Dr. Diego Bohórquez: The Science of Your Gut Sense & the Gut-Brain Axis

welcome to the huberman Lab podcast where we discuss science and science-based tools for everyday [Music] life I'm Andrew huberman and I'm a professor of neurobiology and Opthalmology at Stanford School of Medicine my guest today is Dr Diego borquez Dr Diego borquez is a professor of medicine and neurobiology at Duke University he did his training in gastrointestinal physiology and nutrition and later neuroscience and by combining that unique training and EXP expertise he is considered a Pioneer and leader in so-called gut sensing or the gut brain axis now when most people hear the words gut brain axis

they immediately think of the so-called microbiome which is extremely important but that is not the topic of Dr borquez expertise Dr borz focuses on the actual sensing that occurs within one's gut just as one would sense light with their eyes or sound waves with their ears for hearing our gut contains receptors that respond to specific components of food including amino acids fats sugars and other aspects of food including temperature acidity and other micronutrients that are contained in food that give our gut the clear picture of what is happening at the level of the types and

qualities of food that we ingest and then communicate that below our conscious detection to our brain in order to drive specific patterns of thinking emotion and behavior and of course everybody has heard of our so-called gut sense or our ability to believe or feel certain things based on perceptions that are below or somehow different from conventional language today Dr borquez teaches us about all aspects of gut sensing how it occurs at the level of specific neurons and neural circuits how the brain responds to that how specific foods and components of food impact not just our

feeling of digestion or feeling good or bad about what we ate but indeed how we feel overall how safe we feel how excited we feel whether or not we feel depressed or sad angry or happy today's discussion I promise you is unique among all discussions of neuroscience at least that I've heard previously in that it combines two seemingly disparate Fields nutrition and Neuroscience indeed today's discussion gets into how different foods and food combinations impact how we feel and what We crave and what we tend to avoid we also get to hear the absolutely extraordinary story

of Dr borz upbringing in the Amazon jungle and how his knowledge and intuition about plants has influenced His science and how the incredible science that his laboratory is doing relates to all of us and our ability to better tap into our gut sense before we begin I'd like to emphasize that this podcast is separate from my teaching and research roles at Stanford it is however part of my desire and effort to bring zero cost to Consumer information about science and science related tools to the general public in keeping with that theme I'd like to thank

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Andrew I am super excited to learn from you today as I know everyone else is and if they don't realize why soon they will which is that you work on one of the more fascinating aspects of us which is our gut our gut sensing the gut brain axis which I think most people don't realize is nearby but separate from the so-called microbiome so we're not talking about the microbiome a very interesting and important top topic of course but we are going to talk about this thing that we call our gut sense and how it impacts

everything from our Cravings to our brain health and our cognition so once again welcome and I'll just want to kick things off by asking you to educate us explain you know what is this gut brain axis that we hear about and what's going on in our gut besides digestion well uh Andrew thank you so much for having me here uh thrilled to be here I knew that since we met a few years ago uh that we will have this ongoing conversation and a great conversation um the gut and the Brain you know people call it

an axis because traditionally thought to be an IM imaginary line that was connected through hormones so since 1902 when uh the first hormone secretion was uh a reported by Bailey and Sterling uh um it was known that uh when we eat then hormones these molecules in the gut are released and then they will enter the bloodstream and then eventually will have a cause in distant organs uh and for the next 100 or so years the the the the field focus on the on the hormones and as a consequence there was no direct line of communication

between the gut and the Brain but as often I I say you don't you don't say or we don't say the nose brain axis right like or the eye brain axis right uh and all of the organs are in sync working in sync so H in the gut there are also some sensory cells that are able to detect the outside world ER and then quickly communicate that information to the brain and I say the outside world because the gut is the only organ that passes throughout our body but it is still exposed to the outside

if you think about it uh if you will swallow a marble it still has the chance to get out um please don't do that anybody but uh but is still exposed to the surface you're right I never thought about the gut as the organ that is in contact with the outside world unlike our heart which is not in direct contact with the outside world or our liver or our pancreas but the gut is the gut is uh and if you think about it it's just separated by uh some compartments that have all of these VVS

you the epiglottis the uh gastrosoph gel Junction the pylorus The ilocal Junction the rectum so these are the the sequences of valves of Chambers with valves between them that food passes through air passes through and within each as I understand it there are different functions related to digestion but I think where you're taking us is that there are different modes of sensing what's coming through and signaling to the brain and other organs what's going on in the outside world by what's sensed coming through that passage is that correct that's correct and uh if we think

about it uh um the when we swallow something literally we have to trust our gut perhaps that's why we use this phrase trust your gut right because after that there's not much that you can do at least in uh regular humans that you can do consciously to uh expel something that perhaps is poisonous or toxic right um it is the gut that has to make that distinction and then usually accommodate things for abortion or let them pass uh through digestion and then ultimately they will be secreted right so if you could describe for us the

