SIBO and Endotoxemia: The Silent Epidemic (With Implications for Hormonal Health)

Añadido: 2026-05-26

[00:00:00]Hi, I'm Dr. William Davis. I'd like to talk about this extremely important topic of endotoxmia.

[00:00:07]A topic that I fear is largely misunderstood, not fully appreciated.

[00:00:11]And it's becoming clear that it's an epidemic. It's occurring at epidemic levels in the public. It's including far more people than anyone ever thought.

[00:00:19]And it's a crucial component of anyone's effort to regain health. Now, this is a kind of a highlevel conversation appropriate mostly for people in health care, health care practitioners, physicians, naturopaths, chiropractors, health coaches. If you're here just for a superficial quick and dirty that you won't find that here. This is more of a deep dive into some of the science behind this and how to appreciate when you recognize it and how to what to do about it and why it's so important for health. So, let's get into it.

[00:00:50]So I think of endotoxmia, the implications of endotoxmia is not that much different than what's going on with the James Webb telescope experience of all things. So those of you who've been following me know that there's this a telescope that's now a million miles a million miles from Earth sending back photographs of deep space. And what I found mind-blowing as many I think astronomers did is that what we thought were stars. So if you're outside in a area which has less light smog and you see a night sky filled with stars, it turns out the James We telescope is telling us that a lot of those stars are not stars but entire galaxies. And each galaxy with hundreds of billions of other stars. So the night sky may seem to be filled with stars, but it's actually filled with galaxies. And the last count I've heard is that there are two trillion stars out there. I'm sorry.

[00:01:45]Two trillion galaxies out there. Mind mindboggling, right? Well, the end the gastrointestinal endotoxmia issue is not perhaps that big, but it is almost as revealing that as you really cannot expect to achieve much in health unless you appreciate the contribution of endotoxmia. In fact, I would say that for instance, if you're managing people's hormonal health with such things as bio identical hormones or clomophene or other drugs like that, you might as well just bleed your patients with leeches because you're so far out of touch with the emerging science as it relates to the contribution of endotoxmia that you're achieving only a very little uh what of what you could achieve. And so I'm encouraging everybody to enter the space age in appreciating the role of the the critical role of endotoxmia in overall health, but especially hormonal health.

[00:02:41]So I look at conventional health care as it stands today as little more than looking at somebody who's hitting himself in the head with a hammer and rather than saying, "Hey, quit hitting yourself in the hammer. Why are you doing that?" We say uh can we build stronger helmets? That's how I view modern health care. It's not addressing the actual root cause. Why is this guy hitting himself in the head? But we try to develop stronger helmets in the way of pharmaceuticals and procedures. And you can see put into simple terms like that, it's kind of nuts to do it that way, right?

[00:03:18]And so we're going to recognize that a lot of the things we do in conventional health care are really just building better helmets. And what we should be doing is getting at the cause. Why is this guy hitting himself in the hammer?

[00:03:33]And you're going to find that once you gain this appreciation for stopping the hammer, so to speak, you'll have better solutions for weight loss, management of visceral fat, maintenance of muscle, which is extremely important nowadays in light of the nonsense going on with GLT1 agonists, metabolic health, emotional health, mental health, social health, cardiovascular health. So endotoxim is proven to be a very potent cardiovascular risk factor. And of course, hormonal and reproductive health, much underappreciated, but a major player, just like we didn't know all those stars were actually galaxies.

[00:04:10]Same thing here that if you don't incorporate, if you don't factor in what's going on in the gut with the microbiome and the production of endotoxin, you are going to miss the mark on helping your patients uh develop health successes. So just very briefly I forgive me if you're well schooled in microbiology but we're going to focus mostly on gram negative microbes. These are microbes that when you stain them with the three stains of a gram stain.

[00:04:40]The last one is a violet stain. And if it's gram negative meaning it doesn't take up that violet stain those microbes will look pink or red as you see right here. You can see that they're gram negative basilli in this case. If they do take up the violet stain, they'll look violet or purple or blue. That's gram positive. So that's important because the gram negative wall does not take up that violet stain because it has a very specific composition in its cell wall. And that difference is critical.

[00:05:15]it. There's more to this of course than a distinction between gram negative and gram positive and the composition of your cell walls. But that basic fundamental distinction does help us understand this issue of endotoxmia.

[00:05:28]So we're going to be focusing on so-called gram negative microbes that have this specific component in their cell walls.

