Restore Gut Health: The Science Behind a Healthy Gut Microbiome

What are the Top Ways to Improve Gut Health?

A healthy gut plays a crucial role in the health of our whole body and mind. Dr. Zach Bush joins our medical director, Dr. Dan Stickler, to discuss the latest research in how to restore gut health by understanding the gut microbiome. New studies are showing the surprising effects of antibiotics and the even more shocking effects of probiotics. We discuss why a diverse gut microbiome is best supported by lifestyle choices including eating local, organic foods and exposing ourselves to a variety of the microbiomes existing in nature. Our gut microbiome is influenced by everything we put into our body and everything around us. Although we don’t have all the answers to what makes a healthy gut, Dr. Zach provides unique insights that bring us closer to healing our guts and our bodies. 

"The microbiome is governing human health." -Zach Bush, MD

In This Episode We Discussed
0:00 Intro
2:58 Limitations of microbiome testing
11:04 The types of microbiome testing: Cultures, PCR, 16 rRNA and microRNA analysis
15:45 All about microRNA
20:06 Impact of food and environment on the gut
22:26 Gut-brain connection
25:20 Psychological disorders stemming from an imbalanced gut microbiome
28:12 Repopulating gut microbiome after antibiotics
32:15 The gut isn’t controlled by the probiotics we take, but the nature we touch
36:08 Eating local and seasonal products for a healthier gut
38:22 Science behind RESTORE products: Protecting against glyphosate and gluten sensitivity
44:55 Glutathione production in the gut lining
45:49 The microbiome is governing human health
46:46 Peptides: BPC-157 for gut healing
52:08 Expressions of genetic code are different than our ancestors
53:30 Consuming the genomic sequences of our food: Stress of the food itself
56:32 Dr. Zach’s nonprofit: Helping farmers transition to regenerative farming

Mentions (People, Products, Technology)
Dr. Zach's Biology BaseCamp Program
Dr. Zach's Website
Dr. Zach's Clinic
Viome
Jeff Leach
Farmers Footprint Non-Profit
Restore4Life Products

Full Episode Transcript
Dr. Zach Bush:So there again we [inaudible 00:00:02], okay the brain is not really the brain. It's maybe the second brain and the primary brain is really in regard to an information stream and manufacturing is maybe the gut lining. So we've been arguing over is the brain the first brain and this is the second brain or vice versa with some of our colleagues in recent years. And it's a fun debate because we start to realize wow there's so much information flowing out of the gut up towards the north here. It turns out, for every 10 parts of information exchanged between the gut and the brain, nine parts are information flowing up and one part is information flowing down. And so, from a sheer information volume, it's clear that the gut dominates this relationship between gut/brain.

Speaker 2:Welcome to the Collective Insights Podcast, where we explore topics and technologies revolutionizing human wellbeing. On today's episode, Dr. Zach Bush returns to the podcast and joins our medical director, Dr. Dan Stickler to explore the astounding new research on gut health, including a new insight on something we've all been doing wrong for decades. Dr. Zach Bush is one of the few triple board certified physicians in the country, with expertise in internal medicine, endocrinology and metabolism, and hospice or palliative care. The breakthrough science that Dr. Bush and his colleagues have delivered offer profound new insights into human health and longevity. Since our gut health is the foundation of our physical and mental health, we focus in on what it takes to build a diverse and healthy gut microbiome. Dr. Zach is one of our favorite guests and his first visit with us was one of our most popular episodes. So if you're wanting to learn more from Dr. Zach, check out the previous episode number 23 for more great information on gut and microbiome health. Thank you for joining us, now let's jump into the show.

Dan Stickler:Hi, welcome to Collective Insights. This episode will have me as the new host. I'm Dr. Daniel Stickler. I'm the medical director here at Neurohacker Collective and the co-founder and chief medical officer for the Apeiron Center for Human Potential and the Apeiron ZOH Corporation. It is a great pleasure for me to welcome Dr. Zach Bush. He is one of the few triple board certified physicians in the country. He's got expertise in internal medicine, endocrinology, metabolism, hospice and palliative care, and especially in the gut and healing the gut and the gut microbiome. The breakthrough science that Dr. Bush and his colleagues have delivered offer profound new insights into human health and longevity. His education efforts provide a grassroots foundation from which we can launch change in our legislative decisions, ultimately upshifting consumer behaviors and bring about radical change in mega-industries of farming, big pharma, and western medicine at large. So, welcome Zach Bush.

Dr. Zach Bush:Thanks so much for having me on. Excited to be with the whole community here.

Dan Stickler:Well I'm excited to learn more about the microbiome. After listening to your first episode that you did with Collective Insights, it opened up a ton of new questions for me and a lot of our listeners as well. So it will be an interesting journey on this trip. One of the areas I want to get into first, and this is an area that has been of great interest to me, because I've been through that whole process. In my medical practice people ask me why we're not actually testing gut microbiome, and I had done it for a while. I had been using gut microbiome testing and I was deep diving into functional medicine and doing a lot of different testing and I just didn't find the value of a lot of the current microbiome testing out there. I'd like to dive into really talking about the different forms of microbiome testing. Because there's a lot of companies out there offering this right now. So if you could run through the different ways that the microbiome is tested that'd be great.

Dr. Zach Bush:Fantastic, yeah. I totally agree with your experience there. It definitely is in line with my personal clinical approach with my clinics out here in Virginia. We find that there's some major limitations to what's on the market right now, which is an off-shoot both of the very nascent industry around the science of how to measure these various species within the microbiome. But also, a larger problem that we're still working very hard to define what a healthy microbiome looks like. The real concerted government funded effort to that started in earnest around 2010-2011 at the National Institutes of Health starting the real effort to decode the genome of the entire microbiome and categorize the bacterial microbiome of the human gut to really define what is a healthy gut.

