Kharrazian Institute – Gastrointestinal, Course Two

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Kharrazian Institute – Gastrointestinal, Course Two, Session 1 A Comprehensive Review of How the Gastrointestinal System Works

© 2019, Kharrazian Institute LP Presented by Dr. Datis Kharrazian

Okay guys. Thank you for coming to the Gastrointestinal Module. I have a lot of information to share. We're gonna go through it at a pretty good pace. I'm not gonna be able to cover everything related to the GI tract. Obviously, there's too much stuff. We're not gonna talk about every single probiotic strain, and we're not gonna talk about every single full nutrition product out there. What we're really gonna talk about is the clinical thought process. That's the most important thing. So, I think for many of us that have been practicing full nutrition functional medicine for some time, we are constantly refining our skills. So, I wanna share with you – and I do this all the time. I really sit back and just spend time really thinking about my protocols to not miss anything. What's the most efficient way to evaluate a system like the GI system? So, this is 20 years of updates from me. I'm gonna share with you all the newest research that applies to this model, and I'm gonna teach you a step-by-step approach. The goal I have is for you to not just get a Power Point dump of studies, but to actually have a treatment application, a thought process. Okay? Now, let me tell you where practitioners go wrong and where I've gone wrong, too. And you guys all see patients that come in and they have files from other doctors, and you just go “why didn't I do this? It’s like so obvious.” The biggest problem is: 1.) They just jump to – they don't understand the hierarchy. They just jump to treating the microbiome. They don't take the time to figure out what's going on. They kinda just say “well who doesn't have leaky gut? So, I'm just gonna treat them like they have leaky gut.” Big mistake in being clinically efficient. And then, there are mechanisms that people don't understand the prognosis, too. There are people that will never have their gut ever fixed. Do you guys understand that? That's important. There are people that will have their arm cut off and it'll never come back. There are people that will have massive neurodegeneration of their enteric nervous system. It is gone. There are people that are gonna have demyelinization that's gonna impact their gut. There are those patterns that exist, and they're not hidden infections or weird parasite or something. They're just degeneration of the gut. How do you find that clinically? How do you assess that so you don't have to make these big assumptions? So, that's the key thing. And then, we're also gonna talk about how to do a physical exam, because actually digestion starts with smell. And you guys know that the most common neurodegenerative disease is Alzheimer’s followed by Parkinson’s. In both of those, and especially in Parkinson’s, the neurodegenerative process takes place in the gut 10-20 years before, and the first thing they lose is smell. So, they're actually getting degenerative changes of enteric nervous plexus, and they end up with constipation and gut issues and abnormal comprehensive digestive stool analysis tests, but they have really Parkinson’s, and it's gonna be maybe 10 or 20 years before they show up with tremors. So, how do you pick up those patients?

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So, the goal for me is to really teach you a thought process, and then I'm just gonna go over some basic concepts today in the morning. I’ll show you the syllabus in a second. And then, we’ll go into ultimately how to, step-by-step, evaluate a patient, and then how to develop a treatment protocol. And then we’ll go over case, and then we’ll do some followup and cases if you guys are following our online members only Facebook page. So, simply put, there's three main reasons practitioners treat the gut. Someone comes in and they have GI issues which is the most obvious. Second is immunological issues. Maybe they have an autoimmune disease. Maybe they're trying to treat their gut because they have psoriasis, or maybe they're trying to treat their gut because they have lupus or some type of thing where they're trying to deal with an autoimmune issue and that's why they're going after the gut. They're not concerned about the bloating and indigestion. It might not even be there. They're just after trying to control the immune system. And then, the third reason is they're just looking at different types of brain-gut axis mechanisms. So, lots of great research now showing the gut impacts things like depression and neurodegeneration, and just energy and obesity and metabolism. So, many people that are doing advanced functional medicine are working on diabetes patients by treating the gut, working on depression by treating the gut and not really working with serotonin or dopamine and these neurotransmitter sorts of things. They're really working at the brain-gut axis level. So, those are the three main reasons why you would treat the gut, right? Now, what I wanna do in this course – this is the outline. We're gonna review how the GI system works in a functional from smell all the way down to the gut, and how things can go wrong. You’ve got to know the gut axis. So, how you will be inefficient to treat the gut is “here’s my gut particle; they all get it. Treat the gut. Treat the patient. Fix the gut. Fix the gut first. Here's my cool probiotic. Here's my cool enzyme. Here's the one I use for leaky gut. Here's my protocol. It's already labeled. It's packaged. My staff knows how to use it. And here's my diet where they can't eat anything.” There you go. Good luck. That's the worst inefficient way to practice. If you practice that way, you should probably get about a third of your patients better. Okay? Then what happens to the other thirds. “You didn't get better. Oh, you're so weird. I don't know why. Maybe it's this probiotic strain. Maybe you need another one.” This is exactly what we do not want to do in a thorough workup. In a thorough workup, you don't even wanna recommend water until you know what's going on. Take the time to really figure it out. Figure out the mechanism, figure out the prognosis, get a really good idea, and then really think about your treatment protocol and then jump in. Now, there are gonna be some patients that will have serious gut issues that you won't be able to resolve because let's say they have Parkinson’s issues and the gut’s already degenerated away or something. So, then it's about maintenance, and we’ll talk about

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those strategies and things, too. Now, we're gonna go through all the different aspects of digestion starting north and going south. We're gonna talk about intestinal permeability. Intestinal permeability is more than just giving people glutamine and bone broth. You’ve got to know if they have paracellular, transcellular. You have to know if they have endotoxemia. You’ve got to know what degree of permeability they have, and you have to know if it's one of the types of permeabilities that is responsive to treatment. Not all of them are. Some people will have intestinal permeability for the rest of their life – it's just to what degree. So, we have to figure out the prognosis and how to manage those patients. We're gonna have to talk about the microbiome. There's a lot of popularity in outside research on the microbiome. It's really amazing stuff. It's fascinating stuff. We’ll share some of the research with you and then talk about applications, what's been published about the microbiome. We’ll go over all the main published diet and nutrition lifestyle things that have been shown to help things like microbiome diversity, and make sure you have that tool in your clinical practice. And then, we're gonna talk about unresponsive GI patients. If you're a practitioner and you have patients that are not getting better, it could be because they have mechanisms like we said. Like maybe they have an early neurodegenerative disease in their gut. Maybe they have an autoimmune disease in their gut, and that's an ongoing thing. So, we have to really know how to pick up on patients that are not responsive, and what that really means is you're gonna support their GI tract ongoing, knowing that the prognosis is guarded, that it's not gonna change, that have a limited approach to resolving. So, you shouldn't expect every single patient that comes in to treat the gut and they get better, and if you think that way, it's because you don't have a thought process and a way to really assess it. You know what happens when patients have unresolved GI issues and they find someone that tells them that? And says “hey, we just did your test. You have autoantibodies to your own intestines. What that means is well, there's no cure for autoimmune disease, but we can try to put you in remission and we can try to improve the quality of life, but you have ongoing GI susceptibility.” You know what happens to those patients? What do you think happens? Do they get angry? They don't get angry. They go “thank you, because I thought there was something wrong. I don't understand.” They just – not knowing is worse than anything. Not having understanding of what they need to do and the mechanism involved is the worst thing. So, you really want in there and understand which of these patients who are in this category are unresponsive or that have things that are ongoing. Maybe that's a better word than unresponsive – ongoing care or ongoing chronic GI issues. And then we're gonna get into how to evaluate GI issues step-by-step.

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We’ll start with an exam. Check their sense of smell. Check their sense of taste. Do they have saliva? Do you listen to their abdomen? Do they have bowel motility? Like, we’ll go through the whole steps. Do they have any signs of malabsorption? Those are important. So, actually we’ll talk about physical exam. It isn't just like “okay, jump into the functional medicine arena, order $10,000 worth of tests. And at the end, I'm gonna give you the same protocol is was gonna give you anyways.” That's now what we're gonna do. And then, how to develop treatment protocol step-by-step. So, you’ve got to understand. Is this a brain-gut axis issue that you have to deal with? Is this a neurodegenerative disease? Is this an infection? Or is this an intestinal autoimmunity? They're all different. And then, we’ll do a case study putting all these things together. And we’ll follow up with patient has been very generous to share her case with us, and that’ll be a good learning tool for us to go through. So, we're gonna go over the basic concepts of the microbiome, various health issues. We're gonna review, in this presentation, the clinical mechanism from chewing all the way down. And then, we're gonna talk about a hierarchy approach, and that's another key thing. You can't just treat everything at once. And if you just, for example, jump into the microbiome because you're trying to change the microbiome but they still have a gallbladder issue, you will fail. Now, here's another good question. How many of you guys see gallbladder issues? It's very, very common. If a person has a gallbladder issue, especially a female, you can't fix their gut. You have to fix the gallbladder issues. If you go and try to change their microbiome for psoriasis or for their Hashimoto's, you will not have much success because there's lots of mechanisms involved with having proper bile acid release. Bile acids, for example, are signaling agents. They impact gut mechanisms. They impact the gut microbiome. They're really important. So, it's really important that we cover a hierarchy approach. Why a lot of practitioners fail with chronic gut issues is they don't have a hierarchy approach. They go right into it, and that can really cause you to fail with patients. So, now we know with all the new major research, the microbiome is really, really popular, and this is fascinating stuff. Because in the world of natural medicine, people have always known the gut is really, really important, and you’ve got to treat the gut even if it's not a GI-related issue. And all these different studies are showing how important the microbiome is and how important is type diversity in the microbiome, and how your health is totally dependent upon the microbiome, and they're doing a lot of studies on the microbiome. And then, some of the studies that are coming out are like this. “Oh, we find different strains of bacteria with different diseases, like Parkinson’s and Alzheimer’s disease.” And these models have all been disproven. That's not how it works. It is really way more complicated than this. So, when they look at the billions of different types of bacteria species and the growth of

