The Gut Health Podcast

Is a leaky gut really the root of your ailments? Here’s the science.

• Kate Scarlata and Megan Riehl • Season 2 • Episode 17

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Is "leaky gut" real or just another wellness buzzword? In this episode of The Gut Health Podcast, we cut through the controversy with Dr. Alessio Fasano, a renowned gastroenterologist and microbiome expert from Mass General Brigham. Dr. Fasano explains what happens when the gut’s protective barrier is compromised, resulting in increased intestinal permeability, and how this can affect not only gut health but also overall well-being. 

While some level of intestinal permeability is essential for health, in the presence of an altered gut microbiome, it can allow harmful molecules such as bacterial endotoxins and undigested food particles to pass through the intestinal lining. This can lead to inflammation, immune system activation, and may contribute to a variety of health issues, including autoimmune diseases, gastrointestinal disorders, heart disease, and more. 

We explore the molecular mechanisms that control intestinal permeability, examining how factors like epigenetic changes, diet, stress, and environmental factors can all impact the integrity of the gut barrier. Dr. Fasano breaks down the latest research on how intestinal permeability interacts with the immune system and other organ systems, highlighting the complex bidirectional relationship between gut health and overall wellness. 

Join us as we explore cutting-edge research on gut health, from breakthrough treatments to personalized diets and biomarkers for gut permeability. Tune in for expert insights and practical strategies—like a plant-forward diet and stress management—to strengthen your gut and overall well-being. 


References:

Effects of dietary components on intestinal permeability in health and disease. 

Unfermented B-fructans Fibers Fuel Inflammation in Select Inflammatory Bowel Disease Patients. 

High FODMAP diet causes barrier loss via lipopolysaccharide-mediate mast cell activation

A Randomized Placebo-Controlled Trial of Dietary Glutamine Supplements for Post-Infectious Irritable Bowel Syndrome.

Bovine Colostrum in Increased Intestinal Permeability in Healthy Athletes and Patients: A Meta-Analysis of Randomized Clinical Trials. 

What to do about the leaky gut?






Learn more about Kate and Dr. Riehl:

Website: www.katescarlata.com and www.drriehl.com
Instagram: @katescarlata @drriehl and @theguthealthpodcast

Order Kate and Dr. Riehl's book, Mind Your Gut: The Science-Based, Whole-body Guide to Living Well with IBS.

The information included in this podcast is not a substitute for professional medical advice, examination, diagnosis or treatment. Always seek the advice of your physician or other qualified health care provider before starting any new treatment or making changes to existing treatment.

Kate Scarlata MPH, RDN:

Thank you. The Gut Health Podcast will empower you with a fascinating scientific connection between your brain, food and the gut. Come join us. We welcome you.

Dr. Megan Riehl:

Hello friends, and welcome to the Gut Health Podcast, where we talk about all things related to your gut and well-being. We are your hosts. I'm Dr Megan Riehl, a GI psychologist.

Kate Scarlata MPH, RDN:

And I'm Kate Scarlatta, a GI dietitian. Today we have a very interesting and some may say, provocative topic, and that is "leaky gut. In the scientific community we often refer to leaky gut as intestinal permeability, but when the gut does have enhanced intestinal permeability, there's downstream effects. Things can leak through the gut undigested food, microbes, toxins and this actually may lead to health problems, maybe systemic inflammation. So today we have a very amazing guest, dr Alessio Fasano, and Megan, will you introduce our guest?

Dr. Megan Riehl:

I sure will. Dr Alessio Fasano is a world-renowned expert in celiac disease, autoimmunity and the gut microbiome. He is the W Allen Walker Chair of Pediatric Gastroenterology, Hepatology and Nutrition, director of the Mucosal Immunology and Biology Research Center and Director of the Center for Celiac Research and Treatment, all at the Mass General Brigham. He's also Professor of Pediatrics at Harvard Medical School and Professor of Nutrition at the Harvard TH Chan School of Public Health. As founder of one of the first celiac centers in the US in 1996, Dr. Fasano has been a leader in research, education and advocacy for advancing awareness of celiac disease and other gluten-related disorders. In collaboration with others, his research focuses on developing an alternative therapeutic treatment and finding a way to prevent celiac disease from developing. With more than 450 peer-reviewed publications, he is widely sought after and shares his expertise with many organizations and institutions. He has authored two books that our audience may be very interested in Gluten Freedom and Gut Feelings the Microbiome of Our Health, with co-author Susie Flaherty, published by MIT Press. Welcome, Dr. Fasano.

Kate Scarlata MPH, RDN:

All right. So, Dr. Fasano, we always start our episodes with a little myth busting. So do you have a myth you would like to bust in regards to leaky gut or gut health in general?

Alessio Fasano, MD:

If you believe that you are not an Olympian because you have the leaky gut, or that you would not win a Nobel Prize because your gut leaks, yes, that's a myth that needs to be busted. Meaning the leaky gut. The term is that, by the way, I don't like. I like. Loss of better function or increased gut permeability is indeed involved in many conditions, but cannot be responsible why the elections went that way this year, for example.

Dr. Megan Riehl:

That's perfect. So all right, let's dive into that. Can you explain this term of leaky gut in simple terms? And is it a medically recognized condition, being you know, is the leaky gut the same as leaky gut syndrome? Is there such thing?

Alessio Fasano, MD:

All right, so let's explain first the term and then we will go to the details. Leaky gut or loss of barrier function implies, as a concept, the fact that we have barriers that divide us against the external environment. The most obvious that we see all the time is our skin right so that stuff doesn't come in our body, because we have the skin. The most complex, the most studied and probably the most sophisticated barrier that we have, because it's the largest interface with the environment, is the intestine. An adult's intestinal surface is spread on the ground with a double tennis court. That would be seven times roughly. What is the interface with the skin? Just to quantify that, it's not the only one, again, but it's the most studied for all these reasons. When I was in training so both of you were not born yet- I might have been.

