I am thrilled to have the amazing Kiran Krishnan joining me on the podcast today.
Kiran is a research microbiologist and health and wellness expert who aims to make complex information understandable for everyone. He has founded several successful health and supplement companies over the last 20 years, including Microbiome Labs, the preeminent microbiome therapeutics-focused brand amongst healthcare professionals. Kiran has also conducted many research studies and published chapters in scientific textbooks. He has global patents and has become a sought-after speaker on human health and the microbiome.
In our discussion, we dive into leaky gut, its contributing factors, and the roles of endotoxins and lipopolysaccharides. We clarify postprandial endotoxemia, exploring how perimenopause and menopause affect the microbiome and the impact of oral contraceptives and synthetic hormones. We highlight common symptoms of gastrointestinal issues, including problems associated with bloating, and explain how the immune system- innate and adaptive, impacts gut health. We also discuss the significance of keystone species like akkermansia, the importance of diversity, the role of stool testing, and the value of fiber, touching on the polarizing nature of dietary dogma and improving gut health through supplementation and lifestyle changes.
This conversation is the first in a series on the gut microbiome, and I am confident you will enjoy it.
IN THIS EPISODE YOU WILL LEARN:
Why leaky gut has specific significance for women in perimenopause and menopause
Why it is essential to understand and address a leaky gut
How intestinal permeability lies at the root of most chronic diseases
The factors that contribute to a leaky gut
What postprandial endotoxemia is
The symptoms of a leaky gut
The difference between innate and adaptive immune responses
How chronic conditions like diabetes and obesity impact the immune system
The role of the microbiome in disease susceptibility
Bacterial that are beneficial for gut health
Why it is essential to have a diverse diet comprised of whole foods
Supplements and lifestyle practices that support gut health
Bio:
Kiran is a research microbiologist and a health and wellness expert who aims to make complex information understandable to all. He has founded a number of successful health and supplement companies over the last 20 years including co-founding and leading Microbiome Labs, the preeminent, microbiome therapeutics-focused brand among healthcare professionals. He is currently a co-founder and partner in 3other companies that aim to revolutionize wellness care. He has conducted and published several research studies in scientific journals, has published chapters in scientific textbooks/reference books, has global patents, and is a sought-after speaker on human health and the microbiome
“Intestinal permeability is the root cause of most chronic diseases.”
-Kiran Krishnan
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Transcript:
Cynthia Thurlow: [00:00:02] Welcome to Everyday Wellness podcast. I'm your host, Nurse Practitioner Cynthia Thurlow. This podcast is designed to educate, empower and inspire you to achieve your health and wellness goals. My goal and intent is to provide you with the best content and conversations from leaders in the health and wellness industry each week and impact over a million lives.
[00:00:29] Today, I had the honor of connecting with the amazing, Kiran Krishnan. He's a research microbiologist, health and wellness expert and he aims to make complex information understandable to all. He has founded a number of successful health and supplement companies over the last 20 years, including co-founding and leading Microbiome Labs, the preeminent microbiome therapeutics focused brand amongst healthcare professionals.
[00:00:54] He has conducted several research studies, published chapters in scientific textbooks, has global patents and is a sought-after speaker on human health and the microbiome. With good reason, I was delighted to bring him on the podcast. We spoke at length about leaky gut, what contributes to leaky gut, the role of endotoxins and lipopolysaccharides, what is postprandial endotoxemia, the impact of perimenopause and menopause on the microbiome, the impact of oral contraceptives as well as synthetic hormones, the most common symptoms that point to gastrointestinal issues, why bloating is so problematic, the impact of the immune system, including innate and adaptive immunity, the importance of keystone species and diversity, including Akkermansia, the role of stool testing, why fiber is truly important and why dietary dogma is polarizing and lastly, how to improve gut health, including specific supplements and lifestyle? This is the first of a series on the gut microbiome. I know you will love this conversation as much as I did recording it.
[00:02:07] I would love to really start our conversation today around the significance of leaky gut. I think that traditional allopathic medicine in many ways doesn't acknowledge that this happens.
Kiran Krishnan: [00:02:18] Yeah.
Cynthia Thurlow: [00:02:19] But let's start talking about why this is so significant, especially for women that are in these transitional periods in their lives of perimenopause and menopause.