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these populations in the gut, what they realize is we have to use machine learning. It's not gonna be – they're gonna have to use complicated algorithms to figure out what these things all mean. Because the model of one bacteria just being good and one bacteria just being bad isn't that accurate. It's one bacteria and another bacteria can influence it in the populations of these bacteria together in their host can have an effect. So, when we look at some of these GI panels and we see beneficial bacteria versus non-beneficial bacteria, that is – it's almost laughable. It's some little speck of getting some information, but what's really out there – it's nowhere near what we need to evaluate. So, it's not this model of just good or bad bacteria. As a matter of fact, when they've done all this research of the human microbiome, what they're finding is – the one thing they know about is you have diversity. The more diverse the good microbiome, the more benefits they see for health. That includes all different types of species – some that were labeled pathogenic. So, we like to – there's a problem that we have that's kind of stuck around. When they discovered antibiotics, they found something that killed something and it killed it and everything got better, and we tend to have that translation all the way across into even functional medicine. “The gut’s not there. The gut’s not healthy. Let's kill it. Where’s that bug? Where’s that parasite? Where’s that candida? Where’s that yeast? I wanna kill it all.” And now were realizing that that's not the best model. So, what is a healthy microbiome? So, what are the definitions? How would you describe someone’s microbiome as healthy? Well, we know diversity is part of it. So, there are really a few categories. So, one of the categories is just how much diversity that the gut microbiome has. And remember, there's a microbiome in the mouth, the skin, the lungs, the vagina, your nasal cavity – there's microbiomes all throughout the body. And they all actually communicate and work with each other. So one area is to really look at how many species do you have, how diverse it is. That's one model researchers are looking at for microbiome health. It's one. Another group is looking at function. How do you metabolize hormones with your gut? How do you metabolize end-products? How do you clear toxins with your gut bacteria? And they don't really care about the diversity; they're just measuring functions, and they're not as concerned with how much but what types of responses that actually take place. Can you convert things to lactic acid? Do you have biochemical steps? So, remember this: The bacteria in the gut all have different functions. Some can metabolize hormones to an active state. Some can metabolize flavonoids to an active state. Some can detoxify a toxic compound just like the liver does. So, the more diversity you have, the better function, right? But some of these gut bacteria may have better abilities to let's say metabolize and help clear BPA. Because your gut microbiome is almost like the liver. It helps phase 1, phase 2 biotransformation pathways. So, they're looking at function. So, that's a whole other group of researchers. So, it's not just diversity; it's what the microbiome can actually do. So, they're doing studies with seeing how the microbiome actually changes. And it's not

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always more is better; it's just there are certain species that do better things. Another group is looking at the ecology, going “if you live in this environment, how does your microbiome compare to living in this environment?” And if it doesn't, they can see health problems. So, why is your microbiome not adapting? So, there's certain species you guys will all have if you live in southern California or if you live in Canada, or if you live wherever. And if they check your microbiome and they check people in your area, there should be some similar species there. So, if it's not there or if it's not developing there, there are problems because those species could be helping you respond to pathogens and environmental things in the area. So, there's a whole group of people saying that's what is a key part of healthy microbiome. And then there's another group that are looking at how your microbiome can respond to stressors. What happens when a pathogen comes in? What happens when you change your diet? So, let's say you travel to a different country, start eating food there – how do you respond? Do you totally have dysentery and have problems, or do you adapt? What happens to you if you get a pathogen? You’ve all seen patients. You do a GI panel. There's like six pathogens there and you're going “what's going on?” They're like “I feel great.” And then another person has one little tiny bacterial overgrowth and they're totally falling apart. So, that's a whole other field of study – how well does the gut microbiome respond to change? So, this is a growing field. We don't have all the answers, but there are a lot of people not really invested in doing the research and trying to figure things out, but they're all important. Now, the one thing that we do know is we need to have lots of bacteria of all kinds, diversity, and richness, and how resilient they are, how they can deal with stressors to the microbiome. Those are all the key things. So, this is the paper, and these papers I have included in your course material. So, if you guys wanna dig into any of these papers, they're there. The Intestinal Microbiome and Health. So, the go on to say there's a complicated bidirectional relationship between the intestinal microbiota and the host, which is vital to health and likely promotes disease. What constitutes a normal, healthy microbiome is an area of active research, but key characteristics include diversity, richness, and microbial community resilience and the ability to resist change. And there's a whole host of things that impact this beyond just diet. What we do know is also that the microbiome is shrinking, and the US is one – they're No. 1 with the least diverse microbiome. We won. We’re No. 1, No. 1. So, we have the least diverse microbiomes here. We have lots of things that caused that and we’ll talk about all the different mechanisms. But as a matter of fact, here's a diagram. Here you can see the shrinking human microbiome and you can see this red line. This red line represents US population. So, if you take a look at us here, you can see that in Africa, they're much more diverse. And in different parts of eastern Europe, they're more diverse. And look at this. A squirrel is

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more diverse than us. Look at a gorilla. You see any diabetes, obesity in these animals? No. Have you ever watched any shows from like the ‘80s? Everyone looks so healthy. Everyone’s so thin. They're glowing. You're like “wow.” I mean they all have big shoulder pads and big poofed out hair, but for the most part, they're totally different, and they had different microbiomes. And there are lots of things besides diet that has caused these microbiomes to change. So, even with very health-conscious people that are going to Whole Foods, getting pesticide-free food, working out and exercising, doing all the right things, eating lots of greens. They are still having many environmental factors that are impacting their microbiome. So, I had a friend of mine. We were talking and she goes, “So, do you think everyone has a gut problem?” I go, “I don't know if everyone has a gut problem, but everyone has to focus on their gut now. Like they have to at least have some consciousness, and if they don't, they can have a gut problem.” So, if someone just does the standard American diet, they're gonna have problems if they're just eating fast food and so forth. So, it is a big issue and it is something that we're all susceptible to. Let me show you, really quick, a few interesting studies. This is the paper called Microbiome Health and Reactions in Older People. So, they looked at elderly subjects and they wanted to see how frail they were, how weak they were, how they depended on other people, and they found something really fascinating. They found the more microbiome diversity they had, the more independent they were. They're working out more, they're exercising, they're doing things, and the ones that lose their diversity really become dependent on other people and end up getting sick and end up having serious health problems. So, they go on to say the microbiome diversity scale is really critical for aging and health. Now, when people start to get older, what do they stop doing? They stop eating. They're like barely eating. “Did you eat lunch? Did you eat anything?” “No.” “What did you eat?” And they start losing their diversity because they're not eating anything, and they're definitely not eating diverse, and that is a vicious cycle downhill. And some of the people in the microbiome research are saying in the future, what's gonna happen is you're gonna go in and instead of just getting your blood pressure checked and your blood tests done to see if you don't have high cholesterol. And there should be a microbiome diversity scale, and that will give you a clue of how healthy it is in respect to yours. And this may actually happen because there's just a growing amount of evidence on this. So, if you're looking at the health of yourself and elderly people in your family are patients, the more diverse they are, the better chance they have of staying healthy as far as your gut microbiome is concerned. And this is the paper that was published in the Role of the Microbiome in Health and Disease. And they went through some of the major diseases like IBS, inflammatory bowel disease, obesity, allergic diseases, and

