DR. TINA: Kieran Krishna, I'm so excited to have you here. I you gosh, we are such old friends truly and I'm so happy to have you on the Dr. Tina show today. So, welcome. Thank you for being here.
KIERAN KRISHNA: Thank you so much for having me. It's always a pleasure when I get to chat with you. So, I'm so excited. Let's do it.
DR. TINA: Yes, we have so much fun together. We're going to be talking about a subject I have been waiting to I've just been sitting on it waiting for you to have it. So, I'm really glad to have you here today. We're going to be talking about the intersection of gut health, pmenopause and menopause and GLP1s and the whole hot mess that comes along with it. And I don't think this is being talked about anywhere else. I don't hear anybody even tiptoeing into the conversation deep enough. And so we're going to break it all down today and we're going to do it in under an hour. That's my promise. So [laughter] because we could talk for hours and hours, I do have to say, as an aside, you and the company you worked for in the past were the first sponsors of my old podcast that I had many, many years ago, and we go back a long time. I think almost 10 years now. I I first was introduced to you because you were talking about how dogs were good for your microbiome, and I I was like, [snorts] I love him immediately. [laughter] So that that's awesome. And and look and look at what your show has become. It's amazing. There's a I know. Here we are. I love it. Here we are. All right. So off the air, we were just breaking it down, but we're going to jump right in. Let's start with pmenopause and menopause. What is happening to the woman's gut?
KIERAN KRISHNA: Yeah. Um so, so some very profound things are happening, right? So let's look at early pmenopause, even premenopause. Now, as you know, well, women are starting to enter parmenopause is as as early as their late 30s now, right? And so, anytime you start to see a dramatic fluctuation of estrogen and progesterone, which are both very important for the microbiome, you start to see microbiome shifts. And the thing that's important to note is the shifts in the microbiome actually further exacerbate the hormone changes as well. So, it becomes a a cyclical progressive problem, right? So, let's talk about what's happening there. Um, so as estrogen levels start to fall and progesterone levels start to fall, but mostly estrogen, you start to see a reduction in microbial diversity within the gut microbiome. And this has been shown across the board with women. Is as long as estrogen levels are starting to fall, you're going to start to see a reduction in microbial diversity. Now we know that when you change microbial diversity in the gut microbiome that starts to dismantle certain structural elements of the lining of the gut which means that as diversity falls the gut starts becoming more and more leaky and we start to see a higher amount of endotoxmia. In fact there are studies that look at women in premenopause versus women in pmenopause and the the amount of circulating LPS is dramatically higher. Right. Uh, and for those listening and you have a very smart audience, but if they if they don't know what LPS is, it stands for lipopolysaccharide. It's a component of gram negative bacteria and and a lot of people have around 40 50% of the microbes in their gut made up of gram negative bacteria. So, it's an endotoxin that's always present in the lining of the gut. And when your gut becomes leaky, it's allowed to leak through in circulation. Right now, it's found in circulation. and we'll talk about all the havoc that it can create in circulation. In fact, many of the most prominent symptoms of pmenopause and early menopause are associated with an increase in LPS. Right? So, what we're seeing is low diversity and then uh an increase in endotoxmia and increase in circulating LPS. The other things that occur in the gut microbiome is a reduction in butyrate production. Butyrate is a critical short- chain fatty acid that actually helps manage metabolism. It turns on EMPK which is a energy balancing hormone which is really important for fat burning. It plays a very important role in insulin sensitivity. Uh it plays an important role in fueling your immune cells. Uh it plays an important role in modulating inflammation and lining of the gut. So all of those things are becoming compromised. We also tend to see a reduction in lactobacilli uh and bifidobacteria species as well which both of those reductions then have a weight effect as well because uh reduction in lacto and bifido is associated with an increase in weight and a and a reduction of basil metabolic rate in people. So you become more susceptible to weight gain. You also see a um increase in inflammation. Uh so when you look at systemic inflammation in women entering pmenopause you see a significant rise in things like HSCP which is a global inflammatory marker inucan 6 TNF alpha. All of these are associated with that increase in endotoxmia. Um, and then you also start to see a reduction in something called sacrytic fermentation, which is the microbiome's ability to utilize things like fibers and polyphenols to convert them to useful compounds like short- chain fatty acids, urolithins, and so on. So, so these become some of the like the profound changes that occur in women's microbiome just as a result of hormone fluctuations associated with age. It's it's chaos.
DR. TINA: Yes. Just it's just utter chaos and I I am living through it. I I want to add something here and get your thoughts on this. I remember back during co I was at an event with you and the world was still like playing full out pandemic and you said to me something about how the microbial diversity had plummeted during that period because of the isolation. So I think for the ladies that are my age that are in the thick of this a lot of these symptoms started during that period with the stress of things being what they were and then on top of it our microbial population was just plummeting because we were also isol depending on where we lived many of us were isolated significantly and so I don't think that helps and then the other part on that is that when your estrogen starts to wayne uh I actually just read a whole article about agorophob phobia and low estrogen. So, you you start to selfisolate. It's not uncommon to start to isolate a bit more than you used to. And I've become way less social than I used to be. I just I just don't want to be as social as I used to be. So, I think all of that, you know, if we're not out playing with other people, playing with their microbiomes, we're we're having ours diminished, too.
KIERAN KRISHNA: We are. Yeah. And and and the other aspect of that isolation is um another thing that occurs so so as hormones change in itself sex drive and in and interest and intimacy and all that can go down naturally on you know in addition to this hormone changes um LPS as LPS increases that lipopolyaccharide increases it actually can reduce testosterone production even in women which means that the the one hormone that that drives some of your your uh you know intimacy desires that goes down as well. On top of that, as lactobacilli and levels reduce, that lactobacilli levels don't just reduce in the gut, they actually reduce in the vaginal canal as well. Because estrogen acts as a um metabolite for microbes in the lining of the vaginal canal that increases something called glycogen production. And that glycogen production feeds the lactobacilli that are in the vaginal canal which then create lactic acid and maintain a healthy vaginal canal. So as estrogen levels deplete, you start to see a reduction in lactobacilli in the vaginal canal, an increase in the pH in the vaginal canal, which then leads to dryness and yeast infections and bacterial vaginosis and and creates painful penetration. So now you've got not only a lowered overall desire but sex is actually more painful and so people start isolating from their intimate partners as well right and then that of course has compound compounding psychological effects and emotional effects um and everything we talked about uh that changes within the microbiome. So that lowering of diversity, that increase in endotoxmia, the LPS presence, a lowering of butyrate production, all of those things actually make the microbiome even worse, which then makes the hormone recycling, the estrogen recycling even reduced because of changes in something called estrobolum, which is a constellation of microbes within the gut microbiome that can help recycle and increase the amount of uh estrogen you're reabsorbing to try to maintain healthier levels. But as the gut becomes dysfunctional, estrobolom levels reduce and the amount that you can reabsorb goes down uh significantly as well. Which means that this is a cyclical progressive issue and and that's why you know unless women do something significant, it just gets progressively worse over time.
DR. TINA: It's like the body decided to just burn the ships. [laughter]
DR. TINA: Kieran Krishna, I'm so excited to have you here. I you gosh, we are such old friends truly and I'm so happy to have you on the Dr. Tina show today. So, welcome. Thank you for being here.
KIERAN KRISHNA: Thank you so much for having me. It's always a pleasure when I get to chat with you. So, I'm so excited. Let's do it.
DR. TINA: Yes, we have so much fun together. We're going to be talking about a subject I have been waiting to I've just been sitting on it waiting for you to have it. So, I'm really glad to have you here today. We're going to be talking about the intersection of gut health, pmenopause and menopause and GLP1s and the whole hot mess that comes along with it. And I don't think this is being talked about anywhere else. I don't hear anybody even tiptoeing into the conversation deep enough. And so we're going to break it all down today and we're going to do it in under an hour. That's my promise. So [laughter] because we could talk for hours and hours, I do have to say, as an aside, you and the company you worked for in the past were the first sponsors of my old podcast that I had many, many years ago, and we go back a long time. I think almost 10 years now. I I first was introduced to you because you were talking about how dogs were good for your microbiome, and I I was like, [snorts] I love him immediately. [laughter] So that that's awesome. And and look and look at what your show has become. It's amazing. There's a I know. Here we are. I love it. Here we are. All right. So off the air, we were just breaking it down, but we're going to jump right in. Let's start with pmenopause and menopause. What is happening to the woman's gut?
KIERAN KRISHNA: Yeah. Um so, so some very profound things are happening, right? So let's look at early pmenopause, even premenopause. Now, as you know, well, women are starting to enter parmenopause is as as early as their late 30s now, right? And so, anytime you start to see a dramatic fluctuation of estrogen and progesterone, which are both very important for the microbiome, you start to see microbiome shifts. And the thing that's important to note is the shifts in the microbiome actually further exacerbate the hormone changes as well. So, it becomes a a cyclical progressive problem, right? So, let's talk about what's happening there. Um, so as estrogen levels start to fall and progesterone levels start to fall, but mostly estrogen, you start to see a reduction in microbial diversity within the gut microbiome. And this has been shown across the board with women. Is as long as estrogen levels are starting to fall, you're going to start to see a reduction in microbial diversity. Now we know that when you change microbial diversity in the gut microbiome that starts to dismantle certain structural elements of the lining of the gut which means that as diversity falls the gut starts becoming more and more leaky and we start to see a higher amount of endotoxmia. In fact there are studies that look at women in premenopause versus women in pmenopause and the the amount of circulating LPS is dramatically higher. Right. Uh, and for those listening and you have a very smart audience, but if they if they don't know what LPS is, it stands for lipopolysaccharide. It's a component of gram negative bacteria and and a lot of people have around 40 50% of the microbes in their gut made up of gram negative bacteria. So, it's an endotoxin that's always present in the lining of the gut. And when your gut becomes leaky, it's allowed to leak through in circulation. Right now, it's found in circulation. and we'll talk about all the havoc that it can create in circulation. In fact, many of the most prominent symptoms of pmenopause and early menopause are associated with an increase in LPS. Right? So, what we're seeing is low diversity and then uh an increase in endotoxmia and increase in circulating LPS. The other things that occur in the gut microbiome is a reduction in butyrate production. Butyrate is a critical short- chain fatty acid that actually helps manage metabolism. It turns on EMPK which is a energy balancing hormone which is really important for fat burning. It plays a very important role in insulin sensitivity. Uh it plays an important role in fueling your immune cells. Uh it plays an important role in modulating inflammation and lining of the gut. So all of those things are becoming compromised. We also tend to see a reduction in lactobacilli uh and bifidobacteria species as well which both of those reductions then have a weight effect as well because uh reduction in lacto and bifido is associated with an increase in weight and a and a reduction of basil metabolic rate in people. So you become more susceptible to weight gain. You also see a um increase in inflammation. Uh so when you look at systemic inflammation in women entering pmenopause you see a significant rise in things like HSCP which is a global inflammatory marker inucan 6 TNF alpha. All of these are associated with that increase in endotoxmia. Um, and then you also start to see a reduction in something called sacrytic fermentation, which is the microbiome's ability to utilize things like fibers and polyphenols to convert them to useful compounds like short- chain fatty acids, urolithins, and so on. So, so these become some of the like the profound changes that occur in women's microbiome just as a result of hormone fluctuations associated with age. It's it's chaos.
DR. TINA: Yes. Just it's just utter chaos and I I am living through it. I I want to add something here and get your thoughts on this. I remember back during co I was at an event with you and the world was still like playing full out pandemic and you said to me something about how the microbial diversity had plummeted during that period because of the isolation. So I think for the ladies that are my age that are in the thick of this a lot of these symptoms started during that period with the stress of things being what they were and then on top of it our microbial population was just plummeting because we were also isol depending on where we lived many of us were isolated significantly and so I don't think that helps and then the other part on that is that when your estrogen starts to wayne uh I actually just read a whole article about agorophob phobia and low estrogen. So, you you start to selfisolate. It's not uncommon to start to isolate a bit more than you used to. And I've become way less social than I used to be. I just I just don't want to be as social as I used to be. So, I think all of that, you know, if we're not out playing with other people, playing with their microbiomes, we're we're having ours diminished, too.
KIERAN KRISHNA: We are. Yeah. And and and the other aspect of that isolation is um another thing that occurs so so as hormones change in itself sex drive and in and interest and intimacy and all that can go down naturally on you know in addition to this hormone changes um LPS as LPS increases that lipopolyaccharide increases it actually can reduce testosterone production even in women which means that the the one hormone that that drives some of your your uh you know intimacy desires that goes down as well. On top of that, as lactobacilli and levels reduce, that lactobacilli levels don't just reduce in the gut, they actually reduce in the vaginal canal as well. Because estrogen acts as a um metabolite for microbes in the lining of the vaginal canal that increases something called glycogen production. And that glycogen production feeds the lactobacilli that are in the vaginal canal which then create lactic acid and maintain a healthy vaginal canal. So as estrogen levels deplete, you start to see a reduction in lactobacilli in the vaginal canal, an increase in the pH in the vaginal canal, which then leads to dryness and yeast infections and bacterial vaginosis and and creates painful penetration. So now you've got not only a lowered overall desire but sex is actually more painful and so people start isolating from their intimate partners as well right and then that of course has compound compounding psychological effects and emotional effects um and everything we talked about uh that changes within the microbiome. So that lowering of diversity, that increase in endotoxmia, the LPS presence, a lowering of butyrate production, all of those things actually make the microbiome even worse, which then makes the hormone recycling, the estrogen recycling even reduced because of changes in something called estrobolum, which is a constellation of microbes within the gut microbiome that can help recycle and increase the amount of uh estrogen you're reabsorbing to try to maintain healthier levels. But as the gut becomes dysfunctional, estrobolom levels reduce and the amount that you can reabsorb goes down uh significantly as well. Which means that this is a cyclical progressive issue and and that's why you know unless women do something significant, it just gets progressively worse over time.