[00:05:38]Now we actually have an abundance of research to tell us what happens when you have a high level of lipopolysaccharide the thing in gram negative cell walls endotoxin in the bloodstream endotoxmia because that is the basis of sepsis.

[00:05:57]That is when you have an overwhelming infection and gram negative microbes and their and their lipopolyactor endotoxin enter the bloodstream it makes you very sick. So the level of endotoxin during sepsis is 100fold or more uh greater than it should be. And so let's say you had a urinary tract infection. Maybe it's E.coli or Klebsella. You've got urinary burning, little discomfort, and urine smells funny. Well, you don't want to take an antibiotic. Please, please don't hear this as a plus or minus against antibiotics. Just an illustration. So, let's say you have this bladder infection and you take something like cranberry juice and manos. A few days later, you've got back pain and a fever. And that's because those microbes have ascended up the uriters to the kidneys. You now have pyolonritis, infection of the kidneys.

[00:06:54]And sometimes those microbes, let's say E.coli, enters the bloodstream. And when those microbes break down or die, they release their endotoxin. You've got endotoxmia, which in turn triggers an excessive immune response, what some people call a cytoine storm. And then you have leakiness of the of the lining of arteries and veins so-called endothelial dysfunction. And you create a cascade a wave of inflammation with molecules like TNF alpha, interalucan beta, one beta, interolucan 6 and others. This is where you get tissue damage. So one of the things that happens for instance in sepsis is their leakage of the capillaries in the lungs so-called acute respiratory distress syndrome ARDS. And that's why people who are septic who have sepsis often have to be intubated and mechanically ventilated on a ventilator or they develop kidney failure or they fail to maintain a normal blood pressure. and they go into shock and you have to administer drugs like norepinephrine leoped or dopamine to maintain blood pressure and there's a high mortality rate. A lot of people die of this process. Point here, we have a working model of what happens when you have a high level of endotoxin in the bloodstream because of this issue of sepsis that has been studied thoroughly for the past centuries. So, we know that when endotoxin gets into the bloodstream and it's present at increased levels, it can make you extremely sick, could even cause your death.

[00:08:31]But it helps to think of the gastrointestinal tract as a repository as a place where a lot of gram negative proteacteria we say are located. So those are the species like E.coli, coli, klebsella, sudamonus, proteus, seratia. Those are all gram negatives with that very specific composition of your cell walls that contains endotoxin. Well, why would those microbes overpoliferate and become dominant? Well, antibiotic exposure. So, we now know in the US that there are 650,000 prescriptions written for an antibiotic every day. 650,000 prescriptions every day, 365 days a year. By age 40, most of us have gotten around 30 courses of antibiotic 30 courses. And for every 1,000 children, more than,300 prescriptions are written every year. So we're all wildly over now. Some of those antibiotics are necessary. If you had numacco pneumonia for instance, but many times they're not. So antibiotics for instance are prescribed widely for viral upper respirator infections for which antibiotics are not indicated. Even the CDC concedes that a great many great proportion of antibiotics are prescribed unnecessarily. At least a third are prescribed unnecessarily. And what happens when you take an antibiotic whether you need it or not, there's a dramatic drop off in multiple species and because you've lost species, many beneficial species suppress unhealthy species, but specifically proteacteria species. So you get an antibiotic, there's a sudden rise, a surge in species like E.coli, Klebsella, Fusabactum. These are all gram negatives. So your exposure to a single antibiotic allows the overp proliferation expansion of gram negative proteobacteria and beneficial microbes like bifida bacteria and lactobacillus and ubacterium and acromancia and ficalacterium and lacnosperation rinication many beneficial species are either sharply diminished or lost outright lost. So exposure to antibiotics, proliferation of those gram negative proteobacteria, loss of beneficial microbes such that if we compare the modern gastrointestinal microbiome to other populations that live largely hunter gather or more primitive lives based on eating whole foods, not the garbage that we we eat like processed ultrarocessed foods, foods filled with preservatives and other additives. We have far fewer microbes because of the loss of all those beneficial species the lactobacillus bifida bacteria etc and we have an over proliferation of gram negative proteobacteria. So our modern colons have become a repository for excessive colonic proteacteria ecoli etc. Well, even more remarkably, when you have this loss of beneficial microbes suppressing proteacteria and then the overgrowth of proteacteria, they often ascend. Those proteobacterial species ascend into the 24 ft of small intestine. Here's one of Mark Pimeintel's studies from UCLA. He's done extensive and wonderful work. Here's a one of the reports from their re-imagine series of studies where they did a douadal aspirate that is they went down with an endoscope specially designed to have two channels so it's not contaminated by the mouth the oraf fairings the esophagus or stomach advance the inner canula to obtain a sample from the douadum a couple millimeters of fluid from the douadinum pull back the catheter take it out of the body and then culture it but they use both aerop arobic and anorobic cultures. So you may know that most microbes in the gastrointestinal tract will not grow in culture. So if all you did was submit a douadal asp is often done in most hospitals and lab and clinics. If you just submit it for a culture, the lab will do an aerobic culture and you will fail to identify the majority of microbes that are living in that douadal aspirate. So in this case, Dr. Mark Pimeintel and his team got that dual channel aspirate device.