architecture that is the cells that respond to things in the gut and where they send that information and how they send that information what what is this thing that we call Gut sensing made up of what what's the parts list so the parts uh list uh has been evolving recently and while some of the elements we have known for for a while uh but in in general what we're talking about because is an external surface it is lined by a single layer of cells that are called epithelial cells and essentially these cells are exposed to

the outside world but they also are like attached in like a little membrane and they are the ones that interface with the inside of the body so in the stomach we have an try toi a epithelium for instance that is uh thicker so it can survive digestion chemicals and other things like harsh environment and in the intestine we have a little bit more of a um uh more delicate uh epithelia layer and within this epithelia layer there are several different cell types and one of those is the so-called enteroendocrine cell to put it in more

simple terms is a gut endocrine cell or a gut cell that releases hormones the term was coined in 1938 by a German uh physician uh his name was Frederick fer and at that time it was a major advancement in our understanding of physiology because he came up with the idea that the organs were not only communicating to organs in fact there were cells within the organs that were communicating to other organs through the release of some of these endocrine factors these neuromodulators or these neuropep that we know as hormones and uh so he named uh

the diffus endocrine system of the gut and then he came up with this word enteroendocrine cell and these cells are dispar at a ratio of roughly speaking like 1 to 1,000 epithelial uh cells throughout the digestive tract and we thought for the longest time that these cells were not connecting directly to the nervous system that they will release these neuromodulators and the neuromodulators through diffusion will act on receptors into some of the nerve Terminals and that is true that is a very well established uh system uh but in 2015 we made an observation that some

of these cells anywhere from 1/3 to 2/3 of these cells it depends on like the type of a systems that you use to identify they were contacting directly the nervous system and that brought up a a a new dimension of how it is that the gut could be could be communicating to the brain because as you know in the brain the synapses are the ones that are most predominant however there there is a lot of neurom modulation from endocrine uh functions in the brain too so in the gut uh this was not well described there

had been historically uh a few examples that these cells may be making synaptic contacts but they had not been studied and perhaps one of the main reasons why they hadn't being studied is because the the tools were not there and if you recall in in the um in 1990s uh with the advancement of green fluorescence protein as uh one of the main uh molecules to tag cells now all of a sudden there was a revolution in biology because you could identify the cells you can take them out you can do a a transcriptomic analysis to

see what genes they express uh you could co-culture them you can modify their genome and then you can start to interrogate what is their contribution to the entire body I'll just interrupt you for a second just to make sure that I never else is on board so if I understand correctly it's long been known that there are cells that are in these layers of the gut in the intestine and it's long been appreciated that as food passes through these cells somehow can sense the chemical constituents of the of the food as it gets broken down

and then release hormones into the bloodstream that could influence the brain those hormones could travel and influence things far away in fact um for those that don't know endocrine generally mean signaling at a distance between cells so between gut and brain or gut and liver it can also mean local effects so uh hormones endocrine effects can also be local but if I also understand you correctly it was only about 15 years ago when you mentioned green fluorescent protein we should probably just tell the Tale in a few sentences this is an amazing story in biology

where if you've ever seen fluorescing jellyfish that's because they express a gene for so called Green fluorescent protein and biologists have hijacked that Gene sequence and put it into mice and now actually other organisms as well which allows you to see individual cells and cell types so these cells release hormones the hormones influence the brain and other organs and now I think you're going to tell us that they also are able to make direct communication lines with other organs as well correct uh so maybe here is feeling how it is that I I got into

a starting the system and uh as you know between the 90s and the early 2000s there was an explosion in tools to study uh the brain and neural circuitry and the connection of neurons and each one of the neurons because up until the 1980s um the the tools were were limited electrophysiology you know Behavior Uh but then not only we had a green fluorescence protein we we had optogenetics we had uh a rabies modified to be able to trace how it is the the neurons connect at one synapse which was a it was a dream

I think that in fact that was the dream of Francis Creek when he was at the Suk he he talked about that having the way to control for those who don't know Crick one uh was a co-recipient to the Nobel Prize for the discovery of the structured DNA but then later in his career developed an obsession for neuroscience and yeah he daydreamed out loud about having tools to visualize individual Connections in the nervous system and as uh Diego is pointing out scientists have hijacked the rabies virus which hops between neurons labeled the rabies virus with

