrier, while these guys, they keep going. Again, who is close by may see that. But even if you are not that close, you see the mess that is happening here, and this is all due to the simple difference that here you have bovine serum albumen, and here you have gluten. That’s all.

Wow, indeed. I need the light because I don’t see a freaking thing here. Alright. So to summarize, what is the destiny? What happen when somebody eat the McDonald Big Mac? Well, there are three steps. Step one, number one, that is what we call the epithelial events, and the timeline is very short. The movie that you saw, by the way, was a 60 minutes kind of business that was compressed in a minute.

But within 60 minutes, you have the breach of this barrier, the leaky gut, and the soldiers that come right away to face the enemy. But again, because they have to use weapons, they are creating inflammation. So if you are Joe Schmo and you eat gluten, the gluten is only partially digested, communicated with the cell, zonulin is released, the intestine gut leak, gluten and other stuff comes here. And from what we understand, for the vast majority of the people, these soldiers that come on the forefront will clean up the mess, and we don’t even know that that happened. That’s probably the destiny of the vast majority of people.

 

There are other people though, that when they got at that point and the soldiers come on the battlefield, they got so excited about the presence of these nonself antigens…again, it’s not just gluten, but who knows what else. They start to really fight very adamantly to get rid of these enemies, and they use very powerful weapons that we call cytokines or chemokines. And again, when you shoot, there is collateral damage. And that collateral damage can translate in inflammation, and that inflammation can translate in symptoms.

And these are typically symptoms that are engaged when only the innate immune branch of the immune response is involved. What we’re depicting here is the typical example of a situation of gluten sensitivity. Now if you also, you go to the third level, that beside the innate immune branch, the adaptive immune branch is involved with the HLA and whole nine yards, the reticular cells, and so on and so forth, the B lymphocytes that produce antibodies, and so on and so forth, now you’re talking about 1% of the population.

Now you’re talking about the people we see the disease that eventually will have as a consequence the outer insult and the outer destruction in the intestine that is typical of celiac disease. That’s pretty much it. If I was here three years ago, all this was totally unknown, totally unknown. That’s the news number one, why gluten is toxic. News number two. Until the recent past, we thought that gluten is equal celiac disease, and that created tremendous amount of confusion, particularly among my most traditional and conservative colleagues.

They agreed, there is the dogma, if you got sick with gluten you have to have celiac disease. If you do the test and you’re negative for celiac disease, gluten is not a problem, don’t waste your time. Don’t waste your time with the diet and so on and so forth because the dogma is, you don’t have a celiac disease. You don’t have a problem with gluten. Now, look at this. Anybody knows what is Google Trend? No? Okay.

For those that don’t know this, don’t feel sorry, because I was like you until the recent past when my son, 13, now 14, explained me, showed me about this powerful tool of Google. He was looking at the trend of skirt in girls in United States over time. I told him, “What the heck are you doing?” He said, “This is a science project at school for the length of the skirt of the girls.” I said, “Who approved that project?”

Anyhow, so you can compare also different things. For example, in this case I compared three diets, very popular diets, two of them, at least, and I want you to really pay attention to the timeline. We’re not talking about 1804. We’re talking about 2004 here. The low-carb diet in yellow, the fat-free diet in red, and the gluten-free diet in blue. The gluten-free diet at that time was a ridiculous market, less than $100 million.

Now see the trend over time. From 2008 over, gluten crossed the other two lines and never looked back. Matter of fact, we’re talking about…this number has been just recently updated to $4.6 billion in retail that we had in 2011, and the projection is close to $8 billion, with a B, a year. By the end of this day, 60 million Americans will consume a gluten-free product. Now keep in mind that the projected number of celiacs in the United States is 3 million, of which only 300,000, roughly, have been diagnosed. So who the heck are these other 60 million people?

If gluten is good, I mean, if a gluten-free diet is good only for people with celiac disease, who the heck are all these other people? So there is definitely a fad factor of the diet. I mean, it may well be, it may well be. So if Lady Gaga, August 2012, decided to go on a gluten-free diet because she told me, “I want to lose weight.” I say, “You’ve got to be nuts.” Have you guys seen Lady Gaga nearby? I mean, she’s really anorexic. I don’t think that she has to lose any other weight.

But she decided to go on a gluten-free diet for that. But again, I would be dishonest by saying there is no such a thing as a fad factor. However, however, by the same token, if we want to be honest, we also have to admit that besides celiac disease, there are other condition for which the gluten-free diet becomes a medical necessity, that is not just celiac disease. And these are the people that if they eat gluten, they are sick, no matter how you want to see it.

And the only way for them to be leaved of the pain of the joint, the foggy mind, or whatever you heard already, is to be gluten free. And indeed, the ones that are gluten free now for no medical necessity are the ones that are occasional consumers. And again, I don’t know what to make out of this, folks, because honestly, they have all the rights to do whatever they want, because if they feel more energetic or they feel fine or because they want to go back to the way that our ancestors used to live in terms of lifestyle, they have all the rights to do that.