[00:13:14]Got the douadal aspirate submitted for both aerobic and anorobic culture.

[00:13:20]And look what they found. 37% or more in other studies in the re-imagine study 37 to 40% of the microbes in the douadal aspirate that is just beyond the stomach way up high in the gastrointestinal tract were proteacteria proteob that don't belong there in any significant numbers now we have people who have lots of proteacteria what I would regard as fecal microbes so some people call this fecalization we are converting converting the small intestine contents into fecal material.

[00:13:57]And here's one very vivid illustration of that. 37 to 40% of all the microbes in the douadal aspirate are fecal proteacteria.

[00:14:07]Now species wise in the same study sudamonus entroacterriasia klebsella it's that's another gram negative uh ecoli shagella.

[00:14:18]So we have this excessive proliferation in the douadinum and if it's in the douadum it's also in the jigunum and illium and probably even stomach and esophagus. So now we have this excessive proliferation of proteobacteria in the upper GI tract.

[00:14:34]So I think it's helpful to think as the the current the modern gastrointestinal tract is a repository for gram negative proteobact. It's not supposed to be that way. Gram negative proteobacteria are supposed to be three, four or 5% of the entire colonic microbiome. There's not supposed to be present in significant numbers in the small intestine. But we have this situation now in modern people where the small intestine has become overp proliferated, overpop populated with proteobacteria as high as the douadinum.

[00:15:09]Now here's something to bear in mind.

[00:15:11]Think of the liver as the first recipient of endotoxin. So recall that the colon, small intestine, pancreas, all the abdominal organs, venus drainage is to the portal vein and the portal vein goes directly to the liver. So when you have the entry of endotoxin from the gastrointestinal tract, whether it's from the colon or from the small intestine or both, it goes into the portal vein and then directly to the liver. So it's the liver that receives this very high quantity of endotoxin and the liver takes a beating. So it helps to think of the liver as kind of the canary in the coal mine because the very high level of endotoxin from the GI tract goes to the liver. Now the liver filters that and so the entry of endotoxin into the systemic circulation is lower. We can't access easily the portal vein. Right? Here's a here's a study where they did access and measured endotoxin in the portal vein.

[00:16:13]It was done surgically because you can't get it from the surface. It has to be done with an open abdomen. So, as you can imagine, not very practical. So, the handful of studies done during open surgical procedures has shown that people with liver disease for instance will have far higher levels of endotoxin in their portal venus circulation. Maybe not as high as sepsis, but approaching the levels of sepsis in many cases. So very toxic and we now know with abundant evidence that people with liver disease like fatty liver or non-alcoholic stata hepatitis there's more than enough evidence now to tell us that people who have systemic endotoxmia not portal venus endotoxmia but systemic endotoxmia that the majority uh have it. That is if you have liver disease you are virtually guaranteed to have systemic endotoxmia.

[00:17:06]And if we could sample portal venus endotoxmia, you would find even much higher levels beating up the liver. Is it any surprise that we now have this huge epidemic of fatty liver and non-alcoholic stat? We're talking about maybe half the population now. And a a big driver is portal venus endotoxmia though underestimated when you measure systemic endotoxmia.

[00:17:35]And we know that people who have non-alcoholic liver disease test positive for SIBO. This is probably a dramatic underestimation because it was done with aerobic culture. And so it's probably a lot worse than that. But know that there is evidence that if you have fatty liver disease in any form that you're likely to have SIBO here, 37.5%.

[00:17:57]I think it's far worse than that. And the systemic level of LPS endotoxin tends to be double of that. Uh people with SIBO have double higher than normal. And likewise, if this was true, you'd expect antibiotics to have a beneficial effect. And this in some series such as this one, Refaxamin, the antibiotic often used for SIBO, which I think is a mistake, but nonetheless, there was a reduction in serum LPS.