Kiran Krishnan: [00:02:27] Yeah, absolutely. So, there's a few different aspects of this to think about-- Okay, so leaky gut is really-- to explain it to people, if they're not familiar, it's really intestinal permeability. What does that actually mean? Well, the intestines are a really interesting dynamic barrier. Meaning, that they are supposed to be selectively permeable, because there's lots of things that we want to get through, food items, for example, nutrition and so on. But then there's lots of things that we're constantly exposed to that we don't want to allow through, like toxins and microbes and so on. And of course, we have a lot of microbes in the gut lining itself. So, that dynamic capability of the intestines to allow certain things through and not allow other things through is a really tightly controlled mechanism.
[00:03:11] As it turns out, that mechanism is largely influenced by the microbes that live in the region. That's one of those amazing examples of, what we call, symbiogenesis, which is the development of a symbiotic or mutualistic benefit between different organisms, humans being one of them, and bacteria, where they function in a favorable manner to help the whole system.
[00:03:37] So, there are bacteria in the region that control the dynamic function of the intestinal lining and its permeability. If those microbes start to become disarrayed, let's say you've had courses of antibiotics, you're eating a lot of processed foods, you're heavily stressed, you're not exercising, you've put on excess weight, all of those things that can impact the microbiome in a significant way, then you start losing the selectivity and the dynamic component of the intestinal barrier. So, now the barriers may be still allowing through some of the things it's supposed to, but it's also allowing through a lot of things it's not supposed to, including toxins that are being produced in the lining of the gut.
[00:04:23] And toxins, it's a dirty word. People use it quite a bit for almost everything. But in this case, it's really well understood and profoundly defined as endotoxin. Meaning, there are toxins that are produced by microbes in the lining of your gut. The microbes that make up almost 50% of the microbes that exist there, these endotoxins, and they're called endo because they're produced from with, then allowed to leak through when you lose a dynamic component.
[00:04:53] So, there's a few different effects of this. Number one, the fact that the gut became leaky means that your microbiome is in disarray. That means you've got overgrowth of things that shouldn't be overrepresented, you've got low levels of beneficial bacteria, which means that not only is the dynamic permeability component of it compromised, but so is the other functions of the microbiome. So, in the case of perimenopause, hormone balance. Or, at any age, really for women, once you start producing sex hormones at viable levels, estrogen recycling, for example, is heavily influenced by the microbiome. You can easily become estrogen dominant or deficient in estrogen, estradiol, especially if your gut microbiome is dysfunctional.
[00:05:42] Testosterone levels are also implicated by the microbiome. Progesterone levels are influenced heavily by the microbiome. And then, you've got all whole slew of metabolic hormones, like GLP-1, and PYY, and all these things that impact-- satiety and weight gain and how much food you're eating and energy homeostasis in the system. So, all of these things are going out of sorts while your gut is leaky.
[00:06:09] Now, the consequence of the gut being leaky is that you end up with chronic low-grade inflammation, because those endotoxins that leak through end up in circulation and your immune system sees that as almost like a bacterial invasion. They use the presence of the endotoxin as a way of identifying the potential for sepsis or bacteremia. So, then your immune system goes haywire because it goes, "Oh, my God, we've got trillions of bacteria that are going to flow through into the blood system," which can make you very sick and die within 48 hours.
[00:06:44] So, the immune system is heavily geared towards sensing for risks of bacteremia. One of the ways it does that is through measuring this endotoxin that migrates through. And so, now your immune system's going haywire, so a lot of the other systems I talked about are getting dysfunctional and your immune system is going haywire, which means you have chronic low-grade inflammation.
[00:07:07] Chronic low-grade inflammation throughout the body becomes the foundation for chronic disease. The vast majority of chronic diseases. So, if we look at things like metabolic disease, or diabetes, cardiovascular disease, obesity, immune dysfunctions like autoimmune conditions, lupus, eczema, psoriasis, thyroiditis and so on, all of those conditions have an underlying effect or have an underlying driver in chronic low-grade inflammation. Even brain related disorders. So, if you think about Alzheimer's, Parkinson's, dementia, anxiety, depression, all of these are driven in part by chronic low-grade inflammation.
[00:07:49] So, why leaky gut is so important is because it both signals that your microbiome is in disarray. So, all the important functions of the microbiome are no longer functioning the way they should. And B, because it also means that you're going to end up with chronic low-grade inflammation, which then becomes the foundation of most chronic diseases.