Things That Glow fluorescent and in doing so we now understand a lot about what Crick dreamed for which was the ability to see different specific Connections in the nervous system yes uh so then you could isolate the cells and then you could do sequencing technology to see like what are the genes that the cells are expressing and then you can start to understand the makeup of the cells uh in 2009 uh h cers a scientist u in the Netherlands uh did a beautiful experiment like he he discovered these factors that will trigger a receptor of

the stem cells in the intestinal epithelium and will form literally a mini gut in a in a dish you know these cells will be all lined up and then they will have alumin and I remember like seeing some of these papers coming out uh when I was a PhD student and and I was already studying the gut so it was inspiring to see like all of the things that all of a sudden you could do right so when I began studying the cells um immediately by isolating the cells and simply observing the cells in the

native tissue of these um m models it quickly became evident that some of the cells had a very peculiar Anatomy uh some of them had these very prominent arms at the base like like literally like um in the 16 Chapel uh Adam reaching out to to God right like with a hand uh the cells will have that type of anatomical H features and even ending with a little hand at the end of that arm uh and obviously I I immediately thought like why would a sell that it is supposed to react to food and release

hormones into the bloodstream or just in the vicinity will invest so much energy into developing an arm right so then I started to look well perhaps it is because it's providing a bridge directly into the vasculature into the vessels to put the the hormones into the bloodstream right uh grown you know like a I couldn't find that that direct connection uh so then I started to study perhaps they were associated with nervous system and that's how uh we made some of the first observations that some of them uh with the arm uh or without the

arm they will have a more intimate relationship with nerve fibers and that of course open up um a bunch of new questions and but the first things that the first thing that we had to do it was to come up with a name for this foot and it kind of became organic and I want to highlight this because I think that as we go through the discovery uh trajectory we don't realize the need to also engineer language how we go about language is we start to attach a words that we already knew and we start

to put them together to describe something that new that we're observing right and I say this because at the very beginning uh with my mentor we will start to call these little feet first we call them axon which is like uh the for like the long extending branches of the neurons the main branches of the neurons so we will call them axon like because they look like a a baby axon but then we called them also like Pudo po because it was like a pot but it was Pudo uh and at some point we and

it was coming from like some cells in the in the kidneys that they are called uh po podia or something like that so it was axon like pseudo like basal process to describe that it was on the base so at some point it became so long that we couldn't fit it in an abstract right so a bit of a mouthful so we began thinking about it and then eventually I came up with a term I thought like ah neurot um and I remember pitching it to my mentor and I said like let me let me

think about the weekend and then on the on a Monday he came in and he said like you know it has a ring to it I think that we should use it but but essentially the the the thought was that if these cells are contacting then perhaps they are passing information directly onto the nervous system and that is very different than just spewing a neuromodulators in the vicinity and hoping that some of those catch the nervous system right and like I said while that is still exist and I think that is just like matter of

space and time like they they modulate these terminals in a different space and time the hormones but the transmission uh the neurotransmission is directly and more precise in space and time could I just um interrupt for a moment please so hormone signaling endocrine signaling generally is slower than the forms of communication directly between neurons right um could be on the order of seconds sure but typically on the orders of minutes or hours uh whereas neural communication on the order of milliseconds correct so if I understand correctly these what you decide to called neurop pod cells

and thank you for shortening the name um from the other description um line the gut are we talking about everything from esophagus down to the stomach to the intestine or is it just at the level of the stomach and intestine where where do they this is uh this is where the conversation becomes expansive because uh these neopods or causings of these neurop pods so these neurop pods are simply a specialized neuro epithelial cells meaning that are electrically excitable that they can discharge electricity but they are this type of cells are in every single epithelial cell

epithelial layer of the body because that's how the body creates a representation of the world through sensor cells that are equipped to detect the outside world meaning that they can be exposed to fluctuations in temperature fluctuations in PH fluctuations in concentrations and then they quickly can generate a chemo electrical coat that they pass it onto the nervous system and then ultimately the brain integrates that and says like oh my belly is feeling good but I'm feeling cold in the skin right and that is thanks to all of these neuroepithelial cells that they are even in

um tasting so to speak the uh the seru spinal fluid inside of the spinal cord and the ventricles they are inside of the the inner ears The Taste uh The Taste SPS so it is and in fact there's a beautiful book from the 70s uh from some Japanese scientists uh fuet Canon Kobayashi who uh called the cells Paran neurons and their whole concept is that there was not such a discrete distinction between an entire a neuron that lives inside of the brain or the central nervous system and a A neuroepithelial or a neuroendocrine cell that

leaves exposed to the outside simply that there is a continuum of adaptation so the the organism can bring the information from outside inside into the uh body to be able to process it and then process it and then guide Behavior So based on the way you describe it we have these neurop pod cells that line our gut and we also have these similar cell types in the other organs of the body and these cells are responding to the chemical constituents of what we eat as the food is broken down also to the temperature of the

environment to the pH the that is how relatively basic or acidic something is that we ate and presumably to other features in our environment as well and all of that information is activating these cells to some degree or another and then we're releasing hormones into our body as a consequence but also there's a direct line to the brain and we're not necessarily aware of all of this happening right I mean until you describe it I think most of us are have not been aware that this is happening and we probably shouldn't be aware you know