Alessio Fasano, MD:

We were thought that these barriers to be efficient, should be static, like a sort of wall that divides the external world from our body, so that we would be protected from the inadvertent and uncontrolled passage of the stuff that you were mentioning, you know, toxins, endotoxins, junk, in other words that comes from the environment. Now, coming to the intestine, but this applies to all mucosas, also the airways. The entire layer of the intestine is scored by single-layer cells, just the single-layer cells that are cemented that was the concept that was told to us between them, so that nothing comes through other than in through the cells, what we call technically the transcellular pathway. Because the other difference between you know, the epithelial cells in the gut compared to other interfaces like the skin. We want some stuff to come in, nutrients, otherwise we'll die right, but only under specific circumstances and after being digested, because we have a specific way to bring the stuff in. Nothing else was supposed to come through. This concept was fueled by one, the idea that again we should be otherwise. We don't want harmful stuff to come through. Two, because the resolution of our microscopy at that time, even electromicroscopy, suggested that the two neighboring cells, you know membranes were fused. Given the concept of the cement. And this was until the late 70s, early 80s, when a Japanese group said uh-uh, there's no cement there.

Alessio Fasano, MD:

There are doors, most of the time closed, that technically they called tile junctions. They are very complex structures made by hundreds of proteins with a lot of functional redundancy. That, in biological terms, means it's something important where you have redundancy, you have backup, so to speak, that eventually control the trafficking of stuff from the lumen into our body. Now, the concept of door means that they can be open and therefore they introduce the concept of plasticity, so dynamic structure that can forth from the outside world or not. If you allow me a comparison of how.

Alessio Fasano, MD:

Let's say that you know these are the front door of your house, okay, most of the time. Let's say that you know these are through the front door of your house, okay, most of the time it's closed. If somebody rings, you know the door, you open the door to let the people go in, but you know when they're in, you close the door and that's the way that they are supposed to work. If you forget the door open and you go to sleep at night, then the chance exists that somebody that is inappropriately qualified to come to your house it does, and that is the concept of a leaky gut. Coming to leaky gut syndrome, that does not exist in my book, but of course you know this is my personal opinion, because you know that would imply there is a specific entity that created the problem. Now we know much more of the biology why this stuff opened for too long, how this happened, what are the mechanisms and so on and so forth. So there are conditions in which you lose the barrier function for a specific reason that you know. I'm assuming we're going to go a little bit more in details, but they are not part of a syndrome, because the word syndrome means we don't know the mechanism, we don't know the reasoning, and that's not what is the case right now.

Kate Scarlata MPH, RDN:

hat science has evolved. It just makes me think of all these people making a million dollars on leaky gut syndrome protocols.

Alessio Fasano, MD:

And products to fix it.

Dr. Megan Riehl:

Correct so that's fix it Correct. So that's the thing.

Alessio Fasano, MD:

There's no quick fix with any of this, doesn't exist, but you know again, the more that we learn about the process, the more we know what can be done eventually to mitigate the problem.

Dr. Megan Riehl:

That's right. That's right. So tell us a little bit about the role of this intestinal barrier, right? So tell us a little bit about the role of this intestinal barrier You've started to talk about this and how does its dysfunction contribute to other health issues?

Alessio Fasano, MD:

Yeah, you know I want to make a disclaimer before that we go through the details.

Alessio Fasano, MD:

The disclaimer here is that you know, in general this is a hidden topic, as you mentioned at the beginning of the show, because, you know, because it polarized people. It's like the political life that we live nowadays in the United States. There are believers and non-believers. The believers they're all in and they believe that, again, everything under the sun and that's the reason why I made that provocative myth at the beginning is due to the fact that our intestine leaks. The non-believers said this is a totally voodoo, junk kind of science. Of course the truth is somewhere in the middle.

Kate Scarlata MPH, RDN:

Like everything.

Alessio Fasano, MD:

Correct. And again, I'm not trying to demonize the functional medicine folks. They are the one that took the forefront, you know, on this topic. Actually they had the argument to understand that there was such a thing. The more evidence-based medicine took a long, long time to get there, but now they are on its common ground. So we know that this stuff exists, you know, and we start to understand why that exists and under which circumstances.

Alessio Fasano, MD:

So if you look at the pathogenesis of any disease of humankind, until we resolve the human genome project, we were convinced that there are only two things, two elements that were necessary, sufficient to develop these diseases. One, genetics who you are genetically speaking, what kind of predisposition you have to develop any given disease. And then environmental factors that eventually will put your genetic predisposition you have to develop any given disease. And then environmental factors that eventually will put you know your genetic predisposition to motion, to develop any given condition. And again, you know this was a corollary that we had until probably, I would say, the mid-70s. You know there was an epochal change of our destiny as human beings. You know, for almost two million years of our evolution we mostly got sick and died of infections. That's been our destiny. Until again the mid-70s, when, you know, we start to understand the basics of this, you know infectious diseases, and we start to develop remedies like sanitizers of water, antibiotics, vaccines and so on and so forth. And where we deployed these measures particularly the Western hemisphere, increasing Western lifestyle we saw these diseases plummeting. So rheumatic fever, tb, measles, rubella, just went almost to zero. But during the same period we had this increase, exponential increase, on non-infected chronic inflammatory diseases like neurodegenerative disease, like Parkinson's, dementia and Alzheimer's, or neurodevelopmental diseases like autism, autoimmunity, cancer, metabolic disorders and so on and so forth. That led us to pose about these two pillars to be necessary and sufficient, because again we interpret this phenomenon that of course you can't blame genetics, that takes generations to have these changes and this materialized in a matter of 23 years. So the same generation saw this explosion of chronic inflammatory disease. So we concluded we haven't changed the environment too fast for us for that. That was our conclusion.