[00:08:10] This is why in 2015, there was a publication in the Frontiers of Immunology, where the researchers did a meta-analysis, which means that they studied a lot of studies on this topic, and they concluded that intestinal permeability-- and in this case, they attributed intestinal permeability to chronic stress. We could talk about how stress causes intestinal permeability. But intestinal permeability and the resulting chronic low-grade inflammation was the number one cause of mortality and morbidity worldwide. It's the number one killer. Why is it the number one killer? Because it's at the root cause of most chronic diseases. So, we cannot underscore how important it is to understand and deal with leaky gut.
Cynthia Thurlow: [00:08:56] It's such a beautiful explanation. I think for people that are listening, there can be a lot of contributors. You've identified some of them. I think a great deal about the opportunistic things that happen-- I'm thinking about you-- We think of food poisoning as not being a big deal.
Kiran Krishnan: [00:09:14] Mm-hmm.
Cynthia Thurlow: [00:09:14] I'm one of those people that my husband jokingly says, "If it had been 100,000 years ago, you would have died off long ago," because I seem to be one of those people that's a little bit more susceptible. It's not at all surprising, because I've had a couple autoimmune conditions, so we're constantly working on gut health.
[00:09:30] When you're thinking about the biggest drivers, you mentioned stress. I'm sure we'll probably touch on levels of exercise, life stages. Where do oral contraceptives fall in the interplay with the net impact on leaky gut, vis à vis the microbiome? Is there any research lending itself? Because we do still have listeners that are on oral contraceptives. They're not yet menopausal, but we're always trying to shed some perspectives, different lights on what these things are doing based on research on our own health.
Kiran Krishnan: [00:10:02] Yeah. So, oral contraceptives can have a very significant impact on the microbiome for a couple reasons. Number one is that hormones are a food source for bacteria. Majority of hormones are dumped into the gut at some point. There are microbes that metabolize them. As part of that metabolic process, they recycle the hormone, or they actually create regulatory mechanisms that help control the release of the hormones. And so, when you unusually alter the amount of certain hormones in your system, it will have a direct impact on your gut microbiome.
[00:10:40] So, we do know that. We do know that birth control pills can create significant dysbiosis in women. It's the same way in which menopause creates dysbiosis in women. So, there's a reason why women tend to have-- If you have a balanced hormonal system, you tend to have protection against things like cardiovascular disease, osteoporosis, some of the things that men have a much higher risk for up to a certain age. But then, once women hit menopausal and then they become postmenopausal, their risks for osteoporosis and cardiovascular disease and all go way up. Well, why is that? Well, that's because of the shift in the cycling of hormones in the system.
[00:11:21] One of the results of the changes in hormone levels is that you lose diversity in the gut microbiome. Your gut becomes more leaky, which leads to more endotoxemia, which is that description of chronic low-grade inflammation. So, anytime you alter hormone function or hormone cycling in the body using synthetic alternatives and so on, you can absolutely disrupt the gut microbiome. So, that's one way.
[00:11:47] The second way is, as a secondary effect to things like weight gain or secondary effect to things like anxiety and chronic stress. So, depending on the oral contraceptive that you're on, it can create a side effect of having more anxiety and so on, that stress can create more dysbiosis in the gut when stress is one of the most potent dysbiotic agents in the gut So, absolutely.
[00:12:15] People will often ask me, "Does this impact the microbiome, or does that impact the microbiome?" One of the things I want people to understand is that it's easy to think about the answer if you think about how natural that substance or behavior or therapy is and how your system functions. Because keep in mind that the microbes in our system evolve with us. So, they evolve to learn and work within our functionality. The balance that the microbes strike is driven in part by how our systems function, our cycles, our circadian rhythms, our dietary habits, and all of those things. The microbes achieve a certain degree of balance and resilience based on our natural systems.
[00:13:01] Anytime we alter those natural systems, like we don't sleep enough, or too stressed, or we're eating too much of the wrong thing or we're not exercising, we're not getting any movement, all of these things that alter the normal, healthy function of the human system creates dysbiosis and alterations in the microbiome, because the microbiome has co-evolved with our normal systems. So, that becomes an easy way for people to answer that question for themselves is, "What I'm doing, how my ancestors did it, how we evolved, because that's how my microbiome evolved to function within my system." And if it's not, then you're likely causing an alteration in your ecosystem, and that alteration will make all kinds of problems much worse.
Cynthia Thurlow: [00:13:47] Well, and I think for so many people, because they cannot see the microbiome like they can see their arm, they can see their hand, it seems much less tangible. And yet, what you're really speaking to is that any choices that we're making really do have a positive or a negative net impact on the gut microbiome.