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neuropsychiatric illnesses, and said “well if we test them, these diseases all have reduced microbiomes compared to those that don't have these diseases.” So, they're finding this association with just overall health. Now, if you look at the microbiome, you have diet here. So, that's one thing. But look at all these other things. So, genetics has a role; your host immune function; environmental influences. Do you drink out of plastic bottles? I'm gonna show you some research on BPA that'll mess up your microbiome. We're making all this effort to take enzymes and supplements and make your salad with all these different colors, and you keep drinking out of plastic bottles. That's gonna have a significant impact on your microbiome. Are you around secondhand smoke? Do you get away from it? Do you sit on the freeway with exhaust benzene coming at you? That will change your microbiome. So, it's not just about diet; it's about these exposures. The problem we have in functional medicine is like everyone’s so focused on chemicals being heavy metals and chelated, and in reality it's the little, small things that we can have some changes, like getting our BPA reduction down or not being around secondhand smoke. Those things have a huge impact in our health and our microbiome diversity, so it's not just by taking a probiotic. As a matter of fact, you can't take a probiotic for all the bacteria. Every day you’d be drinking like two gallons of different bacteria all day. It's not possible. Neurotransmitters and metabolites. These are ruling your brain-gut axis. How does your brain fire? How is your motility? You have to have some input for your brain to your gut to move food, which then changes your endocrine function, your immune function, and allows you to release enzymes, have blood flow. It's all got to work. So, what does it mean to you by the way if a patient comes in and says “please don't give me any capsules. I don't like take taking them. I have a hard time swallowing them.” What did they just tell you? They just told you they have a brain-gut axis disorder. That changes everything. Here's another one. “You know, people don't like to eat with me because they say I take forever to eat.” That happens when people can't make saliva. That's an endocrine issue that goes with dysautonomia and early neurodegenerative diseases. It's not just like “oh, they're so enlightened. They're chewing more.” It's because they have to. It's the pathology sometimes. Now, there are people who chew more for health reasons and they focus on it, and that's great. But there's people who have no choice and they don't even realize they're doing it. So, these are the subtle things you have to pick up on to figure out the mechanism of their GI disorders. It's not always gonna be their diet. As a matter of fact, you're gonna see what we all see. Patients coming in – “how’s your diet?” “Great.” “What are you taking?” “Everything.” “What's going on?” “I'm sick.” “Great.” Okay. That's actually the patient we're after this weekend. What do you do with that? Now, when you're looking at some of these interesting studies, here's another good one: The Microbiome and Critical

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Illness. The microbiome represents a key therapeutic target for the prevention and treatment of critical illness, which is what we're all dealing with, and it should be included in discussion with precision medicine and the intensive care unit as well. When you look at the microbiome – so remember, we have the intestinal microbiome; we have skin microbiome; oral microbiome; lung microbiome; some people have vaginal microbiomes; and nostril microbiome. And they all communicate with each other. As a matter of fact, the intestinal microbiome produces things like short-chain fatty acids and it fuels each other. And bacteria have what are called postbiotics. Do you guys understand what those are? Postbiotics are things like polysaccharides. They release different polysaccharides, which are signaling agents. Like polysaccharide A turns down inflammation and autoimmunity. Bacteria make it. So, unrelated to just cytokines and immunokines and neuropeptides and gastric hormones, bacteria actually make postbiotics. And these different feedback systems all communicate. I’ll show you some research on that. So, it is really, really important. So, your mouth health can impact your gut microbiome. Like if you have cavities and you have poor dental hygiene and you have gingivitis, that can completely impact your gut. And you're not really ignoring it. I mean, you have a patient that comes in, like you have to do a mouth exam. You’ve got to see what's going on with their gums. Do they have any bleeding gums? If they open their mouth and it's just a really bad smell, those things can totally impact chronic GI issues. Same with vaginal health. Same with lung health, respiratory health. Someone tells you they have exercise-induced asthma, realize that that's gonna impact the gut microbiome – that their pulmonary microbiome is involved. So, by the way, the way you treat gut issues that nothing helps is to not treat the gut. It's to treat all the other things, which we’ll talk about. And then there's things that impact the microbiome like medications, chemicals, hormones, immunokines – they're all important. And then ultimately, we have all these different axes. So, the ideal picture in the functional medicine model, someone comes in. They have chronic depression. We get them healthy. We get them to have healthy digestive function and maybe as they treat their gut, their depression goes away, or the cognitive decline goes away. Or they have a skin issue – they have some kind of rash or some type of inflammatory skin condition and you treat their gut. You find things they react to and they get better. So, those are the different gut axes. So, one of the most important axes is the brain-gut axis, and the gut-brain axis. So, here's my question to you. Do you clinically evaluate this in your practice now? Good. And if you don't, how do you? And what do you do when you find things that are wrong? So, this is important. So, we're gonna talk about really listening to the gut, looking at gag reflexes, looking at palate contracture, making sure that whole vagal 9-10 pathway is working. Those are absolutely critical to figure out if they have one of the key things that they need to help out the gut function, neurological input to their gut. Then, their gut

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works upwards and has an impact there, too. The patient walks into your office and they have cognitive decline, you should be really concerned about a mechanism impacting their gut. Patient comes in and they're late and they're slow functioning and they forget things, they ask questions all the time, you should be worried about the brain-gut axis, or you should at least test it in a physical exam setting. It's not a lab test. This is also why like the lost art of healthcare – the physical exam. People don't do it. I mean, you see functional medicine people? They order so many tests and then they do a protocol, and they go “okay, let's get your notes.” You're like “exam.” It's terrible. It was almost like made up. Cranial nerves all normal. DTRs are all normal. Yeah, everything. And you're like “they didn't do this.” Like “how long was the exam when you talked to the patient.” They're like “oh, I don't even know.” You're like “yeah, it sucked. I guarantee you.” Sorry. And then you check these things out and you realize “wow, they really do have a brain-gut axis issue.” This is part of it because no one actually did a physical exam. And lots of research now showing that the brain-gut axis really impacts the brain and neuroinflammatory conditions, neurodegenerative conditions. When dendritic cells in the gut get inflamed, microglia get inflamed. When there is inflammatory responses with T-cells in the gut, the brain gets activated. There is a direct connection between pathways from the gut up the vagus – inflammatory messenger pathways that turn on brain inflammation. That is no longer a theory. That is well-established to the point now there are multiple, multiple, multiple review papers on it. You can just go and start reading about it. And then, if we look at the microbiome, we can look at this paper here – the gut-skin axis. So, there are researchers now really understanding the importance of this in the dermatology world. Conclusion: Through complex immune mechanisms, the influence of the gut microbiome extends to involve distant organs including the skin. With the intentional modulation of the microbiome, probiotics, prebiotics, and symbiotics have proven beneficial in the prevention and treatment of inflammatory skin diseases, including acne vulgaris, atopic dermatitis, and psoriasis. There's now research showing that gut microbiome imbalances can cause liver inflammation – the gut-liver axis. Conclusion: An accumulating body of research suggests that disparate observations in liver disease-related studies are unified and explained by the microbiome. It is now widely accepted that liver damage can result from extensive interplay between the gut microbiota via specialized molecule such as TMA pseudo aldehyde LPS and the host immune system via Cooper cell mediated liver inflammation. So, in the liver, you have cells called Cooper cells. These are immune cells. When gut cells like dendritic cells or T-cells in the gut get activated, they send messengers and the liver gets inflamed. And this is the paper that really shows some of these different mechanisms that take place between the gut and the liver.

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So, when there is an inflammatory response in the gut microbiome, there's gonna be some inflammatory response in the liver. And now there's been multiple studies published showing that many of the inflammatory liver diseases like non-alcoholic fatty liver or primary sclerosing cholangitis, they have these direct connections with the inflammatory state of the microbiome. There's research now talking about the gut-lung axis. This biosis and gut microbiota has been implicating in several lung diseases, including allergy, asthma, and cystic fibrosis. The bidirectional crosstalk between the gut and the lung, termed as lung-gut axis, is best exemplified by intestinal disturbances observed in lung disease. Some of the existing probiotics showed beneficial effects on lung disease. And there are these pathways here between how the cells and the gut communicate with the gut microbiome, and how bacteria, specifically bacteria, produced things like pure-chain fatty acids and butyrate and postbiotics like polysaccharides, and they have a direct impact on immune cells in the lung. And then how your lung microbiome can impact your gut. So, if you have someone like you go “man, this person has got this microbiome diversity and their gut’s never getting better, and they have asthma.” And you think “well, I'm gonna treat their gut to fix their asthma.” It could be the opposite way. You may need to treat their asthma to then have a chance to fix their gut. Does that make sense? This is the No. 1 mistake functional medicine people make. “Fix the gut; I’ll fix everything.” Wrong. Sometimes you have to fix everything else to fix the gut. Now, it's okay to start with the gut. You just have to realize that if it's not responding, you have to go the other way. Microbiota and Thyroid Interaction in Health and Disease. An altered microbiota composition increases the prevalence of Hashimoto's thyroiditis and Graves’ disease. Microbiomes influence thyroid hormone levels by regulating iodine uptake, degradation, and enterohepatic cycling. In addition, there is pronounced influence of minerals or interactions between host and microbiota, particularly selenium, iron, zinc in manifest thyroid disorders such as microbiota may affect L-thyroxine uptake and the action of PTU, which they use for hyperthyroidism. So, the gut microbiome impacts how the thyroid metabolizes iodine and uses it, and how thyroid hormones become active. So, there's about 20-30 percent of thyroid hormones that can be activated by gut bacteria. So, when someone has lost their diversity, they can take thyroid replacement, but they don't respond. Look at this. The Role of the Gut and Microbiotic Gut Hormone Axis. The research field focused on interaction between gut microbiota and gut hormones may be referred to as microbial endocrinology and is expected to become a focus of intense interest in the near future. What they're finding is that gut bacteria impact hypothalamic signaling pathways like in the periventricular nucleus that control things like FSH, LH, TRH output, and that these metabolites have a direct impact on endocrine function. And then hormones have a direct impact on microbiome. So, the amount of estrogen, progesterone, testosterone that

