Understanding the Microbiome: Endotoxemia and Translocation

They are somewhat more advanced concepts, but the microbial phenomena of endotoxemia and translocation are proving to be critical processes in initiating or worsening a long list of human health conditions. Because most mainstream doctors have abdicated their responsibility in providing advice to maintaining or regaining health, it is up to YOU to understand these important concepts. 

Here is a basic discussion to help you understand the importance of these fundamental microbiome concepts. 

Transcript

Why Microbiome Science Changes Health

William Davis, MD 0:00

It's becoming clear that emerging insights into the microbiome, gastrointestinal, and otherwise, is causing us to change everything we thought we knew about health. But there are two phenomena in particular that I'd like you to be aware of as this science unfolds, and I predict that over the next 10 years, 20 years, it's going to change everything in the way health is managed, the way you regain health, maintain health, and it's going to take even longer. But the way that physicians, doctors, and the healthcare system manage health, that's going to be the slowest of all, because they're sadly, this is this is a sad truth, and that is, people in healthcare, when it's not a revenue-generating procedure or product offered by pharma or the medical device industry, it turns out it's very slow to be adopted. And so even if something is groundbreaking, revolutionary, world-changing, life-changing, health-restoring, it takes decades to be incorporated into clinical practice if it does not generate a lot of revenue. And that's just a sad reality of human nature and the constant greed and clawing for profit and revenues. But those two phenomena that you need to be aware of are endotoxemia and translocation. Now, if you've been following my conversations in this YouTube channel and elsewhere, my super gut book, my blog, William DavisNB.com, etc., you know that endotoxemia is extremely important. So those of you unfamiliar, I'll just briefly, what it means is we have been, as a society, exposed to huge amounts of antibiotics. 650,000 prescriptions are written for an antibiotic every day. So there's wild overexposure, some of it necessary, much of it not. So wild overexposure to antibiotics, other factors, likely, we need better evidence, but likely, glyphosate, the herbicide and roundup is also an antibiotic, preservatives in food, emulsifying agents, also extremely harmful, by the way. So, and many other factors, microplastics, all kinds of things that disrupt the composition of a gastrointestinal microbiome. But one of the prime consequences is the killing off of beneficial microbes. Now, beneficial microbes, among their many beneficial effects, serve to suppress the excessive proliferation of fecal microbes. We say gram-negative proteobacteria. These are microbes that you may have heard about, like E. coli, Salmonella, Campylobacter, Pseudomonas. You may be somewhat familiar with them because they also are causes for infections, like urinary tract infections and food poisoning. So these gram-negative proteobacteria, fecal microbial species, are harmful. It's okay to have low numbers of them in your colon. Your colon is adapted to that, but you don't want them to over-proliferate. And the loss of beneficial microbes allows that to happen. Now, for unclear reasons, over-proliferated gram-negative proteobacteria are somehow able to ascend, ascend 24 feet to fill the small intestine. The ilium, jejunum, duodenum, stomach, even esophagus and mouth. And so we have 30 feet, 24 feet small intestine, four to five feet of colon, infested by these fecal microbes. You may recall the small intestine is poorly equipped to deal with this. It's not protected by a thick mucous barrier like the colon is. And it's meant to be permeable because that's where nutrients are absorbed. Well, when fecal microbes come to colonize in large numbers in the small intestine, they inflame the small intestine, and it makes the already permeable small intestine even more permeable. And when those fecal microbes die, they shed some of their components, but specifically lipopolysaccharide endotoxin. All that means it's a component of their cell walls. They die. These microbes only live for a few hours. They die, shed their components, some of which, like that endotoxin, enters the bloodstream. That's called endotoxemia. And this is now crystal clear the reason why microbes in the gastrointestinal tract can export their effects to other parts of the body, to the brain, experience, say as depression, or panic, or anxiety, or hatred, or anger, or dementia or Parkinson's disease, in the skin as rosacea or psoriasis or eczema, in the joints and muscles as fibromyalgia, the muscle pain and joint pain of fibromyalgia, as other joint problems like various forms of arthritis. In the prostate gland, as prostate disease, in the heart, as rupture of a caronary atherosclerotic plaque, heart attack, sudden cardiac death, or as the heart rhythm disorder, atrial fibrillation, or as congestive heart failure. On and on. All organs of the body are exposed to this phenomenon, the flood of endotoxin into the bloodstream. Let's say you have depression and anxiety from endotoxemia. And we know with confidence that a major driver of those emotional issues is endotoxin because there have been studies, surprisingly, in which endotoxin was injected