like as I often say like um if you and I are having a conversation we probably shouldn't be aware of the macras and the spleen that is chasing this bacterium that got inside of the lettuce that we swallowed in at launch right like just do your thing so we can keep communicating right except maybe don't eat more of that lettuce right which is the okay so you discovered these neuropodial to selectively label them what did that reveal about their connectivity with you're referring to it as the nervous system which I love because a resounding theme

on this podcast as I always say you know brain and spinal cord and all the connections to the body and back again is the nervous system but what what did you discover in terms of the connections with the brain proper here is where the tools started to make a a big difference you know all of the sudden you could see the resolution of a receptor inside of a cell using certain type of microscopes right so I remember that one of the first questions that I will always get drill on you know how these uh laugh

meetings can get intense right like when I will bring data and showing just very simple um imunohistochemistry meaning labeling to see how the cells were interacting with uh the nervous system um as and I will show some of the images then uh the other scientists will say well you know yeah those are nice images but remember that contact does not mean connection you know and I went thinking about that like at the very beginning I thought that it was silly semantics you know um but I I specifically remember that there was one time I was

running and I was thinking like how do you demonstrate connection between two cells and then I thought that since we had the ability to identify the cells by fluorescence we could isolate them based on their fluoresence and what will happen if we put them in front of a sensory neuron and then just record them inside of a microscope right over time and I thought maybe they will get close to each other and then we can go and do some more labeling and show that they are H contacting or connecting but much to our surprise we

actually saw that in real time they when you isolate them from the mouth and you put them in a dish they both look like these round circles but after a few hours not only they get close to each other but they recapitulate the circuitry in the dish literally they form like two brains in a dish right like it's the gut and the Brain in a dish amazing uh yeah and that that was an eye opener you know I still remember it was somewhere I think it was like June 27 2012 when I saw that experiment

because um it opened my my eyes to so many different things one was that this cells are not a static because since we have been seeing them for decades just in as slices or fixed tissue and we have lost the notion that this thing is constantly moving right the cells are actually moving the cells are actually moving so these cells line the gut meaning they're along the walls of the gut an intestine yeah the intestine they reach a hand into the gut to sense whatever chemicals are there yeah they have Little Celia little hair or

microvi that is literally like little hair that is exposed to the Lumen MH you know so the Lumen folks is the the cavity the empty cavity of the gut not empty but you know the the the internal part and so they're sensing the chemicals there and you're saying they can move okay and they're sending a process by the way folks anytime you don't know whether or not something is a dendrite or an axon just call it a process you you'll get it right uh a process up to the brain underneath that will connect to the

nervous system I see so through a series of of of stations yeah okay um amazing so what we're talking about here is Diego's discovery of a pathway from the gut to the brain that essentially allows sensing of what's happening in the gut to inform feelings decision correct yeah so that that was uh the first experiment like showing H in addition right the next experiment was well does it happen in the in the mouse and then through a series of I have a friend neuroscientist that she calls this Ravis gymnastics because you have to put in

some genes and make things work then we demonstrated that these uh cells that the virus will be capable of infecting these cells specifically instead of infecting the other epithelial cells it will infect these new epithelial cells because rabies likes neurons and then it will jump from that cell into a nerve fiber and these ravies can only jump one connection right and what it was uh surprising is that the fluoresence from that rabies will show up in the brain stem and in the bodies of the cells that are in the noos ganglia which is this cluster

where the cell bodies of the um neurons of the begos nerve are located right underneath the the neck meaning that there was just one stop between the surface of the intestine and the brain stem the two cells were connecting that um that space you know so obviously the information that was the anatomical basis for the information to travel very rapidly up into the brain and rapidly in the subconscious right like we're not necessarily aware of it although uh I've read that there are some instances in which people become more aware of it either in uh

a ag typical uh fashion or with meditation and other things that people can become aware yes people definitely can become more aware of their so-called interoception what's going on at the level of their heartbeat frequency or their gut sensing if they spend time on it some people as you mentioned develop an almost pathologic sense of interception such that they have trouble navigating normal life because they're so aware of what's going on inside their body this is actually an interesting issue in the field of Psychiatry my colleagues in Psychiatry at Stanford tell me that um some

people with a lot of anxiety for instance are so aware of their heartbeat that it becomes um disruptive and distracting to them so it's not always the case that it's better to become more aware of your internal processing sometimes it can be um dilus other times it can be good for us um some people are very unaware of what's happening in their body and they need to develop more awareness of that I feel like as long as we're talking about rabies we should have a little bit of fun and explain to people something about rabies

viruses because what we've been talking about is the use of viruses as uh experimental Tools in order to you know take a virus basically attach or put something in so that whatever cell is infected by it glows a certain color so you can see the cells and visualize the circuitry but as long as we're talking about rabies I feel like it's such a uh a word that has such salience the rabies virus which exists in nature um is amazing because it's um I don't know if it has a Consciousness but it essentially propagates between animals