DR. TINA: It's like the body decided to just burn the ships. [laughter]
KIERAN KRISHNA: Exactly.
DR. TINA: Just burn the ships. Just [bleeped] them. Good luck. [laughter] It's like, you know what? you're not making babies anymore, so just forget about it. You know, good luck. I think that the I always have told my patients, your gut health going into menopause and your adrenal health going in are going to be what carry you and your muscle mass are going to be what carry you through. And my gut health was atrocious going in and it, you know, it was I was that kid with the I mean, I gosh, I out the chute I was put on antibiotics. I don't even think I have a microbiome. And so I was constantly being pumped full of antibiotics as a kid. That's what led me to chiropractors and naturopathic physicians and you know the the journey I took and the the where I ended up. And then on top of it um I mean you knew me back then. I was a single mom trying to build a career and build an empire and I was doing it all by myself. And so stress levels just unrelenting stress for decades that never ceased. And just as I was hitting my stride and just as I was starting to free myself up a little bit from all of it and make a little bit of money and enjoy my life a little more, COVID hits and I'm in Oregon and it's like [snorts] lock down, right? And then I go and open my mouth and [laughter] yeah, all hell breaks loose. So anyway, that gut health piece is so important and I think what you just said might be what literally everything you just talked about even if we did cut it off right there is probably the most important thing that any woman who is in parmenopause or menopause needs to hear because it's not all our fault and we can do all the things to no end and still be suffering because talk about what LPS does in the body. Let's just jump right into that.
KIERAN KRISHNA: Yeah. Yeah. That's that's exactly where my brain was going because I want I want people to understand once LPS starts to increase, how does that drive the things that you're feeling right now, right? So um let's start with with the mood changes in the brain. Um so brain fog for example, right? So LPS is the type of compound it is. It's a lipopolyaccharide which means it has a carbohydrate head and a lipid tail. So it looks physically a lot like the lipid billayer of our cells. Um so it is very pervasive. It can enter into almost any tissue including crossing the bloodb brain barrier. So it does a good job of doing that. When it does cross the bloodb brain barrier, it does induce inflammation in the brain. It activates something called micro gle cells which are the immune cells in the brain and central nervous system. When you when you activate the micro gle cells, it creates a lot of inflammation in the brain. That inflammation can be felt as brain fog. So you might notice that you know you're forgetting things. it's it's hard to calculate things and remember things. You walk into a room and then you forget why you walked into it. Uh you know, all of those things are associated with that increase in inflammation in the brain. Um and then on top of that, LPS also interferes with serotonin and dopamine binding in the brain, which means that your happy hormone and your hormone that drives motivation and reward centers, that's not working very well. So, you have a significant increase in anxiety and depression. In fact, there was a a 9-year long study called the Netherlands study on anxiety and depression where they were looking at a number of biomarkers in people that were suffering from anxiety and depression. And then they followed them for 9 years to look at the best associated biomarkers with the condition. They found only one biioarker was associated with 100% of the cases of anxiety and depression and the level of that biomarker could predict how severe their anxiety and depression was. And in fact, in that nine-year follow-up, for any individuals who that biioarker went away, anxiety and depression went away as well. And that one biioarker was LPS was serum LPS levels. Right? So, we know that LPS has a profound effect on the brain. And we know that women start to to experience some very profound cognitive changes in the brain as they go through permenopause. And that's likely one of the reasons. Um, another effect that is very profound is that LPS can get into areas like the joints. Um, and start creating inflammation in the joints and the muscularkeeletal system, which is I think one of the key reasons why women report increase in muscularkeeletal pain between the ages of 40 and 55 at a frequency 10 times higher than men do in that same age group. Right? Uh, new onset of muscularkeeletal pain, right? So, um, on top of everything that women are dealing with, they're also now dealing with increased pain, uh, which makes it so much harder where to to just doing anything. And so LPS is playing a role there. There's a significant increase in osteoporosis in cardiovascular disease as you get through menopause, permenopause, and menopause. LPS is associated with a significant increase in IL6, inucan 6, which is an inflammatory cytoine, TNF alpha, and IL1. IL1 and IL6 are very important inflammatory cytoines in the aogenic process in in driving aogenesis in the vascular system. Right? So developing the plaques that that cause cardiovascular disease. Uh LPS also drives inflammation in the bone. inflammation in the bone changes these uh cells called osteoplastic cells which build bone into o sorry osteoplastic cells which build bone into osteoplastic cells which actually re reabsorb bone and and uh make makes bone weaker. Um so it drives osteoporosis as well, right? So the the effects are endless. And then this one which is a real pain in the butt if you will one is when LPS interacts with visceral fat in the midsection it actually swells the fat cells the edocytes as we call it three times three to four times its normal volume right which means that all of a sudden you can build a belly what seems like overnight uh you know where where women tend to not have a uh a rounded midsection uh they tend to carry weight throughout their life in different areas. All of a sudden, you've got a belly, you know, and and it's so hard to get rid of. It's no matter how much you're dieting and exercising, it doesn't seem to budge in part because those fat cells are just swelled up, right? And and you're and they're not shrinking, which you know, we we all know when we lose fat, we're not actually losing the fat cells are actually shrinking. Uh we can't get them to shrink because the LPS maintains that volume. So that's just some of the horrific things that increased LPS does in women as they're going through this phase.
DR. TINA: And doesn't it drive diabetes and the progression of that? And doesn't it drive obesity as well?
KIERAN KRISHNA: It does. Yeah. So um in studies even some studies published by the NIH and a big study published by the American Diabetic Association and these institutions are normally way behind on on like the progressive new science. Um but even they published almost now 9 years ago that the primary insult and this is this is quoted from a paper published by the American Diabetic Association. The primary insult that starts the process of insulin resistance is the presence of endotoxins which is the LPS. uh it actually starts um uh affecting how your insulin receptors uh function and it can directly affect your pancreas's ability to produce insulin. Uh and then to compound on that there was a large scale study called the cordial prev study uh which is like 480 people over 60 months. These were people with that that had pre-diabetes risk and then they were following these individuals to look at all the different markers and look at what percentage of them ended up developing type 2 diabetes. Um what they found was again only one marker was serum LPS levels was predictive with over 98% uh hazard ratio or confidence ratio of of being a driver of developing diabetes. Right. And so insulin resistance as you said atyposity so obesity also driven by um LPS. So everything that we that drives us crazy as we get older, right? Our pain, our brain fog, our uh weight gains, our insulin resistance, uh you know, I mean LPS even drives adult onset of acne, right? Somewhere around 40% of adults start to experience adult onset of acne, right? And part of that drive is the presence of LPS in uh increasing inflammation in the sebaceous glands. And so it's just doing wreaking havoc in the body.
DR. TINA: I remember multiple times watching you lecture at different events and you're up there just slide after slide after [laughter] slide like LPS is doing this, LPS is doing and and I'm sitting there in the audience like [laughter] this is everything all at once and oh my gosh how how horrifying, right? This is it's [snorts] it's a lot. And so we're going to tie this into um GLP-1s because this is the important part that I keep trying to get through to people. I am not a fan of high doses of GLP1s for various reasons. And I understand that some people need to take higher doses to actually have an impact on their weight. My argument is if you're not doing all the things diligently, you shouldn't be bumping the dose up yet. There's a lot of work to be done before we start cranking the dose. And one of the reasons why is because there is a correlation to higher rates of SIBO, small intestinal bacterial overgrowth when people are using GLP-1s. I suspect that people are going into the GLP-1 journey with SIBO in many cases like I did. And even at a micro dose, I have never taken even standard dosing. Even at a micro dose, I am experiencing exacerbation of my SIBO because of that gastric stall. you know, it slows the motility down. Um, but SIBO upregulates LPS and LPS drives the obesity and the diabetes that the GLP1's being used to treat. It is so ironic and people need to understand this.
KIERAN KRISHNA: Yeah. Well, and I think the the important point you bring up there is that you know what's happening when you stall the bowels, right? So, and and there's a number of things. So there's a number of documentations on the changes that occur to the microbiome when when people are on GLP1s. Um and and people just have to be cognizant of this if they're going to go down that route. Um some of the natural things that happen is they they eat less, right? So they're they're the consumption of things like fiber goes way down. The consumption of polyphenols goes way down. the consumption of resistant starches goes way down, which means that they're not feeding the microbiome adequately and they're driving further reduction in diversity within the microbiome. And if you're already in parmenopause at that stage and your microbiome diversity is already tanking because of lower estrogen, then you're exa you're actually exasperating that situation. Um, and then your your butyrate production and short- chain fatty acids go down. So that is an underlying um disruption in your body's natural ability to regulate insulin levels. Um so so now you're creating a f foundational change in your metabolic system as a result of it. And the thing is maybe when you're on the GLP1 you're maintaining the, you know, proper insulin function, all that, but if you ever hope to come off of it, right, that's where you're going to see the the the effect of the problem that was created during the course of the GLP-1, right? The acceleration in diversity loss, the acceleration in insulin resistance and or dis d disysregulation of insulin um control and so on. So the the the the effect that the GLP1s have on the microbiome compound the negative effects that pmenopause already has on the microbiome. And putting those two things together can be a very profound change for people. Um you know if they're not really actively thinking about it and working against it.
DR. TINA: This is why I'm not a fan of cranking the dose up high and fast when it just tanks out people's appetite. you know, obliterating someone's appetite is not the jam because of exactly [clears throat] what you just said. be beyond becoming malnourished, beyond wasting away too fast and and losing potentially muscle mass and and what else. This is why I say, and I've said it multiple times, and I've never really extra gotten to extrapolate on it, but this is one of the many reasons I say when people are doing high doses and they crank it up fast and they lose a ton of weight and they don't preserve their muscle mass and they don't take good care of what they're putting in their mouth, they are going to be more metabolically brittle on the other side, they're they're they're destroying they're coming in metabolically compromised and they're leaving metabolically devastating ated and this is one of the biggest reasons why.
KIERAN KRISHNA: Yeah. And and that happens in people in their 20s and 30s, but it happens more profoundly if you're middle age, you know, because of the other factors that are already dismantling your metabolic health and your microbiome, right? The hormone changes. Um, so I think it's a it's it's an it's an area that people have to really pay attention to because we may be creating as a result a population that starts coming off these GLP1s that are way worse off than they were before and and as a result have much bigger problems that they now have fewer solutions for, right? And so um so the consciousness around this has to improve now. And just to me mention a couple other things that that changes. We we know that protein intake naturally decreases with GLP1s as well, right? Um and as a result of that, your microbiome has fewer proteins. As as a result of that you it actually compromises mucin production which is that very important mucous layer that maintains the barrier integrity which when and if you don't have adequate mucin production not only is the barrier function of your gut compromised which means your gut is more leaky and more LPS gets through u but you also then compromise your immune response right because so much of your immune function exists in that mucin layer and so you're compromising a a physical component of where your immune system tends to function. Um the other thing of it is it changes your your metabolic uh your fermentation system. I mentioned this earlier where it it reduces sacryic fermentation but it increases something called proteolytic fermentation and that proteolytic fermentation unfortunately produces more ammonia pressol and these very inflammatory compounds. So it's shifting how your body even deals with food uh that that is coming in even though it's limited amount of food that's coming in. So so yeah all of those things compound together and create kind of a perfect storm of of metabolic disruption uh gut brain disruptions gut skin disruption uh you know midsection metabolic uh disease that you see that that conventional bloating in the midsection and so on. uh and then down down down the line it upregulates immune dysregulation and so on.
DR. TINA: What fires me up about this is that so many clinics and pharmacies and tele medicine companies are now erroneously deceiving people selling them into micro doing GLP-1s for weight loss. There is no such thing. First of all, if you're truly on a micro dose, it is not a weight loss strategy because you acclimate to the GLP1 so fast. There's no version where you're losing appreciable weight. maybe maybe 15 pounds mo at most. If you've got like some inflammatory puff, it'll it'll dial it down oftentimes, but they're being put on standard doses, regular old starting doses of GLP-1s, they're being given 0.25 of semagoglutide or 2.5 of turseptide. That is the standard starting dose. That is the same dose we give folks who are diabetic, folks who are dealing with obesity. And they're telling them it's a micro dose. And these people are messaging me saying, "I'm so sick. I'm having such horrific side effects. I thought I was on a micro dose. I was told I was on a micro dose. And they're selling them by telling them what the maximal dose is and saying, "Well, that is onetenth of the maximal dose." So, you you're good. It's so deceptive. And any anyone listening, if you find a tele medicine group that's trying to sell you in on ads or in their advertising on micro doing for weight loss, you are being deceived. I I guarantee it. And across the board, I've looked into some of these. I've actually gone in and applied as a pseudo patient. They immediately they they don't even have a visit with you. There's no doctor. Suddenly, you're getting a prescription in the mail and it's the standard dose and they're calling it a micro dose. So, not everyone's doing that. I'm not saying they're all bad actors, but this is what's happening out there. Like my original strategy got twisted and this is one of the main reasons why I'm so fired up about it because they are tra some these women are on way too high a dose in many cases and they are trashing their guts in the process of an already trashed system in a process of pmenopause and menopause that's already causing further trashing. Yeah. [laughter] So, it's just it's just a mess and it's it's frustrating to watch because I really think that women are I think my generation is being prayed upon. The women in my you know, Gen X is being prayed upon. Menopause and permenopause are big business right now and everyone's getting in on it. So, you know, everyone's got something to sell us and it's it's frustrating because women, we don't know how to navigate this. I I know everything I know and I have friends like you and I'm still Yeah. a wash of, [laughter] you know, of of frustration. So [gasps] anyway, um I will add that I have been studying this because I always I do the same thing every time I look up a condition, I look up that condition and then I put and exercise and then I look up all the studies for it. And exercise is phenomenal for SIBO. Exercise is phenomenal for LPS. Exercise is phenomenal for gastric motility when it's stalling out on you and in your GLP-1 journey. Um, by the way, diabetes makes the gut stall out, too. There's a lot of reasons why the gut will stall out. So, exercise is a huge, huge, huge win in all of these cases. It's going to be beneficial. So, just a little plug there for the go to the gym that I keep trying to get people to do. So, I know that GLP1's definitely cause a shift in the microbiome. I suspect that part of the on-ramp experience that patients have when they feel such extreme nausea and GI symptoms, I think it is due in part not just to the direct mechanism of the GLP1, but I think it's due in part to the shift in the microbiome. Sometimes this shift is favorable and some of the studies show, you know, you're you're actually shifting to maybe a less pathologic and a more favorable organism. But I think that there's a die- off happening as that shifts going on. And these people are dealing with a Herxheimer reaction. I I honestly think that's what's happening when you go too fast too hard on GLP1s. I think some of that those gut symptoms initially are just your poor gut trying to recalibrate and all hell's breaking loose.