[00:18:24]There's a reduction in liver markers like A and ALT. So all arrows pointing to the fact that SIBO portal venus endotoxmia damages the liver. Systemic endotoxmia can serve as a marker for liver disease and for SIBO and endotoxmia.

[00:18:44]So it helps to think of lipopolysaccharide endotoxmia in SIBO as kind of what I call sepsis light. We know that sepsis is very dangerous, has numerous complications. SIBO and endotoxim not quite as bad, but still pretty bad. Now, when you measure endotoxin in somebody with SIBO, endotoxin levels tend to be 200 to 400% increased over that of controls, healthy controls, which is likely an underestimation. One, it's systemic, not portal. And two, the method used to measure endotoxim is known to it's very controversial is known to underestimate level of endotox. So it's probably higher than that. But if we accept what's currently known if you have SIBO thereby endotoxmia, the level the blood level of endotoxin tends to be two to fourfold higher over healthy control people.

[00:19:40]And of course you and I are exposed to numerous factors that make intestinal permeability worse. So just the fact that gram negative proteobacteria invade the small intestine their presence in a small intestine ill prepared to deal with that increases intestinal permeability further thereby an increase in portal venus endotoxmia and systemic endotoxmia.

[00:20:04]The loss of beneficial microbes, acromancia, ficalact, claustrdia, many others also allows an exaggerated level of endotoxin and thereby endotoxmia.

[00:20:15]The loss of beneficial species which were suppressing overgrowth of proteobacteria species like lactobacil rotary, lactobacilus geride. If you consume wheat and grains that contain the glyadin protein, glyadin is known with good evidence to increase intestinal permeability dramatically.

[00:20:33]Few things increase intestinal permeability as much as the glide and protein of wheat and grains. One of the few other things is colortoxin. So getting wheat and grains is an open door to intestinal permeability and if and done in the consumed in the presence of SIBO and endotoxmia. I would propose that's probably something nearly lethal.

[00:20:53]Wheat germaglutin another component of wheat and grains is also a gastrointestinal irritant and increases intestinal permeability.

[00:21:02]uh ubiquitous emulsifying agents put in pickles, ice cream, salad dressings, emulsifiers like polyorbate 80, caroxymethylos, carrageenan, uh compounds that people think are healthy like an acetylcysteine that they think leads to glutathione, antioxidation, but an acetylcysteine is also a potent emulsifying agent. That's why we use it in hospitals in an aerosolized form in people with cystic fibrosis or COPD who develop mucous plugs thick viscous mucus that blocks their their airways and pneumonia develops behind it and so they can't cough it up. They don't have the strength or the mucous thinness to cough it up. So one of the things they get is aerosolized an acetylcysteine because of it's it's a potent emulsifying agent. No one should be taking an acetylcysteine for beneficial purposes because it's a potent emulsifier and polyethylene glycol and related compounds used in a bowel prep for colonoscopy is a potent emulsifying agent with emulsification lasting several days. So it's a very destructive compound yet ironically is being used as the bowel prep for prevention prevention of colon cancer.

[00:22:15]That's a whole another conversation for another day. But the current efforts to prevent colon cancer are silly and incomplete. And there's a ton more someone can do to prevent colon cancer beyond just getting a colonoscopy and then exposing yourself to the adverse effects of the bowel prep polyethylene glycol. And then common drugs like non-steroidal anti-inflammatory drugs, aspirin also increase intestinal permeability thereby endotoxmia.

[00:22:39]And now we have the problem of micro and nanoplastics that also disrupt the mucous barrier and complicated further by the fact that microlastics have a surface charge that attacks that attracts uh toxic compounds like forever compounds forever chemicals like POS BPA heavy metals and glyphosate. So microplastics are not just about microplastics. They're also vectors we say for those toxic compounds and the and the flood of microplastics you get for inance by brushing your teeth with plastic bristles on your toothbrush or drinking plastic water and plastic bottles where you screw and unscrew the cap and you fragment plastic. Those also have effects on endotoxmia.

[00:23:26]And of course, lack of beneficial things, especially omega-3 fatty acids, vitamin D, both of which have crucial roles in contributing to the integrity of the intestinal barriers. So, we live in a world where the intestinal permeability has been increased and the mucus barrier and intestinal barriers have been impaired. So, we are walking setups for this process of endotoxmia.