Dr. Zach Bush:So far we've categorized more than 10,000 species of bacteria in the human gut and every year or three they update that data bank with another 1,500 or 1,600 species. So, that's their current pace. So we have not run out of effort and data. Those of us in the industry tend to agree that we're going to be somewhere between 20 and 40,000 species of bacteria that we're likely to ultimately categorize out. There may be very interesting subsets within those species where a single species could modify or adapt to serve different purposes as well. Suffice to say, somewhere in that 20 to 40,000 species we may get only half done and even understanding maybe a third done, or a quarter done with even understanding how many bacteria should be there and what kind of diversity. At the big picture we don't even know what the finished gut looks like from a microbiome standpoint, and that's only the bacteria.

Dr. Zach Bush:In contrast to the 30 to 40,000 species of bacteria, we know that the environment around us contains somewhere around five million species of fungi. And those fungi can be present in different forms. They can be in yeast type formats, and spore forms, and mycelia forms, all kinds of different types of manifestations of those five million species. And so, we have no idea how that integrates in. Right now the dogma that's out there in the industry is "Oh, fungi are a very small part of the human gut microbiome, maybe 5%, 10%." However, the new data coming around micro RNA, which is looking at which genes are turned on and active at any given time in the human blood stream, we already know that there's an equal percentage of micro RNA coming from fungi, some 15%, as compared to some 15% of the micro RNA in our blood stream coming from bacteria.

Dr. Zach Bush:So because of that micro RNA data, I would say it's very likely that there's an equal representation of fungi and bacteria in the human gut biome that's affecting human health. And so, cumulatively we already know that at least 30% of the micro RNA in our blood stream is coming from microbiome genome rather than human genome. And the micro RNA we can talk about further later, but in the nutshell it's the on/off switches, or the modifiers, co-suppressors, co-activators of the gene transcription within your human cells. So the micro RNA from the fungi and bacteria within your microbiome is regulating what your genome would produce. What type of body are you creating today? Of your 20,000 genes that are going to make over 200,000 different proteins, which proteins do you turn on a day? Which body do you build today? Do you build a healthy body? Do you build a regenerative body? Do you build yet another day of a decaying, aging body? At least a third of that determination being directly from the genomic information of the bacteria and fungi.

Dr. Zach Bush:Further, there's also parasites, 300,000 species of parasites in our environment. What percentage of those should be in the gut microbiome? We don't know. Then we go to the viruses. We know that every single cell and environment within the body is likely steeped in a virus in some sort of symbiotic fashion. Why am I so confident about that? Because there are 10 to the 31 viruses on Earth. That's one with 31 zeros after it. That is such an enormous amount of biology that there's no way that we're somehow separate from or avoiding 10 to the 31 viruses in our greater environment. So I think that the industry needs to desperately diversify its own understanding of what a gut microbiome is away from just the concept of bacteria. It is a much larger ecosystem, much more diverse and dramatic than that.

Dr. Zach Bush:All of that said, let's take a look now, like you said, what are the clinical tests for your gut microbiome? Some of the best ones out there are testing some 120 different species. Sounds like a lot, and it is a pretty impressive scientific feat to get, in a single test, data around the genetics, and the genetic makeup of your microbiome to be able to identify or parse out 120 species. Big scientific leap forward. But I just told you there's like 30,000 species of just bacteria that should be monitored and categorized to tell you your whole picture. So keep in mind when you get a microbiome analysis of your gut, you're getting a snapshot of a small portion of the microbiome. So for that reason I don't think it's clinically useful.

Dr. Zach Bush:In a research environment, there is some utility to seeing changes within those 120 species. If we can say, "Look we couldn't even find those 120 species, we had 30 species, and then we diversified and found 100 species," now you can say with some confidence that you're starting to change the diversity of the biome. But again, you're looking at one tiny little element or measurement within that greater ecosystem. So I'm in the same boat you guys are, which is I don't intend to test it in any of my patients. I've never sent anybody for microbiome testing clinically. The only test I do in stool is an occasional [inaudible] and parasite if I have a big clinical question around that.

Dr. Zach Bush:Typically I'll just treat for parasite. If I think there's an overgrowth of parasite in the gut I'll go ahead and treat cause it's cheaper than the test itself, and the test itself is very poorly sensitive or specific. And so O&P occasionally and then I'll test for specific species if I thing there's clostridium difficile after an antibiotic exposure that's causing a severe diarrheal inflammatory and then I'll look for that specific species, and that kind of thing. Salmonella, shigella, either of the typical food borne illnesses. And so in those specific clinical situations I'll look for a single species to see if I can come up with an explanation or treatment target. But in general, looking at the whole microbiome doesn't even exist, and when we do look at the microbiome genomics we just need to keep in mind that we're looking at a very limited data set.

Dan Stickler:Yeah, and coming from someone like you I appreciate that insight into that. Because you look at it right now and you look at how many people are truly going out and getting microbiome testing and they're buying into a lot of the hype that's being generated. Especially around the things like using the 16S RNA's or something like that. Now can you explain a little bit about the difference between culture versus PCR versus the 16S RNA in the assessments?

Dr. Zach Bush:Yeah. In a nutshell, you're using a tighter and tighter pinhole to look at the microbiome as you go down that cascade. It's very much like a camera in some ways. A telephoto lens can get you a lot of data at the small level, but you're missing the forest for the trees as you zoom in, if you will. We get different data from each of those sets. Culturing is categorically difficult and fraught with massive problems. We can look at this either in soil or in the human gut. If you try to take a culture of soil microorganisms you only will grow, at best, one to 10% of the different species in that culture because each species requires a very specific niche of oxygen or no oxygen, nutrients or no nutrients, all these different variables of osmolality, pH, and all these different things that would be normally attained in a complex ecosystem of soil or your intestines.