But the ones that have medical necessity, they capture very much my attention, because these are the people that come to clinic. These are the ones they are sick. They are out of commission. And again, our mistake for many, many years was that we were totally blinded to anything other than celiac disease, the autoimmune response to exposure to gluten. Prevalence roughly 1%. Sure, we knew also that that there is a wheat allergy component, much rarer than celiac disease.

But again, what we missed, and we just learned relatively recently, is the third kid on the block here, this non-celiac gluten sensitivity. Gluten sensitivity there, as you heard already, has mainly an innate immune component that drives the inflammatory process. Well let’s talk a little bit about these conditions. I’ve seen the disease. I don’t want to spend too much time, because I have so many other things that are interesting to talk about. This has been said many times.

But again, to set the record straight, for those that don’t know the history of medicine, that it’s always a matter of wisdom to dig into history of medicine. We didn’t know that gluten was the culprit of celiac disease for a long time. This condition supposedly was described the first time 2,000 years ago by a Greek doctor. But it was this fellow here, a Dutch pediatrician, very recently, that connect the dots and link celiac disease with gluten.

Matter of fact, he made a very interesting observation. Before he discovered this link, the destiny of these kids was not great. One third of them, 30 to 35%, would die of celiac disease. That was the destiny. The way they worked was that if somebody will eventually make the suspected diagnosis, a pediatrician, then we’ll send these kids to the hospital and the doctor at the hospital will say, yes, this is celiac disease. Go home and come back in 3 to 6 months.

If your son or daughter is still alive, you can take them back. That was the destiny. And during these 3 to 6 months in the hospital, the only thing that these kids were fed were bananas. That’s the reason why they’re called banana babies. There are still a few around. Now, nevertheless to say that who made through would never touch or smell or look at anything yellow in their lives, because this was really horrible, horrible.

Then this guy made an interesting epidemiological observation. He realized that during World War 2, when there was scarcity of wheat flour, rather than use wheat flour, people would use potato starch flour, the mortality went to zero, and resurfaced to 30 to 35% when the war was over and wheat was available again. To prove the concept, he did a clinical trial that now would be not only laughable but nobody would eventually even…any epidemiologist will kick your ass and say, “Get out of my face.”

Six kids, that’s all. He took six kids and gave them gluten, make them sick, took gluten away, and then make better. That was it. And this happened in the early ‘50s, 1950s. Before this pivotal experiment, or clinical trial, whatever you want to call it, we had no clue what was the problem. And matter of fact, the fact it was gluten in wheat that created the problem became clear only at the end of the ‘50s, early ‘60s. So this is something very, very recent.

Fast forward to 2013, we learned so much more. We thought that this was an exclusive pediatric condition. It’s not anymore. We thought that this was a food allergy. It’s not anymore. We thought that to have celiac disease you have to have fair skin, you’ve got to be from the North Pole, you have to be a first cousin of Santa Claus. It’s not true anymore. What we now know, that this is bona fide a true autoimmune disease. One of a kind, but still an autoimmune disease.

Why one of a kind? It does have the same ingredients of the recipe. You have to be genetically predisposed, peculiarity number one. Many genes involved, like many autoimmune diseases, like MS or rheumatoid arthritis, Type 1 diabetes, and so on and so forth, but with an unbelievable penetrance of these two genes here, DQ2 and DQ8. These HLA genes, they are present in almost the totality of people with celiac disease, 97 to 98%.

There is no other conditions with such high penetrance. Diabetes, they are similar HLA haplotypes, but we’re talking about 70%. Rheumatoid arthritis, 65%. Here, we’re talking about 98 plus. True, one third of the general population will have these genes will never develop celiac disease, so having this gene doesn’t mean that you have celiac disease. It means you are genetically compatible. And we in clinic look at these genes not to confirm celiac disease, rather to exclude it, because the negative predictive value, i.e. that you can predict that somebody does not have celiac disease if they don’t have this gene is extremely, extremely high. Peculiarity number one.

Peculiarity number two. The autoantigen that is responsible for the immune response against our own body is known. It’s this enzyme is called tissue transglutaminase. Matter of fact, the antibodies against these enzymes, the tTG antibodies, is one of the best and most sensitive and specific tests in human biology for diagnostics that we have. Very sensitive, very specific. But what really sets celiac disease aside of any other autoimmune disease is the second element of this equation, the environment.

We don’t know what make people sick with diabetes, or MS, or rheumatoid arthritis. It is indeed gluten, the indisputable trigger of celiac disease. So much so that if you put these people on a gluten-free diet, that we all know this is the treatment celiac disease, and again, and we do this right, the symptoms go away, the autoantibodies go away, the autoimmune insult, i.e. the damage of the intestine go away. If this individual will not share with you that he or she has celiac disease, there is absolutely no way to find it out.

Now, you need to really appreciate what happened in the scientific community when celiac disease was moved out from food allergies and was put into the autoimmune pot. The wisdom that is still strong among many people is that autoimmunity is a one-way street. When you got there, there is nothing you can do about it. It’s a way of no return. The immune system goes in automatic and your destiny is that you will be consumed by the autoimmune disease. Celiac disease is telling otherwise.