KIERAN KRISHNA: Yeah. Yeah. So, you know, one of the things that um we know is very clear when you start a GLP-1 is the transit time of your bowel changes, right? And and transit time is so critical to how your bowel has been functioning because it dictates how long food spends in what part of your bowel. And how long food spends in what part of your bowel dictates what happens to that food in that part of the bowel. So, for example, if food now stays longer in the stomach or stays longer in parts of the intestines than it normally would, that opens up the opportunity for putrification and fermentation of those foods that normally wouldn't happen, causing all kinds of responses in your GI tract that that are hypersensitivity responses that can make you feel nauseous, make you have gird and reflux and all of these kind of common symptomologies because Now, food is stalling out in your system, right? So, the transit time of your bowel is such an important thing that most people need to know about. And and I I always encourage people to test the transit time of their bowel themselves, which is which is relatively easy to do. You can you can basically eat a ton of beets in a given meal and and of course note when you ate it and then look for when it comes out the other end or it starts to starts to come out. It may not all come out at the same time, but you'll start to notice a change in the toilet color when it when it starts to come out. And what you want to see is, you know, somewhere between like 24 to 30ish hours, right? Um, if you're way before, if you're like 12, 13, 14 hours, then your bowels are moving too fast. And if you're in the 40 plus hour range, your bowels are moving too slow. And so, you can adjust that by the types of fibers that you consume, right? If you need to slow down your bowels more, you take soluble fiber, which S for soluble, S for slow down the bowels. If you need to speed up the bowels a little bit, you take more insoluble fiber. So, you can make those adjustments, but then when you get on the on on the GLP1s, it's going to totally slow down your bowels, and that transit time is going to be affected. And now microbes in certain regions of your bowel that are not used to having a prolonged amount of time with food get a prolonged amount of time with food and they start fermenting and producing things. And when they produce those things, your bowels are going to get really irritated and it's going to feel uh very uncomfortable, right? Because you're not used to the things that these microbes are now producing in that region. It's it's no different than kind of a food poisoning like nausea, right? Because what's happening in a food poisoning? Well, there's a new microbe that's being introduced to your bowel and it's producing byproducts and toxins in a region that your bowel normally doesn't experience and that's creating the the need to vomit or the or the need for diarrhea, right? And and those are both reflective responses of your body trying to get rid of stuff, right? nausea and need for vomiting and need for diarrhea is a way that your bowel actually tries to protect itself to get rid of things. Um, so that nauseousness and all that comes to me for a lot from that slowing down of the bowels like you said, but the the noxious fermentation that occurs as a result of that.
DR. TINA: Yeah, it's no good. I think there's a lot happening that needs to be studied with GLP-1 use and the gut microbiome. Yeah, I think there's a multiple I'm sure there's multiple mechanisms going on in there that's causing people to have such this is again why I'm a slow and low fan and I'm not a high dose fan and I I get the question all the time from people well what do I do if I need a high dose and I don't have an answer I that's never what I claim to have any knowledge of I I'm not treating generally speaking I'm not treating patients who are obese who are not also doing all the things because I find when they do all the things we need way lower doses totally to move the needle. And so I think of it more of like using a GLP1 like a whisper instead of a blasting megaphone, right? We're just trying to gently nudge the system. The other thing to note is there is some data showing that GLP-1 use at standard dose and this was in laglutide decreased endogenous production of GLP-1 in the L cells for a substantial amount of time. So I I think what we're seeing is also this downregulation of L cell production and who knows what else is happening there with the other peptide signaling hormones of appetite and it's I don't know I think it's going to be I I am concerned about the higher doses and I'm really concerned because people use my name and they throw it around and say well Dr. Tina said GLP1 ones are safe and I'm like well that's relative. Yes, [laughter] that's that's really relative to how you're using them because I'm talking almost a different mechanism entirely. It's almost a different drug in my brain as to how I use them. And I and I know I realized you know once it's kind of like low dose now trexone. That was really what I was going for in all of this was kind of a lowd dose now trexone impact where if we could give the body a little bit of what it needed would it also help the body utilize what it has better. right? And kind of whispering to it. But we even see with LDN now we see people using I I saw a Stanford pain doc talking recently on Peter Ortia's podcast about how he's using like 8 to 20 milligrams of Nrexone and I'm like dude that's not low dose that's just a half dose, [laughter] you know. So it's it's very we get different mechanisms out of things when we use them at at different not to give a lesson here but just for the listeners to really understand. I never said that. I never said they're super safe at every dose. And there's all kinds of fallout that can happen depending on the body they go into.
KIERAN KRISHNA: Well, and and there's another endogenous mechanism that it kind of circumvents, right? So, there is a very clear gut brain access, right? The gut is talking to the brain through the entic nervous system, which is the neurological system that covers the entire digestive tract connected through the vagus nerve to the brain. And so, there's a very important communication that occurs. In fact, you know, if you look at the nerve um, you know, structure of of that of the vagus nerve itself, it's 80% of the nerves are what we call afrant nerves, which means 80% of the information is actually going from the gut to the brain and only 20% coming from the brain down to the gut, which means that the gut is a massive signaling uh organ to the brain to instruct the brain on all things that are happening in the ecosystem, in the body, and so on. Now, one of the things that that GLP1s do is it skips that gut brain connection, right? It goes right to the brain. Um, and and the signal goes directly to the brain and and kind of skips that that superighway, if you will, which which is, I think, why some of the people, it's it's rare, but some people can get permanent uh, you know, stasis of their bowel, right? So, the bowel stops moving completely and and it can't be reversed. I think part of that is that skipping of the really important gut brain connection and that communication that those two organs need to have. Um so it's hard to know what is going to happen uh with with long-term higher dose use and then you add the the the compounding effect of all the microbiome complications in pmenopause and then it becomes really confusing you know as to what all the the the uh unwanted effects can be and
DR. TINA: aside from the estrogen leaving the body part all of this pertains to middle-aged men as well for sure. Mhm. So this is happening and diabetics have veagal nerve disruption. The the high blood sugars for sustained extended periods of time does damage on the vag nerve and that connection is in many cases already compromised. And so then they're being given, you know, thrown these high doses of GLP-1s which again not a fan of. And they go into gastropreesis and they want to blame the peptide. And I'm like, "Yeah, but we just threw you over the edge of a problem that was already brewing for decades, you know." So, um, how we approach this, I think, needs to shift because it's through education and through a step-wise process that we can do this most elegantly, I believe. So, um, okay, let's talk about stress because I just, when do I not have stress? I think I'm just programmed for it now. I uh I just my listeners know I just went through a pretty rough patch with my mom's health and it was a lot and um I was kind of like the sole person on the scene dealing with it and I came out of it with it was pretty traumatic and I came out of it with some PTSD. No one else remembers what happened but me cuz my mom blissfully gets amnesia. You know, it's a it's a beautiful thing about being sick is you don't get to remember anything that happened. And so I and I've shared this before, but if people are listening for the first time, I gained weight like that. I mean, it just it was overnight. And I can honestly say I don't think I believed my patients when they were in middle age and telling me that similar things had happened to them. I thought they must have just gone on a bender or something, you know. And I was shocked at how fast I literally just blew up. And it wasn't it was in my gut. It wasn't just a belly. It was a gut. But I also had I can't even get my wedding ring on still. There's just this kind of edema. And I'm sure it's elevated cortisol levels. I haven't even ran my labs because I don't want to know. I I don't want to run anything yet. I'm like, I got to get this under control and then I'll [laughter] run my labs because that was just chaos. [gasps] But uh let's talk about what stress does to your gut microbiome. what it does to SIBO, what it's doing to the middle-aged woman.
KIERAN KRISHNA: Yeah. Yeah. And and it's a this is another one of those um self-perpetuating problems because stress alters the gut microbiome significantly and the way it alters it actually then makes you more susceptible to stress, right? So it again is progressive. Um and so so what is actually happening when when you're stressed? So uh cortisol of course when you when you're stressed you're going to kick off your HPA axis, right? your hypothalammic pituitary adrenal axis, you're going to kick in the fight orflight response and as part of that cortisol tends to start scaling in the body to initiate the fight orflight response. Um, one of the things that happens to cortisol is a portion of it gets dumped into the gut. Now, why does it get dumped into the gut? Well, because there are microbes in the gut that can actually metabolize cortisol and the metabolic byproducts of that go to the kidneys and they shift the uh the the solute and solvent ratios in the kidneys. So the potassium sodium ratios which then increases the amount of water that is going back into circulation. So then the kidneys actually press more water back into circulation in order to increase uh blood pressure. Right now, the reason it's trying to increase blood pressure is it's trying to profuse things like your brain, your muscles, your heart because you're going to fight orflight response. This is why chronic stress creates hypertension, right? It's this exact mechanism. So, cortisol dumps into the gut. Now, what what what's clear is when your gut is dysfunctional and you're missing certain key organisms. Uh in fact if you have low bifidtoacteria levels uh and bifidobacteria have this this component to their um to their outer cell membrane that are carbohydrates that they tend to make that actually negates this process that I'm going to talk about. So when you have low diversity and you have low bifroacteria, when cortisol dumps into the gut, it creates profound permeability in the gut, right? The gut just basically ex the the tight junctions and the space in between the cells just expand and you get a whole lot of permeability. You get a whole lot of LPS coming in and as a result of that LPS coming in, we talked about earlier what the effect of LPS is on the brain, which makes you more susceptible to anxiety and so on. But on top of that, LPS also increases IL6, which we mentioned before, but one of the things we didn't mention is that IL6 can actually re-trigger the HPA axis even though you don't have another stimulus, right? So, um, think about it this way. When when your system is vulnerable and susceptible in that way, an outside stressor comes in like your, you know, your your family member almost dying or stressful call or whatever it may be. The external trigger of stress creates this cycle where you're going through the the fight orflight response, but you can't come down from it because every time cortisol enters your gut, IL6 goes up and IL6 re-triggers your HPA axis as if you're going through another stress episode, right? So you maintain this elevated level of your sympathetic nervous system without ever being able to come down effectively back into your parasympathetic which means that you stay at this heightened stress state throughout the day, right? And it and it just makes it so impossible to get a handle on things. And the longer you're in that state, the more dysfunctional your gut becomes. Because the other thing that occurs when you're in that elevated stress state is your immune system starts triggering inflammatory responses in the lining of your gut. Good bacteria start to die off as a result of that. Certain types of pathogens do well under that condition. So they increase their growth. And in fact, some pathogens have learned that when the host is under stress and they're actually measuring your stress hormones like your epinephrine, norepinephrine, cortisol, and so on, when those stress hormones are elevated, that's when they they express their villance factors and their toxin production because they've come to learn that that's when the host is susceptible. The immune system is not functioning properly and so on. So, they're opportunistic and they start to increase their growth during that time. So what you tend to see is that with every little bout of stress that you undergo, it's like taking a little dose of antibi antibiotic because it disrupts your microbiome measurably enough from those individual bowels. So as you can see then as your microbiome becomes more and more disrupted, you become more susceptible to the effects of cortisol and that cycle just keeps continuing. It's so bad. [laughter]
DR. TINA: Yeah, so bad. I was watching uh House of the Dragon last night with my daughter and Queen Rea is under so much stress and she's so overwhelmed and so just like there's just way too much going on for her. And the look on her face and my daughter looked at me and she goes, "That's what you look like, [laughter] mama." And I'm like, "I know. I know that feeling." I said, "I know that feeling well. I know like you I got to hold it together. I'm the one in charge, but you have so many plates in the air." And you're like, "Yep." So, no, it's I I am happy to say that things are calming down and my mom is in good health and everybody is chilling and I told all my family members to chill. Like, no more emergencies for a minute because I [laughter] don't have it in me to to help anymore right now. So, uh we're getting there. But, okay. So, what can we do? Let's let's round this out with a solution because this is all just it's a lot. It's a lot.