Dr. Zach Bush:And so, when we take it to a Petri dish suddenly we create one environment with one nutrient source, one oxygen to CO2 ratio, one pH environment, and so you're going to select for a very narrow chunk of species. And so culture is a very historically inaccurate way of asking what's in a microbiome. As we start going into different levels of analysis, we get a much better sense of the diversity, but we have a harder and harder time of categorization of what the data means. And so, certainly as you move towards the genomics as looking for DNA sequences, for example, in tissue, we can do that. We can say, "Okay, this DNA strip is from bacteria and likely from this family of bacteria," but you get less and less specific as to have we really categorized that DNA from a single species or more from a family or a genera of species or of organisms?

Dr. Zach Bush:Then you move to snips. So you start to look at not just an entire gene, you're now looking at just little tiny nucleotide sequences which could be from the RNA that you mentioned. So if you're looking at RNA snips, from messenger RNA for example, now you can tell which genes are being translated into proteins and you can start to make some differentiation again to what's the spectrum of life that's happening at any given moment. But you're again, as you move into the protein world into this translation from gene to protein, you're again missing the other diversity thing but you are starting to see what's active. Because having 20,000 genes in a genome of a human is not very interesting data if you want to know what's happening today. If you want to know what's happening in biology right at this moment, you would like to know which genes are activated and actively transcribing proteins. So as we start to look towards RNA, we start to get a sense of what is the organism doing right now? Is it trying to repair itself? Is it in that inflammatory state? Is it a non inflammatory state? You start to parse out all of those differences based on the RNA sequences.

Dr. Zach Bush:Micro RNA now is a different phenomenon, and Viome is the first product on the market that I think really starts to try to categorize in a stool study what's happening at the micro RNA level. Our group is very blessed to have John [Gilbey 00:15:13], a PhD in microbiology and zoology in our labs. He's one of the five world experts in isolating micro RNA. There's many, many more than five people working on this in the world, but he's in that top 10 category there. But John, what he's doing is he's isolating from saliva or urine or stool or whatever source, these little packets of information of micro RNA. Micro RNA differs from messenger RNA in that it will never go on to make a protein. Our understanding previous to five years ago or so was that DNA is a template, you need to make it a translation to RNA on top of that, and then transcribe that to a protein ultimately.

Dr. Zach Bush:And so this messenger RNA would line up in the nucleus of your cell, become a mobile template for that protein, move into the cytoplasm of the cell, and then be stripped or read by enzymes that would then build an amino acid for every nucleotide and you would end up with a complex string of amino acids that would then do ordinary and three dimensional folding to become an enzyme. Which might be DPP4 detox enzyme, or glutathione, any of this big antioxidants, et cetera. So that's our classical concept of RNA. It's a template from the DNA to become a protein.

Dr. Zach Bush:The discovery of micro RNA was a huge revolution, because micro RNA is a segment of RNA nucleotide that has been copied not from a gene but in the other 98.5% of our DNA which is non-transcriptional junk DNA. Up until the discovery of micro RNA, we literally thought that 98.5% of our genome was waste product. We didn't think it had a biologic function. That was a stupid conclusion because nature doesn't have waste, but that is how nascent and little our understanding is of genomics as it contains just a limited amount of human information. But 98.5% of our DNA does not code for a gene, it codes for what looked like random little sequences of nucleotides. Turns out those random little junk nucleotide sequences all make code not for a messenger RNA that would become a protein, but these tiny little micro RNA that are so small they're not limited to the cytoplasm of the cell, they actually leave the cell and they can travel in the blood stream, in the lymph system. Ultimately they can be secreted in your breath, saliva, urine, and they go out into the greater world and can actually start to communicate with the bacteria in your gut and bacteria on your skin and to the humans or animals around you, and we actually modify each other's genomic behavior through these micro RNA that are now leaving a single-celled system.

Dr. Zach Bush:The micro RNA, again, do not make a protein. They don't have any transcriptional intention. Instead, they work as the suppressor or activator of genes in distant cells, or even cells of other species. As mentioned, some 30% of these switches, or these activator code suppressors of the micro RNA in our blood stream at any given moment, aren't from even our human DNA. Not only is it being transcribed for junk DNA, it's being transcribed from junk DNA and bacterial DNA strand that doesn't code for a protein but instead for a micro RNA. And so this is why we're so plastic. This is why Darwin could make some observations back in the day that wow a species can actually change its phenotype given a certain environment. The beak of a bird can get longer and specify because of the micro RNA around it changing the behavior of the protein structure that would be transcribed ultimately by that organism because the micro RNA trans-species, cross-species is modifying each other.

Dr. Zach Bush:The interesting result of this is that we actually look more and more homogenous genetically as we swap more and more micro RNA. And have you ever seen that couple who's been married for 50 or 70 years? And you start to recognize that wow if you look at the marriage picture of 60 years ago those people look different actually, and what tends to happen is they start to look more and more alike. Their phenotypic features literally will become a blend of one another and they might look more like each other at 50 years of marriage then they do to their own siblings. What's happened is the micro RNA swapping in the saliva and the breath and everything else over 50 years has transmuted the genetic expression of their own genome over time, and they've turned on the same genes in one another over time to manifest a different body. I also like to think about how people tend to look like their pets, but that's a different story.