by way of the animals that have it bite they they become more aggressive they bite a um a Target animal the virus gets in it's picked up by the nerve Terminals and is carried back from one ner cell to the next across synaptic connections right synapses the G little gaps between neurons and what Dr Diego Boris has been telling us is that scientists have engineered the rabies virus so that it only jumps one station and then stops you can do this by modifying the coat protein there's a bunch of fun virology that can be done

uh to do that but what I find amazing about rabies virus and there's a great book by the way called rabid which is a a essentially a history of the of the study of rabies um is that once it travels from the S of the bite up to the brain what does it do it changes the brain to make the now infected animal or person more aggressive so that then they go bite somebody else um so I mean in some ways that the viruses have a sort kind of unconscious genius to them right what's the

best way to get from one animal to the next well there are a number of different ways but one way is to just make that animal more aggressive so it goes and bites things yeah make wild make the animal work for you right make the animal work for you right it's it's it's almost exploitive right it exploits certain circuit in the nervous system I'd like to take a brief break and acknowledge our sponsor ag1 by now most of you have heard me tell my story about how I've been taking ag1 once or twice a day

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two Stations between these cells or one station really between these cells and the brain and so now these cells can sense chemicals in the gut that are the consequence of the breakdown of food and send that information directly to the brain what does the brain do with that information all so here comes uh the key experiment and this was building obviously on the work of other scientists that had already described that the gut had some uh receptors for uh sugars for specifically for glucose for other nutrients around this area in the early 2000s when we

were starting to be able to identify some of these cells then uh it quickly became uh obvious that uh these cells these enteroendocrine cells throughout the lining of the stomach intestine colon they had multiple receptors for multiple nutrients you know like we have the macronutrients for instance sugars fats proteins but within them we have you know a repertoire of molecules you know multiple uh lipids multiple types of sugars and so on and so forth and these cells depending on their location they will Express a different type of receptors or a combination of those receptors and

I said depending on the location because when we're eating let's say an apple you know the apple is going to be partially undigested by the time that it enters intestine but by the time that it gets to the the colon most of those nutrients have being absorbed and perhaps only fibers are surviving to feed off most of the microbes that live in the colon right so the gut has evolved to mirror and to become a velro to the molecules that will be in that in that specific space so it will detect so um it will

detect sugars more in the proximal intestine but fibers or uh fermented by products more in the distal intestine or in the colon like shin fatty acids beate prop propionate um and so on and so forth you know what other kinds of nutrients do these neurop pod cells detect from food so you mentioned sugars you mentioned ferment fermentation so um presumably short and longchain fatty acids yes the short answer is that uh I think that in due time we are going to realize that they detect just about every single thing that we put on our mouths

every day you know uh that they have some either an a specific receptor that is dedicated to it or a combination of receptors to be able to detect um some of these compounds and not only the chemical compounds but also an area that I think that is going to be fascinating in the future is the mechanical distension plus uh the the adjustment in temperature as the Kim starts to flow from the mouth into the colon like for instance I I I heard this from a bioengineer not long ago that was engineering a artificial gut on

a stomach and he uh shared with me um a piece of information that I was not aware of that uh the esophagus has to adjust the temperature of the food very rapidly within seconds into physiological temperature of the inside of the the body like so we're having hot coffee within couple of seconds it has to be at the physiological temperature of the body by the time that it gets into the stomach right and all of that happens in very rapidly amazing suff right so if I understand correctly these neurop pod cells have a variety of

different receptors depending on where they are located along the trajectory from the mouth to the rectum that's correct and some are sensing sugar some are sensing temperature some are sensing pH so relative acidity some are sensing amino acids presumably I mean I've heard it said and I believe there's a a researcher down in Australia who's been very bullish on the theory that we are not exclusively but we are predominantly amino acid foraging machines because we need amino acids for all sorts of important biological processes um and these cells are essentially evaluating how how much sugar

how much Lucine how much um uh short chain fatty acid how much um you know essential fatty acids of different kinds and then making changes to the gut itself but then presumably signaling that information elsewhere in in the body so um here I'm going to give you a something that will get your gut Ching so to speak so these cells have to make sense not only of the molecule that had been ingested meaning the chemistry of the molecule let's say it's glucose it has to make sense a little bit of The Taste is it sweet

right is it bitter then it has to take into account how much of the molecule is absorbed inside of the cell right so that's the second layer of integration then once the cell has eaten that molecule so to speak then that molecule will be digested inside of the cell to release ATP or some other uh compound ATP is for energy for instance that has also have to be taken into account for instance in the in the in glucose glucose activates the tas1 R3 which is a sweet taste receptor then the glucose is absorbed by some

of the sodium glucose Transporters which are active Transporters and these Transporters uh depolarize the cell and then once glucose gets inside of the cell glucose enters the TCA cycle is catabolized and then produces ATP and the ATP further activates another uh voltage gated Channel further depolarizing the cell and then the cell releases in turn a transmitter for instance glutamate that very rapidly tells the vus nerve within milliseconds you know I got sugar uh and it tells it in two phases because that glutamate will activate two different type of receptors ionotropic which are very fast and