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you produce has an impact on regeneration of your gut and the species you have as well. So, it's this interplay. And then Functional Neurological Disorders. Some studies define its response in the bladder-gut-brain axis. What you're gonna see out there is these papers over and over again. All these studies showing that you have all these different axes with the gut and how they work. So, the key thing that I want you to really understand from this so far is this is the outdated model. Fix the gut to fix the patient. I mean, there's some truth in that for sure, but you cannot let this be like your “I'm gonna keep going. They haven't responded for gut treatment for four months and they're not eating anything anymore that they like, but I'm gonna keep going because I think it's that next probiotic. I'm gonna add in this fermented salad.” It's not gonna matter. There's a point that's not what you do. Another model is fix the gut axis. So, maybe if their gut’s not working, you have to fix their oral health. Maybe they have gingivitis or bacterial issues in their mouth. Maybe if their gut is not working, you have to fix their asthma and get their pulmonary microbiome to function, because you're not getting far with the gut. Maybe you have to do it together. But you have to realize that the microbiome is interacting with these other areas and that is the bidirectional relationship. So, that's why when you look at this diagram, the first thing I wanted you to understand on the left-hand side is these are bidirectional. You could have someone that's getting exposed to a chemical, a lotion they're putting on every day, and their skin is reacting to it. That is gonna throw off their gut microbiome. You're trying to fix your gut microbiome but you're ignoring it. And then you're thinking “well, I just think if I fix the gut, this will be okay.” Well maybe not. Maybe that soap that is causing inflammatory reaction is changing the inflammatory state and the function of the gut. The same with oral health. Always look in the mouth and see what's going on with their health. Poke around. Look at their tongue. Look at their saliva production. Check their breath. Listen to the lungs. See if there's any history of any pulmonary issues. These all matter. Okay? And then the other thing you'll see is that ultimately, the goal of all these things is to fix these microbiome connections to each other so we can change the gut axis to then make a difference. So, the best model is fix the gut axis and the mechanisms that disrupt it to fix the patient. And sometimes you won't even play with the gut, and sometimes you will. But that's the biggest thing. Okay. So, when we look at this gut microbiome, these are all key things. Now, notice diet is one thing, because what you're going to see in many real-life cases is their diet is excellent. When their diet’s excellent, you have to look at other things – hormones, medications, chemicals – all these other types of scenarios. Now, it's okay if you're a practitioner that does start with the gut, but again the key thing is if it doesn't respond, look around. Look and see what else is there. Or initial workup – think of red flags that could be impacting their response. Those are all critical.

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Now, when we actually get into treatment of the GI symptoms, we know in healthcare, it's basically if someone comes in with the most common chief complaints – bloating, gas, diarrhea, constipation – you take something at the Thrifty or Vaughn’s or drugstore to see if they get help, and then if you're a little more advanced, you go and get some orange juice with probiotics in it, or you get some sorbet with probiotics in it, or some yogurt. These are excellent. And then, if you're advanced, then you do the 5-R program. You replace, remove, reinoculate, repair, and rebalance. And those are good, too. I mean, it's an effective strategy. We’ll use the strategy. I'm not saying it's not useful. It's useful. You just can't be limited to it. But here's the problem we have. Gut problem – “here's my protocol. Take it.” It doesn't get better. Because the thing is, you don't know what is causing those symptoms sometimes. You're just jumping into it. Why start there first? Because you understand with a lot of patients, you don't get a second shot. Like if you suck the first few times and they spent hundreds of dollars on supplements – bye-bye. And then you know what they say? I went to see that person and they sucked. They made me order all these tests and all these supplements, and it didn't do anything for me, and you should not go to them because they don't know what they're doing. That's the thing. You can't just jump into random protocols. Now, this could be a very thorough way to support people, but it's a random protocol if you don't know the underlying mechanism. Then, we have the reality. What do you do? Real patient. I don't know. Like these are the questions I always get at conferences. “My husband won't listen to anything I say. What do I do?” The patient that won't change their diet, and what do I do? I don't know. You do nothing and they suffer. Next. So, you have to have a highly motivated patient, too, to even get any chance with GI issues. So, despite everything we go over, if you don't have a compliant patient, you're not gonna get any change because you have to have a compliant patient to manage the gut. Real patients. “My diet’s perfect and I'm still sick. Now what?” Because we've all seen this. How about this one? “I'm a doctor and I don't know what to do for my own gut symptoms.” Hopefully this weekend, we can find out. You haven't looked at some of these things. Maybe it's your chronic asthma impacting your gut and you have to treat that and deal with improving your gut antioxidants or your gut microbiome and epithelium and things that are actually triggering that. Maybe you have early neurodegenerative disease. Maybe you have intestinal autoimmune disease. Those are other factors. So, when we talk about unresponsive things, those are key issues, right? So, are you one of those patients who has a prognosis that's poor because you have an underlying condition that you're just gonna have to manage that you will not be able to reverse. Clinical pearl. Many gastrointestinal conditions fail to resolve because the treatment model ignores the principles of clinical hierarchy. So, this is the first key thing I really hope we get across. You’ve got to go in order – digestion, immune function, microbiome.

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If you just start at the microbiome and just load up people with a bunch of probiotics, you are destined to fail. If you just try to treat leaky gut, but they can't digest their food or have something like a gallbladder issue, you're destined to fail. So, for me, as I've learned from my own mistakes and fine-tuning my own clinical model, I know I have to start with the priority. So, I've got to make sure the digestion’s intact. They can swallow. If they don't swallow, it's a red flag. They have proper intestinal motility. I gotta find out why the motility’s not working. Is it the brain-gut axis issue? Are they releasing high amounts of methane in their gut that's shutting down their gut axis? Do they have electrolyte issues and they can't get water reabsorption, so they're constipated? Are they just sedentary? Like, you’ve got to figure out why – well you have to have motility. You’ve got to figure out motility. You have no chance to fix leaky gut if you don't figure out their causes of motility issues. Does that make sense? This is how we're talking about a priority. Do they produce saliva? That's key. If they don’t, you have to give them some saliva substitute so they can start breaking down their food. Do they produce hydrochloric acid, pancreatic enzymes, bile? Do they have normal gallbladder contraction? Could their microvilli actually assimilate nutrients? Do they have patterns of malabsorption? If they have patterns of malabsorption, what do you think you're gonna do when you give them more supplements? They're not gonna absorb it. So, do you guys know how to find clinical malabsorption? Do you know what they look like on labs? Do you know how they present clinically? That's critical. We're gonna talk about those. And those people – you're not gonna give them more nutrients for the gut because they can't take it. They're not gonna respond to it. Okay? So, once you’ve figured out like “yeah, they can swallow; they have motility; they have normal digestive enzyme function; the gallbladder works.” You can move on. So, if you have, for example, an autoimmune disease patient that comes in and they have Hashimoto's or something, or a type 1 diabetic patient, or an RA patient, and you just try to go to leaky gut, you're gonna guarantee to fail if they have something going on with your digestion. Because you have to break down food particles so you don't have an immune reactivity. You have to properly have motility take place so you can move these things across, and these things change things like pH in the mycology in the environment, and they're all critical. You have to have the HCl to neutralize, sterilize some parts of the gut. You’ve got to have HCl to release different feedback loops. You’ve got to have proper acidity to help create the right pH to have microbiome growth. So, if someone is having chronic gastritis or has a subtle hypochlorhydria and you’ve ignored that; or if someone has – they make bile, but they can't release it; they have contracture issues or they're just constipated, you're going to 100 percent fail with the leaky gut protocol. And maybe that's why they're in here because they have an immune issue.