Dan Stickler:I want to try to simplify this a little bit for some of the listeners because micro RNA is really a fascinating area and that was a great explanation of it. This is something we teach. We teach a lot of epigenetics and micro RNA plays a huge role in the epigenetic expressions. The way we look at it is the micro RNAs are like emails being sent around to inform about what's going on in the environment or in other cells, and I think it's really important to understand that these micro RNAs are phylogenetically extremely old. We share a lot of micro RNAs with species throughout the tree of life down to bacteria even. There are very much similarities between the micro RNAs that are produced. I kind of see this as these micro RNAs are informing the cells in the body of the environment that you exist in. We get micro RNAs from the food we consume. We get micro RNAs from the bacteria. I think it's important to understand the impact of eating the right foods and understanding the bioactive nature of foods and what they can contribute to that micro RNA process, along with the bacteria that are producing these micro RNAs that are going to be signaling the cells in our body of an environment that exists.

Speaker 2:Let's take a quick break. Next up, we're going to dive into the newest research on the gut/brain connection. Dr. Zach then provides us with practical advice to build a diverse and healthy gut microbiome. Thanks for listening to Collective Insights. Our podcast is brought to you by Neurohacker Collective, where we offer a line of cognitive enhancement supplements. Check the website to see how you can save 50% off your first order of Qualia Mind or Qualia Focus. If you liked this episode then please share it with your friends and leave us a review on iTunes. Remember, for full show notes visit neurohacker.com/collectiveinsights. All right, let's jump back in.

Dr. Zach Bush:Perfect, and there's an opportunity here to tie this into your neuro topic, your Neurohacker network here. As we start to think about brain and the neurotransmitters that would ultimately go on to create neurologic simile and balance and homeostasis in the brain, we think a lot about things like serotonin and dopamine. Serotonin, let us take that as an example, some 90% of the serotonin made in the body is not made in the brain but in the human intestinal lining. In that production center is the enteric endocrine cells. These little [inaudible] are about 10% to 15% of the cells that compose the lining of your gut are not epithelial cells that are barrier/boundary cells that are responsible for protection and absorption. They're instead endocrine cells, and those 10% to 15% of those billions of cells that are endocrine cells are the manufacturing plant for serotonin.

Dr. Zach Bush:So there again we [inaudible 00:23:21], okay the brain is not really the brain. It's maybe the second brain and the primary brain is really in regard to an information stream and manufacturing is maybe the gut lining. So we've been arguing over is the brain the first brain and this is the second brain or vice versa with some of our colleagues in recent years. It's a fun debate because we start to realize wow there's so much information flowing out of the gut up towards the North here. It turns out, for every 10 parts of information exchanged between the gut and the brain, nine parts are information flowing up and one part is information flowing down. And so, from a sheer information volume, it's clear that the gut dominates this relationship between gut/brain.

Dr. Zach Bush:But it gets more complex and it gets into this micro RNA situation when we start to realize that the enteric endocrine cells can't actually produce serotonin unless the correct species of bacteria is sitting on the gut side of that cell. And so you have to have a direct influence and relationship between the secretions of a bacteria and that enteric endocrine cells before you can get the production of serotonin. I think this is just a very direct way of saying if you take an antibiotic you're going to screw up your production of serotonin and dopamine and therefore you're going to predispose yourself to a collapse of mood stability or cognitive capacity.

Dr. Zach Bush:In fact, we can prove that and it's been published many times now. There's a couple great studies showing that one course of antibiotics leads to somewhere around a 17% increase in a risk of anxiety disorder in the next 12 months. For major depression it's a 24% increase in risk of disorder within the next 12 months. If you have two courses of antibiotics or more in that 12 month period, then your risk of major depression goes up at 45%, risk of anxiety disorder's around 40% and so this huge increase in risk by disrupting the microbiome that would be secreting micro RNA and other precursors for your serotonin delivery by disrupting that microbiome.

Dan Stickler:I read something recently too about the impact of the gut microbiome on BDNF expression in the brain and how, I believe this is through micro RNA processes that are more systemic than they are local on the vagus nerve level, but looking at the outcome of that they were saying that it actually reduces the activity of the NMDA receptor and can lead to a glutamate toxicity and overload in the brain, over-activation that may relate to some ADD and other psychological disorders.

Dr. Zach Bush:Yes. We see that a lot in autistic children and obviously as well. This very nuanced balance between the parasympathetic and sympathetic nervous system we think of as being a primary neural environment, but if we look at the actual architecture of the afferent nervous system in the gut lining we find out that the nerves within your gut lining are actually bypassing the epithelial boundary that would make you human. The human boundary is one that says outside of this space is the external world, microbiome, and everything else, inside this boundary of that is the human.

Dr. Zach Bush:So you would think that the nervous system of the human would limit itself to the human environment, but were now seeing three dimensional imaging showing that the tendrils of the afferent nerve at the epithelial layer, which we've known has been integrated with the enteric endocrine cell and so that you can have a transmission of serotonin, for example, from the endocrine cells straight into the nerve so you don't have to traffic that serotonin through the blood stream and then impossibly get it through the blood brain barrier to the brain. Instead it goes straight into the neurologic system from the endocrine neurologic junction there.

Dr. Zach Bush:Now, find out that there's tendrils of that afferent nerve that are reaching past, not only the endocrine cell but the whole barrier system itself, to stick its snout out into the microbiome directly. So we've been able to show that the bacteria have the exact same ion channel on their surface that the human nervous system does that can get direct ion exchange or communication from the bacteria of the microbiome directly to the afferent vessels bypassing even the endocrine cells. And so fascinating situation here where the vagus nerve and its tone, whether parasympathetic or sympathetic, may be being determined directly by the microbiome before we even can take into consideration the whole inflammatory cascade and everything else that could be induced by a leaky gut, or some other insult to that gastrointestinal lymphatic tissue.