metabotropic which are a little bit more you know more delayed uh but then the metabolism of that glucose that produces the ATP and farther polarizes the cell we believe that um it will cause the release of the hormone of the neuropeptide so then the neuropeptide comes on top of that and gives you that full experience of what it means to uh consume sugar right um so that happens at the level of one cell and at the level of one molecule so imagine like all of the computation that the gut has to be making for each

one of the molecules throughout the digestive tract so if I stand back from the picture um what I get is there are very interesting cell types that line our gut that are evaluating all of the not just macronutrients proteins fats and carbohydrates but micronutrients within the food we eat as well as some of the other qualitative features temperature for instance maybe even quality of the amino acids or the sugars you know simple versus complex sugars Etc if we could just further zoom out for a moment and take a human perspective on this at the level

of experience I once heard you tell a story about um someone you knew who changed their gut radically and that changed their entire perceptual experience of food including certain Cravings would you mind sharing that story yes uh thank you for uh bringing that story Andrew that story is very personal to me I of often say when I get on stage that we are constantly influenced by two things in life the food that we eat and the people that we meet you know like now I uh we have known each other but now we meet in

person and we are knowing other people right and I remember that when I was uh starting my PhD in nutrition at North Carolina State University I was uh so I didn't grow up in the United States I uh grew up in Ecuador and uh I was invited to my first Thanksgiving celebration so I sat at dinner and you know as we began chatting with uh the people that were next to each other uh all of a sudden I was uh enthrall in this conversation of a woman telling me this story about her experience with gastric

bipass surgery for treating obesity so gastric bipass surgery uh was begun to be um developed by surgeons uh in the 60s and by the 90s it had become a mainstream uh type of surgery for the treatment of uh chronic obesity so she told me that there were primarily three things that happened she said well within uh six months of the surgery I had lost about 40% of body weight you know she said like I was about 300 pounds you do the math you know so it was a it was a significant amount significant amount she

said within one week of the surgery my diabetes was gone she said I did not need more insulin shots so I had the same reaction that that you're having I was like that you know I don't know much about diabetes but I know that is is a major health uh burden right but the thing that really caught my eye was when she said but since you're studying nutrition I want you to answer this to me she said why is it that before the surgery I could not even look at sunic Side Up X she said

uh just looking at the Yoke will make me quizy you know but after the surgery no not only I can eat sonide up eggs I actually have a craving for the yolk she said every time we go on Saturday to a restaurant for breakfast I will take the toast and will actually clean the plate uh of the Yol so how is it that rewiring the the gut uh alter my perception of uh of flavor alter my my cravings and my mind to to get the the Yol she said and even inverted her sense of what

was aversive versus repetitive and and I guess for those of us that don't know meaning me um I understand the gastric bypass surgery involves the removal of a portion of the of the gut um how much gut tissue do they actually take is it centimeters inches I mean the guts a long distance so what what what do they do for gastri in in in simple terms the most um the classic surgery is called uh ruin y gastric bypass surgery which involves a a reduction of the stomach and short cutting the uh connection of the stomach

to the intestine so you will cut you know 1/3 which will be the dadum uh one third of that will be uh cut and then that portion will be reconnected to the stomach meaning that you're short circuiting the the gut and the whole idea was at the very beginning was like well if we reduce the surface that is exposed to food then we can reduce body weight by the simp L um reduction of surface that is exposed to the food that is absorbed right and uh what it became very clear is that well before the

body weight uh changes got taken place uh there was already like some dramatic changes in physiology like like the hormones the neuropeptides that we release from uh the intestine in response to nutrients you know will change very rapidly then as I mentioned the food choices will change diabetes will be resolved um so then it became obvious that it was not necessarily just the the uh reduction in the surface of of the gut so that's one of the main uh surgeries the other one um as I understand is vertical isaf gastrectomy and this vertical s gastrectomy

is simply a a reduction in the size of the stomach so is now the stomach is very tiny and the idea is that will accumulate uh less it could hold less food and then the food will go very rapid rapidly into the intestine and what is very is becoming very obvious is that there is a rapid change in the sensory function of the gastrointestinal tract so the gut seems to rapidly shift perhaps become more so to speak in general terms more sensitive to the presence of nutrients right interesting so this woman that you met at

Thanksgiving had G gastric bypass surgery and presumably I think it's fair to assume a good number of these neurop hot cells that sense different nutrients were removed and as a consequence she completely shifted her craving of a particular food and is there any sense whether or not no pun intended the lack of sensing of what was in uh you know Sunnyside egg yolks was somehow related to a shift in appetite or something else or is it merely a a a um a qualitative albeit a dramatic qualitative sh in in what she craved so two uh

contextual pieces of information uh so I remember leaving that dinner and I was like wow this is Major you know like I'm sure that people have green about this or don't research um and I realized that it was very little was known even gastroenterologists knew very little about this the first clinical report that um the alteration in food choices was common in these patients uh came out I believe in 2011 uh and then later on scientist replicated that even in rats or in mice uh we have done it in the laboratory and consistently they they