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So, the key thing is when we talk about the clinical model, I'm not here to teach you protocols. I'm here to kinda remind you – be efficient. The gut works a certain way. You have to start north and go south. You’ve gotta make sure if you're gonna treat leaky gut immune issues, there are no digestive issues. And you might go in stages or you might do it simultaneously. That's up to you. It depends on your case and how you wanna do it. So, then you get into immune issues. That's when you're talking about leaky gut. And we’ll talk about tolerance. Lots of patients have reactions to food and multiple food sensitivities, and they don't have a leaky gut. They have what they call loss of oral tolerance. We're gonna talk about that tomorrow, and a little bit today. And then, eventually you get to the microbiome. That's when you can change the psoriasis issue. The gut – the microbiome skin reaction. That's when you can treat the microbiome lung issue; the exercise-induced asthma that you have to fix the gut to treat. Does that make sense? Or maybe you do it bidirectionally. So, if you don't go through the steps, you have failure. So, a lot of practitioners do like a lot of nutritionists when they're not – they're new. They'll go “oh, I went to this conference. They said these are megaspores. They're amazing.” Or “these are fantastic probiotics. They're so much of them. I just need to give my patients that.” And you're like “good luck.” That's not how it works. What works is you actually fix the other things. I can tell you in my own practice, just as you kinda do different things at different times in your practice – we all do that. I use very little probiotics. I'm so much more focused now on getting diversity going and using things like short-chain fatty acids and changing the richness and stuff than trying to give them one strain of probiotics that only works for a few hours after they ingest it. It's like you're trying to change the environment. So, this is the first basic concept. You’ve gotta think about north to south. So, we're gonna – when we talk about making a very efficient clinical protocol, because again, my goal this weekend isn't to give you a bunch of protocols and a bunch of different things you can give patients. My goal is to make sure you have a very efficient clinical model where you start from the top, work yourself all the way down, and not miss anything. Does that make sense? Because this is why patients come into your office that have seen other practitioners. They were on a probiotic. They were on enzymes. They were on a diet restriction. They were being treated for leaky gut. But, they didn't understand the concepts. Okay, now. Clinical pearl. In addition to understanding the clinical hierarchy of the gastrointestinal system, you must find the mechanism of action and the prognosis. So, if a patient comes in and these are their chief complaints: bloating, constipation, increased reactions to foods, fatigue, and depression. If you just jump to 5-R program, you're gonna miss it. Which is, 5-R is replace, remove, reinoculate – like a supplement cocktail. You’ve gotta figure out what's going on. You guys, if they have celiac disease causing these, it's a whole different scenario. And they can be gluten-free; it's not enough because there's other cross-reactive foods.

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All these symptoms may be a gallbladder issue. You can then replace, you give them enzymes, you give them probiotics, you can reinoculate, but the gallbladder is still a problem. So, you'll never fix those symptoms. So, the key thing is not to jump into each other’s protocols, but just to see what's going on. Now, let's say they have increased food reaction. They have increased food reactions; maybe they just have a digestive enzyme deficiency. That's easy to treat. Maybe they have intestinal permeability. That's a little harder. Maybe they've lost their oral tolerance and more than just leaky gut. That's where their Tregs dysfunction. That's where their dendritic cells dysfunction. That's where their immune system and their gut just becomes abnormally activated, and unrelated to just leaky gut. Maybe they actually have intestinal autoimmunity. They're two totally different things. So, somebody comes in and goes “man, I can't eat anything anymore. I can't eat gluten. I can't eat dairy. I'm off everything.” This matters. Like where they are in the process makes a difference. They come back and you go “hey, do you have ASCA/ANCA antibodies, and you have some parietal cell antibodies. This is a whole different ballgame.” Like “oh, okay.” Now, one of the things that we also wanted to cover, the gastrointestinal clinical axis. So, you need to know everything that can go wrong from top to bottom. Here's a list. You’ve got to start at the top and go all the way down. So, like I said before, don't give a protocol until you know the mechanism. Now, when you look at some of these – so look at where we start: smell and taste. Big red flags for you. Again, smell and taste are gonna be lost with early neurodegenerative diseases. You’ve got to figure out if they have smell and taste issues. It's actually more important than many functional tests you'll do. If they have smell and taste issues, you should be really concerned. And then, you have to realize you’ve got a whole different cascade of events impacting the gut, and this may now put you on more of a chronic, unresolved case than something before. And not just smells – specific smells. So, we’ll talk about the smells you lose first with Parkinson’s disease. We’ll talk about how to actually do very strategic smell testing when we get to the examination, and really evaluate this effectively. And then, the research behind this as well. And smell and taste go together. You’ve got to see if they can chew. And how long does it take for them to chew and do they have any like TMJ – people that have TMJ problems and don't chew much – they're gonna have gut problems. Just simply putting your hands on the jaw, open and close your mouth. If you see it go da-ding, ding, ding – you're like whoosh. Write down how many chews you have for the next few meals. If they're like “four” – “okay, I've got some stuff to do.” You’ve got to open their mouth. You’ve got to see if they make saliva. You should see a wet, glowing, shiny mouth and tongue. If it's dull – we’ll show you pictures of these – you're gonna have a problem. You’ve got to make sure they can swallow. The most common thing we talked about earlier is the patient saying “please don't give me lots of

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capsules because I have a hard time swallowing. Do you have any powders or oils?” That should be a good red flag for you. So, think about that vagal response. And then, things like cyclic vomiting syndrome – that's when people vomit all the time. Globus significus -- you’ve all experienced this when you get really nervous and you feel like you have something in your Adam’s apple. These are neurological issues. They totally impact the gut. Some people have them all the time. Achalasia – their esophagus, lower esophagus, doesn't work. Do they have hydrochloric acid? Do they have ulcers? Do they have dyspepsia or gastroesophageal reflux issues? Do they have autoimmune gastritis? That's important to know. Do they have an infection in their gut causing their HCl issues? Can they lube? They've lost the ability to empty their stomach – gastroparesis. Gallbladder – do they have sludge? Can they not contract their gallbladder? Is there an infection there? Do they have stones? Small intestine – does the valve between the small and large intestine close properly? Do they have permeability? Do they have microvilli loss? Do they have an autoimmune issue with their gut, and then inflammation of the gut? Do they have a tumor? These are all important to know. Do they have any motility issues? So, we’ll go through the list. Now, once you know the basic concept – we’ll review these – then you’ve got to know… Clinical pearl – you need to know the underlying mechanism to everything that can go wrong. So, if you have this, these are the mechanisms. I did it for you. I did it all for you just so you guys know. I'm not gonna leave you hanging. So, if you look at these, these are all the different mechanisms and they have different treatments. You can't treat a neurological brain-gut issue with a probiotic. You're gonna have to do things to impact that differently. Now, which of these disorders are autoimmune? There are a few of these that are autoimmune. Why is that important? Because you guys, these patients are having an ongoing issue. Remember, autoimmune disease is incurable. No one’s figured out how to cure it. No one has figured out how to cure autoimmune disease. Remission is real. People can go into remission, but it's not cure. Don't confuse remission with cure. So, all remission has relapse at some time. No one stays in remission forever – mostly. Most people will have flare-ups. And many times, people with bowel remission will relapse throughout their whole life. So, if the person has an intestinal autoimmune disease, it's a totally different story. So, we're like “oh, well I don't need to check for celiac disease because they're gonna be off gluten anyways.” No. Because they could have transglutaminase-2 and it doesn't have to be gluten anymore. Let me give you an example. If someone has transglutaminase-2 autoantibodies, which is the autoimmune marker for celiac disease – if they eat gluten, they're gonna have significant inflammatory reactions, no question about it. There's a direct T-cell response, so they're gonna release zonulin – it's a bad, bad scenario. But

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once the autoimmune disease develops, it's an autoimmunity. They don't even have to eat gluten anymore. They cannot have sleep and have stress and flare up their gut. What that transglutaminase-2 or celiac diagnosis tells you is that there is an intestinal autoimmune response happening, and it's not just the food protein. So, that's why these things matter – like that you know the mechanism. Which of these disorders are due to metabolic conditions? Well, like gallstones or really insulin resistance, bowel incontinence. You may have some metabolic issues you have to go after. Which of these disorders are due to an infection or neurological mechanism? So, you’ve got a lot of these that are really related to really addressing an infection or immune-related issue or pathogen. And which of these mechanisms are due to a neurological mechanism? Well, here's a list. You’ve got quite a bit. And you guys, when I say neurological, it can be two things. It can be neurodegenerative or it can be neurodevelopmental. You guys understand? Neurodevelopmental means you have a kid that has a learning disorder. And they're going “get them off gluten and dairy. Put them on a bunch of supplements. Put them on protein.” Cool. But, you check their palate – it doesn't work. Listen to the abdomen – there's no bowel activity. That's a different scenario. That's where you have to also activate their brain with whatever you need to do. I mean, we could talk about different things later, but that's the key issue. So, you have to know these mechanisms. So now, these are the neurological ones. So, they're also considered either neurodegenerative or neurodevelopmental. The three most important clinical questions for gastrointestinal issues. How's their diet? Let's say we have a group of people who come in all with GI issues – bloating, distention, motility problems, all this stuff. How’s their diet? Does their diet account for their symptoms or their diet does not account for their symptoms? If someone comes in and is eating really healthy and they have lots of GI issues, that immediately puts them in a different category. If someone comes in and they're eating bad, that's easy. That could just be it. But honestly, how many of those patients do you get anymore? You're practicing functional medicine for more than two weeks you stop getting those because your referrals won't be that. And the patients that have it because of their diet? Guess what. They're not coming to see you because they don't care. It could be like the spouse that the wife brought in with their arms crossed. Good luck with that one. Now, second question – how long have they had their condition? Recent, less than a year? Or more than a year? Because when someone walks in and goes “I've been dealing with this for 15 years,” it's probably autoimmune. The patient that comes in and goes “my only focus in life right now is getting healthy.” “How long you been focusing on that?” “Ten years.” “Okay, you have an autoimmune disease. Let's find it.” That's a key thing. So, these are important questions to figure out. No one’s cursed. No one has a curse. Everyone has their mechanism that you have to figure out.