into normal, non-depressed volunteers, and they were depressed within two hours, clinically depressed, and MRI evidence showed all the hallmarks of depression in their brain. So we have pretty good evidence that endotoxemia is a driver of multi-emotional, social, and other physical phenomena. But it's now clear that the microbiome, via at least this and other methods, can impact health body-wide. Now, another phenomenon to be aware of is translocation. And this science is just unfolding now in the last decade or so. And so while endotoxemia means the entry of endotoxin into the bloodstream, translocation refers to the actual migration of microbes themselves from the GI tract, from the gastrointestinal tract, as well as other locations into other parts of the body. One of the best examples is the microbe Fusobacterium nucleonum. Well, this microbe starts in the mouth, especially if you have bleeding gums, gingivitis, or periodontitis, where it thrives and reproduces the high numbers for unclear reasons. But fusobacterium then enters the bloodstream with any kind of micro trauma, like flossing or brushing or dental cleaning. And that fusobacterium colonizes through the bloodstream the colon, where the evidence is quite strong, it is a major driver of colon cancer. So think about that. Risk for colon cancer can begin in the mouth. And so you can appreciate that a real effort to prevent colon cancer should involve, among other things, an examination of the oral microbiome and an effort to eradicate fusobacterium nucleotid and perhaps dress the oral microbiome in general. But point being, that's a beautiful example of translocation. How about the brain? If you examine the brains of people who have dementia, people after their death, of course, you'll see that they have brains filled with porphyromonis gingivalis, fusobacterium nucleatum, tenorello forsythia, and other oral microbes. So that people who die of dementia have brains filled with oral microbes. Those microbes can occur elsewhere, but usually not high numbers. It's almost all concentrated in the mouth, mouth being the second only to the colon in density of microbes in a normal person. So if oral microbes can be found in the brain, how'd they get there? Well, they must have somehow migrated. Did they use the sinuses? Did they use some nerve like a cranial nerve? No one knows exactly. Maybe somebody in future will radioactively label a microbe in the mouth and then see how it migrates to the brain if it if that's a source. But it's virtually certain, right? Just logically, that oral microbes can by some method obtain access to the brain. Now, is that a cause for dementia? Or is it just a curiosity, an accompaniment? No one's done that. The evidence to prove it would be very difficult. For instance, if I said to you, I'm going to give you a probiotic filled with a mouth pathogen, like porphyremonis, or placebo, and see if you get dementia in five to ten years. No one's going to do that. It's unethical, right? No one would do that. So we have to rely on this kind of indirect evidence. But the evidence is pointing towards this idea that there's micro, polymicrobial infestation of a diseased brain in this situation of Alzheimer's dementia. Now, beyond bacteria, there's also fungi. So the work from the Spanish group, but Dr. Ruth Alonzo's group has done extensive work looking at fungal infestation of brains in people, people who died of car accidents and other traumatic injuries, people who died of old age, people who died of dementia. And it's the people who died of dementia who have brains that are heavily infested with candidate species, mostly, fungal species. Where'd they come from? Well, maybe from the mouth, maybe from the sinuses, but those tend to be in most people only thinly populated by fungal species. So my suspicion is it comes from the small bowel or colon, that is, CIFO, small intestinal fungal overgrowth, or of course colonic overgrowth of fungi, both of which are fairly common and massively underappreciated. So that's my bet, but no one knows for a fact. But the point is, it's an example of translocation from someplace, mouth, sinuses, GI tract, we don't know, to the brain. Now, once again, like with bacterial infestation of the brain, we don't know how much of it is a cause or just a curiosity, but you gotta wonder, right? Because all these microbes, bacterial or fungal, also bring a lot of inflammation with them. Their presence alone is sufficient to generate a lot of inflammation. And we know that inflammation is a principal driver of the changes that occur in dementia. Now, sometimes translocation is bad, like when it comes from the mouth and goes presumptively to the brain or from the mouth to the colon, but there are times when translocation can work to our favor also, such as a woman can take Lactobacillus crispotis. So lactobacillus crispatis, we now know with good science, is meant to be the dominant microbe in a healthy human vagina. And many ladies have lost it, like many other beneficial microbes, because of its susceptibility to common antibiotics. It could be something as benign or common as amoxicillin, for instance, or clothromycin or azithromycin, or many of the other antibiotics. So it wiped out the crispatis. That leaves a woman more likely in reproductive years to have a miscarriage or to have premature labor of a child, which can be catastrophic, to be more prone to sexually transmitted diseases. And later in