Alessio Fasano, MD:

But there was another more positive, optimistic reading of the phenomenon. We were convinced that if I'm born with the genes for breast cancer or Alzheimer, that's my destiny, can't do anything about it. But this epidemiological observation that originally was called the IGene hypothesis and now being revisited. It's not called that anymore. It taught us another lesson If I'm born with these genes, it's not my destiny that I will get that disease. If I do, it do not depend on my lifestyle. In other words, I will play my genetic cards.

Alessio Fasano, MD:

Understanding what we've been doing wrong by embracing the lifestyle like the Western lifestyle will give us a hint of what's going on, and that leads a huge amount of efforts to say what else is at play, and three other elements surface.

Alessio Fasano, MD:

This is a long way to answer your question. These two worlds are normally segregated by barriers. You've got to lose that segregation in order that they have to interact. So, in other words, these elements from the environment need to be seen by our genes, particularly the ones that control the immune system, in order to develop a problem. The fourth element, because we're talking about chronic inflammatory diseases, is that an immune system becomes hyper-religion. And, last but not least, the ecosystem that we have in our body, particularly in the gut, what we call the microbiome, is also involved. So, with that understanding, the more we've been studying the critical leading gut world, the more we realize, no matter what kind of disease you see, because all five pillars are necessarily sufficient. You've got to have lots of barrier function, some shape or form, in order to develop these problems, because you got to have increased antigen trafficking or endotoxin trafficking that will lead to the beginning of that march from genetic misposition to being a outcome.

Dr. Megan Riehl:

It's fascinating. I'm just taking it all in and thinking about how gut health then. It is so broad, it affects all of us. It affects every cell in our body and you've just beautifully demonstrated that with this explanation of the cells in our body.

Kate Scarlata MPH, RDN:

I know it's almost like you have to like pause and just take it all in. I felt like both Megan and I were just like sitting here like just contemplating everything that you said. And it's not just one thing, but there's a lot of factors here and many of them are modifiable with lifestyle. You know. You do see, just I saw a picture from the 1970s. It was from old orchard beach, Maine and I showed the picture to my husband just last night and I said what looks different? And not everyone was fat. I mean, it was so obvious in striking in this particular picture. So you know that lots going on that's affecting that's right.

Alessio Fasano, MD:

So now you struck another note here, because when we're trying to figure out what we've been doing wrong by increasing lifestyle that is conducive of this chronic inflammatory diseases, so what have we been doing wrong in the Western atmosphere? So the last three elements, by the way that we didn't know, gut permeability, the immune system the become hyper belligerent and the microbiome. They're highly interconnected. So typical example if you have an imbalance of microbiome, that is the strongest stimulus to have your intestine leak, and if your intestine leak, your microbiome goes off balance. And now we know, and I don't have to elaborate too much about that the microbiome really dictated our destiny, because with only 24,000 genes or 28,000 genes, whatever, it is that reasoning that we had when we did the Human Genome Project one gene, one protein, one disease is out the window. So it's all epigenetics and it's the microbiome to decide if, when, why and how some genes are put in motion, that we start that march from genetically disposition to clinical outcome. And therefore the reading of all this is because we change that friendly relationship with the microbiome that we have this surge of chronic inflammatory disease. These genes that put our risk for those conditions has been always there but never been put in motion and now it seems to be that because of the fact that we're not taking good care of our microbiome talk about gut health, including the microbiome that's the reason why we're in trouble, and all this stuff that we can do when we embrace a worsened lifestyle can affect negatively the microbiome and therefore our clinical destiny.

Alessio Fasano, MD:

Yeah, c-section versus vaginal delivery, but that's one episode in my life. You know antibiotics. Yeah, I can take three or four antibiotics a year, but I eat three or four times a day. So probably the most impactful reason why we got in this mess is because we radically changed our nutrition. And this will go back to what you're saying, kate. In the 70s everybody was on the lean side and now we have, just in pediatrics, 30-40% of child obesity and these are the kids that bring comorbidities. When I was in training again, I had never seen a kid with hypertension or fatty liver or cardiovascular diseases, and now we see this in clinic. That was unconceivable. All type two diabetes unconceivable.

Kate Scarlata MPH, RDN:

I just think of growing up in the 70s TV dinners, the Betty Crocker cake mixes, everything was out of a box growing up and then I think, okay, that I was creating like probably the worst microbiome, and then I had three kids and they got a piece of that you know. So you see the generation you know, and antibiotics were like candy. I mean, I was on antibiotics all the time, all the time as a kid, so you can see how you can have generational effects and this problem get bigger and bigger and bigger. I want to just comment on so the intestinal permeability I want to make sure I got this right for our listeners is a big piece to the advent of these chronic diseases that we're seeing. Like that has to be there. Is that what you were saying earlier?

Alessio Fasano, MD:

That's right.

Kate Scarlata MPH, RDN:

That is a part of this picture.

Alessio Fasano, MD:

That's right. But again, it's one of the five pillars that you got to have to have these problems. And the point of why I focus on microbiome and therefore nutrition is because of all the stuff that you know can bring you to a quote-unquote leaky gut. This biosis is the strongest stimulus that can happen to you. Of course, if you take, you know, non-steroidal anti-inflammatory drug that will leak your gut, or it's, if you are, you know, eventually are stressed, your gut can leak and so on and so forth. But you know I can make any argument that all this stuff will affect your microbiomania. So maybe that directly will affect gut leakness, but maybe it all translated and transduced by the microbiome dysbiosis.