It’s telling us if you find a way to stop this interplay between the genes you are born with and the trigger from the environment, you can stop the autoimmune process and you can bring everything back. And now, this is used as a one of a kind autoimmune model to study conditions for which we have no understanding what are the triggers from the environment. What is the results when these two elements, genes and environment, they come together?

That’s been the other confusion. You look in a classic textbook, that’s where you look at. What we called in the past the classic celiac disease, again, pediatric conditions, Caucasians, typical GI symptoms like chronic diarrhea, big belly, lack of appetite, failure to thrive, and so on and so forth. When I was in medical school they told me this is a common denominator. You don’t have to run tests or do anything to these kids. Look at the parents. If they have their hair up in the air, bag under the eyes, and the kids is pissed off, this is celiac disease unless they prove otherwise.

That was the way that I was taught to make the diagnosis. Now this is a picture taken in London in the late ‘30s. If you look at something like this, the first thing that click in your mind, it should click in your mind at least, are the malnourished kids of the third world country, because they look exactly the same. These are malnourished kids, by all means. It’s like kwashiorkor. The difference being, that the malnourished kids in the third world country, they look like this because they don’t have food.

These kids look like that because they have all the food in this world, but it would just go through, because it would not be digested and absorbed, and therefore it’s like they were starving, and that’s the reason why they were dying. Now look very, very carefully, very carefully to this picture, because if you will see anybody in your clinic that would look like that, take your iPad, iPod, iPhone, i-something and take a picture, because you’re not going to see this anymore.

This is extremely, extremely rare. Extremely rare. What you see now is this. This the real celiac disease. The list is too long to go through all this. It suffice to say that rather to be a gastrointestinal disorder, celiac disease as truly a systemic disease. There is no organ of tissue of our body that is spared by the autoimmune inflammatory attack triggered by celiac disease. And this goes back to a concept that I’ve been telling now for a long time, and I apologize again to repeat myself, the gut is not like Las Vegas.

What happen in the gut does not stay in the gut. So if you have these attackers that come through and immune cells are activated, sometimes these immune cells they stay in the gut. They stay just in there and you create the inflammation that created the typical GI symptoms. But some of the times, once they’re activated, they leave the gut, they go somewhere else. They go in the joint and they do joint pain. They go into skin and you will have the blistery conditions that’s called dermatitis pediformis.

They go to the brain and you develop symptoms that can go from headaches all the way to seizures. And I can go on and on and on. And matter of fact, the most frequent way the disease present itself nowadays, sure enough, is not diarrhea, weight loss. It’s anemia and chronic fatigue. That’s by far the most frequent way the disease presents itself nowadays.

Long story short, this is a clinical chameleon. If you don’t know what you’re dealing with and you are an hematologist that you are looking at an individual that has anemia that is not corrected by iron supplementation and you don’t know about celiac disease, the risk is that this guy will go through gazillions of tests, taking tons of iron that you can build a second Eiffel Tower, and that will not solve the problem when the solution should be very simple under your nose.

Now I was skeptical because I also was among the folks that believed that problem with gluten has to be celiac disease. And I was really reluctant to really change the state of mind, because I didn’t see it. I just didn’t see coming. And again, this is a shortcome, guys, when you have two camps with a wall, not a line in the sand, a wall, that is the conventional medicine and the complementary alternative medicine that don’t talk each other. That’s the reality of the story. So I think that the best way to exemplify how moron I was is to present a case.

This is a lovely lady, 40 years old, with history of stomachache and heartburn. So, reflux, classic gastroesophageal reflux. She was put on the purple pill, and sure enough, the reflux didn’t go away. This also not a major, strange outcome. I don’t know if you know, when protein pump inhibitors were approved by the FDA, the clinical trials, efficacy was 38%. Thirty-eight percent means that you know already, two out of three people that take the purple pill would not respond. That’s pretty much it.

But that’s not what really worried the situation. The situation was really taking a turn for the worse here. A month later, she started develop headache, dizziness, numbness of fingers, and paresthesia. And the primary physician immediately got extremely concerned, because she thought that her patient was going through a situation of multiple sclerosis. And indeed, I believe correctly so, first thing that she did was MRI and evoked potentials, and thank God everything was negative.

Then other conditions were entertained, like Lyme disease, Epstein-Barr, various pernicious anemia, Lupus. Everything was negative. Now it’s two months pass by, she has these problems, and they don’t know what’s wrong with her. Because of this persistence of the symptoms for the reflux, and not for none other reasons, she underwent an endoscopy that was reported as normal. The only thing that they said, there was a slight increase in the soldiers in the forefront, what we call technically the intraepithelial lymphocytes.

She was also screened for celiac disease and test negative, meaning that she had anti-tissue transglutaminase antibodies negative. The only thing that she had positive were the anti-gliadin antibodies of a classic IGG. But because the tTG was negative, she was told that she had no celiac disease, and therefore no business to go on a gluten-free diet. She came to us for a second opinion. I gave her the same response.

This was roughly six years ago, seven years ago. So I said, “Look, your antibodies are negative. These anti-gliadin antibodies doesn’t mean too much. You need to go back and regroup, and definitely focus on other conditions, because otherwise you miss the boat here, and eventually you’re not going to be treated correctly.” Despite that advice, she went on a gluten-free diet, and managed to come back to me not for anything, but to tell me how moron I was.