life, it leaves a woman much more likely to have candid vaginitis, bacterial vaginitis, also dryness, irritation, discharge, especially in menopausal years, and the lack of crispatis leaves a woman much more susceptible to urinary tract infections and incontinence. And preliminary evidence suggests restoration of crispatis addresses all those factors. Now wait a minute here. So if a woman takes crispatis orally, will it colonize the vagina? Yes. But how? There's no direct connection. There is nearness or contiguity in the we say the perineum, that's the area, the groin area, because there's not, there's only a few inches at most between the vagina and the rectum. And so we presume, don't know for a fact, but presume, that microbes in the gastrointestinal tract can migrate through the skin into the vagina. And even more remarkably, that lactobacillus crystal can also colonize the bladder, where it provides beneficial effects. So that's an example of beneficial translocation, uh, presumptive translocation. How else would it get, say, from the gastrointestinal tract to the vagina or bladder? Is there some hidden connection we're not aware of? Maybe, but no one knows where that is or what it looks like. So presumptively it's through a skin transmigration. Another example of a bad form of translocation is in the prostate in men. So this surprised me that if you biopsy the prostate glands of men who have prostate disease, it could be prostatitis in some form, it could be benign prostatic hypertrophy, we say BPH, that's a situation where the prostate enlarges and then pinches off the urethra and you can't urinate, it's hard to urinate, eventually they have to treat it surgically, or even prostate cancer. So in all those situations, if the prostate is biopsied and DNA sequencing is performed, you find that there are microbes from the mouth, like porphyremonis gingivalis. There are microbes from the skin, like Staphylococcus epidermitis. And of course, there are fecal microbes also. After all, when a man when a guy gets his prostate examined, it's examined by having a finger inserted into the rectum, and the prostate's right there, only a couple of millimeters away from the rectal microbiome. So it'd be no surprise, right, if there's some translocation of gram-negative proteobacteria from the rectal microbiome into the prostate. And that has been shown to be true. But what are skin, oral, and other microbes doing in the prostate? Well, it's some form of translocation, presumably through the bloodstream. And how much does that contribute to making a guy susceptible to prostate disease? Or is that, once again, just a curiosity, tough to prove. But I kind of regard the prostate gland, I call it the grand central station of the microbiome, because it seems as if the microbiomes of multiple body sites seem to take up resonance. The microbes tend to take up resonance in the prostate gland. Does that mean then, if you want control of the pro over prostate disease, a male has to pay attention to the microbiomes of the entire body mouth, skin, rectum, gastrointestinal tract, and elsewhere? Don't know. That's a work in progress. But another thing to be aware of for guys with prostate disease is it's become clear that prostate disease is also driven by SIBO and thereby presumptively endotoxemia. I was surprised by that. I wouldn't be surprised that the rectal microbiome plays a role, but the small intestinal microbiome also, because of its permeability to endotoxin, endotoxin blood-borne has access to the prostate gland. So likewise there too. There's also some very interesting but emerging, very preliminary evidence that, as in a woman, lactobacillus crispatis may be important. Once again, if you biopsy a male's prostate gland who's got a diseased prostate, prostatitis, BPH, prostate cancer, they don't have crispatis. If you biopsy normal prostates, they have crispatis. Now, once again, just a curiosity, or somehow causative. Don't know. But it's a very compelling, interesting question. It needs to be settled. Anyway, so think about these things. The microbiome through two major processes, two fundamental processes, endotoxemia, the entry of breakdown products like endotoxin into the bloodstream, and translocation, the actual migration of microbes from the GI tract to other places or from other locations like the mouth to other locations. These are proving to be or starting to look to be in preliminary evidence, very powerful driving factors in multiple forms of disease. Now, we manage this, of course, by addressing the health of the microbiomes in each of those locations. We manage the gastrointestinal microbiome. We try to manage the oral. That's that's the toughest part because the science is still very preliminary. Um, and the vaginal microbiome. If this is of interest to you, I encourage you to see my super gut book, my blog, William DavisMD.com. If you need guidance and further support, I invite you to join the conversations we have almost every week via two-way Zoom in my inner circle.drdavisinfinethealth.com. But we live in a very exciting age where insights into the microbiome are proven to be extremely powerful. Unfortunately, it's a lot of this wisdom is not going to come from your doctor because there's not a revenue stream being generated. So it's up to you and how much you acquire in knowledge, how much you learn, and the and the strategy that you engage in to make improvements in those microbiome locations.