Kate Scarlata MPH, RDN:

And so is there any biomarkers used in clinical practice to help assess? I know there are some that are, you know, used in clinical practice to help assess. I know there are some that are used in research settings, zonulin being one of them. No, patients really don't have any way to assess for this.

Alessio Fasano, MD:

The honest answer is no. However, I want to make a little disclaimer here. For many, many years in the research setting, we use very complex and sophisticated measures of gut permeability, like the double sugar test, the lateral mannitol test. It is very cumbersome and not doable under clinical practice. Then you mentioned zonulin. Just for the benefit of the people that are listening, just what the heck is zonulin? You know if, going back to the parallel of your tight junction, this spacing between cells being a door, zonulin is the key. So in other words, it's what happened at that door. And if you produce too much zonulin, that's been, you know, associated by almost more than 1,000 papers now since they scored this molecule by our group, like 20 years ago, to a variety of chronic inflammatory diseases. So all this to say, yeah, that is a common denominator what the people in science have been doing to manage your gut permeability in the human setting. I don't care about the animals, because that cannot be that important, of course, because you can do it with an animal model, something that probably is not doable with humans. Over the years there have been three biomarkers that surface that are very meaningful to us. One is zonulin. That is, again, if I produce too much. I know that my intestine leaks because you know I opened these doors. But you know what Many of us. They have a leaky gut and they don't have any consequences. All depends how long the gut leaks and, as I said, the intestine and any other barrier is built to be open at some point, not for too long. So it's not important just to know is my door open? The next question is who came through the door? Do I have a smuggler or you know a robber guy that came through? And the biomarker for that? Because most of the inflammation not all, but most of the inflammation is caused by endotoxins. In other words, you know stuff that comes from the bacteria in the gut. The second biomarker that people use is what we call the LPS. That is an endotoxin lipopolysaccharide. LPS is binding protein. So now I'll answer the second question. One the zone is up. My door is open. LPS binding protein is up. A bad guy came through the door. And then the third biomarker that people they use in research is what we call Soluble CD14. That is a biomarker is telling me, because of all this, my immune system is fighting and it's generating inflammation. So, bottom line, back to the parallel my door is open, a bad guy came through and he's stealing my stuff because I know that it's been stolen.

Alessio Fasano, MD:

There is now an effort to bring this to clinic, for example in Europe. In Germany, where functional medicine doctors are a sizable number of healthcare professionals, the zone assays use routine in clinic. Some companies here. They start to offer zonulin testing here, sometimes by itself, sometimes in combination with the microbiome analysis, so they too test together as gut health kind of testing. Are these ready for prime time? Probably not, but you know, once this validation will become more and more substantiated, I will anticipate that. You know again and I see this in my clinical practice A lot of people that come there with these results. I say can you?

Alessio Fasano, MD:

tell me, what that means.

Alessio Fasano, MD:

So there are companies that you know in a name that they are cashing on this already, right.

Kate Scarlata MPH, RDN:

But it's just not ready.

Dr. Megan Riehl:

Yeah, and what do you tell those patients? Because we see it too, and especially my anxious patients where they don't feel good. They don't feel good and they're desperate and they will spend whatever money they could find to try and understand what's going on. They read the word leaky gut on some report and they say I have this, Dr. Fasano, it's here. What do you say to them? That's based in science and that gives them some hope on where do we go from here. That's right.

Alessio Fasano, MD:

So, Megan, you're already at the next step. So let's say that this stuff is validated and some people they believe that it is to the point that they're using the clinical practice. So the reality of the story is that we are at the verge of a revolution of how we practice medicine. The early doctors were healers and they were all focused on the patients. Then evidence-based medicine said oh no, we don't look at the patient, we look at the organ, we look at the specific piece of the car here and we lost track of what is the reality of the story because we made the assumption okay, if I have breast cancer, we're an homogeneous population. That's not true. How you reach that final destination can be different from one individual to others. In other words, what I'm saying now, the focus is back on the individual versus personalized medicine, the future, and to do that then you need to put this kind of testing in perspective what that means for your patients. One key element when we do this kind of measurements, let's say you know I do the zonulin tests and my intestine leaks, and then I do my microbiome testing, and what was in dysbiosis, you know, will require that capability to standardize and validate all this testing in the context of a complexity that we stretched in the surface just now. Let me explain what I mean for that People believe, some people believe that there's a normal microbiome. There is no such thing. It's like to say what is the normal length of my hair? Everybody has a different length. It's not that it's normal or not. It's very subjective. The microbiome is very personalized. It has to fit with our genome. So each of us, they have a different microbiome. What we have in common, though, is the results of the genetic and macrobial interaction, because we all have to have, let's say, the glucose level within a certain range, right? So, metabolically, we have similarities, but how that metabolic state is reached is very personal from one person to another. Once we got that and this will require huge data, ai modeling and so on and so forth that we are already doing this research. So it's coming.

Alessio Fasano, MD:

Then, and only then, I can have an intelligible answer to the individual. Because, megan, to answer your question, if we want to be honest with these people and they say you know I am here, where I'm going, I cannot tell you if you don't tell me where are you coming from? How did you start your journey. So the future is going to be we all will have our genome done when we're born. We all will have our microbiome done when we start this journey of life on the face of earth. And we will see the dynamic over time where we introduce baby food and all my yards, and every single time that we got sick we would do that again.