Dan Stickler:You mentioned the antibiotics and I wanted to go down that path a little bit, because there's been some more recent studies that are fairly impactful in that regard. Two that I want to mention is, one that they're finding that some people's microbiome are resistant to probiotics. They really have no change with it and others have a more receptive response to them. But beyond that, there was a study, and it may have been done by the same lab out of Israel I think, where they put three groups of people on antibiotics and they sampled their stool prior to the antibiotics. One group, they actually collected their stool and froze it and then they ran them on a course of antibiotics. After the course of the antibiotics they left one group alone to recover their microbiome. They had one group that they re-infused their stool to recover the microbiome. And the third group they put on probiotics. And there were some pretty surprising results from that.

Dr. Zach Bush:Shocking results, really. I mean, embarrassing results really, because here we are as doctors, we've been prescribing probiotics from the beginning of time. If you're a clever doctor and even gastroenterologist you have been resistant to the whole science of the microbiome. Even gastroenterologists in the last 10 years have started using VSL number three as the typical one that's prescribed for Crohn's, colitis, and other conditions like that, and so here we are prescribing and filing probiotics and thinking that we're doing something for the microbiome diversification. I started preaching against these some time back just because of the simple fact that three species of bacteria could never be 30,000 species. So if we're overwhelming the gut microbiome or augmenting the microbiome with billions of copies a day of the same few species, we're going to create a monoculture, not a diverse thing. So it was obvious just from conceptualization that a chronic use of a probiotic is a bad idea.

Dr. Zach Bush:But I kept the argument that a short-term treatment of probiotic probably makes sense, especially after antibiotic therapy. And so then, the study that you're talking to now is published in September of 2018 in Cell, which is one of the most rigorous science journals in the world, and they did it first in rodents and then the human study that you just talked to. And in rodents they showed that as soon as you start the probiotic you freeze the recovery of the microbiome. Within 30 days, those on placebo, with nothing to help augment their microbiome, within 30 days they had recovered pre-antibiotic levels of biodiversity.

Dr. Zach Bush:Keep in mind, they're checking 120 species rather than 30,000 species but it's the best assay we have to look at that collapse. The antibiotic induced about 80% loss in biodiversity. So they had a good assay to show the damage from the antibiotic and to see that freeze with a probiotic was stunning. It froze it with no recovery for about 50, 60 days in that animal study. So then they did the human version of it. The same model in both, as you mentioned, a group gets fecal transplant with their own biome, a group gets placebo, and a group gets probiotic. The human, again, within 30 days with no help recovers their biodiversity. I think it is funny in that study, if you look at the diversity of bowel flora in the mouse in a lab, sterile lab, horrendous no nature environment, there's actually more species diversity in the mouse than there is in the human in a normal living environment.

Dr. Zach Bush:So it's a little embarrassing how toxic our human food chain is that we would be so limited in microbiome diversity to begin with. But nonetheless, we see the 80% drop in the human. And again, we see some recovery. We never get back towards normal at six months. But they followed them for six months out and the probiotic arm continued to be suppressed in its recovery. Again, at 30 days, everybody's back to their baseline. And so, it's so humbling as a doctor to be preaching this stuff for a decade and find out that I'm still completely wrong about the role of probiotics. So at this point, I've eliminated probiotics from my clinic entirely as of last September realizing that there is not a safe moment to try to micromanage a complex system like the microorganisms that should be there.

Dr. Zach Bush:We need to back off of the micromanagement understanding and start to see our gut microbiome as a direct extension of the nature that we touch. And this has been proven out. The American Gut Project, one of the largest studies being done worldwide, there's six universities involved and all that ... It was started by Jeff Leech who's a genius of a gentleman. He is not a cell biologist by training, he's actually an anthropologist I believe, or archeologist, one of the two. I think he's an anthropologist. And when his daughter was diagnosed with type one diabetes back in 2001 he started to get really frustrated there was no answers to how this autoimmune disease had cropped up in his young daughter. And so he started diving into some esoteric science. At the time, nobody was talking about the microbiome in 2001. But he found some data out of Asia that was starting to talk about the relationship between gut genomics and autoimmune disease.

Dr. Zach Bush:So he decided to put his entire retirement savings into studying this. So he's been at it for 18 years now. One of the world experts in microbiome research and the six universities that have joined him over the years have really empowered him greatly to do some phenomenal work. They're working primarily in hunter-gatherer tribes in Africa, and they're looking at the genomic variety there. They're about 10 times more complex, it seems, and they haven't been able to categorize all the species variations that these guys have. But it's clear by the sheer genomic variety that we're seeing that it's at least 10x the variety that a western gut would have in these hunter-gatherers. And what they've been able to show in those hunter-gatherers is their gut microbiome is directly influenced by everything that they literally touch. So a significant portion of their gut microbiome has some very strange species that we've never seen in the human gut in the western world that are dominant on the hides of zebras, which is one of the main foods they eat.

Dr. Zach Bush:So, these guys kill and butcher a zebra in the bush, throw that hide on their shoulder and carry that bleeding hide of microbiome for many days back to the village. They're just covered in zebra biome which then becomes their own gut microbiome as well. And so they diversify their microbiome by literally everything they touch. Now you look at the typical American experience, you've never touched any of the animals you're eating. You have some weird, homogenized, highly sterilized, processed version of it. Even if it's a chicken breast at the counter, that thing has been pasteurized by some chemical processing and other things, and injected with junk, there's just nothing natural. No healthy microbiome being touched by your nutritional environment or skin, et cetera. So, if you want to get away from probiotics you immediately simply just get yourself and your patients into a natural microbiome as often as possible.