KIERAN KRISHNA: Yeah. Um but the good thing is there's a lot you can do um of it, you know. So, so let's talk about LPS to begin with, right? So um you know that became actually endotoxmia and LPS became my motivation to get into this industry because I saw this very very early on almost 20 years ago that this increase in LPS through this process called endotoxmia was arguably one of the uh biggest drivers of chronic conditions uh that that we deal with in the western world. And in fact a paper published in 2015 in frontiers of iminology concluded the same. They said that stress induced endotoxmia or endoxmia on its own is the number one cause of morbidity and mortality worldwide because uh how it sets up the body for all of these disease conditions that we talked about. So um then the question became what can you do about it? So so we started looking at microbial solutions for it. Um and the first probiotic that I developed was a sporebased mix. And the reason we developed a sporebased mix is number one, I wanted a probiotic that would survive through the gastric system. Uh so that I didn't have to do all these special capsules and all kinds of stuff. I wanted it to survive and get to the the intestines alive so it can go to work. The second thing I needed it to do was to have this capability called cororum sensing. Quorum sensing is the ability of microbes to read other microbial signatures and then start to make metabolic changes in that environment to bring down dysfunctional bacteria and increase the growth of beneficial bacteria. So then that way a probiotic can go in there and start modulating the microbiome effectively. The third thing I wanted it to do was some evidence that these that these bacteria can increase the expression of tight junction proteins. Right? Those are the proteins in between the intestinal cells that get dismantled as a result of inflammation and and stress and all of these things. But you you need to increase the expression of those tight junction proteins in order to sin them both back shut and start to seal up the lining of the gut again. Um, then I also needed the probiotic to increase the production of short- chain fatty acids, especially butyrate because butyrate feeds the goblet cells that make the mucin layer and you need to have an adequate mucin layer to have any semblance of an intestinal barrier at all. Right? So we looked at some of these features, formulated a consortium of probiotics uh and then started doing studies and we published in 2017 the first time a paper has been published on a probiotic that alleviates that LPS endotoxmia. Right? So we showed in a 30-day study in a simple randomized control trial 38 30-day study with people who had profound endotoxmia meaning we were screening people for those that had a huge amount of LPS that leaks through. we were able to show a 75% reduction in that LPS in just that 30-day period. Right? So, so that was very exciting to see and we saw all the effects of LPS reversing. So, for example, gut brain communication, we saw the the uh the reestablishment of the leptin AMPK cycle after these people ate food, right? So, what does that mean? Uh so, leptin is a satiety hormone, right? And and in order for your body to stop producing the hunger hormone ghrein once you eat, you need the you need your gut to communicate to your brain through in part through GLP1 receptors but then other receptors as well that we have enough food coming in turn on the satiety hormone not only does the satiety hormone then make you stop eating it also activates fat burning and all these metabolic processes. So what we saw in these individuals, even though they were of normal BMI, their leptin response was completely compromised, meaning that we would give them a 2,000 calorie meal after they came and fasted and their ghrein levels, their hunger hormone levels would barely drop after the meal, right? And their leptin levels would just remain flat, right? And and so these individuals, they were 22, 23, when they become 28, 29, 30, they're going to start putting on weight quite significantly, right? And so what we saw then after just 30 days of not adjusting diet, lifestyle, or anything else, just taking the this the sporebased probiotic formula, what we saw was a um after we gave him the 2,000 calorie meal, we saw about a 60 70% drop in the ghrein, the hunger hormone, and a significant increase in leptin. So we're reestablishing the gut brain connection. We also saw all of those inflammatory cytoines associated with elevated LPS. All of those came down as well, right? So, all that was achieved through a sporebased probiotic, the Just Thrive probiotic, um that you can take once a day to to help with this endotoxmia issue that's going to occur um both in men and women as we get older.
DR. TINA: That's awesome. And talk about the sporebased probiotic because it's different than other probiotics in a myriad of ways.
KIERAN KRISHNA: Yeah. Yeah. you know what I was looking at it, you know, as as looking at this from a microbiologist lens, I was really looking at our natural interactions with microbes, uh, and and I was starting to look at in the environment, in other areas. Are there microbes that we would naturally consume that could survive through the gastric system because, as we know, the gastric system is called a gastric barrier for a reason. It's really good at killing microbes, right? Uh, the pH is very low in in normal physiological pH. It could be 1.2, 2 1.3 that's a very very acidic environment. In fact, humans have I think the third uh or the fourth lowest pH in the animal kingdom only next to like vultures uh who can of course eat dead things and be perfectly fine, right? Because their gastric system is so powerful. Uh we are omnivores and we can eat lots of different things in part because our pH is so low. But that same pH also kills the vast majority of microbes coming in. And so I honed in on bacteria that could naturally survive this gastric system. And to me, if nature offered it that that feature, that very unique feature, there must be an importance to that, right? There must be some sort of co-evolution importance. And as it turns out, these spores can cover themselves with a protein calcified coating that allows them to survive the gastric system. And the the moment they hit the intestines, there's receptors on the outside of the spores that come into contact with receptors on our mucosa and the spores pop out of this spore uh coating and they become normal functioning vegetative cells in the gut and and as a result of that humans have been consuming them and they've been living in the human gut for hundreds of thousands of years. Right? So they have this really unique innate relationship with the human gut.
DR. TINA: Weren't they found in mosquitoes in amber? Did I am I getting that right?
KIERAN KRISHNA: No, you remember that right? You totally got that right. So I I saw that study like 15 years ago and it fascinated me. And then here come full circle. I just about 3 months ago I started working with a retired professor who's a microbial ecologist. We're doing a bunch of work on on on things that move the needle on the microbiome. He's the guy that did all that research.
DR. TINA: No way.
KIERAN KRISHNA: Yeah. His name is Raul Kano. He did all of that work. Basically, what they were looking at was u number one, he was looking at what what the ancient microbiome looked like of animals and all that, right? And the other thing is he was supporting a group of scientists who were looking for uh microbes that have never been discovered looking for new antibiotics because of course microbes make antibiotics and they make very unique ones and as antibiotic resistance increases, they're looking for new ideas from these microbes. So he actually and listen to this is actually a fantastic story. So so him and his team did all the work where they found um microbes in the guts of ancient fossilized honeybees that were fossilized in amber just like the mosquito in Jurassic Park, right? Uh and he was able to isolate basillus endospores from them that were 50 million and as as old as 250 million years old. And he also found yeast from uh from the the ancient yeast from these from these uh bees and whatnot. Um and they [clears throat] were able to ferment things with the basillus and the yeast. And in fact, for his daughter's wedding, he made like kombucha and and wine by fermenting with these ancient 50 millionyear-old microbes, right? Like how cool is that?
DR. TINA: That's that is that's amazing. That's that's that's some nerd stuff right there. [laughter] scariest nerd stuff, right? I love it. I love it. And I love [laughter] that that's where their brain went. It's like we should with these things,
KIERAN KRISHNA: which means that these organisms are still alive, right? So, it's been fossilized and it's still alive. You can still plate it once you remove it out of the ancient honeybee. Um, so these organisms are incredibly robust. They've been here well before us. Uh, you know, humans have only been been around for a couple million years. These have been here for 200 million years. Uh and so they started all of this microbiome communication and ecosystems for us. And so you know what my group was able to do is that we were just smart enough to know what nature had already created and and study it and utilize it. Uh and so these these sporebased organisms can be incredibly profound and I think anyone going through middle age needs it uh because we have to stop that endotoxmia, right? And then there's some very important dietary things people need to do as well.
DR. TINA: So I recently got a shipment of the probiotic, the Just Thrive probiotic and the bitters and I'm about to start them. I haven't yet because I was kind of doing my own thing and I ended up with a an old bottle of Just Thrive that I found and I was like, "Oh, my dog was my dog has been he got giardia when he was a puppy and it's just been like a constant thing for him, you know. So he's Gardia really does a number on you for like for the rest of your life. It's it's a thing. And so anyway, gave him a little bit. Super helpful. And I was like, "Oh, I should take these." So I'm going to get back on the the horse on that one because I just I'm a little scared because I'm I'm finally starting to feel myself again. And I was like, "God, the sensit the system is so sensitive at this point, right? I just feel so I hate to say that. You know me, you've known me a long time. Like I did not enter into pmenopause unfit. I was in the best shape of my life. I was incredibly fit when I entered into permenopause. And I have always been fit and lean. And I'm just at this I try to tell middle-aged women and now I'm living it. It's like we're kind of a it's a little brittle. It's a we got to be careful. So I'm really excited to get back on these and put them into my gut protocol because I'm kind of self- treating my SIBO right now with the knowledge that I have. And I think that it's going to be really helpful. talk about bitters because I think bitters are huge here. I've been using some other bitters but I bitters are just amazing.
KIERAN KRISHNA: They are they are the unsung heroes of the nutritional field, right? So So it's it's really fascinating. So we have these bitter taste receptors that start in our mouth and basically are throughout our entire body. So our entire digestive tracts, our stomach, our small intestine, large intestine, our pancreas, our liver, even places like your heart have bitter taste receptors. Now, we call them bitter taste receptors even though you're not tasting in these regions, but they're just these receptors that bind bitter compounds. Now, when you look at the evolutionary significance of these receptors, basically a few different things. Number one is that our ancestors basically consume bitters with everything they ate, right? They were foragers, gatherers. They ate lots of berries and herbs and things like that. And so, they're getting bitters in virtually everything they ate. Now, the one of the reasons why you'd have uh really strong bitter taste receptors in your mouth is because potentially poisonous things have a very aringent bitter taste. And that that um there's an automatic reflex to make you spit those things out. Right? That's one of the ways in which our ancestors learn what you should eat and what you shouldn't eat by using the bait bitter taste receptors in the mouth. Now, at the same time, you've got lots of other bitters that'll go through that don't have the same intensity. And as a result, binding of the bitter taste receptors is another example of the signaling that occurs from the gut to the brain because it tells the brain where the food is and how much food is coming in and what to turn on, right? The brain doesn't know this stuff, which is so fascinating, right? So, you could be eating something. The brain doesn't doesn't necessarily know that the food's in your stomach or is in the distal part of your stomach uh or in the very proximal part of your small intestine or it's moving down midway through your intestine. It doesn't know when to kick up bile. Doesn't necessarily know when to turn on uh the digestive enzymes. It needs information to send those signals down. And that information comes from these checkpoints that are the bitter taste receptors. And the the crazy thing about it as I dug more and more into the research around bitter taste receptors is turning on of the bitter taste receptors throughout the digestive tract accounts for almost 50% of all of the digestive signaling. Right? So think of them as switches going through this massive machine. Turning on these switches to effectuate the digestive process requires bitter taste receptors being activated by bitter compounds. Which means your average American that consumes no bitters at all, right? We've basically cultivated bitters out of our agriculture and all that because no one likes the taste of bitters. And so we're not consuming any bitters with our meal, which means we are not turning on upwards of 50% of the digestive signaling in the body, right? which which then makes it so easy to understand why we're so horrific at digesting food and breaking it down and not allowing it to cause gas and and immobility and all of these things that occur due to indigestion, right? So indigestion is still one of the big biggest reasons people go to see the doctor in the hospital um and and they're not turning on about half of the digestive signal. So adding bitters back into your system is one of the most foundational things you can do with how your digestive system is designed.
DR. TINA: Aren't bitter taste receptors what signal the L cells of the gut to kick up too? And that that's what that's the L cells are what secrete GLP1.
KIERAN KRISHNA: That's exactly right. Yeah. Several other digestive uh signaling peptide hormones. So totally. Yeah. It it it kicks up um you know CCK GLP1s, GIPS. It it kicks up the the PY. PY. Yep. Um and AMPK as well, which is like the master regulator around fat burning. Um and then it also kicks up all of the signals for releasing bile and recirculating bile over and over again, you know, which is huge, which is another big issue with why people develop SIBO is we have an inadequate bile acid pool. And as a result of that, we don't circulate enough bile through the small intestine when food is there. One of the reasons that one of the things that bile does is it acts as an antimicrobial. So it prevents the microbes in the small bowel from fermenting the food that's in the small bowel and keeps those microbial numbers low. The other thing that bile does every time it circulates through the digestive tract when food is present is that it uh it upregulates something called a nuclear FXR receptor. That nuclear FXR receptor which is in the distal part of the small bowel tells your intestinal cells in the small bowel to produce antimicrobial compounds when food is present to suppress the growth of bacteria in the small intestine. So it cannot utilize the food that's in the in the small intestine. Right? When those signals are all suppressed, you're going to develop SIBO because those bacteria now in the small intestine can utilize the food and overgrowth and ferment and create gas and all kinds of things.
DR. TINA: I if I think of middle-aged woman, my automatic thought is bile issues. Like those two things are in my head when I see well the the the phenotype I have right now literally like what happened to me after that big stress load? I'm just like, oh, I need bile. And the thing about taking bile, like if you use an ox bile supplement, is it's really easy. I know people are going to come for me on this one, but I find it too easy to go overboard on that. You can take a little bit too much and then all of a sudden now you've got like really painful dumping of diarrhea. So, it's it's a fine line and I think bitters are a wonderful way to sort of be the checkpoint in there because you really can't overdo it with bitters, but you can overdo it with bile.
KIERAN KRISHNA: Yeah, you definitely can. Now, what what happens when you overdo it with bile is um there are microbes in your gut that'll convert that bile into what we call secondary bile salts. And those secondary bio salts can be very useful and helpful, but if you do too much of it, it can actually uh create inflammation in the large bile. Um and so, so yes, you can definitely overdo with bile and that's an important part of the message. So, you know, for me, I if if you're middle-aged at all, men or women, uh, and and when we did our leaky gut studies, we were doing it in in people in their in their mid20s who were by FDA standards healthy normals, right? So, they didn't have any conditions, they didn't have any issues, weren't on any drugs or management of any disease, and they were all normal BMI and so on. But about 55% of them had very profound leaky gut, right? Very elevated levels of LPS. And so as you're entering middle age and you have any issues like you have any digestive issues, skin issues, anxiety, you know, any of those things, there's strong indication that you have significant leaky gut and significant LPS. So everyone should be on the sporebased probiotic. And then uh add to that, you know, adequate fiber intake. Uh, and especially if you're considering a GLP1 in your middle age, you want to keep in mind that your diversity in your microbiome is already shrinking naturally, which is affecting your body in very significant ways. You need to take extra steps to ensure that your diversity gets maintained or maybe even improved, right? And so maybe look at hormone balancing before you consider GLP1s, right? Which is which could be super simple, right? look at progesterone and estrogen supplementation, you know, and and stabilize those levels before you go into a GLP1 that'll further create disruption. So, stabilize some of those other things. Work on the diversity of your microbiome with polyphenols, with fiber, um with with more diverse diets, and then the sporebased probiotics and prebiotics and all that. Start to get all of those things in line and build those pillars before you start considering the GLP ones.