Because she said, “Call me whatever. Maybe I don’t have celiac disease. I don’t dispute that, but within a week my neurological symptoms pretty much resolved. I only have some occasional tingling. And within three weeks, all my GI symptoms are gone, the reflux and so on and so forth.” So what is gluten sensitivity? What we define as gluten sensitivity? Well, again, now we’ve been convened twice. One in London three years ago, and the other one in Munich last year, to try really to grasp the concept of what it is so that we can understand each other, at least we can give definition.

So what we came up with, you can imagine the amount of animosity about this around the table to discuss the matter, is what it is not. So we can tell for sure that the people that have gluten sensitivity, they react to exposure to gluten, but both allergic autoimmune mechanisms have been ruled out, meaning that all the tests for checking for wheat allergy are negative, the serology test results on disease are negative, the biopsy is normal.

They may have, indeed, these anti-gliadin antibodies positive, not all of them, and the symptoms are present but they are not of any help, because they overlap tremendously with celiac disease, so we cannot distinguish on a clinical ground. And they resolve the symptoms following implementation of a gluten-free diet, possibly on doing a double-blind challenge so that you avoid the placebo effect. That was the definition that was given in London.

This is our experience, our center, because in the last seven years we’ve been digging into this. And again, as usual, what happened to us, we were super-duper crucified about this. But our numbers, and again these are estimate that means nothing, because if I have to tell you how frequent it is, the answer is, I don’t know, because we don’t have tests like we do have for wheat allergy and celiac disease have been validated to make these numbers strong and valid.

In our experience, based on the criteria I just told you, roughly 6%, meaning 6 times more people than celiacs, seems to be affected this condition. What are the symptoms? These are the list. On the top of the list, abdominal pain. These folks are diagnosed, or labeled, as IBS. And matter of fact, now there are clinical trials published double-blind and so on and so forth that support the notion. Forty percent eczema, one third with headache.

 

This is fascinating to me, this foggy mind. I tried the gluten-free diet, strict, for myself. I still foggy-minded, so I’ve got to have something else. Also, my fatigue did not resolve. So one third of the people, they have fatigue, diarrhea, depression. So you see the list of the symptoms. There is no way that you can distinguish people with gluten sensitivity with celiac disease. There are tremendous overlap there.

So this is the classification that we decided to give to the situation here of the gluten-related disorder based on the pathogenesis. Autoimmune, you talk about celiac disease. Allergic, you talk about wheat allergy. Non-autoimmune, non-allergic, possible innate immunity. Now the question mark is pretty much out of there, gluten sensitivity. The problem, again, that while we have a biomarker for celiac disease and wheat allergy, we don’t have biomarker for gluten sensitivity yet. We’re working on it. Several people, they are trying to validate biomarkers.

This is a table that I put together more for myself. It’s a cheat sheet to really navigate what are the differences among these three conditions. And again, based on different parameters, you can really have an educated guess what you’re dealing with. For example, the time interval between gluten exposure and certain symptoms can be measured in years with celiac disease. We know people that can eat gluten for 50 years and then develop celiac disease later on.

Not definitely gluten sensitivity. We’re talking about a much shorter period of time. We’re talking about hours or days, while wheat allergy can be minutes. You can develop anaphylaxis in a matter of seconds, by the way. Pathogenesis, we know that for celiac disease it’s autoimmune, gluten sensitivity now, again, there is quite a strong consensus innate immune and allergic for, of course, wheat allergy.

HLA, tremendous penetrance as I was telling you, the HLA here. Gluten sensitivity is half the way, 50% they are HLA positive, 50% they are negative, while in the general population it’s 30%, 35% percent. That is pretty much what we see in wheat allergy. Autoantibodies, by definition, are almost present here, always absent here. Enteropathy, so the autoimmune insult is always present here, never here. Here there is only an increase of this intraepithelial lymphocytes, but not damage of the villi.

Symptoms, complete overlap, you can’t make the distinction. Complications. We know there are comorbidities with celiac disease, long-term complications like diabetes, Hashimoto, you can develop osteoporosis and so on and so forth. As far as we know, so far, we don’t know, but assumes that there are no such thing. In other words comorbidity with gluten sensitivity.

So what are the take home message in terms of diagnosis? This is not rare, cannot be distinguished from celiac disease purely on a clinical basis, can present with vague, nonspecific systems like IBS-like. A gluten-free diet can be considered only when another forms of gluten reaction and other cause of the patient’s symptoms have been ruled out. This is an important concept guys, because if you give it a try on a gluten-free diet, the tools to establish in which part of the spectrum this individual is are gone.

The autoantibodies will not be positive anymore. And because for celiac disease this is a commitment for life and needs to be done in a very strict, compliant way, you’ve got to rule out celiac disease and before that you give it a try with this diet just to see if you’re dealing with gluten sensitivity. That one is for me, not for you. Listen to your patients. Yeah, do that. So, where are we with the time? Wonderful.