[00:23:51]Now, endotoxmia has metabolic consequences. Here's one study that showed that higher levels of endotoxmia provoke formation of VLDLDL. If you've been following my conversations, you know that the real causes of coronary disease, not this absurd, outdated idea of LDL cholesterol that should have been abandoned decades ago. We know that endotoxim drives VLDL, the real cause for coronary disease via liver denovalogenesis. If you don't know what I'm talking about, see my many other YouTube videos, my thousands of blog posts, my books where you talk about this phenomenon that is the liver's creation of VLDLDL particles from carbohydrates and sugars such as the amalopectin A of wheat and grains. So we also know endotoxin drives formation of uh intermediate density lipoprotein something I've not talked about much but there's this IDL is a very potent cardiovascular risk factor in and of itself as is VLDL and the availability of VLDL and IDL leads to small dense LDL. So endotoxmia is a major driver of excessive quantities of small LDL parts.

[00:25:02]The real driver of coronary aththeroscerosis not LDL cholesterol.

[00:25:08]Now these changes also contribute to essentially turning off the protective effect of HDL particles. Endotoxmia reduces HDL and also makes the HDL particle abnormally small and thereby nonprotective against aththerosclerosis.

[00:25:25]So if this is all true, if endotoxmia causes these distortions in lipoproteins, you'd expect it to be reflected in cardiovascular events and it is. So people who have higher levels of endotoxin have reduced um survival. In this case higher levels represent by serum zulin which is a marker for intestinal permeability. And the people who have the highest level of intestinal permeability, highest level of zulin also have reduced survival. Likewise this is serum LBP which is LPS binding protein which is a very good marker for lipopolyaccharide endotoxin. So people with higher levels of serum LPB have severalfold greater mortality death from heart disease. So it's looking like endotoxmia is a potent cardiovascular risk factor and among its consequences an increase in VLDL increase in IDL increase in small dense LDL reduction in protective HDL.

[00:26:31]So rather than ask can we make stronger helmets but that's what they do in conventional health care right so if if if people in conventional health care recognize that endotoxmia is a risk factor for numerous diseases they're going to ask questions like how can we pharmacologically block it using biologics for many thousands of dollars per month they're going to use blockers of TNF alpha of interlucans of TLR4 one of the mediators of the effects of endotoxin and then charge you and your patients a lot of money to do so, but never getting at the root cause. They may suggest treating with an antibiotic, right? That targets more so the gram negative species. Or they may even talk about how to monetize the microbiome by fecal transplantation. That's the conventional approach. I hope you and I are not going to take that path. We're instead gonna ask that basic silly question. Why is this guy hitting himself in the head in the first place? And so we're going to go get at the root. We're going to help reconstruct a gastrointestinal microbiome that reduced the presence of proteacteria and restores microbes that were doing good things pre before you lost them.

[00:27:44]Species that are keystone that is foundational and cultivate the return of other beneficial microbes. Beneficial microbes that are butyricogenic. They produce butyrate that's healing to the gastrointestinal tract and exerts numerous metabolic advantages like a reduction in blood glucose, reduction in insulin resistance, reduction in inflammatory measures and other beneficial species. So we're not going to be administering biologics to block a mediator of inflammation. We're going to get at the root cause, the disruption in the gastrointestinal microbiome that was responsible for endotoxin entry into the bloodstream.

[00:28:19]Let's go through this exercise. How common is this? Is this something that occurs only one in a hundred people? Is it something that occurs rarely? So here's here's a basic question, basic exercise.

[00:28:32]Let's ask this question. In condition blank, what proportion of participants in the studies test positive for SIBO, usually with breath hydrogen gas testing? Another conversation, right?

[00:28:44]That's the most common method measuring hydrogen gas in the breath that microbes produce that you can't produce. You can use the timing of hydrogen gas release as a way to map where microbes are living in the gastrointestinal tract. So in condition blank, what proportion of participants tests positive by H2 breath testing? Well, let's take irrital bowel syndrome. There's about 60 to 70 million Americans with IBS. And while it varies anywhere from 12% to 84% test positive, on average about 31%.

[00:29:15]Well, 31% of 60 to 70 million people is 18 to 20 million people who have SIBO.

[00:29:21]How about obesity? Well, about half about 50% of people who are obese will test positive for SIBO. That's another 55 million. How about some of these skin conditions? 6 million Americans have it.

[00:29:34]40% test positive. That's another two and a half million or so, right? Type 2 diabetes, 34 million Americans, about 40% test positive for SIBO. Of course, there's some overlap, right? Obesity and type 2 diabetes, hypothyroidism, another few million. How about all the other conditions? Neurodeenerative diseases, sleep apnnea, fibromyalgia, restless leg syndrome, autoimmune condition, depression, anxiety, fatty liver, on and on and on.