Alessio Fasano, MD:

And now we model and I said you know what you were supposed to be left? And now you're right, I need to bring you back to left. Then I can answer your question, what I can do about it. Can I give you some prebiotics so I can feed the good guy to help you to go back to left? Should I give you probiotics? Which one Depends on which one you lost? Should I give you postbiotic or symbiotic or whatever?

Alessio Fasano, MD:

The reality of the story is that until we reach that level of sophistication, common sense needs to be shared and say listen, lifestyle will help you to bring this back. There you go so good, exercise, control the stress, good nutrition. As I told you, this is going to be instrumental. That will provide the natural source of prebiotics symbiotic, postbiotic, all-night-yards, probiototic and so on and so forth sleep, hygiene, respect to the environment. So some of that are under our control and we should take ownership of that and some would not. What is the caveat of what I just said, megan? A lot of people will push back because people they don't want to work on goals. I have headaches. Give me a pill. I'm obese. Give me my famous GLP-1 receptor agonist so that I can lose 20 pounds without working toward that goal. There is no such a thing.

Dr. Megan Riehl:

It's really this issue of truly understanding that our health is multifactorial. And you are so right that I have patients that have been diagnosed with IBS they would rather have cancer and say this is the treatment. You go through this chemotherapy and ideally we will get this in remission and onward with your life. You will go, and I'm not joking when I say that I've literally had patients say they would rather have a chronic illness. That will respond ideally, again with hope and prayer and science and they will be cured. And when we're talking leaky gut and we're talking many of these other issues, there is no cure. There is a understanding, appreciation and time devoted to living a lifestyle that is going to incorporate the expertise of lots of people that can help you get to where you're hoping to get with your health.

Alessio Fasano, MD:

Yeah, now, both for leaky gut and IBS. It's not true that there is nothing that we can do about it, because now we understand much more than we understand before. Let's take IBS as a typical example. We don't call that IBS anymore, by the way, because IBS means irritable. So there's something that is not right Bowel that has happened in the intestine Syndrome. I have no freaking clue what is going on. Now it's not called this anymore IBS. Why? Because this is the quintessential example of miscommunication between the gut and the brain, what we call the gut-brain axis. That, megan, this isn't a smash of what you do for a living, I guess. So you know, a while ago I read a book that is called Gluten Freedom.

Alessio Fasano, MD:

That has to do with gluten in your health and so on and so forth, and I put a quote in there that I didn't have any idea that was going to be a quote that would go on the shirts when I said you know, the gut is not like Las Vegas. What happened to the gut doesn't stay in the gut, meaning it is a battlefield, but the consequences can spread everywhere in your body, and the gut-brain-access communication is one of the examples of how we are highly interconnected and how we miss the boat if we don't take this in the context of the complexity, how we interact with the different pieces of our body and different systems to really achieve a specific goal. Now, IBS is nothing else than this motility in my gut, because this communication between the gut and the brain cannot coordinate that kind of motility and therefore it's multifactorial. Can be due to dysbiosis, for example, small intestine battery overgrowth can be one reason why you have IBS. It can be because, of course, you have a threshold of stress that's very low and therefore this will translate in communication through the vaginal nerve. That will mess up your motility and therefore you create the condition of IBS, you can do an infection, and I can go on and on and on.

Alessio Fasano, MD:

So the key element is to try to understand which three I have to bark to in order to fix the IBS. Again. We don't call that anymore. So that's fixable, provided that we have an understanding, and I am very sympathetic with your patients. They say you know what much better chronic conditions that have a target. So I'm giving me a drug and I will fix it. Tell me there's not much I can do about it. Because that's very debilitating. I understand that. But some people resolve IBS with biofeedback because it's stress-relieving. Other people then they fix by fixing SIBO, and I can go on and on and on, or by doing an elimination diet because it's driven by gluten, whatever. So it's all a question that how can I put people out of this pot that I put in there because I don't know exactly what's going on with them? That's the essence of the story.

Kate Scarlata MPH, RDN:

It's interesting I think of like IBS and IBD and just talking a little bit about nutrition and the need for personalization, because there's been some interesting studies looking at inflammatory bowel disease and in a small subset of those individuals, when they consume fructans, which are found in wheat barley rye the same gluten foods which are found in wheat barley rye the gluten, same gluten foods it stimulates there's inflammatory markers.

Kate Scarlata MPH, RDN:

And in IBS, when we look at some of the recent data done out of UMichigan, in the people that responded to a low FODMAP diet they found adding FODMAPs back incited immune activation, created a dysbiosis with LPS. You know they measured for LPS, they had this immune activation and colonic barrier dysfunction was measured as well. But not everyone that has IBS needs a low FODMAP diet or benefits and not everyone with IBD is sensitive to fructans. And so you know these one size fits all recommendations or I feel, for patients that are like, okay, my diet's lousy, I got to eat more fiber, and they go out and buy like a bunch of whole wheat bread and feel miserable. And it's finding the right foods too that'll work for your body, based on this very complex system and the individual nature of it, right, the gut microbiome being so different person to person.

Alessio Fasano, MD:

Yeah, before then I answer, I have to make a disclaimer. Besides to be professor of pediatrics, I'm also professor of nutrition, so I'm a little bit biased here. But precision nutrition, in my humble opinion, is going to be the future to solve or to ameliorate at least many of these issues. So you made the right example. Let's say IBD, for example. We know that if you're newly diagnosed with IBD, most of the time we don't use steroids anymore to put the IBD under control. We use an elemental diet. It's as efficacious as the steroids but no side effects, not sustainable because it's awful, but you know at least to take control until I will kick in with biological or anything else that can eventually do the trick.