So, I’m going to dig into the most controversial questions about gluten sensitivity. Not for you guys, but for the other side of the coin here. Schizophrenia and autism. There is a huge debate, far from being settled, if indeed gluten has anything to do with these two conditions. And again, particularly for autism, there is an aura about the intervention and the gluten and casein, how they can eventually be part of it, and so on and so forth.

Well, there are two papers that have just been published back-to-back, one from our group, and the other one from Peter Green’s group in New York. Now you see here the anti-gliadin antibodies level…these are, again, the old anti-gliadin antibodies were the ones that were pooh-poohed. They said, “We don’t want to use anymore, blah blah blah.” They have been reshoveled back.

You see in red, the autistic kids versus the unaffected sibling versus the healthy controls. You see both IgG, particularly IgG, less IgA, how this is more elevated in kids with autism. So it seems that at least a subgroup of kids with autism, they may have elevated anti-gliadin, IgG antibodies.

And then you see here the comparison of gliadin, deamidated gliadin, and tTG. By definition, TTG is negative, and that’s created tremendous, again, confusion, because people, they were skeptical about this role of gluten and autism.

Say, “If these kids, they don’t have celiac disease, how can they have a problem with gluten?” And again, now I believe there is an open mind approach that gluten can give you problems outside celiac disease. But this, once again, you see that it is the anti-gliadin antibody, the IgG, and not the deamidated or tTG that give a problem. A much more complex study was done and published.

Actually, this is not impressive anymore result, in which…what the heck is going on here? Anyhow, in which pretty much these kids, these are still kids with autism, but these are kids on a regular diet compared to the ones who go on a gluten-free diet. And you see how the antibodies will go down once these kids will be placed on a gluten-free diet. So you have anti-gliadin IgA antibodies, anti-gliadin IgG antibodies. They all pretty much will go down when they go on a gluten-free diet.

And here, you see the same phenomenon here, but also the total IgA, and the milk Ig antibodies, same destiny. When they go on a gluten-free diet and a casein-free diet, these antibodies, they go down. So definitely, the culprit, the instigator that is gluten and casein in this case, are the ones that drive this increase in antibodies. They go back to normal when these kids they are placed on an elimination diet.

Gluten and schizophrenia is an unbelievable field. And again, I don’t have the time to go through. But again, this is a matter that’s been discussed for ages. And once again, back to World War 2, people they made interesting observations. On one side of the pond, i.e. Europe, there was scarcity of wheat during the war, and the number of schizophrenic cases decreased dramatically. On this other side of the pond, we still have wheat in the United States.

Actually, because of the scarcity of meat and other commodities, there was an overuse of wheat and there was an increase of people with schizophrenia that were admitted in mental hospitals. So that was how this debate started. And then there was this papers, there was this gluten connection between schizophrenia and celiac disease. And then this paper that really settled the debates, because once again, the skeptic will say, “If gluten would be important to instigate this schizophrenia, you will expect that rather than be 1%, the prevalence of celiac disease among schizophrenic patients should be 10, 15, 20%. It is not the case. It’s 2%. That means 98% of these people, they have no business to go on a gluten-free diet.”

Here, this paper was the first of a series of papers. This was published by our group and then followed by at least another three groups. This was in 2009, already now four years in which gluten sensitivity tends to be responsible for almost 20% of cases of schizophrenia patients. And again, this is another paper that followed after that. And once again, this other paper that talk about the recent onset psychosis and multiple episodes of schizophrenia.

And finally, in China, that we thought that China didn’t have celiac disease. What an interesting epidemiological phenomenon there. When the first McDonald’s was opened on Tiananmen Square, and now using the staple gluten versus rice is a social statement. That means you are climbing the ladder of the wealth in China. And we’ve seen parallel this increase of gluten-related disorders, including the situation with schizophrenia, in China.

So, how this comes about? There are two non-mutually exclusive theories how gluten can create problem in terms of behavior. They both start the same way. You eat gluten, partially digest it, leaky gut comes in, and there is these cells that will go after, you have seen in that movie, and they’re armed. Now the problem is that once they got there, one theory said, “Well, there is no inflammatory business here. These fragments that come through, some of them, they are structurally similar to chemicals that control our behavior.”

They are called endorphins. As matter of fact, from gliadin they’re called gliadorphins, for casein they’re called casomorphins. I’m pretty sure that you know all this. And eventually once they are absorbed, they go through the bloodstream and go through the blood-brain barrier, reach the brain, and makes these people change behavior. And depending on their genetic background, they can develop schizophrenia, autism, or whatever.

The other theory, that is more the inflammatory theory that is taking more and more and more steam because now we have evidence in animal models. Not only that, but on biopsies on cadavers and autopsies and so on and so forth, is that again, when these steps they come and these cells are activated, because again, the gut is not like Las Vegas. Some of this, they travel and they go to the brain and they create this state of neural inflammation.

 

Now we have evidence of that. This is a paper that we just published. The increase of this enzyme, the Transglutaminase 6, there is a nicer form that is specific for the brain. tTG2 is the gut, tTG3 is the skin, tTG6 is the brain. We see a huge elevation of tTG antibodies in a very large proportion of schizophrenia patients, so much so that we believe that this represent a biomarker of a gluten-driven schizophrenic neuroinflammation process.