[00:30:00]We can easily exceed a 100 million Americans. I think more towards 150 million Americans, meaning about one in two people have this condition and thereby endotoxmia driving all those phenomena including cardiovascular risk. This has been borne out and confirmed in a metaanalysis looking at numerous different conditions that people with all these conditions are likely to test positive for SIBO and thereby have higher levels of both both portal and systemic endotoxmia.

[00:30:34]Now, how about the implications for reproductive health? We won't have time to go through each in detail, but we know that endotoxmia disrupts hormonal release at the hypothalamic and pituitary levels. So it diminishes for instance the release of the release of luteinizing hormone and a follical stimulating hormone in females. It thereby reduces progesterone and estrogens. It disrupts the maturation of eggs of the oasite and the maturation of the embryo once it it's implanted into the uterus. It disrupts the process of ovulation. It blocks or impairs the implantation of that embryo into the uterine lining. It inflames the endometrium and it increased the likelihood of miscarriage, still births, recurrent pregnancy loss. Very serious implications, right? And then it impairs the maturation growth of the fetus once implanted in a woman's uterus. And it's responsive for contributing to pre-term delivery. And you know that delivery of a pre-term child, let's say at 28 weeks, is catastrophic. That child's going to have problems for a lifetime.

[00:31:40]neurological, imunological, psychological problems, not to mention mom and dad getting a hospital bill from weeks or months in neonatal ICU for a million dollars or more. So, this has major implications for a woman's health and of course a child's health. And there's increased potential for preeacclampsia and a clampsia and seizures when you have endotoxmia and a woman is pregnant and it increases likelihood of infertility quite significantly.

[00:32:06]And if the child in uterero is exposed to endotoxmia, the evidence tells us that that child later in life will have impaired ability to socialize, to learn, to memorize, to learn new things, and it will be prone to increase its food intake, increase weight, more likely to become obese and a diabetic as in as an as an adolescent have high blood pressure. In other words, endotoxmia has major implications for a woman's reproductive capacity. It has major implications for a woman woman's ability to carry a fetus to term and it impairs the health of the child with implications for a lifetime.

[00:32:48]Beyond reproductive health, endotoximia increases osteoporosis. A woman is more prone to lose muscle and strength, which is awful because that sets a woman up for falls, fractures, frailty, loss of independence, and earlier death. It exaggerates insulin resistance thereby accumulation of abdominal fat and inflammation.

[00:33:08]It increases all the phenomena of polycystic ovarian syndrome, ovary syndrome. It increases the inflammation of endometriosis.

[00:33:16]It increases a woman's risk for coronary disease, cognitive impairment, various cancers. Here's a an example which has been studied in polycystic ovary syndrome or what's now being called polytabolic ovary syndrome. So women with PCOS have higher levels of lipopolysaccharides significantly higher levels in their bloodstream also of the LPS binding protein. So we know that ladies with PCOS have endotoxmia and it is likely the major driver of some of the phenomena such as irregular menstrual cycles, infertility, the excessive levels of testosterone and heretism. It's responsible for expansion of abdominal visceral fat. It's responsible for the insulin resistance and inflammation that's characteristic of PCOS. In other words, if all you're doing is focusing on giving a woman clomophene and anti-hypertensives like beta blockers and ACE inhibitors, but you're not paying attention to the endotoxmia, you've not done that patient a service by ignoring the SIBO and endotoxmia because remember SIBO outside of POS has major implications such as risk for colon cancer, diverticular disease, um risk for other conditions, cognitive impairment, coronary disease, coronary plaque rupture, rosacea, psoriasis. In other words, not identifying SIBO, not identifying endotoxmia can have very serious consequences while you're treating a person say with uh testosterone blockers or uh in vitro fertilization. Those are not solutions.

[00:34:55]Those are band-aids.

[00:34:58]How about level of inflammation in the oasite?

[00:35:02]And so here's a here's a graph of a study done where serum LBP was was grafted against um the level of IL6 in follicular fluid. These are expplanted follicles and you can see that the greater the LBP the more inflammation is present as represented by IL6 in the follicular fluid.

[00:35:24]Likewise the higher the serum LBP the lower the progesterone. Right? So lower the capacity for full protestation.

[00:35:32]So we know now with good evidence that lipopolyaccharide endotoxmma is an impairment for fertility and a woman's capacity to carry a child to term.