DR. TINA: I completely agree. I have been trying to beat this drum and tell people this and they don't want they just want that GLP-1. And I'll tell you what happens, Karen. When I start working with people, nine times out of 10, once that GLP-1 gets to a dose where appreciable weight loss starts happening, everything goes out the door. Yeah. They are like, maybe I'll skip the gym or maybe I'll stop taking the supplements or may, you know, it's like, no, no, no, no, no. This is a this is a comprehensive integrative approach and we're trying to hit all the bases because some of these nuances that aren't being discussed that we thankfully have addressed here today are super important. This is truly root cause medicine. Like this is what's driving a lot of issues for people and they're taking things out here to try to fix what this is driving. So gosh, we could go on. We we need a part two. You you and I get together and it's just like have a brain meld and go for it. But you guys have been so generous over at Just Thrive. You guys are offering my listeners of the Dr. Tina show if you start a 90-day subscription to the probiotic, the sport-based probiotic you were just speaking of, you guys are going to throw in a 90-day supply of the bitter product, the new digestive bidters. So, this is a huge value. It's a $90 value. And I think the two of them together are it's a beautiful combination. So, I hope people will check that out. It's at justthrivehealth.comdtina. And again, I'm going to repeat it. If you're listening to the show, it's going to be in the show notes, but for those of you just listening, it's just thrivehealth.com/dtina and do the 90day subscription to the sporebased probiotic and you'll get the free 90-day supply of the digestive bidters because you guys are awesome and generous.
KIERAN KRISHNA: Well, it's and it's so important. I mean, I I cannot emphasize how much people need bidters. Um, you know, and it's it's just overlooked all the time. Uh, most people aren't even familiar with it. Uh, what a bidder is, you know, and and and it controls upwards of half of all your digestive signals, which is which is amazing, right? I mean, if you think about like imagine you were missing something in your daily diet that that turned on half your brain and you were only walk working with half the brain, right? And we think of the gut as a second brain. And so it's really important to make sure we're utilizing all of the functions of the gut. Um, and so bters and bitters do that. And this this particular product has uh 12 different bidters in it at at doses that are clinically relevant. So it makes it super easy to take because if you had to consume all of those 12 bitters, it'd be very difficult because of taste, of course. So it's in a capsule. it sends it down to the digestive tract um and and you know activates all of those signals. Now one of the most common questions I get is what about don't you need bitters for the for the mouth right so um what about that you know skipping it so as I mentioned earlier one of the most important aspects of the bitters for the mouth is to detect potential poisons so we we don't have to worry about that the second thing is to trigger something called the syphalic response the syphalic response is just your brain getting ready for food right so it's it starts increasing salivation it starts increasing some gastric secretions gets your body ready for food coming in. But you can actually increase the syphalic response just by smelling food and seeing food. And we all have done that, right? You smell bacon, for example, and you're like, "Oh," your mouth starts watering, right? That's a syphalic response. So, you don't necessarily need to do that through bitters either. You want to get the bitters in the digestive tract and throughout all the bitter receptors.
DR. TINA: I like that it's in a capsule because I looked over the ingredients and they would be nasty in a tincture. Yes. Like super. That is my biggest hesitation. I like bitters. I like putting a little bit of bitters in my water when I start a meal. It's not a therapeutic dose though. And if I do try to get to a therapeutic dose with some kind of tincture, it's the some of the ingredients in there are I looked at over and I'm like, these are lovely, but man, they would taste bad if we were trying to do that in a tincture. So, I'm glad you guys got them in a capsule. It's much easier to do. And I would say just take one. I I don't know how you and I'm not trying to give people medical advice. This is how I use bitters. I use bitters at the onset of a meal. I just I take it with some water. I don't take too much water because I don't want to dig uh dilute my digestive enzymes. I don't want to dilute the HCL in my stomach, which is that's a whole other conversation. That's probably low too in the middle-aged woman. But I love um I love a sort of a premeal bitter. I think it's a wonderful adjunctive. It gets everything stimulated. Just in the terms of herbal medicine, it gets the gallbladder to wake up. It gets the pancreas to wake up. everything kind of wakes up and says it's time we're let's let's do this and so not necessarily overriding the higher doses of a GLP1 which is causing a lot of stagnation and I think in terms of Chinese medicine too I think in terms of just stagnation and cold and damp and I think GLP-1 I'm not I'm not a Chinese herbalist medicine herbalist but I think of GLP1 as being kind of cold and it it does create that stagnation and bitters are beautiful override if you will to some degree I think it's a nice I think it's a nice thing to do and you guys have offered a really generous bundle there. So, if they do the subscription. So, thank you.
KIERAN KRISHNA: Yeah, of course. Yeah, we're we're here to support everyone's gut and especially, you know, the the middle-aged woman that is struggling right now. And we know that the gut is the center of a lot of her problems. And so, uh, being able to control that LPS, being able to improve digestion, um, you know, get the bowels moving, that's going to make a profound difference for them.
DR. TINA: I love it. It is so amazing to talk to you always. I learned so much every single time and I hope that people listen to every minute of this episode because it probably is one of the most important ones I've done in a really long time and this is the topic that I've been wanting to breach with people and just wanted the gut expert your you. I wanted you. [laughter]
KIERAN KRISHNA: Thank you. Thank you. It's it's I was so excited when uh when you told me about us doing this together and and the topic that you wanted to cover because yeah, you're totally right that nobody's really talking about this. Uh and it's so important. Um and and the and the thing is there are solutions to it, right? Uh people don't have to suffer and and when they when they know of some of these solutions, I I think it empowers them to take action and uh hopefully lots of people listening to this will will see some improvements moving forward. So, thank you. so much for having me.
DR. TINA: As always, thanks for listening to the Dr. Tina Show. This is a Wellness Loud production produced by Drake Peterson. Theme song is by John the Guilt. You can watch the full video version of this podcast inside the Spotify app or on YouTube. As always, you can email the podcast at podcasttina.com. That's drt na. And if you like this episode, please rate, review, and subscribe on your favorite podcast app. You can also find all of my offerings on my website at drtina.com. For more shows by my team, go to wellnessloud.com. See you next time and thanks for listening. This podcast is for generalformational purposes only. It does not constitute the practices of medicine, nursing, or other professional health care services, including the giving of medical advice. I am a doctor, but I am not your doctor. No doctor patient relationship is formed. The use of this information and the materials linked to this podcast is at the user's own risk. The content on this podcast is intended not to be a substitute for professional medical advice, diagnosis, or treatment. Users should not disregard or delay in obtaining medical advice from any medical condition they have, and they should seek the assistance of their health care professionals for any such conditions.
KIERAN KRISHNA: Exactly.
DR. TINA: Just burn the ships. Just [bleeped] them. Good luck. [laughter] It's like, you know what? you're not making babies anymore, so just forget about it. You know, good luck. I think that the I always have told my patients, your gut health going into menopause and your adrenal health going in are going to be what carry you and your muscle mass are going to be what carry you through. And my gut health was atrocious going in and it, you know, it was I was that kid with the I mean, I gosh, I out the chute I was put on antibiotics. I don't even think I have a microbiome. And so I was constantly being pumped full of antibiotics as a kid. That's what led me to chiropractors and naturopathic physicians and you know the the journey I took and the the where I ended up. And then on top of it um I mean you knew me back then. I was a single mom trying to build a career and build an empire and I was doing it all by myself. And so stress levels just unrelenting stress for decades that never ceased. And just as I was hitting my stride and just as I was starting to free myself up a little bit from all of it and make a little bit of money and enjoy my life a little more, COVID hits and I'm in Oregon and it's like [snorts] lock down, right? And then I go and open my mouth and [laughter] yeah, all hell breaks loose. So anyway, that gut health piece is so important and I think what you just said might be what literally everything you just talked about even if we did cut it off right there is probably the most important thing that any woman who is in parmenopause or menopause needs to hear because it's not all our fault and we can do all the things to no end and still be suffering because talk about what LPS does in the body. Let's just jump right into that.
KIERAN KRISHNA: Yeah. Yeah. That's that's exactly where my brain was going because I want I want people to understand once LPS starts to increase, how does that drive the things that you're feeling right now, right? So um let's start with with the mood changes in the brain. Um so brain fog for example, right? So LPS is the type of compound it is. It's a lipopolyaccharide which means it has a carbohydrate head and a lipid tail. So it looks physically a lot like the lipid billayer of our cells. Um so it is very pervasive. It can enter into almost any tissue including crossing the bloodb brain barrier. So it does a good job of doing that. When it does cross the bloodb brain barrier, it does induce inflammation in the brain. It activates something called micro gle cells which are the immune cells in the brain and central nervous system. When you when you activate the micro gle cells, it creates a lot of inflammation in the brain. That inflammation can be felt as brain fog. So you might notice that you know you're forgetting things. it's it's hard to calculate things and remember things. You walk into a room and then you forget why you walked into it. Uh you know, all of those things are associated with that increase in inflammation in the brain. Um and then on top of that, LPS also interferes with serotonin and dopamine binding in the brain, which means that your happy hormone and your hormone that drives motivation and reward centers, that's not working very well. So, you have a significant increase in anxiety and depression. In fact, there was a a 9-year long study called the Netherlands study on anxiety and depression where they were looking at a number of biomarkers in people that were suffering from anxiety and depression. And then they followed them for 9 years to look at the best associated biomarkers with the condition. They found only one biioarker was associated with 100% of the cases of anxiety and depression and the level of that biomarker could predict how severe their anxiety and depression was. And in fact, in that nine-year follow-up, for any individuals who that biioarker went away, anxiety and depression went away as well. And that one biioarker was LPS was serum LPS levels. Right? So, we know that LPS has a profound effect on the brain. And we know that women start to to experience some very profound cognitive changes in the brain as they go through permenopause. And that's likely one of the reasons. Um, another effect that is very profound is that LPS can get into areas like the joints. Um, and start creating inflammation in the joints and the muscularkeeletal system, which is I think one of the key reasons why women report increase in muscularkeeletal pain between the ages of 40 and 55 at a frequency 10 times higher than men do in that same age group. Right? Uh, new onset of muscularkeeletal pain, right? So, um, on top of everything that women are dealing with, they're also now dealing with increased pain, uh, which makes it so much harder where to to just doing anything. And so LPS is playing a role there. There's a significant increase in osteoporosis in cardiovascular disease as you get through menopause, permenopause, and menopause. LPS is associated with a significant increase in IL6, inucan 6, which is an inflammatory cytoine, TNF alpha, and IL1. IL1 and IL6 are very important inflammatory cytoines in the aogenic process in in driving aogenesis in the vascular system. Right? So developing the plaques that that cause cardiovascular disease. Uh LPS also drives inflammation in the bone. inflammation in the bone changes these uh cells called osteoplastic cells which build bone into o sorry osteoplastic cells which build bone into osteoplastic cells which actually re reabsorb bone and and uh make makes bone weaker. Um so it drives osteoporosis as well, right? So the the effects are endless. And then this one which is a real pain in the butt if you will one is when LPS interacts with visceral fat in the midsection it actually swells the fat cells the edocytes as we call it three times three to four times its normal volume right which means that all of a sudden you can build a belly what seems like overnight uh you know where where women tend to not have a uh a rounded midsection uh they tend to carry weight throughout their life in different areas. All of a sudden, you've got a belly, you know, and and it's so hard to get rid of. It's no matter how much you're dieting and exercising, it doesn't seem to budge in part because those fat cells are just swelled up, right? And and you're and they're not shrinking, which you know, we we all know when we lose fat, we're not actually losing the fat cells are actually shrinking. Uh we can't get them to shrink because the LPS maintains that volume. So that's just some of the horrific things that increased LPS does in women as they're going through this phase.
DR. TINA: And doesn't it drive diabetes and the progression of that? And doesn't it drive obesity as well?
KIERAN KRISHNA: It does. Yeah. So um in studies even some studies published by the NIH and a big study published by the American Diabetic Association and these institutions are normally way behind on on like the progressive new science. Um but even they published almost now 9 years ago that the primary insult and this is this is quoted from a paper published by the American Diabetic Association. The primary insult that starts the process of insulin resistance is the presence of endotoxins which is the LPS. uh it actually starts um uh affecting how your insulin receptors uh function and it can directly affect your pancreas's ability to produce insulin. Uh and then to compound on that there was a large scale study called the cordial prev study uh which is like 480 people over 60 months. These were people with that that had pre-diabetes risk and then they were following these individuals to look at all the different markers and look at what percentage of them ended up developing type 2 diabetes. Um what they found was again only one marker was serum LPS levels was predictive with over 98% uh hazard ratio or confidence ratio of of being a driver of developing diabetes. Right. And so insulin resistance as you said atyposity so obesity also driven by um LPS. So everything that we that drives us crazy as we get older, right? Our pain, our brain fog, our uh weight gains, our insulin resistance, uh you know, I mean LPS even drives adult onset of acne, right? Somewhere around 40% of adults start to experience adult onset of acne, right? And part of that drive is the presence of LPS in uh increasing inflammation in the sebaceous glands. And so it's just doing wreaking havoc in the body.
DR. TINA: I remember multiple times watching you lecture at different events and you're up there just slide after slide after [laughter] slide like LPS is doing this, LPS is doing and and I'm sitting there in the audience like [laughter] this is everything all at once and oh my gosh how how horrifying, right? This is it's [snorts] it's a lot. And so we're going to tie this into um GLP-1s because this is the important part that I keep trying to get through to people. I am not a fan of high doses of GLP1s for various reasons. And I understand that some people need to take higher doses to actually have an impact on their weight. My argument is if you're not doing all the things diligently, you shouldn't be bumping the dose up yet. There's a lot of work to be done before we start cranking the dose. And one of the reasons why is because there is a correlation to higher rates of SIBO, small intestinal bacterial overgrowth when people are using GLP-1s. I suspect that people are going into the GLP-1 journey with SIBO in many cases like I did. And even at a micro dose, I have never taken even standard dosing. Even at a micro dose, I am experiencing exacerbation of my SIBO because of that gastric stall. you know, it slows the motility down. Um, but SIBO upregulates LPS and LPS drives the obesity and the diabetes that the GLP1's being used to treat. It is so ironic and people need to understand this.