How many people we’re talking about? We’re talking about roughly 15% to 20% of schizophrenia patients. That means that 80%, eventually, if this is true, will not respond to a gluten-free diet. So the idea, the working hypothesis, again, you eat gluten, partially digest it, the fragment that releases zonulin, leaky gut, this is activated. These folks will eventually either stay in the gut and create the enteropathy, or travel to the brain.

Whether the gut or brain, you damage the cells. The enzymes, tTG6, there is an intracell enzyme, leaks out. The immune system never seen this enzyme before, consider this something that does not belong to our body, will mount an immune response that eventually can be detected in the blood as a biomarker of neuroinflammation. And we are using that to do the ultimate proof. We’re doing a clinical trial in which we take schizophrenic patients with positive anti-tTG6 antibodies, we bring in-house because they will not comply with the diet, and they go on a gluten-free diet.

Now we have handful of patients that are part of this report. Amazing results. No drugs whatsoever. These folks are almost together as I am. That does not mean that much, but you know. And this is the ClinicalTrial.gov, where you see that this clinical trial is registered. I will spend my last 20…what is that? Time? Twenty-five minutes on the most exciting part that I want to share with you. This I am very passionate, because after all, I am a pediatric gastroenterologist.

And in general I am known among my young patients as the poop doctor. Now we’re going to talk about shit. Are we recording this? We are. Oops. We’re talking about poop. So the idea about the evolution of autoimmune diseases, as I told you, it was always based on the question you born with those genes, it is destiny. You will develop celiac disease. You will develop diabetes. You will develop breast cancer, Alzheimer’s, whatever, because it’s destiny. You are born with these genes and it’s destiny.

You already heard from Dave that actually now people are starting to think about epigenetics and that the story changes, and so on and so forth. But what is behind this epigenetic concept? So this fantasy or is factual? Well, tomorrow we will talk a little bit more about the recipe for pathogenic autoimmune diseases, because we spoke at length about the genetic component and the environmental today.

We spoke very little about this mucosal barrier, just a touch, but that’s what we’re going to discuss mostly. But if this indeed, genes and environment are important, and you see these epidemics. Look at the epidemics of autism spectrum disorder. I mean it. Look at the timeline here. We’re not talking about centuries. We’re talking about decades. If you have these epidemics, cannot be due to mutation of genes.

The mutation of genes are measure in centuries. It takes generation to mutate a gene. This is in a single generation within these tremendous epidemics, from 1 in 5,000 to 1 in 88. That’s what we’re facing right now with autism. We see the diseases even more mind-blowing, because…stay with me for a second. Because we know the environmental trigger, our proposition, our dogma was, “You’re born with the genes of celiac disease, you eat gluten, and gluten comes indisputably in the first year of life, when baby food comes in, that’s the time in which the autoimmune process starts.

Now if you develop symptoms at 2 years of age or 72, it depends how aggressive is the immune system. The more aggressive, the more damage you create in the intestine, the sooner you develop symptoms. The more slow-paced, the more time it would take.” That was the premise. And then we did this study that was focused and aimed at totally different reasons that really trashed this out of the window.

Now talking about the difficulty to publish a paper. If I tell you the tribulation to go through this, first of all to myself, to believe in this study. This was a cohort of 3,000 healthy adults followed for 50 plus years. The purpose of the study, we wanted to know that 1%, i.e. 30 people that have celiac disease, how they switched from no symptoms to symptoms over time. That was the purpose. We were shocked to learn that in this period of time, celiac disease doubled every 15 years.

 

Now these are the same Joe Schmos. There is no mutation here. So in the ‘70s, 1 in 500, 1 in 250 in the ‘90s, and in the 2000, 1%. There were people that were eating gluten for 56…there were two ladies that were eating gluten for 70 years, they had no problem whatsoever with it. And all of a sudden they lost the luxury to tolerate gluten, and they switched from tolerance, i.e. state of health, to disease, and they developed celiac disease.

So, sure, you’ve got to have the genes. Absolutely you have to have the environment. But to develop the autoimmune insult, you’ve got to have something else, because they are necessary but not sufficient. So what else we are talking about? Now these two questions are the holy grail of the future of the desire of the impossible mission that we’re going after. First question. What kind of tricks did these two ladies use to tolerate something that is indisputably a trigger of autoimmunity? Because if we learn how they did that, imagine what we can do.

Prevention, primary prevention of all diseases of human kind, that’s what you’re talking about. That is an impossible mission, and I believe this is going to win a Nobel Prize who is going to figure it out. I would definitely play bocce by then. The second, that is more approachable is, what happened to them that made them to lose their luxury? They lost the capability to tolerate gluten.

So how we rewrite the natural history of celiac disease? The epidemic of celiac disease is driven by many factors. They are not all mutually exclusive. The quality of gluten, the quantity of gluten, the breastfeeding, the maturity of gut function. But this guy here, the change of the bacteria that live with us, it is now the ones that’s been the focus of an extremely aggressive studies by many, many researchers.