Dr. Zach Bush:So I have my patients try to seek out a new ecosystem whenever they can. If that's just the weekends, so be it. Get out to a waterfall, get out to the jungle, get out to the ocean. Get yourself in touch with a big piece of natural environment, breathe it. The microbiome we breathe will ultimately populate our gut through different mechanisms. Touch it. Consume it through fermented foods. All of these different things are really powerful ways to go far beyond the limited impact or maybe harmful impact of a probiotic.

Dan Stickler:Do you think that also translates into really consuming foods and products that are more locally based? Do you think that that is a major impact on the health of the microbiome in general?

Dr. Zach Bush:I definitely do. I think eating local is very interesting. It forces you to eat seasonally and I think that's one of the things that's ... Even in our health food industry we've become very monotonous through the year. We're eating tomatoes and avocados year round now. That's not how anybody's ever eaten in human history before. And so I think that it's very notable that a high intake of a single fruit or vegetable or food source seasonally is historically how it's always been done. Not just by humans, but by any large mammal or rodent and the like, on the planet. So eating seasonally, eating locally, all of these things are going to reinforce natural patterns of behavior in your microbiome. Because the microbiome is changing your genetics, it's probably important that you eat root vegetables and your winter greens in winter so that that food is turning on the right genes in your body to handle the nutrients and calories differently than as if it was summer.

Dr. Zach Bush:You should spend an inordinate amount of energy on heat production in the winter. And so, the mitochondria should uncouple their ATP pumps so that they would produce heat rather than ATP, all of this when you digest food. So these changes and the way in which we utilize fuel is very likely to be modified by the monotony or the diversity or a pertinent seasonal expression of our food itself. If you feel like you're locked in body that's always obese and not losing the weight and not behaving correctly with your basal metabolism, take a look at your diet. Are you locked in the same diet day in and day out, week after week? It may look healthy, but if there is no variety and seasonal shift, you may be missing an opportunity for real metabolism to set in.

Dan Stickler:When we talked about really the impact of antibiotics and really the question of if whether using probiotics has any utilization, I'm like you, I've gotten away from it since that recent study, but, the fact of the matter is, we do the best with what we have available to us. When you run into the people in the medical industry that will resist, when I was a surgeon and we started doing laparoscopic surgery there were so many surgeons that were very resistant to it and they really became the dinosaurs because they were not open to the new information that was coming in. We're finding this with a lot of this gut work, too. Especially with the gut because it's so exponentially growing in our knowledge base. So if you have somebody with leaky gut or dysbiosis or something, what's your typical protocol with that right now?

Dr. Zach Bush:Yeah, so, disclaimer here is I'm very biased because my discoveries in 2012 around this issue led to a product called Restore and my company Biomic Sciences produces that product. It's become one of the industry leaders in managing this situation so know that I have a conflict of interest in this portion of the discussion here. But, instead of talking to you about the product, I'll talk to you about the science of the product which has been proven now. University labs have confirmed all of this data but the approach that we're using is instead of trying to add a few species of bacteria, in 2012, I discovered that each species of bacteria and fungi made a different subset of large carbon molecules that have redox potential. So they have different oxygen-hydrogen binding capacity and properties depending on which species of bacteria and fungi are making these large carbon molecules.

Dr. Zach Bush:As we taka a diverse cross section of these carbon molecules, we find we can create a very fluent communication network within the human environment. Ultimately, when you see a leaky gut or an inflammatory cascade, or any number of cellular dysfunctions, we can guarantee that in the midst of that is a lack of response from a natural human repair system. The lack of response is the result of a lack of communication. Leaky gut is induced by alcohol, anti-inflammatories like ibuprofen, NSAIDs, motrin, et cetera. It's injured by a lot of the constipation medicines on the market, MiraLAX being a big dangerous one. It's induced by Roundup probably more than anything else. Roundup is the primary weed killer present in the human food chain worldwide. The active ingredient in there is glyphosate.

Dr. Zach Bush:When these compounds, pharmaceutical, nutritional, or chemical from our food chain hit the gut lining, we do an immediate damage to the tight junction Velcro system, everything gets leaky, the permeability increases. And now we've shown in our labs, we've been able to grow a blood/brain barrier adjacent to the gut membrane, induce that injury of the gut, and the peptides of the gut, then go on to injure the blood-brain barrier and you get leaky brain. And it goes on to actually make leaky kidney tubules and the rest. You get leaky kidneys, leaky gut, leaky brain, all from the same Roundup glyphosate injury, and that's leading to this diffuse injury source.

Dr. Zach Bush:What we're finding is that if you add enough of the carbon redox signaling from the bacteria and fungi back into the matrix, you get an extremely robust healing event that actually can outpace the injury, and so if you have enough of this carbon molecule family in the matrix, you're actually gonna see an increase in tight junction integrity, more tight junctions made within minutes and hours of exposure, which means that you are shifting from kind of an [inaudible] inflammatory leaky vulnerable state to one of an acute inflammatory regenerative reaction because you have enough information. It's very important to realize that these carbon molecules made by the microbiome don't actually do anything in and of themselves. They're very passive.

Dr. Zach Bush:The passivity is very important for safety because it actually doesn't do anything to your gut membrane. It doesn't force a receptor response. It doesn't change genomics. It doesn't change proteomics. It doesn't change signaling cascades in the mitochondria. All it functions as is the wireless communication network between the cells. So in the benevolence of this kind of matrix that's produced by the microbiome, we get robust communication and at that point the nucleus within the human cell of the enteric system can recognize that there's an insult happening by glyphosate or alcohol or whatever it is and it immediately starts making the zo-1 protein which is the big constituent of the tight junction and everything else within minutes. It's up-regulating, up-regulating, making tons of proteins. The Velcro's rebuilding and becoming stronger and not weaker.

