The Dr. Hyman Show - Exclusive Dr. Hyman+ Functional Medicine Deep Dive: Leaky Gut

Episode Date: November 30, 2021

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Hey podcast community, Dr. Mark here. I'm so excited to offer you a seven-day free trial of my revolutionary new platform called Dr. Hyman Plus. For seven days you get special access to all the private content included in Dr. Hyman Plus entirely free. It's so easy to sign up. Just go to Apple Podcast on your phone and click try free button on the Doctors Pharmacy podcast. You'll get exclusive access to ad-free Doctors Pharmacy podcast episodes and functional medicine deep dives where a practitioner dives into topics like heart health, muscle health, insulin resistance, and more to help you understand the root cause of specific ailments and walk you through the steps to improve your health today. You'll also get access to all my Ask Mark Anything Q&As,

where I answer the community's biggest health and wellness questions. Because I'm so sure you're going to love this platform, I'm offering you free access to all of this content for seven days and a teaser of my brand new functional medicine deep dive episode diving deep into one of the most important topics in health. Head on over to the Doctors Pharmacy podcast on Apple podcast and sign up for your free trial right now. Okay, here we go. Hi, and welcome to another functional medicine Dive with Dr. Hyman Plus. I'm Dr. Cindy Geyer, an internist by training who first started training in functional medicine over 20 years ago when I was working with Dr. Mark Hyman at Canyon Ranch in Lenox, Massachusetts.

I went on to obtain my board certification in both lifestyle medicine and integrative medicine, and I joined the Ultra Wellness Center team in June of this year. Today, I'm really excited to talk to you about the role of the intestinal barrier in keeping us healthy or contributing to disease and adverse health outcomes. We're going to explore the interconnected components that make up the intestinal barrier, review the factors that can disrupt its integrity or cause leakiness or increased permeability, why that matters, and most importantly, outline the key steps that we can take to maintain or restore intestinal barrier function. Now, the concept of

leaky gut goes back many, many years, especially in naturopathic medicine. But it wasn't until about the last 10 years that the concept of increased intestinal permeability, which is the more preferred term, I believe, has found its way into mainstream medicine. There are two key papers, one by Dr. Alessio Fasano in 2011, and another by Dr. Biscoff and colleagues in 2014 that I'm going to touch on in a few moments that really opened the door to an increased awareness and an, the state, the current state of the evidence, and recognize that we have a lot more to learn. And every time I learn more, I feel like I develop an increasing sense of humility and appreciation for the complicated systems in our bodies that when supported can really keep us healthy. So if you remember the small intestine, which is where we absorb most of the nutrients from our food is folded into loops and loops inside our bodies. And if

you cut open the small intestine, that surface is that surface has been folded again into millions of microvilli, these hair-like projections that greatly increase the absorptive capacity and the sampling capacity of the small intestine. In fact, if you stretched it out, our small intestine would cover the area of a tennis court. That's how much these folds increase the surface area. And when we bring in foods, the foods that are inside the lumen of the small intestine are technically outside our bodies. So the intestinal barrier has to be selected in helping bring in the nutrients from our digested foods so it can nourish our bodies, but keeping out undigested food particles and the commensal microbes that also make a makeup part of the barrier function.

So this is looking at schematically at the surface of the villi and the physical component of the barrier. One of the biggest components of it are these intestinal epithelial cells. It's a single cell layer that lines the villi that also line the inside lining of the small intestine. These are connected by tight junctions and tight junctions zip together these intestinal cells and they're made up of proteins such as zonulin and occludin, which we're going to come back to. There's a second component of the physical barrier and that's these mucin layers. So there's an inner mucin layer that's very closely, tightly adhered to these epithelial cells and protects them. And there's an outer mucin layer as well. The commensal bacteria inside the lumen actually play a role with part of the physical barrier as well.