What is interesting that if you talk about the microbiome, there are already 29 papers published on the matter. Most are cross-sectional studies, so they take a population of kids with celiac disease, a population of kids without celiac disease, other certain agent, they compare them. There is only one prospective study that we finished relatively recently in which you take kids from birth and you follow over time. And you see who develop celiac disease and who does not, and see what kind of different composition of bacteria they have in their guts.

So why the microbiome is important? We know already, for example, by this study, that if you are born by C-Section, so that you do not inherit bacteria from your mother, the chance that you develop celiac disease, and matter of fact, many other diseases is two to three times more than normal vaginal delivery. Because if those bacteria that live in peace with our mother will be transmitted to us during normal delivery, they probably will live in peace with our genes as well, because we’re genetically similar to our mothers.

But if we are born by C-Section, bad guys and good guys will come in, some that will live in peace, and some will be very belligerent. So this is a study that we published, again, very recently, that changed completely the landscape. And in my humble opinion, is representing a shift of paradigm, at least the way that I think about this entire ordeal. Why? Because there is no question, at least…

Well, let’s put it this way. I thought that there was no question that we are the most sophisticated beings on the face of the earth. I mean, after all, have you seen a congregation of ants to have a meeting like this, or chimpanzees? No. We are definitely the most sophisticated dogs around the block here. I don’t know about you guys, but the Human Genome Project was completed and found out that we’re…actually, this is 25,000 now.

We’re made by only 25,000 genes. My self-esteem went to the toilet. We are genetically rudimental. While we were in elementary school to section the worm, the one that live under the ground, we’re talking about 90,000 genes there. The worm. Do you remember what I told you, pay attention to that number of the genes in wheat? Hundred fifty thousand genes. So wheat, a plant, is five times more complex than we are, genetically speaking.

Not only that, but we are 99.95% identical to chimpanzees, only 400 genes different. We are 92% identical to a mouse. A mouse. Have you ever seen a mouse give a speech? Or did you entertain in a political discussion with a mouse? So how come that we’re so complex? Unless we do not open our mind and realize that we live from birth to death together with a parallel civilization that is this complex mix of bacteria that together generate 100 times more genes than we are, then we would not understand our complexity.

So in other words, it is my opinion that we are made of two genomes. The human genome is very rudimental, that we inherited from both parents, that is stable. If there is defective in the genome, will not go away, because if you have the genes for celiac disease or autism or schizophrenia or Alzheimer it will not go away and that’s the end of the story. But we also have a second genome that is microbiome that again, as I told you, if we’re lucky, we inherit them from our mothers, and different from the human genome, is extremely dynamic, can change all the time.

And that’s the essence of epigenetics. So in other words, if you consider, and forgive me again, I shared this many times, but if you consider the human genome as a piano with 30,000 notes, or 25,000, whatever we have, one for each gene, and let’s say that 300 of these notes are defective because if you struck this you play the song celiac or diabetes or whatever you like it. That piano would not give any sound unless there is a piano player, i.e. somebody that sits there and play the piano, and the piano player, in my humble opinion, is the microbiome that is extremely dynamic.

It can change over time. Depends who sits at the piano. You have different kind of music comes out. So back to these two ladies that for 70 years were able to tolerate gluten. Let’s say that they have, for 70 years, Elton John sitting there, touching 200 or 300 notes that you’ve got to touch in order to play the song celiac. Despite that they had those genes, they didn’t develop it. And let’s say that at some point, when they turned in their 70s, they had a surgery, they took antibiotics, they took a trip to Cancun to have fun down there, or whatever.

Now they have the microbiome that changed from this guy, let’s say, to Ray Charles. So Ray Charles now can touch all the notes, and here we go, to play the song of celiac even at 70. Because this is the only way that I can explain the inexplicable. And how you can figure it out? Now we have a way, i.e., when these two parallel world, the human genome and the microbiome will play together, what you do, you active the specific metabolic pathways. And when you do that, you produce substances, metabolites, that can tell you who is sitting at the piano.

So if you hear music pop, so you have a metabolic profile that suggested these guys sitting, you know they are safe, because this guy cannot touch all the genes that make you develop celiac disease. But if you all of a sudden, you see this coming up, you know that this guy is sitting there, and therefore it’s a matter of time, and this individual will develop whatever. Is this fantasy? Absolutely not, guys.

Let me go straight to the point. So this is, for example, the metabolome analysis of these prospective studies that I was telling you about celiac disease. Yeah, right. I don’t see that either. What is 15, 10, 5? What is that?

Man in Audience

Eighty.

 

Dr. Fasano

What?

 

Man in Audience

Twenty.

 

Dr. Fasano

Twenty. I’m done. No, no, no. I’m done. So, see this blue line? This was a kid that developed celiac disease. Look at this black line. This is a kid that developed Type 1 diabetes. Now that metabolite, that happen to be lactate, that is a metabolite produced by a microorganism that is a good guy, that’s called lactobacillus, went up, and as soon as it start to go down, six month later, this guy lost tolerance and developed celiac disease.