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Number three – has anything helped their condition? “Yes.” “Fantastic. What is it?” Whatever they tell you is like golden. The two most important questions you can ever ask: What has ever helped you and what has made you worse? You start getting to those mechanisms, you can really figure out what to do and what not to do. Some things have helped. When nothing helps, you're probably thinking autoimmune or neurodegenerative, or one of these unresponsive issues. Does that make sense? Or here’s the other thing they'll say. They work for a little bit and they stopped working. That means they don't work. And let's say people have autoimmunity. They have regular flare-ups that come and go at different times. Let's say someone has celiac disease or intestinal autoimmunity of some kind. They are sleeping well; they're happy; life’s good. They're getting exposed to traffic exhaust fumes they didn't get exposed to. Their friend that wears chemicals on their hair that they smell every day at work and get sick, and they've had a little break from that, and now they're feeling great. At the same time they're feeling great, they tried a new supplement. What are they gonna think? “That supplement’s great.” And then, they go back to their regular supplement – “oh, it's not working anymore. Maybe I should take more. Or it's not working.” You're gonna see a lot of overlap with people that have autoimmunity. Autoimmunity is gonna flare up and go off and on at different times, have different changes. And this is a reality. So, you have to be very careful they're not overlapping these conditions. Now, these are the 10 goals we have for this course. The next time I show you this slide will be Sunday, at the end of Sunday. Goal 1. Identify every major mechanism of impaired digestion, north to south, starting with chewing. How to find it. What do you do? Identify malabsorption syndromes. You’ve got to know when the patient actually has malabsorption syndrome. It's a whole different ballgame. They're never gonna tell you they have it. Goal 2. Identify the severity of intestinal permeability. They're not all the same. Identify the mechanism of intestinal permeability. Because if you have someone that has leaky gut but they also have endotoxemia, meaning their LPS is high, it's a whole different ballgame. Do you guys understand what I'm saying? So, if someone has let's say some mild leaky gut, but their LPS levels are normal, that's no big deal. They probably might not even have any symptoms. If someone has transcellular or paracellular where the gut is totally destroyed and their LPS is high – like if you can't get that under control, they will have serious, serious health problems if they don't already. It's a completely different game. So, we're gonna talk about understanding different stages of leaky gut. Goal 3. Understand the clinical concepts of oral tolerance. Leaky gut is not the only thing that goes wrong in the gut immune system. So, there are different things that can happen –overactive dendritic cells, dysfunctional regulatory T-cells in the gut, overactive T-cells, overactive Cooper cells. These can all impact tolerance. Immune activity in the gut.

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Understand the concepts of clinical malabsorption. You have to use blood work for this. You have to look at their exam. You’ve got to see the patient that is pale, that looks they're barely hanging on, can't gain any weight. That's a complicated case. That's a malabsorption case. Understand the clinical hierarchy of gastrointestinal source. We already talked about that. Start with digestion, then immune, then microbiome. Understand the appropriate clinical prognosis of gastrointestinal sources. Are they unresponsive, that you just have to try to manage, or is this something you can turn around quickly? Understand the clinical symptoms and presentation of all gastrointestinal disorders. You’ve got to know from top down, every single mechanism – gut-brain issues, motility issues, reabsorption issues, mineralocorticoid issues, gallbladder issues – all that stuff – and not just jump into protocols. Understand how to do a physical exam to identify mechanisms of gastrointestinal disorders. Understand how to choose and interpret gastrointestinal lab tests and how to develop specific diet, lifestyle, and nutritional treatment approaches. So, that's the model. Very clinical model. Now, let's start with the basics. These are the things you just have to make sure that you have consciousness of. Basic function of the GI tract. Number 1 – transitive ingested food through the alimentary tract. This has to happen. Let me put it to you this way. Motility and constipation is a really, really, really big deal. It might not even be their chief complaint because it might not be. They may come in and go “man, I've got psoriasis. I've got autoimmunity.” “How many bowel movements do you have a day?” They're like “well, I kinda have one.” Kinda have one. You're like ding-ding-ding. No chance for their gut to work. So, then you have to figure out what their motility issue is. There are some people that are like the Starbuck junkie – four coffees a day, no water, no bowel reabsorption of water, no bowel movement. Gut function is gone and now they're just spending all this time in there trying to fix their leaky gut, but they don't have motility, so they can't even change their gut environment or their microbiome. So, does that make sense? So, you have to always dig in and it's critical you figure out they have normal bowel – like say two to three bowel movements a day. That would be normal. If they don't, you have to figure out why. Then, you have some patients say “I've always had this, my whole life.” That's also important. If someone’s had this their whole life, they could have developmental delay or developmental issues in their enteric nervous system. That does happen. Just like people

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have a learning disorder and they never have good balance. Ever seen those? Walk around all flaily, even as an adult. They kinda control it, but then when you play sports or something, it comes out. They never develop their cerebellum. Some people never develop their gut enteric system very well. So, these are important and now they're way more susceptible to any kind of inflammation or motility issues. So, you have to have motility. That's critical. The patient has to have motility in order to balance the gut. And the key thing is, it's easy to miss when patients don't tell you that as their chief complaint. Because when it's been happening for a while, they just consider that to be normal for them. But you can't fix the microbiome, you can't change bacteria issues if they're not having food movement that's taken through the gut. Because as you transit food, you're changing the pH, you're changing the metabolites, and you're changing the diversity of the bacteria. So, you have to have proper motility. Number 2 – you have to breakdown foods, food particles. So, gallbladder contractions and enzyme release. There are people that just don't release digestive enzymes. And just realize also, there's a new term being used out there – it's called gastropause. Have you heard of this? It's your gut degenerates as you get older. So, you just don't make as much enzymes. Wow, that sucks. People develop it and they may need to take replacement enzymes to improve their health because their gut’s not making it anymore. You’ve got to have microvilli that can absorb nutrients. So, when we talk about malabsorption syndrome, that's critical. Enterocyte microvilli. You have to have a mineralocorticoid system, and this is micronutrients in water. Now, lots of people have constipation issues because they have electrolyte imbalances. They're not just drinking coffee all day. We’ll talk about how to find the symptoms and then what to do for them, but it's not uncommon. And then, the mesenteric vascular system. You’ve got to have proper blood flow, perfusion to make the gut work. You guys, when you see a patient that comes in with blood pressure of 90/60 or something like that, they're not getting perfusion in their gut. I'm gonna show you some studies on what that does to the gut. You're not gonna heal their gut. They can't get blood flow pushed into their tissues, which is their distal hands and their feet, they can't repair their gut. So, you might have to look at a chronic leaky gut patient and go “I've got to get your blood pressure up to fix your leaky gut because you're not getting any perfusion there.” Once again, the chronic GI issue that isn't responding to the 5-R program anymore – replace, reinoculate – you have to go outside the gut. So, these are also micronutrients. So, your blood carries all the micronutrients. That's why it's so critical. Immune barrier function. This is the leaky gut. We’ll talk about paracellular, transcellular. The gut has to biotransform. It's critical to have diversity so it can biotransform toxins. And then, microbiome also activates flavonoids. So, lots of supplements will not work until they get diversity of their gut just so you know. Things like resveratrol, curcumin, anti-inflammatories – they may not work until the gut’s healed

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because the microbiome converts them to active metabolites. And then ultimately, you want systemic communication and then when you look at the basic functions of the gut, you have dendritic cells. They sample food. They sample food proteins. Have you guys heard of sIgA? They surround food so dendritic cells don't have as much exposure. If you lose your sIgA count, dendritic cells become overactive. In a person who reacts to every single food, then it has nothing to do with leaky gut. So, it's an oral tolerance mechanism. We're gonna get into everything more. Regulatory T-cells. They're gonna determine whether you have an inflammatory response in the gut or not. Lots of things can change this unrelated to diet and leaky gut. We’ll talk about those. And then B-cell responses and just the lymphatic system altogether. Everybody with me so far? My goal this morning is really not to go deep into any of these yet – we're going to go deep. I just wanna try to give you the big picture… what we're gonna do, what we're really focused on, and really the mindset. So, the mindset isn't protocol, protocol, or a gut issue – here's the best new supplement. Make sure you don't miss anything; go north to south; understand hierarchy; understand what's essential that you have to have for the patient in order to get them better. These are the key clinical steps. So, let's start with north to south. So, we talked about smell. So, smell is really critical that you test when you do an exam. Patient comes in with chronic GI issues, you’ve got to check smell. Very easy to do. You just get a few things that smell, like coffee, peppermint, mint, and you can get more advanced testing. We’ll talk about those things you can test. And you see this olfactory bulb over here – you see that? This is where Parkinson’s hits first. So, alpha synuclein, that protein buildup, that protein aggregation that takes place in the dopamine centers of the brain? Before it hits the dopamine centers in the brain – the substantia nigra, compacta – when they start to get tremor, it starts in the enteric nervous system and it starts right here in the olfactory bulb. Do you guys understand that? So, Parkinson’s disease is – it's actually a disease called the alpha synucleinopathy. There's a protein called alpha synuclein and it starts to clump together. And when it clumps together, neurons start to degenerate because they can't transmit through this clumped protein. That's what Parkinson’s is. It starts in the gut. New studies show it goes up the vagus. Some studies – animal studies show when they cut the vagus, they don't get any change in the brain; they just stay in the olfactory bulb, so it's kind of a progressive alpha synucleinopathy thing, and it starts in the olfactory bulb. So, when you start to see changes in the olfactory bulb, you're probably have neurodegenerative changes in the gut. Big clue to you – a patient has lost their smell. Because if you lose smell, by the way, you lose taste because they work together. They integrate in the brainstem to give you the