KIERAN KRISHNA: Yeah. Well, and I think the the important point you bring up there is that you know what's happening when you stall the bowels, right? So, and and there's a number of things. So there's a number of documentations on the changes that occur to the microbiome when when people are on GLP1s. Um and and people just have to be cognizant of this if they're going to go down that route. Um some of the natural things that happen is they they eat less, right? So they're they're the consumption of things like fiber goes way down. The consumption of polyphenols goes way down. the consumption of resistant starches goes way down, which means that they're not feeding the microbiome adequately and they're driving further reduction in diversity within the microbiome. And if you're already in parmenopause at that stage and your microbiome diversity is already tanking because of lower estrogen, then you're exa you're actually exasperating that situation. Um, and then your your butyrate production and short- chain fatty acids go down. So that is an underlying um disruption in your body's natural ability to regulate insulin levels. Um so so now you're creating a f foundational change in your metabolic system as a result of it. And the thing is maybe when you're on the GLP1 you're maintaining the, you know, proper insulin function, all that, but if you ever hope to come off of it, right, that's where you're going to see the the the effect of the problem that was created during the course of the GLP-1, right? The acceleration in diversity loss, the acceleration in insulin resistance and or dis d disysregulation of insulin um control and so on. So the the the the effect that the GLP1s have on the microbiome compound the negative effects that pmenopause already has on the microbiome. And putting those two things together can be a very profound change for people. Um you know if they're not really actively thinking about it and working against it.
DR. TINA: This is why I'm not a fan of cranking the dose up high and fast when it just tanks out people's appetite. you know, obliterating someone's appetite is not the jam because of exactly [clears throat] what you just said. be beyond becoming malnourished, beyond wasting away too fast and and losing potentially muscle mass and and what else. This is why I say, and I've said it multiple times, and I've never really extra gotten to extrapolate on it, but this is one of the many reasons I say when people are doing high doses and they crank it up fast and they lose a ton of weight and they don't preserve their muscle mass and they don't take good care of what they're putting in their mouth, they are going to be more metabolically brittle on the other side, they're they're they're destroying they're coming in metabolically compromised and they're leaving metabolically devastating ated and this is one of the biggest reasons why.
KIERAN KRISHNA: Yeah. And and that happens in people in their 20s and 30s, but it happens more profoundly if you're middle age, you know, because of the other factors that are already dismantling your metabolic health and your microbiome, right? The hormone changes. Um, so I think it's a it's it's an it's an area that people have to really pay attention to because we may be creating as a result a population that starts coming off these GLP1s that are way worse off than they were before and and as a result have much bigger problems that they now have fewer solutions for, right? And so um so the consciousness around this has to improve now. And just to me mention a couple other things that that changes. We we know that protein intake naturally decreases with GLP1s as well, right? Um and as a result of that, your microbiome has fewer proteins. As as a result of that you it actually compromises mucin production which is that very important mucous layer that maintains the barrier integrity which when and if you don't have adequate mucin production not only is the barrier function of your gut compromised which means your gut is more leaky and more LPS gets through u but you also then compromise your immune response right because so much of your immune function exists in that mucin layer and so you're compromising a a physical component of where your immune system tends to function. Um the other thing of it is it changes your your metabolic uh your fermentation system. I mentioned this earlier where it it reduces sacryic fermentation but it increases something called proteolytic fermentation and that proteolytic fermentation unfortunately produces more ammonia pressol and these very inflammatory compounds. So it's shifting how your body even deals with food uh that that is coming in even though it's limited amount of food that's coming in. So so yeah all of those things compound together and create kind of a perfect storm of of metabolic disruption uh gut brain disruptions gut skin disruption uh you know midsection metabolic uh disease that you see that that conventional bloating in the midsection and so on. uh and then down down down the line it upregulates immune dysregulation and so on.
DR. TINA: What fires me up about this is that so many clinics and pharmacies and tele medicine companies are now erroneously deceiving people selling them into micro doing GLP-1s for weight loss. There is no such thing. First of all, if you're truly on a micro dose, it is not a weight loss strategy because you acclimate to the GLP1 so fast. There's no version where you're losing appreciable weight. maybe maybe 15 pounds mo at most. If you've got like some inflammatory puff, it'll it'll dial it down oftentimes, but they're being put on standard doses, regular old starting doses of GLP-1s, they're being given 0.25 of semagoglutide or 2.5 of turseptide. That is the standard starting dose. That is the same dose we give folks who are diabetic, folks who are dealing with obesity. And they're telling them it's a micro dose. And these people are messaging me saying, "I'm so sick. I'm having such horrific side effects. I thought I was on a micro dose. I was told I was on a micro dose. And they're selling them by telling them what the maximal dose is and saying, "Well, that is onetenth of the maximal dose." So, you you're good. It's so deceptive. And any anyone listening, if you find a tele medicine group that's trying to sell you in on ads or in their advertising on micro doing for weight loss, you are being deceived. I I guarantee it. And across the board, I've looked into some of these. I've actually gone in and applied as a pseudo patient. They immediately they they don't even have a visit with you. There's no doctor. Suddenly, you're getting a prescription in the mail and it's the standard dose and they're calling it a micro dose. So, not everyone's doing that. I'm not saying they're all bad actors, but this is what's happening out there. Like my original strategy got twisted and this is one of the main reasons why I'm so fired up about it because they are tra some these women are on way too high a dose in many cases and they are trashing their guts in the process of an already trashed system in a process of pmenopause and menopause that's already causing further trashing. Yeah. [laughter] So, it's just it's just a mess and it's it's frustrating to watch because I really think that women are I think my generation is being prayed upon. The women in my you know, Gen X is being prayed upon. Menopause and permenopause are big business right now and everyone's getting in on it. So, you know, everyone's got something to sell us and it's it's frustrating because women, we don't know how to navigate this. I I know everything I know and I have friends like you and I'm still Yeah. a wash of, [laughter] you know, of of frustration. So [gasps] anyway, um I will add that I have been studying this because I always I do the same thing every time I look up a condition, I look up that condition and then I put and exercise and then I look up all the studies for it. And exercise is phenomenal for SIBO. Exercise is phenomenal for LPS. Exercise is phenomenal for gastric motility when it's stalling out on you and in your GLP-1 journey. Um, by the way, diabetes makes the gut stall out, too. There's a lot of reasons why the gut will stall out. So, exercise is a huge, huge, huge win in all of these cases. It's going to be beneficial. So, just a little plug there for the go to the gym that I keep trying to get people to do. So, I know that GLP1's definitely cause a shift in the microbiome. I suspect that part of the on-ramp experience that patients have when they feel such extreme nausea and GI symptoms, I think it is due in part not just to the direct mechanism of the GLP1, but I think it's due in part to the shift in the microbiome. Sometimes this shift is favorable and some of the studies show, you know, you're you're actually shifting to maybe a less pathologic and a more favorable organism. But I think that there's a die- off happening as that shifts going on. And these people are dealing with a Herxheimer reaction. I I honestly think that's what's happening when you go too fast too hard on GLP1s. I think some of that those gut symptoms initially are just your poor gut trying to recalibrate and all hell's breaking loose.
KIERAN KRISHNA: Yeah. Yeah. So, you know, one of the things that um we know is very clear when you start a GLP-1 is the transit time of your bowel changes, right? And and transit time is so critical to how your bowel has been functioning because it dictates how long food spends in what part of your bowel. And how long food spends in what part of your bowel dictates what happens to that food in that part of the bowel. So, for example, if food now stays longer in the stomach or stays longer in parts of the intestines than it normally would, that opens up the opportunity for putrification and fermentation of those foods that normally wouldn't happen, causing all kinds of responses in your GI tract that that are hypersensitivity responses that can make you feel nauseous, make you have gird and reflux and all of these kind of common symptomologies because Now, food is stalling out in your system, right? So, the transit time of your bowel is such an important thing that most people need to know about. And and I I always encourage people to test the transit time of their bowel themselves, which is which is relatively easy to do. You can you can basically eat a ton of beets in a given meal and and of course note when you ate it and then look for when it comes out the other end or it starts to starts to come out. It may not all come out at the same time, but you'll start to notice a change in the toilet color when it when it starts to come out. And what you want to see is, you know, somewhere between like 24 to 30ish hours, right? Um, if you're way before, if you're like 12, 13, 14 hours, then your bowels are moving too fast. And if you're in the 40 plus hour range, your bowels are moving too slow. And so, you can adjust that by the types of fibers that you consume, right? If you need to slow down your bowels more, you take soluble fiber, which S for soluble, S for slow down the bowels. If you need to speed up the bowels a little bit, you take more insoluble fiber. So, you can make those adjustments, but then when you get on the on on the GLP1s, it's going to totally slow down your bowels, and that transit time is going to be affected. And now microbes in certain regions of your bowel that are not used to having a prolonged amount of time with food get a prolonged amount of time with food and they start fermenting and producing things. And when they produce those things, your bowels are going to get really irritated and it's going to feel uh very uncomfortable, right? Because you're not used to the things that these microbes are now producing in that region. It's it's no different than kind of a food poisoning like nausea, right? Because what's happening in a food poisoning? Well, there's a new microbe that's being introduced to your bowel and it's producing byproducts and toxins in a region that your bowel normally doesn't experience and that's creating the the need to vomit or the or the need for diarrhea, right? And and those are both reflective responses of your body trying to get rid of stuff, right? nausea and need for vomiting and need for diarrhea is a way that your bowel actually tries to protect itself to get rid of things. Um, so that nauseousness and all that comes to me for a lot from that slowing down of the bowels like you said, but the the noxious fermentation that occurs as a result of that.
DR. TINA: Yeah, it's no good. I think there's a lot happening that needs to be studied with GLP-1 use and the gut microbiome. Yeah, I think there's a multiple I'm sure there's multiple mechanisms going on in there that's causing people to have such this is again why I'm a slow and low fan and I'm not a high dose fan and I I get the question all the time from people well what do I do if I need a high dose and I don't have an answer I that's never what I claim to have any knowledge of I I'm not treating generally speaking I'm not treating patients who are obese who are not also doing all the things because I find when they do all the things we need way lower doses totally to move the needle. And so I think of it more of like using a GLP1 like a whisper instead of a blasting megaphone, right? We're just trying to gently nudge the system. The other thing to note is there is some data showing that GLP-1 use at standard dose and this was in laglutide decreased endogenous production of GLP-1 in the L cells for a substantial amount of time. So I I think what we're seeing is also this downregulation of L cell production and who knows what else is happening there with the other peptide signaling hormones of appetite and it's I don't know I think it's going to be I I am concerned about the higher doses and I'm really concerned because people use my name and they throw it around and say well Dr. Tina said GLP1 ones are safe and I'm like well that's relative. Yes, [laughter] that's that's really relative to how you're using them because I'm talking almost a different mechanism entirely. It's almost a different drug in my brain as to how I use them. And I and I know I realized you know once it's kind of like low dose now trexone. That was really what I was going for in all of this was kind of a lowd dose now trexone impact where if we could give the body a little bit of what it needed would it also help the body utilize what it has better. right? And kind of whispering to it. But we even see with LDN now we see people using I I saw a Stanford pain doc talking recently on Peter Ortia's podcast about how he's using like 8 to 20 milligrams of Nrexone and I'm like dude that's not low dose that's just a half dose, [laughter] you know. So it's it's very we get different mechanisms out of things when we use them at at different not to give a lesson here but just for the listeners to really understand. I never said that. I never said they're super safe at every dose. And there's all kinds of fallout that can happen depending on the body they go into.
KIERAN KRISHNA: Well, and and there's another endogenous mechanism that it kind of circumvents, right? So, there is a very clear gut brain access, right? The gut is talking to the brain through the entic nervous system, which is the neurological system that covers the entire digestive tract connected through the vagus nerve to the brain. And so, there's a very important communication that occurs. In fact, you know, if you look at the nerve um, you know, structure of of that of the vagus nerve itself, it's 80% of the nerves are what we call afrant nerves, which means 80% of the information is actually going from the gut to the brain and only 20% coming from the brain down to the gut, which means that the gut is a massive signaling uh organ to the brain to instruct the brain on all things that are happening in the ecosystem, in the body, and so on. Now, one of the things that that GLP1s do is it skips that gut brain connection, right? It goes right to the brain. Um, and and the signal goes directly to the brain and and kind of skips that that superighway, if you will, which which is, I think, why some of the people, it's it's rare, but some people can get permanent uh, you know, stasis of their bowel, right? So, the bowel stops moving completely and and it can't be reversed. I think part of that is that skipping of the really important gut brain connection and that communication that those two organs need to have. Um so it's hard to know what is going to happen uh with with long-term higher dose use and then you add the the the compounding effect of all the microbiome complications in pmenopause and then it becomes really confusing you know as to what all the the the uh unwanted effects can be and
DR. TINA: aside from the estrogen leaving the body part all of this pertains to middle-aged men as well for sure. Mhm. So this is happening and diabetics have veagal nerve disruption. The the high blood sugars for sustained extended periods of time does damage on the vag nerve and that connection is in many cases already compromised. And so then they're being given, you know, thrown these high doses of GLP-1s which again not a fan of. And they go into gastropreesis and they want to blame the peptide. And I'm like, "Yeah, but we just threw you over the edge of a problem that was already brewing for decades, you know." So, um, how we approach this, I think, needs to shift because it's through education and through a step-wise process that we can do this most elegantly, I believe. So, um, okay, let's talk about stress because I just, when do I not have stress? I think I'm just programmed for it now. I uh I just my listeners know I just went through a pretty rough patch with my mom's health and it was a lot and um I was kind of like the sole person on the scene dealing with it and I came out of it with it was pretty traumatic and I came out of it with some PTSD. No one else remembers what happened but me cuz my mom blissfully gets amnesia. You know, it's a it's a beautiful thing about being sick is you don't get to remember anything that happened. And so I and I've shared this before, but if people are listening for the first time, I gained weight like that. I mean, it just it was overnight. And I can honestly say I don't think I believed my patients when they were in middle age and telling me that similar things had happened to them. I thought they must have just gone on a bender or something, you know. And I was shocked at how fast I literally just blew up. And it wasn't it was in my gut. It wasn't just a belly. It was a gut. But I also had I can't even get my wedding ring on still. There's just this kind of edema. And I'm sure it's elevated cortisol levels. I haven't even ran my labs because I don't want to know. I I don't want to run anything yet. I'm like, I got to get this under control and then I'll [laughter] run my labs because that was just chaos. [gasps] But uh let's talk about what stress does to your gut microbiome. what it does to SIBO, what it's doing to the middle-aged woman.