This is incomplete, but it was the same story. This guy went up, and then went down, and in roughly two and a half years, this guy developed Type 1 diabetes. So if this pilot study can be expanded to large numbers, do you realize what we have in our hands here? The power to see in the future who is going to come down with an autoimmune process. Imagine that. Imagine that. If you take the urine and look at metabolites, now you can start to segregate, who are the normal people, the one in black, who are the siblings or people with autism, the one in blue, and the ones that have autism, they are way different from the others.

 

Magic? No. This is what we’re going to do in terms of our profession here. Same story here. You see control here, autistic here, well separated. So what is pretty much the future, and how this will be translated, let me go straight to the point. The best way to predict the future is to create it. Yes, it’s cheating, but this is the way to do it. Because if we create it, we know what’s going to happen.

And the reason why there is a lot of animosity between traditional medicine and complementary medicine is because we see life in a polarized way. We are both wrong and there is a word of wisdom when you say it’s like dating. You’ve got to really give in a little bit and find ourselves on a common ground. How? What I’m talking about? Classical example. Traditional medicine debated this issue on a gluten-free diet. It’s true, not true, and so on and so forth, and go for what they called the Cochrane analysis, that is the ultimate way to say who is right, who is wrong.

And the Cochrane analysis concluded that of all the studies so far that have been published in autism and the goodness of put these kids on a gluten-free diet boils down to six studies. Three of the six studies said that a gluten-free diet does nothing, and therefore is useless. The other three studies say that the gluten-free diet is very useful, and therefore the kids should go on a gluten-free diet. Conclusion? We don’t know.

The best way to do it is to increase the number of studies to see who is right, who is wrong. Like to say, this is garbage. If you put more garbage, we will find out what the heck is going on. The reality of the story is that if we accepted these conditions, all the conditions humankind are not homogeneous conditions, but are final destination and how you got there can be different path. For example, with autism.

It is possible that a certain percentage, they have autism because of dysbiosis in the gut, others with a genetic mutation, other with oxidative stress, and so on and so forth. And let’s say that 20%, they reach their final destination through the gluten sensitivity. Now if you do the intervention, let’s say the gluten-free diet, and you take 100 kids with the assumption that only those 20 that have gluten sensitivity will responded, and you put them on a gluten-free diet, only the 20 will respond.

 

The conclusion is failure, because 80% did not respond, so the efficacy of the gluten-free diet is crap. We should not use it because it doesn’t work. Now take the same population, and before they put them on intervention, again it’d be the gluten-free diet or probiotic if you think of dysbiosis, you start to see who is who, and say, “Oh, I know that these 20 kids, they have the gluten sensitivity”, and put only those on a gluten-free diet. Now you have 100% efficacy. Success.

So let me tell you, as a poop doctor, how I see the future. Not us. This is not going to happen in our generation. The next generation of physicians will do the kind of business, personalized medicine this way. The patient comes in. First of all, they take the chip of their genome and put in the computer so that they know what kind of genome they have. While they do this, they will collect stools, will go in the machine.

By the end of the visit, half an hour, they will have the microbiome of these people. They match the group in the computer and say, “You have the microbiome that is living in peace with you. There is no dysbiosis. Despite that you have the genes to develop Alzheimer’s, you’re going to be fine.” Or, if they find that there has been a modification of the microbiome that now put at risk the individual to develop the problem, or the problem is already in the making because the metabolites shows how, they will be intervened so that this is not going to happen.

That, in my humble opinion, is the future. Am I a visionary? Am I a dreamer? Absolutely. No question about that. But guess what? I don’t know if you saw this amazing movie. Anybody saw Ratatouille? Anybody who has kids did it. If you have no kids, or you never seen this movie, you got to see it. There is a lot of wisdom there. One of the most hateful figure was this individual that Anton Ego, the guy that insisted that a cook cannot just be anybody.

You born and you are great as a cook. Imagine a rat to be a cook. But at the end, he had to change his mind. And the quote that I love to share with you is this. “The world is often unkind with new talents, new creation, or new ideas. The new needs friends. Not everyone can become a great artist, but a great artist can come from anywhere.” If we all will have that kind of open mind, we will do the best service possible to the people that come to us to seek help because, after all, if we decide to embrace this profession, it’s because that’s our mission. Thank you so much guys.

 

Dr. Blyweiss

You’re listening to the first of two lectures presented by Alessio Fasano, MD. In this last lecture, Dr. Fasano discussed the science behind the spectrum of gluten-related disorders, from celiac disease to gluten sensitivity, and its impact on other chronic diseases. Cell Science Systems has several assays relevant to this lecture series, the first being markers which determine genetic predisposition for celiac disease.

This includes the HLA-DQ2 and DQ8 genes. Also available are various antibody markers, such as tissue transglutaminase, tTG, and deamidated gliadin peptide, DGP. As well, ASCA, anti-Saccharomyces cerevisiae antibody, found primarily in inflammatory bowel disease patients with Crohn’s disease. Additionally, cellular analysis for gluten and other food sensitivities using the Alcat methodology is available.

These assays are available to providers in various single and multiple assay configurations. To inquire for additional literature or research, you can contact the lab at info@alcat.com.