[00:35:44]Here's a very interesting study from Italy looking at ladies who've had recurrent pregnancy loss, recurrent miscarriages. Blood levels of LPS much higher in ladies who are experienced repeated miscarriages. Likewise, zy hyro xyulin representing intestinal permeability. And they went further.

[00:36:02]They got endometrial fluid and looked at the LPS level in the endometrial fluid.

[00:36:07]You can see that it's about twice as high in ladies who've had recurrent miscarriages. Likewise, measures of inflammation like IL1 beta four or fivefold 400 to 500% higher levels of inflammatory mediators in the ind end indometrial fluid in ladies who've had repeated pregnancy losses. They went further. I don't know why they picked this one microbe but it's a strain of bifidobacterial longum uh small numbers 1 billion CFUs per day over 90 days and given delays orally there was a reduction significant reduction in serum LPS also zulin and there was near normalization of endometrial LPS not full normalization but partial normalization as well as inflammatory mediators so that's just one microbe of course at low numbers surely there are other things that we could do, but he at least sets the stage for this idea that an orally consumed probiotic species can have effects on issues like fertility, on ability to carry a child to term. And so this is just a start, I think, of some revoly findings that can change how pregnancy is managed. This is just one thing, of course.

[00:37:22]And then quick word about male health.

[00:37:24]Male health reproductively of course is simpler than females but a very common uh similar phenomena that endotoxmia disrupts hormonal function at the hypothalamus and pituitary level reducing LH and FSH. It increases visceral fat which has complic implications for reducing testosterone.

[00:37:42]It activates the aromatase enzyme to convert testosterone to estrogen. So guys with endotoxmia visceral fat have higher levels of estrogen and that's why they have such things as accumulation of fat in a female pattern in the buttocks as well as expansion of uh of breast tissue and it can be responsive for infertility or at least this decreased sperm production in males and a decrease in testosterone. Now here's a very interesting observation. So as serum LBP LPS binding protein goes up, testosterone levels go down. Now that observation doesn't prove cause and effect doesn't prove that endotoxmia causes a reduction in endotoxin. So this group took a step further. This is a very active group a lot of this work from Trelan's group and they injected lipopolysaccharide into these men and watched testosterone plummet. So that pretty much clinches it that there is likely a cause effect relationship.

[00:38:47]Higher levels of endotoxin lead to a reduction in testosterone.

[00:38:53]So how do you undo this mess?

[00:38:56]Well, there's a number of choices.

[00:38:58]Refaxment of course is the conventional uh solution which has about 60% efficacy and of course is plagued by high cost and and repeated recurrences of SIBO.

[00:39:11]There are two herbal antibiotic regimens that have been partially validated by comparison to Refaxamin the Kandabactin regimen the FCIL and dispioide regimen.

[00:39:20]I've used them. They do seem to be pretty effective. They don't the the way they were concocted makes no sense, but they do seem to work and they seem to be reasonably benign uh among people who've used them. U but recall that taking an antibiotic, whether it's conventional or an herbal, does not really rebuild or restore beneficial microbes. All it does is kill off some of the bad and some of the good microbes. Probiotics in general do not have that much of a track record in success in eradicating SIBO. You can expect if a probiotic is taken to eradicate both the 24 ft of protoacteria in the small intestine and the excessive protoacteria in the 4 to 5 ft of colon, you can't really hope for much. The so the results of probiotics has been spotty at best. And so here's a question I asked. If a probiotic, if a commercial probiotic concocted haphazardly, which is the the way most probiotics are created, and you can't hope for much of a of a an effect, what if we got a little bit smarter?

[00:40:23]Well, before we get there, let me go over a couple other studies where probiotics were indeed used to reduce LPS.

[00:40:30]Here's a study from my friend's group, uh, Rald Ko, Dr. R. volcano and they use a consortium of microbes that's sold as the commercial product shooker shift for which I have no relationship uh and this is a combination of microbes including some interesting ones like bif bifact longum lactobacilus plantarum lucostto methroididis lactobacilus roerite and there was a marked reduction in serum LPS you can see that purple bar compared to placebo and baseline dramatic reduction in serum LPS and even better there was a reduction inter entroacteration which is a a subgroup under proteacteria.

[00:41:10]So this collection of microbes was effective over 3 months in reducing both proteacteria and serum LPS. So very promising.