Dr. Zach Bush:So the genomic response is simply an appropriate intrinsic quality to the human cell not coming from the supplement itself. It's simply turning on a normal intrinsic response in the human cell based on new information from outside the cell. The new information is not coming from the supplement. The new information is propagating from another spot, the extracellular matrix and an adjacent cell, et cetera, and so this big healing response is again not triggered by but supported by the carbon matrix made by the bacterial biome. So that's our step one of addressing somebody with gut permeability issues. Get the bacterial communication network back in there.

Dr. Zach Bush:This is a sterile product. There's no bacteria, there's no fungi. We're not trying to micromanage the microbiome just as we're not trying to micromanage the response in the human cell. So, get the whole matrix fueled with an information stream, get the wireless communication back up and you get a very neat, very rapid response. So tight junctions we've proved out again and again but we've now moved on to other compounds, big complex proteins like the enzymes. The DPP4 enzyme is one of the main mechanisms of detox in the pathway, has a lot to do with insulin maintenance in the body, how you manage calories, et cetera. We find that Roundup and glyphosate shuts down DPP4 production at the epithelial layer and the carbon molecules of the bacteria and fungi turn it right back on. So we get an up-regulation of DPP4 enzymes, better detox, better protection of the tight junctions, et cetera.

Dr. Zach Bush:Then we've moved on to the second part of that potential injury response which is glutathione production. Glutathione is the primary antioxidant made in your body. We traditionally think of glutathione as primarily being produced in your liver but it turns out that in the enteric system, the gut lining itself, those epithelial cells can also produce glutathione and that's probably the most important side of glutathione production in some ways because the vast majority of your immune system, some 70% of your immune system, lies in the one millimeter, two millimeters right behind that epithelial boundary. So it's appropriate for you to make your antioxidant reservoir right there locally.

Dr. Zach Bush:Once again if you give glyphosate or Roundup, you shut down glutathione production. Many things can do it. If you get overgrowth of specific bacteria, the Lyme spirochete for example will shut down glutathione production. Different mold spores from the environment can shut down ... Or mold toxins can shut down glutathione production. If we add back the carbon matrix, get back the microbiome communication network, we see as much as an 800% increase in the production of glutathione. So very exciting reality that we're starting to find out that the microbiome is governing human health through many different mechanisms.

Dr. Zach Bush:We believe this carbon matrix is the very foundation of it because it's a much more elemental, literally elements on the periodic table, elemental communication network that's even deeper and more broadly utilized than the micro RNA contribution in a microbiome. So, a microbiome produces the wireless communication network between the human cells, produces the micro RNA that would regulate the genomics of that human cell and then also produce the DHEA and other mentholated compounds, methylcobalamin and all of this, that would then be precursors to a lot of the larger hormones and other things made within the human body.

Dan Stickler:I think it's important to emphasize here too that this is an intervention to get the gut to respond but if you're not changing that lifestyle that created it in the first place, it's not going to be something that's going to be a lasting effect ever. Also really that lifestyle factor of everything still needs to be implemented in these situations. Now, I have a question about peptide because peptides are an area of interest for me. What's your view on using BPC-157 for gut healing? Because I've seen that in clinical practice have pretty profound effects overall and I know the data is pretty strong with it in the Robert Sider protective model and everything like that with the gut's response to BPC.

Dr. Zach Bush:Yeah, and so I'm excited by the peptide research. Again, it's like getting deeper and deeper down the track from the genome down, getting into smaller and smaller communication pieces. I believe the redox signaling environment is one level deeper and I believe it doesn't render the importance of peptides at all unimportant. So, the peptide that you were talking about I think was the BPC 157 that has been kind of championed by a lot of the functional medicine and the hacking community and the one cautionary thing that I would say about any peptide science ... When I used to develop chemotherapy there was a lot of interesting peptides that has moved on to a lot of active chemotherapy agents that are immune modulators.

Dr. Zach Bush:Any time you have a peptide based therapy, you have ... You're once again dealing with receptors, and so any time you have a receptor-based mechanism of action, you're gonna have a limited beneficial effect because if you start to overwhelm a single pathway, keep in mind that any single peptide should be secreted in a natural environment at the same and appropriate fraction to thousands of other peptides that would be produced and maintained in a complex homeostatic environment within the single cell, for example. So any time we take a single hormone for example, a thyroid hormone or estrogen or testosterone and we try to give that exogenously, we can overwhelm that natural balance immediately and the body has to make an adaptive, unbalanced response to that.

Dr. Zach Bush:So we can see a benefit in the short run to something like testosterone, increased muscle metabolism, maybe more lean muscle build, that kind of benefit, but if we maintain that person on this exogenous single action hormone or peptide, the system starts to get unbalanced over time. They get fatty liver, they're gonna go on to increase their cardiovascular risk. Lots of different things keep pounding them with exogenous testosterone, for example. In the same way, the peptide, being a receptor-based action, is going to ultimately stimulate cascades within the internal cell, which might be [inaudible] or any other number of enzymes within the cell which are then modifying genomic information at the genetic level.

Dr. Zach Bush:So while I believe you can get a really nice beneficial one time punch, if you keep the person on that peptide, that's where I think you have the risk of ultimately, A, diminishing the clinical result from that compound, and B, really chronically unbalancing what should be a very tightly controlled and eloquent balance of different peptides within the human body. So, I feel that way about digestive enzymes. I feel that about any time we take an exogenous one thing of anything that has a single mechanism of action, we're gonna risk long term perturbation of balance. So that would be my only concern.