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sensation of your taste. One key clinical thing is you ask your patients “hey, do you have any favorite foods?” “Not really.” “Do you ever eat out? Do you have a favorite restaurant?” “No.” “Why?” “Can't taste it.” Because when you can't taste stuff anymore, you don't have the joy of going out to eat or trying new foods. You're not a foodie. Foodies have good smell and taste. So, when they don't wanna go anywhere, like their spouse is like “I just wanna go out and eat one night and they don't wanna go. They don't wanna do anything.” It's probably because they don't have any joy doing it and have to deal with the waiter and all this other stuff. Doesn't give them any dopamine opioid release. So, be aware of that. So, olfactory dysfunction is an early pre-clinical sign of Parkinson’s disease by 10-20 years before tremor, more towards 20. So, the protein aggregation builds up in the olfactory bulb and then it spreads into stages. With Parkinson’s disease, they have things called Braak’s stages. Braak 1 and 2 stage – you start to get autonomic and olfactory dysfunctions, autonomic being the enteric nervous system. This is where it starts. Now, if you start to get degenerative changes also in the enteric nervous, like the gut – if you start to lose smell, you can guarantee that there is buildup of the neurons in the gut. This is alpha synuclein aggregate. Do you guys see this in here? Alpha synuclein aggregate. So, this protein buildup takes place not on the olfactory bulb, but it aggregates in the gut and then it goes up the vagus and starts to infiltrate the brain. So, when they look at where the alpha synuclein buildup started in Parkinson’s disease, it's the smell and gut pathways first, then they spread throughout the rest of the brain. So, when you see a patient that has chronic constipation and motility issues, you really have to check their sense of smell. Everybody with me so far? Now, once you check smell, then you’ve got to talk about chewing, saliva, swallowing – what are those things? And I would definitely make sure you just check their jaw really quickly in your physical exam – we’ll talk about this – just open their mouth, close their jaw, see if they have TMJ. If they have TMJ, you’ve got to find out how many chews they have. How often do they chew their food? So, normal chewing is about 30-40 bites. Steak and nuts are like around 40. Most foods are around 30. If they're chewing less than 20, they're not digesting their food very well. Now, when you look at the brainstem, you have different columns. Do you guys see this? This is the phylogenetic column. You guys remember the basic neurodevelopmental issues? You have like ectoderm and mesoderm and neuroderm. Well, these things form different columns and they become pathways in the brain, and if you take a look at this pathway here – the parasympathetic pathway – you guys can see in yellow – 5, 7, 9, and 10. You see this yellow – 5, 7, 9, and 10. Five is chewing – your jaw, trigeminal, for chewing. Seven – inferior salivatory nucleus – saliva production. Nine – glossopharyngeal – swallowing, and ten – vagus – digesting. They're all lined up together, right here, this yellow. I’ll show you a better way. There's five – you see the

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nuclei. Seven – saliva production. Nine and ten – swallowing and motility. And these things control intestinal autonomics – 5, 7, 9, and 10. When you activate one, you activate the other. The minute a person starts chewing, they activate digestive enzyme release. They get blood flow to their gut. So, when a person has lost their ability to chew, they're not getting blood flow to their gut; they're not activating enzyme release; they're not changing their autonomics. So, the way we're designed is we actually start our digestion with chewing at the gut level. So, as soon as you start firing trigeminal – chewing – you're activating the whole column. Now, you start producing saliva; you start producing digestive enzymes; you start increasing motility; you start getting blood flow to the gut, and the whole process starts to work. So, you wanna see if they're producing saliva. You wanna see if they can swallow, if they can chew. Because lots of neurodegenerative diseases happen in the brainstem. You have lots of people who have autoimmune diseases and guess what else they have with their Hashimoto's? They have demyelination. They've got a little plaquing in their brainstem. And then, the saliva itself also starts the immune response. Your secretory IgA starts signaling your dendritic cells and your immune cells of what's going on. There are actually dendritic cells in the mouth. These are sampling cells. So, your gut immune system is already kicking in and determining friend or foe from the minute you start to bite into food. So, saliva production is absolutely critical for healthy GI function. And lots of drugs cause saliva production to go down. We’ll go over the list of them. If you have patients with chronic GI issues and a leaky gut you can't fix, and they're on a drug that is stopping their saliva production, you're gonna have a problem. You may not have a chance fixing their gut. You guys, it's these subtleties that make the difference between homerun with a chronic case or not. Okay, enteric nervous system. So, then you have your gut nervous system. Your gut nervous system is actively involved with your digestive functions and if you look at the vagus, the wandering nerve that goes all the way through the esophagus, swallowing, all the way into the gut, and there's feedback loop all the way back through the GI tract. And you can see the gut itself is well-enervated; there's just plexus all over there. And have you guys ever gone to those exhibits where they plasticize the human body and they have one of the nervous system? I mean, you can see the entire gut is one big nerve bundle. And this problem is this enteric nervous system can degenerate. Look at the title of this paper – Enteric Nervous System Manifestations of Neurodegenerative Disease. Conclusion: Given the many commonalities between the CNS – central nervous system – and the ENS – enteric nervous system – it is highly likely that disorders that affect CNS function also affect ENS function, and that the enteric nervous system dysfunction contributes to the GI symptoms experienced by patients with neurodegenerative diseases. They're saying if you have something causing neurodegeneration in the brain, this is gonna cause the same thing in the gut. So, when you see the neurodegenerative patient in

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the brain, you probably have a neurodegenerative response in the gut. It's still neurons. Whatever they're susceptible to to cause them to degenerate are involved. So, that's the key thing – especially if you're working with elderly. You’ve got to make sure you're not dealing with a neurodegenerative disease. And if you are, that's fine. That means you have a different prognosis for their gut issue. You're gonna treat their gut ongoing. You're gonna make sure they take enzymes ongoing and that you're not gonna fix this in three weeks or something. It's a whole different scenario. And these are all the different conditions that are related to the enteric nervous system in this whole brain-gut axis pathway. And then you have digestion starting with saliva production, which we talked about, producing hydrochloric acid, then into the gallbladder. How a person responds to food is really critical. They can't tolerate fats or they can't tolerate proteins, or they can't tolerate starches or carbs, or they can't tolerate all foods is different. So people who can't tolerate fats, greasy food – gallbladder. People who can't handle carbs and starches, you're thinking pancreatic enzymes. People who can't handle protein, you're thinking of hydrochloric acid. People who only can eat by portion size, like “I can only have a small meal or I feel sick,” that's dysautonomia. That's where they can't swallow and digest their food well. Totally different mechanism. So, I’ll give you a chart where we break down each of these mechanisms, but how they respond to food digestion is really critical as we go from north to south. Then, the other key thing is you have to have the microvilli brush borders working. If you guys are looking at blood work and you see early anemia, you see iron deficiency, you see really beat up nails, you see that they look pale, their capillary refill time is gone – you can measure something called preglobulin. If that preglobulin is off, you know you’ve got a malabsorption syndrome. So, we’ll talk about how to identify malabsorption syndromes. They are really, really important to assess. In my entire 20-year career, I've never had a patient properly diagnosed with malabsorption syndrome before they came in. Because people just assume they're just gonna treat the gut. So, make sure you know how to evaluate those patients that are really critical. And then as you go into the gut, that's all digestion. So, that's the first priority. Those are all the key things. And then you get into the immune system. And when we talk about the immune system, we're gonna get into dendritic cells, sIgA, regulatory T-cells, T-cell function, Cooper cell interaction, this microbiome-Cooper interaction with immune tolerance, how these things get into pylorus patches into the mesenteric lymph nodes. These are all critical. And how the microbiome impacts these things. This is just an illustration of how they spread throughout the body, but we’ll go into that in more detail. And that's the immune issue. And then we've got to get into this concept of just the overall microbiome health and their diversity. And then you look at these brain-gut axis issues, and then you go through those key pathways.