They can resist harmful bacteria. They process fiber in our foods to create signaling molecules like short chain fatty acids, such as butyrate that play a role as fuel for enterocytes to constantly replenish and grow and they biotransform bile acids. So the physical components are the enterocytes, the mucin layers, and the commensal bacteria that colonize inside the lumen. There's a biochemical layer as well. The biochemical layer is made up of bile acids secreted by the gallbladder into the lumen to help emulsify fats. And it also has some antimicrobial effects, but bile acids actually are antimicrobial against staphylococcus and spirochetes. And there are antimicrobial peptides,

many of which are produced by the PAMIS cells. There aren't very many of them, but they also live in this epithelial layer. They produce antimicrobial peptides and the epithelial cells can secrete another antimicrobial peptide called intestinal alkaline phosphatase. Intestinal alkaline phosphatase plays a role in deactivating lipopolysaccharide, which is a component of bacterial cell walls that is very pro-inflammatory. The final component of the intestinal barrier is the immunologic component, which really doesn't show up on this slide. Behind the wall of that intestinal layer or that epithelial layer, there are B cells and T cells and neutrophils and mast cells that can present antigens to the immune system. So the immune

system can learn over time what warrants a reaction and what does not warrant a reaction. It secretes molecules called cytokines that regulate inflammation, either stepping it up or turning it down again. It can generate antigen binding proteins to things that it views as being an invader or a threat. And then there's also secretory IgA, which is an immunoglobulin that protects everything with the mucus layer and acts in concert with those commensal bacteria to protect against pathogens. So those are the three areas of the intestinal lining, the intestinal barrier. So when the barrier is intact and doing its job, you can see inside the lumen, you have food particles, you have gut bacteria, you have lipopolysaccharide that are staying in the lumen. You have the intestinal alkaline phosphatase

secreted by the epithelial cells that's deactivating that lipopolysaccharide and foods and nutrients can get into the bloodstream and not cause a problem. When that barrier is disrupted, those tight junctions get broken. There's a gap created between these epithelial cells and the immune cells can try to respond and they might be exposed to gut wall bacteria or food proteins, which triggers an inflammatory response and the generation of cytokines, which can lead to systemic inflammation. More concerning still, lipopolysaccharide and gut bacteria can actually migrate through these gaps between the epithelial cells and get into the bloodstream. And once that happens, it has wide-reaching systemic effects ranging anywhere from depression to insulin resistance

and cardiovascular disease to autoimmune conditions. So think of the intestinal barrier as the proverbial canary in the coal mine for the negative effects of lifestyle and exposures. Some exposures and some lifestyle styles affect primarily one component of the intestinal barrier, such as non-steroidal anti-inflammatories, for example, medications like ibuprofen and aspirin. They predominantly disrupt and destroy the mucin layer. Dietary factors, on the other hand, affect a wide range of the components of the intestinal barrier, including production of IgA, the diversity and resilience of the commensal microbes, unzipping the tight junctions between those epithelial cells. But there's a whole host of factors that we know can negatively impact the intestinal barrier,

dietary, non-steroidals, alcohol, chronic stress, sleep apnea, and disordered sleep in general, infections, that kind of makes sense, an imbalanced or dysbiotic microbiome, small intestinal bacterial overgrowth, celiac disease, non-celiac gluten sensitivity, other food allergies and sensitivities. And don't forget an unhealthy vascular system. So high blood pressure, having metabolic syndrome, insulin resistance, loss of elasticity in our arteries, that also can have a negative impact on the intestinal barrier. Now, one thing I want to underscore here, and I will never forget sitting down to lunch once with Dr. Fasano, I may misquote him, but one of the questions he raised is, is there ever a time that it's normal or appropriate to have an increase in intestinal permeability?

And I think there probably is because it's a two-way street. You know, remember where all those immune cells are lying behind the wall of the gut? If you have a gut infection or a parasite or a virus, you can understand how a protective mechanism might be to open up the barrier and get those immune cells into the lumen so they can actually address and deal with an unhealthy bacterium. So when we say increased intestinal permeability,

we always wanna be thinking, is this something that the body's trying to do to respond to something else, or is it a condition that's really gone awry and contributing to ill health and disease? This to me is mind-boggling. Since all the research has been coming out about measuring intestinal permeability, looking at changes in the microbiome and correlations with disease processes, there is probably not a condition out there that doesn't have some link to the intestinal barrier function and to the microbiome. The ones on the left seem pretty intuitive because they're

directly related to the gastrointestinal tract, like gastric ulcers, inflammatory bowel disease, irritable bowel syndrome, infectious diarrhea, but colon cancer, esophageal cancer. And then you have these ones that at first glance aren't connected to the gut. Well, non-alcoholic fatty liver disease and cirrhosis, but insulin resistance, type two diabetes, cardiovascular disease, depression, dementia, autism spectrum disorders, autoimmune conditions, allergies, arthritis, and frailty. So this is one of the two papers I mentioned earlier with Dr. Fasano that was published in 2011, the first paper of his, and he started off as a cholera researcher and is now one of the premier best respected gluten and celiac researchers in the world. And he started really getting interested in celiac disease. And one of the things he discovered is that gluten,