Alessio Fasano, MD:

That's very telling to me that the mucobomb composition and function and the antigen trafficking big time. They have a role in creating an inflammatory situation. If I'm genetically predisposed to IBD, there are some people, for example, that you know they have seizures. They don't respond to an anti-epileptic drug. Then if they go specific diets they control it. So meaning that eventually in this subgroup of individuals there are some stuff that you know. We change the GABA levels and all that and eventually subsidize.

Alessio Fasano, MD:

You know the problem there, and I can go on and on and on. I have the biased vision that once we understand the basic of these chronic inflammatory diseases, why we develop them inflammatory diseases, why we develop them, what kind of the element that this triangulation between my immune system, the gut permeability ie leaky gut and the microbiome is at play, I can customize the nutrition intervention that can substitute any drug that you can imagine, because think about IBD, for example, the drug that we use now I treat in the consequence inflammation Now. Now the reason why I have inflammation. It's like that. I have pneumonia and I take Tylenol. Of course the fever will go away. I'm testing the consequence fever Now, the reason why I have fever. Unless I already get the pneumonia with antibodies, that will stay there.

Dr. Megan Riehl:

Right, so the conversation.

Alessio Fasano, MD:

That's right we are going after are going after the consequences, not the cause. Changing my nutrition that will change my microbiome, that will change my antigen trafficking and give a break to my immune system so I don't have the chronic inflammation, will be the future of the personalized nutrition and food as medicine, so to speak. Of course that approach doesn't have too many friends because you don't make too much money out of it.

Kate Scarlata MPH, RDN:

I know you can't sell it as a drug.

Alessio Fasano, MD:

So drug companies are not very pleased to hear that song.

Dr. Megan Riehl:

That's where the conversation of prevention starts to come in.

Alessio Fasano, MD:

You know, Kate, what you were saying. This has been amazing because, at least at my age, I've seen this change. Generation speaking, my mother used to cook from scratch. We live in the fast lane of life and we were raised with the boxes that we see on advertisement there as an efficient and logical way to do stuff. And now we understand that we're paying consequences.

Alessio Fasano, MD:

My wishful thinking is that one of the things that was a bad habit when I was growing up was smoking. You know, if you didn't smoke you were a loser. Thankfully I was a loser because I never smoked in my life. But look what happened in single generation, maybe two generations. Now it's the opposite. If you see somebody smokes, it's kind of weird, but the vast majority don't smoke. It took an educational campaign to explain that. That was a remarkable bet for you. A bet for what? One single disease lung cancer. But bad for what? One single disease lung cancer.

Alessio Fasano, MD:

If we will go back to the notion that eating well will take care of a variety of chronic inflammatory diseases, that will change completely the landscape. If I can give an example, during COVID I had the blessing to have my grandchild born, my daughter and my son-in-law very busy. I was busy as well because I was every day in the hospital and so on and so forth. Time came that, you know, this little fellow that was four or five months old has to be, you know, introduced to baby food. And my wife and I said we take care of this and we win this fellow on a Mediterranean diet. Never use anything pre-done, cook from scratch. Now he's five. His favorite food is, I believe, pizza escarole that he eats very methodically. Capers first, then olives, then the escarole, then the dough. He doesn't know what a French fries is.

Alessio Fasano, MD:

He has no desire of a French fries. Junk food. Never done. A taste. What I'm coming from with this. Oh, by the way, and I need to rush it up, you know, because you know Wednesday is dedicated to these folks, because he's my sous chef, we cook together every Wednesday. Yes, to rush it up, you know, because you know Wednesday is dedicated to these folks, because he's my sous chef, we cook together every Wednesday.

Kate Scarlata MPH, RDN:

Yes.

Alessio Fasano, MD:

What I'm trying to achieve with this, that transformational change to do not smoke anymore, if the next generation knows that to cook healthy would not take that much, because you know he spent only an hour with us. Would not take that much because he spent only an hour with us, including. He needs to eat what we cook. It takes 20 minutes, maybe half an hour. You've got to be prepared with food shopping. But again, think about this no-transcript. I take a tray out and put it in my microwave because it's prepared by somebody else. I don't know what junk is in there. Why do we want to do this to our body? So my hope is that this guy, when he will become a father, will change the attitude and will break that vicious loop and say you know what? Cooking is not a big deal and this is the way that we need to eat, and this is the way that we need to eat. And finally, we will reverse this trend of childhood obesity and chronic inflammatory diseases due to inappropriate nutrition.

Dr. Megan Riehl:

And people will feel the effects of that right. You feel better when you have those foods and, to your point, exactly last night my kids had soccer. It was late, it was 7.30 at night. I looked in the refrigerator. I'm like I could do a frozen pizza, but that will not make me feel good. I don't feel good when I eat that. So I threw asparagus in the oven with some peppers and I had some white rice that had already been cooked for dinner for the kids. So while I was doing bath time, the oven was on and I did eat it late. I ate it later at night, but I didn't go to bed feeling bad about the food choice that I had made and I felt full and good and I didn't have any consequences the next day. So it's not that hard. I'm a working mom with three kids. It just takes to your point planning and getting outside of some of the habits that we've identified that just probably aren't going to be sustainable for us long-term.

Alessio Fasano, MD:

And then also sharing with the others the duty of cooking and cleaning. It's one thing. The families that make the kids appreciate, you know, the value of food. You don't trust that you recycle for you know, as you did, you know, with the rice that was left over from the previous day. Modern nature will not be able to sustain the way that we're doing this stuff. 30% of our, you know food is trashed every day.