Kiran Krishnan: [00:14:03] Yeah.
Cynthia Thurlow: [00:14:04] One thing that I thought was interesting as I was preparing for this discussion with you today, we talked about this endotoxin, and so we're talking about lipopolysaccharides. What's interesting is we know that the exposure to these endotoxins in and of themselves can impact healthy neurotransmitters, and can impact mood and anxiety and depression, but also can put us at risk for things like dementia, Alzheimer's.
[00:14:30] Now, I know my listeners, in particular, are very, very proactive about maintaining good cognition. As we were making these transitions from perimenopause and menopause, the hormone conversation is so important. When we're looking at the gut microbiome, when we're looking at the net impact of these endotoxins and lipopolysaccharides, which is just one component of these endotoxins, how do you like to think about this? When we're talking about whether it's a meal where we were exposed and we developed food poisoning or developed this postprandial endotoxemia, how do you like to think about it? How do you like to describe it, so that it makes it a little bit more accessible for people to understand?
Kiran Krishnan: [00:15:10] Yeah. So, the key to that is in the term that you just described. It's called postprandial endotoxemia for a reason. Postprandial, for people who aren't familiar, means after a meal. So, postprandial endotoxemia basically describes what tends to happen in your system after you eat a meal.
[00:15:30] Now, if your gut is not resilient, it's dysbiotic, it's leaky, the lining of your gut is dismantled and leaky, then what tends to happen is, every time you eat a meal, you get a massive rise in these endotoxins in circulation. They can end up in all parts of the body. They can end up in your heart, they can end up in your joints, in your brain and so on. And they often do end up in most of those regions.
[00:15:53] So, if you think about a tsunami of inflammation that occurs in your system after every meal, and it doesn't matter as much what the meal looks like-- Yes, more unhealthy meals will create a higher amount of endotoxins, but even healthy meals will create endotoxins just as a result of your gut being dysfunctional. You get this massive tsunami that goes to all different parts of your body. It's very pervasive, including deep recesses of the brain, and it creates inflammation and the inflammation creates damage to those tissues.
[00:16:28] So, every time you eat a meal, you're going through a sepsis, because a mechanism of action is exactly the same as what happens when people become septic. It's like a mini sepsis in your body. And if that continues to happen in your brain day after day, meal after meal, then you end up with enough damage to your brain where your body can't fix the damage overnight when you're resting, and then you start to see cognitive decline. You start to see function in the brain reduce.
[00:16:56] If it starts to happen in the enteric nervous system and then up the vagus nerve and so on, then you have the risk of issues like Parkinson's or chronic constipation. Your bowels just stop moving. It can happen in your skin, it can create acne and it can create eczema rosacea. It can happen in your joints. This is a big driver of things like osteoarthritis and why those conditions are very common. It can happen in your thyroid and create thyroiditis in your heart and create a pericardium, inflammation.
[00:17:26] So, this little tsunami of endotoxins ends up in all different parts of your body and creates inflammatory damage. That has a cumulative effect, meal after meal after meal. You can't stop eating food. That's not a corrective measure. So, you do have to go back to figuring out how to reseal the gut and stop this influx of endotoxins after each meal.
[00:17:50] When we did our first study on postprandial endotoxemia, and we published it in 2017, what we saw-- and at least the researchers that were doing this model before we did our study, what they saw was that in people with severe leaky gut and dysbiosis, they would give them a meal, and then they could measure the amount of inflammation in these individuals' bodies, two to three hours after the meal. In some cases, it took those individuals upwards of two weeks to normalize the inflammation from a single meal.
[00:18:21] So, imagine every meal makes you sick, effectively from a metabolic and immunological standpoint in your body. You may not necessarily feel it at the time, but know that there's all kinds of damage happening throughout the system. Your system is being bombarded by it. So that's, to me, the primary way to think about it and to visualize it, you’re losing your resilience, your ability to be resilient against these negative effects.
Cynthia Thurlow: [00:18:50] It's so interesting to me, because I think that the more I understand about small intestinal hyperpermeability, which is really what we're speaking to, the more humbled I am that we plod along in life, in many instances, not even realize that we're dealing with these issues. Our bodies do such a beautiful job of trying to do some degree of self-repair.
[00:19:11] In your clinical experience, what are the most common symptoms someone will experience if they are having a fairly new issue related to this permeability? Is it bloating, is it nausea, is it dyspepsia? What are some of the most common things that you're seeing reported, self-reported by patients, that give them clues that this maybe becoming problematic? They may not be yet diagnosed with metabolic disease, etc., but little clues that maybe their bodies are trying to identify that there's something going on that's a problem.