Chang their food preferences their their um food choices so er in in recent years we have been we have been uh studying that that system um and I will tell you that in 2022 this is another important contextual piece that we have gotten have not gotten to it so after we uh found and we describe that these cells were connecting to the nervous system and that they were sending information up to the brain very rapidly the challenge was well if this is a sense what behavior is affecting right like how is it that is affecting

the the responses of the organism and that took a little bit of a a technical hdle and here is where optogenetics uh comes in yeah please um explain for people what optogenetics is in at least at a top Contour level yeah so optogenetics uh 205 uh Professor Carl daero Ed boen and other scientists had been able to make this this dream of an experiment which was uh isolate the the genes that encode for these opsins that are sensitive to specific wavelengths of light and put them into neurons and now by turning that light they could

make the neuron activate and then ultimately then later on they went on to describe that that could be used to control specific cells that are regulating behavior and then by that Define what cells are orchestrating certain type of behaviors like movement food intake thirst anxiety so on and so forth so in 2014 we we began H trying to adapt that technology to the gut very quickly we realized that the way that was that light was brought into the brain was through a fiber optic cable that was rigid and uh and in the brain you know

it it helps that it's actually rigid but in the gut it doesn't help because the gut is constantly moving and so on and so forth so it's not compatible for running those experiments and here's where I usually say like you know we really don't know what is going on because some some forces like move around us and in 2017 uh Professor Paulina Nika from MIT came to give a talk at Duke and uh she reached out to me and literally she came and as we were chatting she said like Diego I see that you're you're

working between uh in this interface of the gut and the brain and I have this fiber optic that is flexible you know would you have any use for it so with that H fiber optic that made a big difference to study interrogate the function of these cells to behavior so when we were able to put those opsins the light sensitive uh proteins inside of these neurop pods and now when we turn the light on to shut off these cells very rapidly we found something very interesting so normally animals when you give them the choice between

a suer which is the void of caloric value so like a like a aspartame or or Stevia or something y uh and you give them sugar table sugar the animal invariably will go to Sugar they prefer sugar they prefer sugar you know uh if they have never seen sugar it will take them a little bit more time but regularly um by the second day is within 90 seconds that they detect what is sugar so they're drinking out of one tube they get some water with stevia they drink out of another tube water with sugar and

they invariably prefer the water with sugar that's correct and uh people have described this um this phenomenon for a while and in fact in 2007 There Was An Elegant experiment done by Professor Ian Deo at Duke University in which the uh sweet taste receptors were or the The Taste uh receptors were genetically erased and the animals um were not capable of distinguishing the sugar the sweetener from the water but they could still distinguish sugar from uh water meaning that there was something else that was detecting that that sugar so just to make sure people are

on board an experiment where sensing of sweet taste at the level of the mouth is eliminated does not disrupt the preference for sugar water correct which means that there's something going on below the depth of Consciousness that causes mammals presumably us included to prefer things that have sugar yes and uh then uh Professor ton clani he had been studying these uh these behaviors and he went in so far to suggest that perhaps the sodium glucose Transporters are some of the ones that are detecting the the sugar as it enters the intestine and that's what is

causing the behavior um so we began working on the system and we we Wonder Could these cells be the ones that are guiding that Behavior Uh and around the time that uh we published this work uh Professor uh Charles zuker at uh Colombia also further uh Advanced that that area by uh building on the on the previous work and demonstrated that um there were a population of neurons in the brain stem that were integrating this information from the gut uh and by that ER the gut and the Brain were guiding this this Behavior so and

it is true that from the earliest of Ages We crave sugar or at least if we are exposed to the taste of sugar it tends to drive seeking of more sugar you can see that in babies even correct and as I usually say um I call it instinctively because our mother doesn't have to teach us hey uh Diego that is glucose you know uh it may present Us in some ways but uh at the end of the day I have to go and get my glucose get my am acids right because eating is very simple

we're just trying to solve this issue of getting our carbons getting our nitrogen getting our phosphorus our potassium our sodium and our chloride in so many different ways shape or forms right so I went back to the experiment the key experiment so when we were able to put these opsins and bring the light and shut off these cells very rapidly when we had presented the animal with a choice of sweetener over sugar then all of a sudden the animal became blind to the solutions it couldn't discern between the the the stevia so to speak or

the sweetener from the actual sugar and the entire manipulation the experimental manipulation that is is occurring at the level of the gut the intestine that's right right after the stomach it's like just a small portion of the intestine so if we make an attempt to transfer this to the human Real World Experience um um if I have some ice cream it tastes sweet I like it and now I'm thinking about it and I'm craving it just a little bit I don't have a huge craving for sweets but um I do like some of them so