KIERAN KRISHNA: Yeah. Yeah. And and it's a this is another one of those um self-perpetuating problems because stress alters the gut microbiome significantly and the way it alters it actually then makes you more susceptible to stress, right? So it again is progressive. Um and so so what is actually happening when when you're stressed? So uh cortisol of course when you when you're stressed you're going to kick off your HPA axis, right? your hypothalammic pituitary adrenal axis, you're going to kick in the fight orflight response and as part of that cortisol tends to start scaling in the body to initiate the fight orflight response. Um, one of the things that happens to cortisol is a portion of it gets dumped into the gut. Now, why does it get dumped into the gut? Well, because there are microbes in the gut that can actually metabolize cortisol and the metabolic byproducts of that go to the kidneys and they shift the uh the the solute and solvent ratios in the kidneys. So the potassium sodium ratios which then increases the amount of water that is going back into circulation. So then the kidneys actually press more water back into circulation in order to increase uh blood pressure. Right now, the reason it's trying to increase blood pressure is it's trying to profuse things like your brain, your muscles, your heart because you're going to fight orflight response. This is why chronic stress creates hypertension, right? It's this exact mechanism. So, cortisol dumps into the gut. Now, what what what's clear is when your gut is dysfunctional and you're missing certain key organisms. Uh in fact if you have low bifidtoacteria levels uh and bifidobacteria have this this component to their um to their outer cell membrane that are carbohydrates that they tend to make that actually negates this process that I'm going to talk about. So when you have low diversity and you have low bifroacteria, when cortisol dumps into the gut, it creates profound permeability in the gut, right? The gut just basically ex the the tight junctions and the space in between the cells just expand and you get a whole lot of permeability. You get a whole lot of LPS coming in and as a result of that LPS coming in, we talked about earlier what the effect of LPS is on the brain, which makes you more susceptible to anxiety and so on. But on top of that, LPS also increases IL6, which we mentioned before, but one of the things we didn't mention is that IL6 can actually re-trigger the HPA axis even though you don't have another stimulus, right? So, um, think about it this way. When when your system is vulnerable and susceptible in that way, an outside stressor comes in like your, you know, your your family member almost dying or stressful call or whatever it may be. The external trigger of stress creates this cycle where you're going through the the fight orflight response, but you can't come down from it because every time cortisol enters your gut, IL6 goes up and IL6 re-triggers your HPA axis as if you're going through another stress episode, right? So you maintain this elevated level of your sympathetic nervous system without ever being able to come down effectively back into your parasympathetic which means that you stay at this heightened stress state throughout the day, right? And it and it just makes it so impossible to get a handle on things. And the longer you're in that state, the more dysfunctional your gut becomes. Because the other thing that occurs when you're in that elevated stress state is your immune system starts triggering inflammatory responses in the lining of your gut. Good bacteria start to die off as a result of that. Certain types of pathogens do well under that condition. So they increase their growth. And in fact, some pathogens have learned that when the host is under stress and they're actually measuring your stress hormones like your epinephrine, norepinephrine, cortisol, and so on, when those stress hormones are elevated, that's when they they express their villance factors and their toxin production because they've come to learn that that's when the host is susceptible. The immune system is not functioning properly and so on. So, they're opportunistic and they start to increase their growth during that time. So what you tend to see is that with every little bout of stress that you undergo, it's like taking a little dose of antibi antibiotic because it disrupts your microbiome measurably enough from those individual bowels. So as you can see then as your microbiome becomes more and more disrupted, you become more susceptible to the effects of cortisol and that cycle just keeps continuing. It's so bad. [laughter]
DR. TINA: Yeah, so bad. I was watching uh House of the Dragon last night with my daughter and Queen Rea is under so much stress and she's so overwhelmed and so just like there's just way too much going on for her. And the look on her face and my daughter looked at me and she goes, "That's what you look like, [laughter] mama." And I'm like, "I know. I know that feeling." I said, "I know that feeling well. I know like you I got to hold it together. I'm the one in charge, but you have so many plates in the air." And you're like, "Yep." So, no, it's I I am happy to say that things are calming down and my mom is in good health and everybody is chilling and I told all my family members to chill. Like, no more emergencies for a minute because I [laughter] don't have it in me to to help anymore right now. So, uh we're getting there. But, okay. So, what can we do? Let's let's round this out with a solution because this is all just it's a lot. It's a lot.
KIERAN KRISHNA: Yeah. Um but the good thing is there's a lot you can do um of it, you know. So, so let's talk about LPS to begin with, right? So um you know that became actually endotoxmia and LPS became my motivation to get into this industry because I saw this very very early on almost 20 years ago that this increase in LPS through this process called endotoxmia was arguably one of the uh biggest drivers of chronic conditions uh that that we deal with in the western world. And in fact a paper published in 2015 in frontiers of iminology concluded the same. They said that stress induced endotoxmia or endoxmia on its own is the number one cause of morbidity and mortality worldwide because uh how it sets up the body for all of these disease conditions that we talked about. So um then the question became what can you do about it? So so we started looking at microbial solutions for it. Um and the first probiotic that I developed was a sporebased mix. And the reason we developed a sporebased mix is number one, I wanted a probiotic that would survive through the gastric system. Uh so that I didn't have to do all these special capsules and all kinds of stuff. I wanted it to survive and get to the the intestines alive so it can go to work. The second thing I needed it to do was to have this capability called cororum sensing. Quorum sensing is the ability of microbes to read other microbial signatures and then start to make metabolic changes in that environment to bring down dysfunctional bacteria and increase the growth of beneficial bacteria. So then that way a probiotic can go in there and start modulating the microbiome effectively. The third thing I wanted it to do was some evidence that these that these bacteria can increase the expression of tight junction proteins. Right? Those are the proteins in between the intestinal cells that get dismantled as a result of inflammation and and stress and all of these things. But you you need to increase the expression of those tight junction proteins in order to sin them both back shut and start to seal up the lining of the gut again. Um, then I also needed the probiotic to increase the production of short- chain fatty acids, especially butyrate because butyrate feeds the goblet cells that make the mucin layer and you need to have an adequate mucin layer to have any semblance of an intestinal barrier at all. Right? So we looked at some of these features, formulated a consortium of probiotics uh and then started doing studies and we published in 2017 the first time a paper has been published on a probiotic that alleviates that LPS endotoxmia. Right? So we showed in a 30-day study in a simple randomized control trial 38 30-day study with people who had profound endotoxmia meaning we were screening people for those that had a huge amount of LPS that leaks through. we were able to show a 75% reduction in that LPS in just that 30-day period. Right? So, so that was very exciting to see and we saw all the effects of LPS reversing. So, for example, gut brain communication, we saw the the uh the reestablishment of the leptin AMPK cycle after these people ate food, right? So, what does that mean? Uh so, leptin is a satiety hormone, right? And and in order for your body to stop producing the hunger hormone ghrein once you eat, you need the you need your gut to communicate to your brain through in part through GLP1 receptors but then other receptors as well that we have enough food coming in turn on the satiety hormone not only does the satiety hormone then make you stop eating it also activates fat burning and all these metabolic processes. So what we saw in these individuals, even though they were of normal BMI, their leptin response was completely compromised, meaning that we would give them a 2,000 calorie meal after they came and fasted and their ghrein levels, their hunger hormone levels would barely drop after the meal, right? And their leptin levels would just remain flat, right? And and so these individuals, they were 22, 23, when they become 28, 29, 30, they're going to start putting on weight quite significantly, right? And so what we saw then after just 30 days of not adjusting diet, lifestyle, or anything else, just taking the this the sporebased probiotic formula, what we saw was a um after we gave him the 2,000 calorie meal, we saw about a 60 70% drop in the ghrein, the hunger hormone, and a significant increase in leptin. So we're reestablishing the gut brain connection. We also saw all of those inflammatory cytoines associated with elevated LPS. All of those came down as well, right? So, all that was achieved through a sporebased probiotic, the Just Thrive probiotic, um that you can take once a day to to help with this endotoxmia issue that's going to occur um both in men and women as we get older.
DR. TINA: That's awesome. And talk about the sporebased probiotic because it's different than other probiotics in a myriad of ways.
KIERAN KRISHNA: Yeah. Yeah. you know what I was looking at it, you know, as as looking at this from a microbiologist lens, I was really looking at our natural interactions with microbes, uh, and and I was starting to look at in the environment, in other areas. Are there microbes that we would naturally consume that could survive through the gastric system because, as we know, the gastric system is called a gastric barrier for a reason. It's really good at killing microbes, right? Uh, the pH is very low in in normal physiological pH. It could be 1.2, 2 1.3 that's a very very acidic environment. In fact, humans have I think the third uh or the fourth lowest pH in the animal kingdom only next to like vultures uh who can of course eat dead things and be perfectly fine, right? Because their gastric system is so powerful. Uh we are omnivores and we can eat lots of different things in part because our pH is so low. But that same pH also kills the vast majority of microbes coming in. And so I honed in on bacteria that could naturally survive this gastric system. And to me, if nature offered it that that feature, that very unique feature, there must be an importance to that, right? There must be some sort of co-evolution importance. And as it turns out, these spores can cover themselves with a protein calcified coating that allows them to survive the gastric system. And the the moment they hit the intestines, there's receptors on the outside of the spores that come into contact with receptors on our mucosa and the spores pop out of this spore uh coating and they become normal functioning vegetative cells in the gut and and as a result of that humans have been consuming them and they've been living in the human gut for hundreds of thousands of years. Right? So they have this really unique innate relationship with the human gut.
DR. TINA: Weren't they found in mosquitoes in amber? Did I am I getting that right?
KIERAN KRISHNA: No, you remember that right? You totally got that right. So I I saw that study like 15 years ago and it fascinated me. And then here come full circle. I just about 3 months ago I started working with a retired professor who's a microbial ecologist. We're doing a bunch of work on on on things that move the needle on the microbiome. He's the guy that did all that research.
DR. TINA: No way.
KIERAN KRISHNA: Yeah. His name is Raul Kano. He did all of that work. Basically, what they were looking at was u number one, he was looking at what what the ancient microbiome looked like of animals and all that, right? And the other thing is he was supporting a group of scientists who were looking for uh microbes that have never been discovered looking for new antibiotics because of course microbes make antibiotics and they make very unique ones and as antibiotic resistance increases, they're looking for new ideas from these microbes. So he actually and listen to this is actually a fantastic story. So so him and his team did all the work where they found um microbes in the guts of ancient fossilized honeybees that were fossilized in amber just like the mosquito in Jurassic Park, right? Uh and he was able to isolate basillus endospores from them that were 50 million and as as old as 250 million years old. And he also found yeast from uh from the the ancient yeast from these from these uh bees and whatnot. Um and they [clears throat] were able to ferment things with the basillus and the yeast. And in fact, for his daughter's wedding, he made like kombucha and and wine by fermenting with these ancient 50 millionyear-old microbes, right? Like how cool is that?
DR. TINA: That's that is that's amazing. That's that's that's some nerd stuff right there. [laughter] scariest nerd stuff, right? I love it. I love it. And I love [laughter] that that's where their brain went. It's like we should with these things,
KIERAN KRISHNA: which means that these organisms are still alive, right? So, it's been fossilized and it's still alive. You can still plate it once you remove it out of the ancient honeybee. Um, so these organisms are incredibly robust. They've been here well before us. Uh, you know, humans have only been been around for a couple million years. These have been here for 200 million years. Uh and so they started all of this microbiome communication and ecosystems for us. And so you know what my group was able to do is that we were just smart enough to know what nature had already created and and study it and utilize it. Uh and so these these sporebased organisms can be incredibly profound and I think anyone going through middle age needs it uh because we have to stop that endotoxmia, right? And then there's some very important dietary things people need to do as well.
DR. TINA: So I recently got a shipment of the probiotic, the Just Thrive probiotic and the bitters and I'm about to start them. I haven't yet because I was kind of doing my own thing and I ended up with a an old bottle of Just Thrive that I found and I was like, "Oh, my dog was my dog has been he got giardia when he was a puppy and it's just been like a constant thing for him, you know. So he's Gardia really does a number on you for like for the rest of your life. It's it's a thing. And so anyway, gave him a little bit. Super helpful. And I was like, "Oh, I should take these." So I'm going to get back on the the horse on that one because I just I'm a little scared because I'm I'm finally starting to feel myself again. And I was like, "God, the sensit the system is so sensitive at this point, right? I just feel so I hate to say that. You know me, you've known me a long time. Like I did not enter into pmenopause unfit. I was in the best shape of my life. I was incredibly fit when I entered into permenopause. And I have always been fit and lean. And I'm just at this I try to tell middle-aged women and now I'm living it. It's like we're kind of a it's a little brittle. It's a we got to be careful. So I'm really excited to get back on these and put them into my gut protocol because I'm kind of self- treating my SIBO right now with the knowledge that I have. And I think that it's going to be really helpful. talk about bitters because I think bitters are huge here. I've been using some other bitters but I bitters are just amazing.