Kiran Krishnan: [00:19:47] Yeah, any primary GI symptom. So, even things as simple as indigestion, where frequently you experience stasis of the bowel. Meaning, it's not really moving, you feel like a big heavy lump there after you've eaten, you're not getting proper gastric emptying, you're not experiencing regular bowel movements that are fairly well formed. If you do have regular bowel movements, you've got all kinds of consistencies with your movement. Sometimes it's really watery, sometimes it's well formed, sometimes it's constipated and you're struggling to get it out. So, if you're going through those changes on a regular basis, then you know that something's disrupted there.
[00:20:28] Bloating, gas absolutely is an early-stage indicator of dysbiosis happening. But also things that you may not directly connect to the gut, like for example, sleeping issues or stress issues. If you feel like you're waking up and you're stressed out, or midday, you've got this brain fog going on and you're like, "Ah." You can't put thoughts together, you're getting really sleepy, but then at night, you have a hard time sleeping. All these things are indicative of dysbiosis happening in the gut that leads to leaky gut.
[00:21:00] Metabolic issues, if you find yourself putting on weight more. Metabolic issues are a great sign of loss of diversity, keystone species and then, thereby leaky gut, that's starting to happen. And then, other issues are like immunological issues. So, if you have allergies or asthma or sensitivities to things, if you develop rashes, if you have acne, if you get dermatitis or some sort of eczema in different parts of your body, especially in response to eating food. If you have intolerances to lots of different foods. If you used to say, "Well, I used to be able to eat this, I can't now." Anything that indicates a loss of tolerance is a part of leaky gut.
[00:21:42] When we did our first study, what was so interesting about it, if you really deep dive into what you're feeling, what you're experiencing, a lot of things that you might just chalk off to age or, "Ah, I just haven't been working out, so I feel more like this," or whatever it's going on in your life, if you really dig deeper into it, lots of them are probably driven by this early onset of leaky gut, or at least are driving early onset of leaky gut.
[00:22:11] But when we did our first study, the average age individual in our leaky gut study was-- These were college students with the most part. It was around 23, 24 years old. We were doing a study on healthy normals. There's such a thing as a healthy, normal college kid, but by FDA standards, they're healthy normal. Meaning, that they have no diagnosed chronic diseases, they're not on any medication, they have normal body weight, all of that stuff. You would consider them, physically, at least, to be in the prime of their lives if you look at them. 55% of them had profound leaky gut. Meaning, a single meal would cause just the most massive increase inflammation throughout their body. They wouldn't necessarily feel it, because their systems can kind of repair and rejuvenate that a little bit. But as you get older, you keep experiencing that, you will feel the difference.
[00:23:00] It even comes down to areas like your mitochondria. It can really affect how your cells at a cellular level functions, and thereby create things like lethargy and being tired all the time and so on so. So, that's a lot of things we just described. But believe it or not, and this is without hyperbole, those things are all signs of a dysbiotic gut and likely early stages of leaky gut.
[00:23:27] Just to explain for people what that looks like, we mentioned the small intestine, that's where a lot of this hyper permeability exists. The small intestines are really long organ. We've got like almost 20ft of small intestine. So, you can have about six, seven inches of it being leaky, or you could have 15ft of it being leaky. It progresses from that few inches onto the vast majority of your small intestine being leaky, and there's very different feelings throughout that process. The good news is you can recover it and repair it. Your intestines are designed to rebuild, and recover and repair if you make the right moves.
Cynthia Thurlow: [00:24:04] It's so interesting to me that the 20 somethings are the ones that did have evidence of leaky gut but are less symptomatic, because their bodies are younger, more able to rebound. I just dropped our oldest child off at college. Based on what he shared with us for his first week of college, there's a lot that goes on. They're not necessarily getting good night sleep, they may not be eating the right foods, they may be indulging some things like occasional alcohol use, which we know have a profound net impact on the gut microbiome versus someone north of 35 or 40, where it's more common to see some degree of mitochondrial dysfunction, it's much more common to perhaps be more symptomatic.
[00:24:43] Now, before we pivot away from the bloating piece, I do want to talk a little bit more about this, because in many ways, differentiating as a clinician trying to differentiate bloating is as ambiguous sometimes as a patient telling you they're nauseous. It's like that can be from a myriad of different reasons. But when you're looking at the research trying to differentiate, you alluded to sometimes it can be related to an immune response, it can be related to underlying food sensitivities.