Kate Scarlata MPH, RDN:

Yeah, we can't afford that. No, it's good meal planning. I feel like when I meal plan I'm really excited to cook what I am going to have for dinner, because I have the fresh basil, I have whatever fresh vegetables to put everything together and it just it's easier. I don't have to get creative looking like what can I put together tonight?

Alessio Fasano, MD:

So if you think about again back to evolution, when we were gutter hunters 10,000 years ago, what were we eating? Because that's the other way that I answer to my people. So, okay, you say good nutrition, what do I have to eat to stay healthy? I said you know what? We've been built for two million years to eat a lot of fruits, a lot of vegetables, tubers, nuts, olive oil, that kind of stuff. Meat, absolutely.

Alessio Fasano, MD:

Once in a while you have to be a good hunter and eat lean meat, because these animals were escaping predators, including human predators, so they were lean, not fatty stuff, and if the proportions are right, then you are pretty much in the right track to do the best thing you can. What I described pretty much is the Mediterranean diet bottom line. That has been proved to be good for you. But why? Back to the microbiome and gut licking here. The microbiome is like a farm with different animals. They are chicken, they are cows, they are pigs, they are rabbits, and so they eat different stuff.

Alessio Fasano, MD:

And, evolution speaking, we decided that we need 100 chicken and two cows. Okay, now we feed only the cows and we don't give the food to chicken. What's going to happen to my farm? I'm not going to have eggs anymore, I don't have chicken anymore, and we were wondering why we're in trouble. So all this to say? If you don't have enough fibers in your diet, if you don't have good stuff, anti-inflammatory stuff that protects your gut barrier in your food, like polyphenols and so on and so forth, you pay consequences, and that's the reason why it's not just the sterility to be fat. Obesity is an inflammatory process, now we know. So you really instigate your immune system to fight, and obesity comes with comorbidity. That is all inflammatory based, and all this is due to the fact that there is dysbiosis and increased antigen trafficking and therefore leaky gut. That leads to all this.

Kate Scarlata MPH, RDN:

Get your vegetables. Get your vegetables.

Alessio Fasano, MD:

You know fruits and pizza, it's okay, but once in a while that's right. That's right. I mean for the dish-free situation. Absolutely Choose wisely, though.

Dr. Megan Riehl:

Choose wisely, to the best of your ability.

Alessio Fasano, MD:

We do make pizza ourselves and in general we make enough that we freeze them. So you have your own frozen pizza or any kind of dish that takes a little bit extra time. I don't know. You do a lasagna or whatever. Freeze down, that's your stuff.

Dr. Megan Riehl:

I'll send you my address so that the Fasano family can ship their frozen lasagna and pizza to my house. That's the pizza.

Alessio Fasano, MD:

I want. No, we can do it better. We do cook classes so you become independent. You're going to need me to do this.

Kate Scarlata MPH, RDN:

Sign me up. Sign me up. I think so many people don't really know how to cook, especially in my generation again, because so much was out of a box. I always loved cooking, so I'm one of nine kids so my mother couldn't feed us out of a box all the time we had to eat. You know she cooked a lot of fresh fruit but, yeah, a lot of people don't know how to cook and I'm constantly giving tips on just simple how to roast vegetables. You know they've never done it before. It's like oh, it's really simple.

Alessio Fasano, MD:

There are many hobbies that we're engaged in. Yeah, cooking, I believe, is something that we should look very seriously into because, again, you need to do that anyhow. Make this something fun sustainable, bonding the family around, preparing meals and not just putting on the shoulder a single individual. It's a lot of fun.

Kate Scarlata MPH, RDN:

I have to agree with you, so I just want to like peek back into the topic a little bit more. I know our listeners are going to be curious. Are there any supplements that you would recommend? I know there was a study on glutamine and post-infectious IBS as being potentially beneficial as far as their intestinal permeability markers they used and as well as IBS symptoms. But, like colostrum, there's been other things that have been put out there, so I'm just curious do you ever dabble in that? Is there any evidence-based supplements that you would consider in certain patients?

Alessio Fasano, MD:

So glutamine is the fuel for the gut. You know, no matter how old are we, our cells are one week old. So we change the entire layer of cells every week and the reason why we do that is because they need to stay up to speed to be extremely efficient. One of the major jobs they have to do is to maintain that barrier function. That it takes a lot of energy and glutamine is the fuel that they use to do that. So glutamine is bona fide, a good supplement to consider. The same.

Alessio Fasano, MD:

Colostrum is very much in reach to favor a subgroup of microorganisms. There are probiotics that produce postbiotic, like butyrate or acetate, that have been demonstrated to fortify the barrier. I mentioned polyphenols. They've been also demonstrated to be anti-inflammatory because they fortify the barrier. Anything that again helps that component of the microbiome that is there to help to maintain the barrier function, because that's something that the microbiome contributed to, it's important.

Alessio Fasano, MD:

But if I have to pick one: fibers.

Kate Scarlata MPH, RDN:

Fibers.

Alessio Fasano, MD:

Fibers is the staple for any kind of microorganism that you can imagine that is in our ecosystem. That's what they eat. You know they don't eat anything else. If they eat anything else, like sugars, they're stealing. You know 99% of our microbes are in the colon. There's no nutrients there. The only thing that will reach there is stuff that we cannot digest ie fibers. There's no nutrients there. The only thing that we reach there is stuff that we cannot digest ie fibers. And we as a society particularly US we eat, you know, one-tenth, one-fifth of what is recommended doses of fibers, I know so. That's the reason why fruits and vegetables that, unfortunately, I don't want to introduce.