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So, let me point out a few things. Let's just take a step and reflect before we get into some summary. Ask yourself this question: Are you a protocol person? Are you the protocol person? Do you just have your batches of protocols you just throw out, or do you do an assessment and diagnosis and mechanism? So, there are two types – mechanistic approaches and protocol approaches. Which comes first? So, a mechanistic approach is the key thing. And if you're mechanistic – so, if you're a protocol person, we have a lot to share with you and you're gonna help a lot more patients if you follow the steps. Now, if you're a mechanistic person, then how tight can you make your diagnosis workup? How clean? How much depth can you have? Hopefully, we can give you some new things to add to your tool bag, but you’ve got to be able to pick up on the system from top all the way down and those protocols. Next thing. Are you the fix the gut to fix everything practitioner? If that's you, that's a problem. You're gonna not help a lot of patients. You'll definitely help some people, because some people just truly need to treat their gut. But the key thing is, if you're the fix the gut to fix the patient, or I always start with the gut – I don't know how to say this. You don't know what you're doing. That's a very basic model. It's not a thorough model. It's an inefficient model. Do you wanna go and see your doctor and they treat everyone the same? No. No one wants that. That's laziness, that's sloppy, and it's inefficient. So, you really wanna get in there and find the mechanisms and find the protocol. Right? Okay. Now, the next question is do you have the same diet for everyone? Does everyone get the same kind of leaky gut diet? Does everyone have leaky gut? Is that an issue? Or even go deeper. Are you that everyone has leaky gut; no point to test? Am I gonna get them off gluten anyway so why check to see if they have celiac? If you are, you're missing some major things. This is just kind of a reminder. Just fine tune your clinical skills. I mean, that's the key thing. Hopefully, you'll leave this weekend, and lots of review for you, lots of good things maybe that are new, but the key thing is you go through the thought process and you find each of the mechanisms that are really involved for each of these things. Now, you may need to look through this list and when you think about a patient, just start from the top and go all the way down. When we go into a physical workup, I mean the workup of a patient, we're gonna dissect the history and go all the way down. So, your key thing is, from your history, you should be dissecting from north to south. And then, as you go into your initial survey, just taking a look to get some clues. Like if someone comes in and they have pale skin or they have healthy skin, or someone has a skin rash or someone doesn't, or someone comes in all bloated and distended and someone doesn't. If they're overweight and if they're a female, the gallbladder issues are more likely, so you have to do your initial survey and kinda think through all that stuff. Right? Okay. Then, you’ve got to do your exam – smell, mouth. You're gonna have them smell. You're

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gonna check taste. You're gonna look for any signs of neurodegenerative diseases. You're gonna look at their mouth and make sure there's no oral infections or anything going on with their mouth. You're gonna make sure that they have proper saliva production, their tongue is healthy. We're gonna show y'all different things that go wrong with the tongue. You're gonna have them open their palate and they're gonna contract. You're gonna see if their palate works. You're gonna repeat test that because sometimes you have fatigue issues. You're gonna check the gag reflex and make sure the vagus is working. Now, you're ready to go. Now, you go down the gut. You listen to the abdomen. You see if you hear bowel sounds and what kind of bowel sounds do you hear – motility? Now, you're starting to look at the gut. Now, you look at their fingernails and hands to see any signs of malabsorption. Then you go through and you do some routine lab work to see if you see any malabsorption issues, any anemia issues. Then you get into more of your special types of testing and you look at your GI panels, and then you take a step back and go “okay. I'm not gonna have you on any supplements for a while. We need to get your enteric nervous system to work. Or “I can't go anywhere until we fix your gallbladder, and then we can do other stuff.” Or “I think we may have to treat an infection,” or whatever the case may be. So, those are the big pictures. Now, the other key thing that we talked about is this hierarchy. This is the biggest issue. So, I’ll give you the great example here again as a review. You can't just go into leaky gut. If they have a digestion issue, you can't fix the immune system. If you can't fix the digestion in the immune system, you can't fix the microbiome. So, those are the key things that you really have to really think about. If you always start with north to south as like a clinical workup, then you won't miss it. If you just jump into it, then you’ve got a problem. So, your patients that have leaky gut, you have to make sure that they can chew; that they actually produce enzymes; that they don't have a gallbladder problem. Fix those things first and then go through. And then once you get through and you get into the immune system, you’ve got to figure out exactly what degree of intestinal permeability they have. They could have significant endotoxemia, and that's totally different. And do they get better or do they not get better? That's a big deal. So, the other key thing to understand is digestive issues, you work through them. You don't always have the answers. How they respond to care or don't respond to care is a big clue. Now, where clinicians fail is they're too optimistic. They go in – “we're gonna make you feel great in no time because I'm awesome.” Don't do that. Like yehhh, whoosh. You wanna burn yourself out? Keep it going. If you wanna survive, we’ll do the best we can and see how you respond. We don't know our diagnosis yet. How you respond to this protocol will tell us what to do. We know you have intestinal permeability and we're gonna try a protocol. We don't know if you'll respond. If you don't respond, we have a whole different clinical strategy to take than if you do now. Does that make sense?

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So, also why a lot of practices fail and why a lot of practitioners have a hard time building their practices is because of how they set up the management of the patient, and they don't work through the steps and the patient doesn't understand. You have to really make sure you go through the steps. Say “hey listen, I know you have” – here's a great example. “I know you have like Hashimoto's and autoimmunity, and you know how important leaky gut is and all that stuff. But we need to really find out – do you really have celiac or not? That changes your complete picture. And we're gonna see if your chronic GI issues are autoimmune or not. But we can't even get into that leaky gut and autoimmunity because you're not digesting your food. Like he can't even eat protein because you feel like you have a brick in your stomach. And if you have any fried foods, you get bloated or distended, so we know your gallbladder is unhealthy.” “So, we're gonna have to go through like this process. We may start with getting your digestion under control first because we always start north to south. We're gonna really make sure that you don't have any mechanisms that impact that, so our first goal the first six weeks is just to get you to be able to digest protein and intake fats, and not get sick.” Or like some patients will take fish oils and they burp them up. Then you'll say “hey, keep that fish oil,” because you can then recheck it in a month and see if you burp it up still. Or if there's a fatty meal they can't tolerate. “I went to so-and-so, had this, I got sick.” “Great. You're gonna go there in six weeks and try it again.” So, you wanna get to the point where that's done. So, if they can understand the steps, then you can work through it. Does that make sense? So, it might take you three months with an autoimmune disease patient to get to the point where you can actually treat their leaky gut. Then you go after the leaky gut, and then as you treat their leaky gut, you're going “do a followup. Do they respond or not respond?” “It's even worse.” That's a different scenario than if it starts to respond. Make sense? Or maybe they were worse. You got rid of the LPS so they don't have endotoxemia anymore and they feel a lot better, but you still have some leaky gut. And maybe you have an ongoing issue with their leaky gut because they have an autoimmunity. And then you explain that, and you tell them “when you have flare-ups, you might really have to support your gut more. And then when you don't have flare-ups, you take a break.” Does that make sense? So, the clinical approach, like sitting back and really thinking what's going on, and then working through the case starting north going south, making sure you communicate that with the patient is absolutely critical to help with chronic GI issues. The reason most practitioners fail with patients is they jump into protocol. They don't wanna work through their case. They have too many high expectations when they go into treatment. They don't understand hierarchy, how these things are important. And they're a little

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overconfident. So, those are the things you really want to kinda [inaudible] [01:24:00]. Now, what we've done so far is we've talked about the big picture. And then, what I really wanna do when we get back is we're gonna spend our next session starting with digestion. I wanna go through digestion in a lot of great detail. And then as we go through digestion, we’ll talk about saliva; we’ll talk about hydrochloric acid; we’ll talk about H. pylori infections; we’ll talk about gallbladder issues, all different types of gallbladder issues, what all the research shows to help with them, how to treat them. And then we’ll get into malabsorption syndrome issues and SIBO because you add maldigestion to the spectrum of malabsorption. So, you’ve got to go north to south and figure the whole thing out. So, that's our next area. Once we finish that, then we're done with the basic concept of digestion and we can start to creep into immune function. So, as we get into it after lunch, we're gonna talk about all different patterns of intestinal permeability, all the different causes, and how to figure out what severity of leaky gut they have, and then how to follow them up and how to manage them. And some are not gonna ever respond and some will, and how to know which ones are which. Then, we go from immune to the microbiome, and that's where we’ll end up by the end of today. We’ll talk about the microbiome, all the things that have shown with lifestyle to impact diversity, how that kicks in, and then the different axes, and that'll take us through today. But what I want you to understand is the way that I've organized the course is from the hierarchy perspective, starting with digestion, then immune. And that perspective is exactly how – the model we teach is evaluating it. And then on part two, the next day, we're gonna then get into going over all the research of non-responsive gut issues because that's a critical issue. The patients that what do you do with when they're not getting better, how to help those patients. And then right into the workup from history all the way down, and then the treatment protocol, and then we’ll do a case. So, it's a hierarchy-based approach, and the reason the hierarchy is there is not because of philosophy, it's because of physiology. You have to have breakdown of food particles or you can't fix the immune system down below. You have to have enzyme releases to change to neutralized things in order for the microbiome to work. You have to release bile acids because bile acids are signaling agents for the gut microbiome. Like this hierarchy model isn't the Kharrazian method or anything. It is just physiology. Okay? So, we're just respecting physiology and going through each of the steps, and that's how the course is designed. Okay, we’ll take a break. [End of Audio] Duration: 87 minutes

Documents

Kharrazian Institute – Gastrointestinal, Course Two