[00:25:10] But when we're talking about bloating in terms of the fermentation process, that should not be going on but is, obviously, we do expect some degree of fermentation in the large intestine, not in the small intestine. When do you feel like bloating becomes more problematic? Is it the individual that says, "I eat a meal and two hours later, I'm bloated,” or is that the individual that says, "Anything I eat, I become bloated. Anything I drink, that's my de facto go to symptom that I can't seem to get rid of"?
Kiran Krishnan: [00:25:41] Yeah. So, the individual that bloats no matter what they eat or drink-- I've met individuals that bloat from a glass of water. That indicates a very different thing to me than the fermentation issue. But the fermentation issue probably preceded this result. So, to me, this is what is happening in these individuals. The fermentation issue means that the small intestine, where you really shouldn't have any fermentation happening, you're supposed to break down the macronutrients that are coming in through food and then absorb the things that the body's designed to absorb and then the rest of it goes down to the large intestine for actual fermentation. You don't really have fermentive bacteria in a natural, healthy small intestine.
[00:26:26] In fact, you have very low levels of bacteria in the small intestine. You have less bacteria in the small intestine from a concentration perspective than you do on your skin even. So, the small intestine is not designed to have a huge amount of bacteria, because when you do have a large amount of bacteria in any given space, they're going to ferment things. And so, it's designed and as many checks and balances, like bile acids and antimicrobials that are secreted by the lining and pancreatic enzymes, HCL, all of these things that prevent an overgrowth of bacteria.
[00:27:00] So, if you start to get bloating about two hours after you eat food, it means that you're eating food, it's probably being dealt with in the right way in the mouth, maybe dealt in the right way in the stomach, but then once it drops into the small intestine, you've got too much bacteria there, so it starts to do the fermentation and then you feel the bloat and the distention and the discomfort.
[00:27:23] The small intestine is not designed to expand as much as a large intestine is. It doesn't have as thick of a lining as a large intestine. So, you will feel a lot of discomfort from the bloating. But that has to be something that takes a couple hours after eating, because it takes that much time for the food to even get to the small intestine and fermentation to kick off. But if that is happening all the time, what happens is it damages the lining of the small intestine, and it creates more and more dysbiosis and more overgrowth of microbes.
[00:27:53] So now, when you have this situation where you have an overgrowth of microbes, often called SIBO, and you have dysbiosis in the small intestine and the small intestine is leaky, you've got an overtly active immune system in the lining of the small intestine. The reason for that is the immune system is constantly waiting for things to rush through, so it can try to protect the host, which means that anything that now touches the digestive tract, starting in the mouth, which is the first part of the digestive tract, and it sends signals all the way down the moment something's in the mouth. Anything that touches the digestive tract recruits immune cells immediately, because the immune system is highly nervous, that the barrier is not functioning the way it should, that things are in disarray, and so the immune system is going to be prepared and going to attack virtually everything.
[00:28:43] So, the moment you drink water, you chew something that sends signals down, that's a very normal part. So, chewing and all that has send signals to the gastric system and then the intestines. So, now, the immune system gets recruited to the lining of the intestines, the lining of the intestines inflame a little bit. So, imagine your small intestines are all folded up in this small area right here. You've got 20 or so feet of a small intestine all folded up. If the lining of that folded up system swells just a little bit, all of it balloons out together. This is how you can drink something that doesn't get fermented and it still creates this bloat.
[00:29:25] So, it's not a gas related bloat. It's massive amounts of inflammation. So, that concerns me more, because that's a farther stage of dysfunction now than it was where two hours later, you're starting to get bloat. That's a gas fermentive bloat, and you haven't gone to the stage yet where everything is causing inflammation, even just something touching your mouth.
Cynthia Thurlow: [00:29:49] It's so interesting to me, because until probably 5 or 10 years ago, the concept of small intestinal bacterial overgrowth was not on my radar or even SIBO small intestinal fungal overgrowth. But whether it's greater awareness, it seems like it has much more-- We're much more cognizant of it as a medical community. It seems to be notoriously challenging to address, because I remind people, “We don't develop SIBO overnight. It's not going to be gone overnight. It takes time.” I think anything related to improving the quality of the gut microbiome vis à vis different, both lifestyle medication, supplements, etc. It's not a one and done. It's like running a marathon. I always tell people, "It's not a race. It's a marathon."