Alessio Fasano, MD:

Also, another variable here when I grew up in Italy, I didn't know that I was raised the right way by eating the Mediterranean diet that was called the diet of the poor. I come from an humble family. We can't afford to buy meat more than once every two weeks. If so, our protein sources were from legumes, for example, lentils, beans, peas, that kind of stuff. Yeah, meat, but you know, once every week or two weeks, but that's what we were, and fruits and vegetables were extremely cheap.

Alessio Fasano, MD:

Now this is a diet of the wealthy. Who's going to kind of afford that? If I'm a single mother with two kids with $10 a day, am I going to buy fruit and vegetables that will fill their belly? I will buy fat, you know, junk food. That's another source of discrimination, but for people that can afford it and be savvy. I will say that's the way to do it. Every Saturday, every Friday Saturday is a produce market in Boston here, and when I was a little bit younger, as a joke, my family gave me one. You know the carts, the old ladies they used to go shopping.

Kate Scarlata MPH, RDN:

Yeah, yeah.

Alessio Fasano, MD:

I take that. I don't use car, by the way, because, you know, I want to be contributing to my health and also to the health of the planet, so I use public transportation, I go on the metro, get to the market and I spend a couple hours there. I'm a busy man, by the way. That's very valuable because I talk with the people, I got in a relationship with them and they say, oh, you know, no, no eggplants this week. They are not good. And you know, that is my preparation for the week and that's the reason why the rest of the week, my wife and I, we can do this in 20 minutes. So, all this to say, and again, if you go to the markets, they are more affordable than Whole Foods or any other big retail stores, and so on and so forth. So it's doable, but you have to take the effort to do that.

Dr. Megan Riehl:

And if you do have a limited budget, you know frozen fruits and vegetables.

Alessio Fasano, MD:

Those are still wonderful ways to Sea reach of vitamins, minerals, fibers, absolutely.

Kate Scarlata MPH, RDN:

Yep, I like having the frozen fruits and vegetables, but when you're not planned, or like this afternoon for lunch, I wanted a smoothie and it's just so nice to have that handy, all frozen, ready to whip up, so you can get them for a little less money too. Less food waste as well.

Dr. Megan Riehl:

That's right. So, Dr. Fasano, what is the emerging research or therapies, as we kind of wrap up here, what holds the most promise in addressing our intestinal permeability? And you've talked about this revolution. Anything else to share on that?

Alessio Fasano, MD:

There are a couple approaches that people are taking. They've been now for a while. This inhibitor, zonulin, that's been done in clinical trials for celiac disease has been used also for long COVID and remdesivir. So this is to block that mechanism if you produce too much zonulin. Similarly, the same kind of goal has been tackled by using probiotics that eventually fortify your barrier function and possibly decrease zonulin levels. That's also a very active, you know, line of research. And third, postbiotics. A lot of research on using postbiotics fortified plus or minus with glutamine to see if that can fortify your barrier.

Kate Scarlata MPH, RDN:

Can you just tell our listeners a little bit about what a postbiotic is, because that's kind of a newer kid on the block.

Alessio Fasano, MD:

That's right. So prebiotics are stuff that feed the good bacteria. In general they're sugars, human monogamy, saccharides, breast milk, classical example. The probiotics are, you know, the good bacteria. The postbiotics are the product of this bacteria, in general the good bacteria that communicate with the host for good gut health, in this case including fortified the barrier. And, you know, short-chain fatty acids like propionate, acetate, are the classical example of postbiotics.

Kate Scarlata MPH, RDN:

I like the postbiotics too, because they're not live and viable, so that's probably good for the little ones too, or someone that's at risk for that's right.

Alessio Fasano, MD:

They're a little bit more costly to make than probiotics, but there's a lot of efforts and technologies coming along to make that more affordable than that can be used. But you're right, I mean, you know, if we know the mechanism, why not use it directly?

Kate Scarlata MPH, RDN:

The actual. Thing.

Alessio Fasano, MD:

That's right.

Kate Scarlata MPH, RDN:

Yeah, is therea particular postbiotic product that you are looking at?

Alessio Fasano, MD:

No, because again, there is a lot of research on the matter. You know which postbiotic you use. But you know because, again, there is a lot of research on the matter of which postbiotic you use. But in general, this combination of postbiotics would be ideal.

Dr. Megan Riehl:

Okay, awesome, all right Well you've shared some definitely inspiring ways in which you live your lifestyle. You're taking public transportation, you're at the farmer's markets, you're cooking with the family. Is there anything else that you do that you prioritize for your own health and well-being?

Alessio Fasano, MD:

I drink good wine, good red wine, good Italian red wine. Of course, a little glass a day will do it.

Dr. Megan Riehl:

You know what We've said moderation is key. And when you're doing all the other things that you're doing, you know, I'm sure, that little glass of Italian wine really boosts your endorphins.

Kate Scarlata MPH, RDN:

With meals, by the way. There you go. Yes, that's good gut health. Yeah, not on an empty stomach.

Alessio Fasano, MD:

Nope.

Kate Scarlata MPH, RDN:

That's good. Well, that wraps up our episode today. Thank you so much, dr Fasano, for sharing your expertise in such a unique and complex way, because it's a complex science, and dispelling some myths around leaky gut syndrome, which I think need to be dispelled because a lot of people get caught up in the snake salesman out there on the internet. So, thanks again for coming on and listeners, thanks for listening, subscribe and share The Gut Health Podcast. Thanks, friends.

Dr. Megan Riehl:

Thank you for joining us as we grow this gut health community. We hope you enjoyed this episode and don't forget to subscribe, rate and leave us a comment. You can also follow us on social media at The Gut Health Podcast, where we'd love for you to share your thoughts, questions and experiences. Thanks for tuning in, friends.

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Kate Scarlata

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Megan Riehl

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