Dr. Zach Bush:So if I was gonna use it clinically or personally, I would think about using it as a one-time, once a week kit. Use it intermittently so that you might stimulate a pathway but then back off so that the receptors free manifest and you don't overly tax the situation by ultimately depleting yourself of other compounds that are used up in the processing of that single peptide.

Dan Stickler:Yeah, and I've typically seen it used in a 30 day period, and I've seen really good results with it in my clinical practice as well as other reported results with that short-term use. A lot of athletes are using it for muscle and tendon healing as well. It's a fascinating area and peptides, I think, is a new realm of going beyond what is possible from a lifestyle optimization standpoint. We're in a state of medicine where we have technologies and science that is looking at enhancing the human state and we're learning as we go with this. It will be fascinating to see where this goes, and I think we're also getting into that area with gut health as well, and identifying some of the things that are available from a more kind of research and optimization standpoint than just core levels.

Dan Stickler:I see a lot of people that are like, "Let's be ancestral," but ancestrally we're not the same. I mean, we may carry the same genetic code but we're not sharing the same epigenetic expression that is adjusted over time to the environments that we're living in and we're passing on a lot of that code, so I think it's important to really pay attention to that. I tell people if you took somebody and dropped them back 12,000 years ago and expected them to thrive, they wouldn't. Even though they carry a similar genetic code, their expressions of that code have been adjusted over centuries of evolution and trans-generational epigenetic marks that have shifted the expressions of that code. So, I think that's important to keep in mind when we look at a lot of this ancestral stuff.

Dan Stickler:But I love what you're saying about that dietary pattern and getting that local foods ... I mean, I'm a huge believer that those micro [inaudible] are really signaling the body to what's happening in the environment and that's why I think you get benefit from eating local foods, is to signal to our cells of what's happening in our local environment and our cells can be able to make those adjustments to the environment where we're living. But we've kind of [crosstalk] ...

Dr. Zach Bush:The last aspect that we could add to that is the stress of the food itself, and so when you eat local, know your farmer, grow the food yourself, have a nice balanced ecosystem that that plant is raised in, you get a non-stressed plant, which is obviously more resilient against disease and dysfunction, which makes it easier to grow organically, et cetera, but importantly when you're eating from your more conventionally grown crops and this is amplified obviously when you go to conventionally grown meat protein, and so if you think of a chicken for example, your typical chicken breast that you get on a chicken sandwich or a chicken salad at a restaurant, that chicken was raised completely apart from nature, never saw sunshine, never seen grass, it's never scratched on the soil, raised in a little one by one cage, can't turn around, beak's been chopped off and just horrendous six week, eight week life that that boiler chicken has had, and now it ends up on your plate.

Dr. Zach Bush:Frighteningly the micro RNA that were turned on at the moment that chicken was butchered are very present in that food and so what was present as far as a genomic signal in that animal was terror, a sense of hopeless, a sense of fear, a sense of isolation, loneliness, disconnect from purpose. Every wrong pathway, not to mention all the inflammation and everything else, that's turned on in that chicken as it's butchered almost dead, almost dead from its invasive infections and everything else, that information is now sitting on your plate.

Dr. Zach Bush:So within an hour or two of consuming that chicken salad, it's very typical that the woman goes into a heightened state of anxiety or a panic attack because she just consumed the genomic sequences or the information that nobody cares, it's hopeless, you're dying and they go into a panic attack and they feel this impending doom that has absolutely no bearing from their experience and their reality that they're seeing around them when in reality they stepped genetically into the experience of that chicken in the moments before its death. So that's a pretty startling reality now.

Dr. Zach Bush:When we check the microRNA in a typical human bloodstream, at least 5% of the microRNA is from the food itself, and so that's not ... It's a real life situation where we've said for centuries really, you are what you eat. We now can prove that ... what the science is.

Dan Stickler:I love that you said that because that's ... You know, we used to laugh years ago about people saying the energetics of the food that you're eating and now we actually have science behind why that's happening. I mean, yeah, that microRNA that's signaling your cells to say, "Oh, the environment is this," which is what that chicken has gone through is preparing your body for that type of an environment and that's a huge disconnect that we really need to get, so I love ... That's a great way to close this out, too, is finishing up on that note because I think it brings it all together and helps people to understand the importance of the foods that we eat and how it's going to impact the whole system for the microbiome up to the entire human organism. So I appreciate all that you've shared today and taken the time to come back on to Collective Insights. I look forward to conversations with you in the future.

Dr. Zach Bush:Thank you so much for having me on and if I could give one kind of unprecedented plug for my nonprofit, I started a nonprofit to teach farmers how to switch from chemical farming to regenerative agricultural paralysis is the more people we can get aware of this, we're connecting consumers back to chemical farmers now to create an economic incentive for them to make the very difficult transition from chemical farming over to regenerative ag, and you can check out our documentary series regarding that at FarmersFootprint.US, and so if you can help support these farmers, I think we can radically change the agricultural environment on a very large scale to help save our young generations and preserve a future for our species.

Dan Stickler:Yeah, that's amazing. We will definitely put a link to that in the show notes. Again, Zach, it was a pleasure having you on and I enjoyed our [crosstalk] ...

Dr. Zach Bush:Awesome. Thanks so much for having me.

Speaker 2:Thank you for being with us for this conversation with Dr. Zach Bush. If you like this episode then please share it with a friend and leave us a review on iTunes. If you're hungry for more information to take control of your overall health and wellbeing, check out our free ebook that offers a well rounded approach to brain health, the foundational guide to neurohacking at Neurohacker.com/guide. If you're wanting to hear more from Dr. Zach Bush, check out episode 23 of the collective insights podcast. Make sure you subscribe to our podcast wherever you listen to them so you don't miss an episode. See you next time.





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