when people eat a meal that has gluten, it has a direct impact on those tight junction proteins that are zipping together those intestinal cells. After a gluten-containing meal, you can see a rise in zonion levels in the blood, which is indicating that they've, in essence, been unzipped, unzipped. And it explains, it actually created a model to really understand how foods may actually be a trigger for autoimmune conditions. So if we start looking at the correlation between gluten sensitivity, celiac disease, and autoimmunity, it goes something like this. About 30% of Americans have at least one of the two genes that are associated with higher risk of celiac disease. The prevalence of celiac disease is only about one in 110. So 30% of Americans don't have celiac disease, but one in 110 do.

And interestingly enough, the prevalence has increased in recent years. And one of the questions is, well, are we just getting better at diagnosing it and looking for it. But I think it kind of comes back to what we talked about very early on that as modern society, we've changed our diet, which changed our, the health of our, and diversity of our microbiome. And we have more chronic stress and we have more exposures that can disrupt the health of the gut microbiome and the intestinal barrier function that may allow more people who have a genetic predisposition, create a scenario where those gluten proteins are coming in contact with the immune cells and leading to disease. But if we take people who have autoimmune conditions,

where the immune system starts to inappropriately react to one of our own organs, like the thyroid and Hashimoto's thyroiditis, or the insulin producing cells of the pancreas in type one diabetes, or the joints and rheumatoid arthritis, there is a higher prevalence of celiac disease and gluten related disorders in people with autoimmune conditions than there is in the general population. So what we're now starting to understand is that somebody who has a predisposition to autoimmunity and eats more gluten in their diet, which further disrupts the health of the gut lining, it may create the environment where more bacterial proteins come in,

more food proteins come in, and that immune system that's part of the immunologic barrier who is getting bombarded starts making antibodies not just to gluten or to those bacterial wall proteins, but to those organs. So this was a foundational model for understanding the link between increased intestinal permeability, autoimmunity, and other health conditions. And as I mentioned, that was really one of the pivotal papers. The second pivotal paper with Biscoff convened an expert panel and reviewed all the literature to pose this question of, well, wait a minute, now that we're learning how much increased intestinal permeability may be playing a role with chronic conditions,

is there a role for targeting intestinal barrier function for disease prevention and therapy? So this was in 2014, and the conclusions of the expert panel, they defined intestinal permeability and intestinal barrier. They reviewed assessment methods. Unfortunately, none of them are perfect. We do have some tools to try to get a snapshot of whether somebody has increased intestinal permeability, but also highlighted the need to develop reliable non-invasive markers, not just a permeability, but some of those other functions like mucus quality. We really need a lot more research on the role of the intestinal microbiota in regulating

intestinal permeability. How do we define a healthy microbiome? Is there one definition or are there multiple health, healthy microbiota? And is it cause or effect with inflammatory bowel disease, irritable bowel, and other conditions? We're going to come back to that cause and effect issue in a few minutes. What's the role of pre and probiotics? And probably my favorite conclusion of all is really acknowledging the importance of food. Food as the probably biggest impact on modulating the

intestinal microbiota composition, as well as intestinal barrier function. Because to me, that is always the first place we're going to start when we're talking to people about how they can maintain, preserve, or improve intestinal barrier function is what's coming in in your diet that's going to either support a healthy barrier or take away from a healthy barrier. Well, I hope you enjoyed that teaser of exclusive content that you get every single month with Dr. Hyman Plus. If you want to teaser of exclusive content that you get every single month with Dr. Hyman Plus. If you want to listen to the full episode and get access to ad-free podcast episodes,

plus Ask Mark Anything episodes, plus monthly functional deep dive episodes, I guess that's why we call it Dr. Hyman Plus, then head on over to the doctor's pharmacy on Apple Podcasts and sign up for your seven-day free trial. Hi, everyone. Just a reminder that this podcast is for educational purposes only. This podcast is not a substitute for professional care by a doctor or other qualified medical professional.

This podcast is provided on the understanding that it does not constitute medical or other professional advice or services. If you're looking for help in your journey, seek out a qualified medical practitioner. If you're looking for a functional medicine practitioner, you can visit ifm.org and search their find a practitioner database. It's important that you have someone in your corner who's trained, who's a licensed healthcare practitioner, and can help you make changes, especially when it comes to your health.