KIERAN KRISHNA: They are they are the unsung heroes of the nutritional field, right? So So it's it's really fascinating. So we have these bitter taste receptors that start in our mouth and basically are throughout our entire body. So our entire digestive tracts, our stomach, our small intestine, large intestine, our pancreas, our liver, even places like your heart have bitter taste receptors. Now, we call them bitter taste receptors even though you're not tasting in these regions, but they're just these receptors that bind bitter compounds. Now, when you look at the evolutionary significance of these receptors, basically a few different things. Number one is that our ancestors basically consume bitters with everything they ate, right? They were foragers, gatherers. They ate lots of berries and herbs and things like that. And so, they're getting bitters in virtually everything they ate. Now, the one of the reasons why you'd have uh really strong bitter taste receptors in your mouth is because potentially poisonous things have a very aringent bitter taste. And that that um there's an automatic reflex to make you spit those things out. Right? That's one of the ways in which our ancestors learn what you should eat and what you shouldn't eat by using the bait bitter taste receptors in the mouth. Now, at the same time, you've got lots of other bitters that'll go through that don't have the same intensity. And as a result, binding of the bitter taste receptors is another example of the signaling that occurs from the gut to the brain because it tells the brain where the food is and how much food is coming in and what to turn on, right? The brain doesn't know this stuff, which is so fascinating, right? So, you could be eating something. The brain doesn't doesn't necessarily know that the food's in your stomach or is in the distal part of your stomach uh or in the very proximal part of your small intestine or it's moving down midway through your intestine. It doesn't know when to kick up bile. Doesn't necessarily know when to turn on uh the digestive enzymes. It needs information to send those signals down. And that information comes from these checkpoints that are the bitter taste receptors. And the the crazy thing about it as I dug more and more into the research around bitter taste receptors is turning on of the bitter taste receptors throughout the digestive tract accounts for almost 50% of all of the digestive signaling. Right? So think of them as switches going through this massive machine. Turning on these switches to effectuate the digestive process requires bitter taste receptors being activated by bitter compounds. Which means your average American that consumes no bitters at all, right? We've basically cultivated bitters out of our agriculture and all that because no one likes the taste of bitters. And so we're not consuming any bitters with our meal, which means we are not turning on upwards of 50% of the digestive signaling in the body, right? which which then makes it so easy to understand why we're so horrific at digesting food and breaking it down and not allowing it to cause gas and and immobility and all of these things that occur due to indigestion, right? So indigestion is still one of the big biggest reasons people go to see the doctor in the hospital um and and they're not turning on about half of the digestive signal. So adding bitters back into your system is one of the most foundational things you can do with how your digestive system is designed.
DR. TINA: Aren't bitter taste receptors what signal the L cells of the gut to kick up too? And that that's what that's the L cells are what secrete GLP1.
KIERAN KRISHNA: That's exactly right. Yeah. Several other digestive uh signaling peptide hormones. So totally. Yeah. It it it kicks up um you know CCK GLP1s, GIPS. It it kicks up the the PY. PY. Yep. Um and AMPK as well, which is like the master regulator around fat burning. Um and then it also kicks up all of the signals for releasing bile and recirculating bile over and over again, you know, which is huge, which is another big issue with why people develop SIBO is we have an inadequate bile acid pool. And as a result of that, we don't circulate enough bile through the small intestine when food is there. One of the reasons that one of the things that bile does is it acts as an antimicrobial. So it prevents the microbes in the small bowel from fermenting the food that's in the small bowel and keeps those microbial numbers low. The other thing that bile does every time it circulates through the digestive tract when food is present is that it uh it upregulates something called a nuclear FXR receptor. That nuclear FXR receptor which is in the distal part of the small bowel tells your intestinal cells in the small bowel to produce antimicrobial compounds when food is present to suppress the growth of bacteria in the small intestine. So it cannot utilize the food that's in the in the small intestine. Right? When those signals are all suppressed, you're going to develop SIBO because those bacteria now in the small intestine can utilize the food and overgrowth and ferment and create gas and all kinds of things.
DR. TINA: I if I think of middle-aged woman, my automatic thought is bile issues. Like those two things are in my head when I see well the the the phenotype I have right now literally like what happened to me after that big stress load? I'm just like, oh, I need bile. And the thing about taking bile, like if you use an ox bile supplement, is it's really easy. I know people are going to come for me on this one, but I find it too easy to go overboard on that. You can take a little bit too much and then all of a sudden now you've got like really painful dumping of diarrhea. So, it's it's a fine line and I think bitters are a wonderful way to sort of be the checkpoint in there because you really can't overdo it with bitters, but you can overdo it with bile.
KIERAN KRISHNA: Yeah, you definitely can. Now, what what happens when you overdo it with bile is um there are microbes in your gut that'll convert that bile into what we call secondary bile salts. And those secondary bio salts can be very useful and helpful, but if you do too much of it, it can actually uh create inflammation in the large bile. Um and so, so yes, you can definitely overdo with bile and that's an important part of the message. So, you know, for me, I if if you're middle-aged at all, men or women, uh, and and when we did our leaky gut studies, we were doing it in in people in their in their mid20s who were by FDA standards healthy normals, right? So, they didn't have any conditions, they didn't have any issues, weren't on any drugs or management of any disease, and they were all normal BMI and so on. But about 55% of them had very profound leaky gut, right? Very elevated levels of LPS. And so as you're entering middle age and you have any issues like you have any digestive issues, skin issues, anxiety, you know, any of those things, there's strong indication that you have significant leaky gut and significant LPS. So everyone should be on the sporebased probiotic. And then uh add to that, you know, adequate fiber intake. Uh, and especially if you're considering a GLP1 in your middle age, you want to keep in mind that your diversity in your microbiome is already shrinking naturally, which is affecting your body in very significant ways. You need to take extra steps to ensure that your diversity gets maintained or maybe even improved, right? And so maybe look at hormone balancing before you consider GLP1s, right? Which is which could be super simple, right? look at progesterone and estrogen supplementation, you know, and and stabilize those levels before you go into a GLP1 that'll further create disruption. So, stabilize some of those other things. Work on the diversity of your microbiome with polyphenols, with fiber, um with with more diverse diets, and then the sporebased probiotics and prebiotics and all that. Start to get all of those things in line and build those pillars before you start considering the GLP ones.
DR. TINA: I completely agree. I have been trying to beat this drum and tell people this and they don't want they just want that GLP-1. And I'll tell you what happens, Karen. When I start working with people, nine times out of 10, once that GLP-1 gets to a dose where appreciable weight loss starts happening, everything goes out the door. Yeah. They are like, maybe I'll skip the gym or maybe I'll stop taking the supplements or may, you know, it's like, no, no, no, no, no. This is a this is a comprehensive integrative approach and we're trying to hit all the bases because some of these nuances that aren't being discussed that we thankfully have addressed here today are super important. This is truly root cause medicine. Like this is what's driving a lot of issues for people and they're taking things out here to try to fix what this is driving. So gosh, we could go on. We we need a part two. You you and I get together and it's just like have a brain meld and go for it. But you guys have been so generous over at Just Thrive. You guys are offering my listeners of the Dr. Tina show if you start a 90-day subscription to the probiotic, the sport-based probiotic you were just speaking of, you guys are going to throw in a 90-day supply of the bitter product, the new digestive bidters. So, this is a huge value. It's a $90 value. And I think the two of them together are it's a beautiful combination. So, I hope people will check that out. It's at justthrivehealth.comdtina. And again, I'm going to repeat it. If you're listening to the show, it's going to be in the show notes, but for those of you just listening, it's just thrivehealth.com/dtina and do the 90day subscription to the sporebased probiotic and you'll get the free 90-day supply of the digestive bidters because you guys are awesome and generous.
KIERAN KRISHNA: Well, it's and it's so important. I mean, I I cannot emphasize how much people need bidters. Um, you know, and it's it's just overlooked all the time. Uh, most people aren't even familiar with it. Uh, what a bidder is, you know, and and and it controls upwards of half of all your digestive signals, which is which is amazing, right? I mean, if you think about like imagine you were missing something in your daily diet that that turned on half your brain and you were only walk working with half the brain, right? And we think of the gut as a second brain. And so it's really important to make sure we're utilizing all of the functions of the gut. Um, and so bters and bitters do that. And this this particular product has uh 12 different bidters in it at at doses that are clinically relevant. So it makes it super easy to take because if you had to consume all of those 12 bitters, it'd be very difficult because of taste, of course. So it's in a capsule. it sends it down to the digestive tract um and and you know activates all of those signals. Now one of the most common questions I get is what about don't you need bitters for the for the mouth right so um what about that you know skipping it so as I mentioned earlier one of the most important aspects of the bitters for the mouth is to detect potential poisons so we we don't have to worry about that the second thing is to trigger something called the syphalic response the syphalic response is just your brain getting ready for food right so it's it starts increasing salivation it starts increasing some gastric secretions gets your body ready for food coming in. But you can actually increase the syphalic response just by smelling food and seeing food. And we all have done that, right? You smell bacon, for example, and you're like, "Oh," your mouth starts watering, right? That's a syphalic response. So, you don't necessarily need to do that through bitters either. You want to get the bitters in the digestive tract and throughout all the bitter receptors.
DR. TINA: I like that it's in a capsule because I looked over the ingredients and they would be nasty in a tincture. Yes. Like super. That is my biggest hesitation. I like bitters. I like putting a little bit of bitters in my water when I start a meal. It's not a therapeutic dose though. And if I do try to get to a therapeutic dose with some kind of tincture, it's the some of the ingredients in there are I looked at over and I'm like, these are lovely, but man, they would taste bad if we were trying to do that in a tincture. So, I'm glad you guys got them in a capsule. It's much easier to do. And I would say just take one. I I don't know how you and I'm not trying to give people medical advice. This is how I use bitters. I use bitters at the onset of a meal. I just I take it with some water. I don't take too much water because I don't want to dig uh dilute my digestive enzymes. I don't want to dilute the HCL in my stomach, which is that's a whole other conversation. That's probably low too in the middle-aged woman. But I love um I love a sort of a premeal bitter. I think it's a wonderful adjunctive. It gets everything stimulated. Just in the terms of herbal medicine, it gets the gallbladder to wake up. It gets the pancreas to wake up. everything kind of wakes up and says it's time we're let's let's do this and so not necessarily overriding the higher doses of a GLP1 which is causing a lot of stagnation and I think in terms of Chinese medicine too I think in terms of just stagnation and cold and damp and I think GLP-1 I'm not I'm not a Chinese herbalist medicine herbalist but I think of GLP1 as being kind of cold and it it does create that stagnation and bitters are beautiful override if you will to some degree I think it's a nice I think it's a nice thing to do and you guys have offered a really generous bundle there. So, if they do the subscription. So, thank you.
KIERAN KRISHNA: Yeah, of course. Yeah, we're we're here to support everyone's gut and especially, you know, the the middle-aged woman that is struggling right now. And we know that the gut is the center of a lot of her problems. And so, uh, being able to control that LPS, being able to improve digestion, um, you know, get the bowels moving, that's going to make a profound difference for them.
DR. TINA: I love it. It is so amazing to talk to you always. I learned so much every single time and I hope that people listen to every minute of this episode because it probably is one of the most important ones I've done in a really long time and this is the topic that I've been wanting to breach with people and just wanted the gut expert your you. I wanted you. [laughter]
KIERAN KRISHNA: Thank you. Thank you. It's it's I was so excited when uh when you told me about us doing this together and and the topic that you wanted to cover because yeah, you're totally right that nobody's really talking about this. Uh and it's so important. Um and and the and the thing is there are solutions to it, right? Uh people don't have to suffer and and when they when they know of some of these solutions, I I think it empowers them to take action and uh hopefully lots of people listening to this will will see some improvements moving forward. So, thank you. so much for having me.
DR. TINA: As always, thanks for listening to the Dr. Tina Show. This is a Wellness Loud production produced by Drake Peterson. Theme song is by John the Guilt. You can watch the full video version of this podcast inside the Spotify app or on YouTube. As always, you can email the podcast at podcasttina.com. That's drt na. And if you like this episode, please rate, review, and subscribe on your favorite podcast app. You can also find all of my offerings on my website at drtina.com. For more shows by my team, go to wellnessloud.com. See you next time and thanks for listening. This podcast is for generalformational purposes only. It does not constitute the practices of medicine, nursing, or other professional health care services, including the giving of medical advice. I am a doctor, but I am not your doctor. No doctor patient relationship is formed. The use of this information and the materials linked to this podcast is at the user's own risk. The content on this podcast is intended not to be a substitute for professional medical advice, diagnosis, or treatment. Users should not disregard or delay in obtaining medical advice from any medical condition they have, and they should seek the assistance of their health care professionals for any such conditions.
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Overview:
Could the answer to menopause belly fat, brain fog, and stalled weight loss be hiding in the gut? In this episode of The Dr. Tyna Show, host Dr. Tyna Moore sits down with longtime friend and Just Thrive Chief Microbiologist Kiran Krishnan to unpack the surprising overlap between gut health, perimenopause, menopause, and the GLP-1 conversation so many women are having right now.
Kiran and Dr. Tyna dig into how declining estrogen reshapes the microbiome, why GLP-1 medications can quietly disrupt digestion even while helping with weight, and what's really behind the middle-age midsection.
They also connect chronic stress and the vagus nerve directly to gut function, and explain why leaky gut and endotoxins may be driving insulin resistance more than most people realize. The conversation closes with a practical look at spore-based probiotics and digestive bitters, and why supporting bile flow and digestion matters just as much as anything happening on the scale.
Episode Highlights:
- How declining estrogen during perimenopause reshapes the gut microbiome
- The surprising gut-related side of vaginal health during menopause
- Why lipopolysaccharide leaking from the gut may be behind menopausal brain fog
- What's really driving the "middle age middle" weight gain pattern
- How gut-related endotoxins may be quietly worsening insulin resistance
- The truth about microdosing GLP-1 medications for gut and metabolic health
- Why bowel health often gets worse on standard-dose GLP-1s
- How the vagus nerve links stress directly to gut function
- Why spore-based probiotics behave differently in a stressed, changing gut
- The connection between digestive bitters, bile, and SIBO