[00:41:23]Here's a study from Dr. Dr. Kieran Krishnan's group and Brian McFarland, North Texas and another consortium of microb spore forming microbes four billions per day for 30 days. They did something very different. They fed PE people so and then measured LPS before and after. So a post pande study and what was remarkable is that yes there's a marked rise in endotoxin with eating food like that and that's blunted by the use of these spore formers. Now this raises important questions. If this level of endotoxine was unmasked by feeding people something unhealthy, should we always do this and look to unmask this kind of a concealed level of endotoxin that only gets expressed during uh in the postprandal period. So an unsettled issue but a very interesting collection of observations from uh Kieran Krishnan and McFarland's group.

[00:42:20]So I asked a different question. I said, "What if we take microbes that survive stomach acid, colonize the small intestine where SIBO occurs as well as colon and produce bacteriains, natural antibiotics that mostly kill proteobacteria. So I started with a strain of lactobacilus rody, but it was a strain made for infants and so it was sold commercially in very small numbers, 200 million, which is trivial of course." So I reasoned let's ferment it even though I was told by multiple people scientists and the supplier of this probiotic that it's impossible. Well I did it and you can though it takes different conditions. So you ferment for 36 hours because rotary doubles every 3 hours at human body temperature. I add prebiotic fiber like inulin and you get about a thousandfold increase in microbes. I performed about 30 flowcytoometric measures of the count number of microbes in this yogurt. It's not yogurt of course and we get about 300 billion per half cup or 120 millit serving and we get marked acidification probably from the lactic acid. We get a pH 3.5 which is 10fold more acidic than conventional yogurt but it's not yogurt.

[00:43:39]Okay. So this is a way that we can use, your patients can use, you can use to increase a thousandfold or thereabouts number of microbes you're playing with because if you're going to do a battle against SIBO, you're going against trillions of microbes. You can't go in with millions or a few billion. You want to go with big big numbers.

[00:43:58]So this is a thing I call SIBO yogurt.

[00:44:00]We're going to do a clinical trial.

[00:44:01]We've not we're only setting up for it.

[00:44:03]Haven't done it yet. So with microbes chose for those three characteristics, high survivability, small intestinal colonization, bacteras in production. I chose three and we ferment them. And the strains I've been using the ATCC 6475 as well as one of the strains I've been working with that I characterize gene sequence to show that it produces rotorin which is the major bacteriain of rotoy the ga a strain of gastray that's known to produce several bacteriains and basilicetylus. Here I'm using Kieran Krishnan's HU58 strain. I also have a strain I've characterized via gene sequencing that has seven genes for bacteras as well as a gene for a surfactant.

[00:44:43]So we ferment for 36 hours and get hundreds of billions. We consume or we have our patients consume half cup per day for a minimum of four weeks. And this has proven so far anecdotally to be hugely successful. Now we will perform the formal clinical trial to validate this. But think about this. If I told you the solution for this problem, SIBO and endotoxmia, is something like surgical removal of the small intestine, you should say, "Well, I hope you have at least a half a dozen clinical studies to prove this is true and necessary, right?" But what if the solution is something you make in the comfort of your kitchen that tastes and looks like yogurt that you can enjoy with some blueberries and has dramatic other benefits on skin, emotional health, muscular health, hormonal health. Well, how high how confident you have to be? I would I'd say you don't have to be confident. You can use H2 breath testing. You can use some phenomena you and your patients are experiencing like food intolerances for instance or IBS symptoms or fat floating in the toilet. You can use signs to show whether you're responding or not and can consume this yogurt. I do think there's value to consuming it even after you normalize your uh SIBO to doing this periodically forever maybe three times a week something like that until we figure out how to get these microbial species take up permanent residence they will not take up permanent residence rotary gas probably for a few uh for a week maybe subtle maybe a little longer but subtle doesn't really ger it germinates but does not colonize and so we don't have a way to make them take up permanent residence. That will happen perhaps over time. So stay tuned. Until then, we consume it for a minimum of four weeks, longer if you have SIBO really bad, and then intermittently thereafter forever until we have better answers. Now, I call this human fermentss to distinguish this from what they do with commercial yogurt.

[00:46:48]Commercial yogurt is yogurt fermented using microbes traditionally used to make yogurt. Lactobacillable garag streptococcus thermophilus. That's not what we're doing here. We're using microbes lost by humans but are adapted to the human body. Lactobacills rotate, lactobacilus gastray, and others. By the way, there are numerous other microbes you can ferment sourced from the human body. They could have come from the gastrointestinal tract stool. They could have come from the vagina. They could have come from the oral microbiome. They could have come from other sources.

[00:47:20]We're going to ferment human source microbes and restore them to the human microbiome. And that's why we're seeing some pretty interesting and often magnificent effects. Thanks for listening.