eating ice cream it tastes sweet the tendency is to crave more that's correct right you have to eat a lot of ice cream before you're truly full yeah um and most people self-regulate or their parents regulate for them um by limiting the number of Scoops or something um and that sweet taste is part of the motivator but what you're saying is that as the ice cream enters the gut there are neurop pod cells there that are also sensing the sugar and signaling to the brain and the brain is responding to pursue more of that sweet

containing substance that's correct and it's happening below our awareness it is independent from the Sweet Taste of the ice cream correct the the conscious sweet taste the conscious sweet taste which if you think about it it's not fully conscious right you know as a what we detect of the world it's just a very tiny little portion right even sight you know like we think we are looking for light but I don't know what is happening behind my my back I trust that everything is going okay right so um so when we shut off uh the

cells uh the animal and as I usually say like became blind to the sugars because it's kind of like uh a keing to having turn off the cells that are able to detect light the wav length of light for us to be able to discern color right and it's not that the animal is losing its memory because then you if you remove the light and now the the cells are functional again then the animal again is able to distinguish one solution over over the other uh and then we did a couple more experiments in there

and what happens uh if we do the reverse if we turn on the cells now and the fascinating thing is that when we turn on the cells now the uh the mouse will eat the sweetener as if it will be sugar interesting so the activation of these cells makes them crave non-caloric sweetener or low calorie sweetener as if it were sugar but is it blinding them to the difference between sugar and low calorie sweetener so here's another piece of information if we will offer them water and we will turn on the cells the animal will

drink the water as if it will be sugar like it will be appetizing even though it's just plain water yes and what is becoming very obvious is that uh the gut has this sense at the most basic level what the senses are uh doing is calculating a couple of things one is um in the salience of the stimulus is like how intense is the stimulus and the other one is the veilance of the stimulus is a pleasurable or painful so to speak in like broad terms and I say this because on the on the pain

side um uh Professor David Julius professor hly in uh jinra at UCSF they have done some beautiful work demonstrating that there are these serotonin releasing cells specifically in the colon they have focus in the colon that they couple two a nerve fibers of the spinal cord and when they are activated now all of a sudden they drive what we call in the clinical uh realm visceral hypers sensitivity so they are responsible for triggering the hypers sensitivity of the nerve fibers the colonic nerve fibers because they detect no noxious stimuli and then ultimately they gate that

noxious stimulate and pass it on to the nerve fiber as a in Broad terms as a painful stimulus so is this irritable bowel syndrome it is we could call it as the biological bases of what could degenerate into irritable ball syndrome and so on and so forth or these chronical GI uh they call them uh disorders of gut brain interactions in the clinic I'd like to take a brief break and acknowledge our sponsor inside tracker inside tracker is a personalized nutrition platform that analyzes data from your blood and DNA to help you better meet your

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ear that respond to sound waves not directly but through a number of different transducers and this kind of thing and then of course Where You Are all familiar with the skin and that it responds to pressure light touch tickle itch Etc what I'm understanding based on what you're telling me is that all along the pathway from our mouth to our rectum we have sensory cells that are evaluating the chemical constituents of the foods that we eat emitting broad kind of maybe even crude slow signals in the form of hormones to change our appetite our feelings

of well-being maybe our feelings of not wellbeing um but also sending direct signals to the brain to drive certain types of thinking emotions and behavior what sorts of thoughts emotions and behaviors are foods known to evoke through this pathway from the gut because the story about the your friend that had the gastric bypass and then changed the relationship completely to the craving of or the aversion to uh Sunnyside eggs indicates that it's a pretty crude as I'm describing a system to begin with but It ultimately converges on pretty fine scale decision-making you order this and

you avoid that um you really like this and you really are almost nauseous at the thought of something else that's pretty high level decisions it might not seem like it to most but um you know it's impacting you know significant be Behavior or impacting Behavior at a significant level that's correct um and and uh when I think about that specific example uh is that after there has been this rewiring of uh of the intestine then now the intestine is very sensitive so to speak to the stimuli and when those lipids from the Yoke start to

enter the intestine if that sensitivity has changed meaning it could have change in how fast it reacts to the stimulus or how fast it communicates to the stimulus and how s sensitive it is to the saliency or like the the the strength of the stimulus it could communicate that o what it used to be repulsive with a tiny little bit of amount now it is actually pleasurable with a tiny little uh bit of amount and here's a a clear example so it has been very well um I will say that it has been documented uh

in the clinic that patients that undergone gastric Bass surgery they're actually more prone I think that the the the it goes from like two to Sevenfold uh the likelihood that they become they they will they will develop alcoholism really yes uh because now the way that they describe it is like well you know either before I didn't like wine um and then now I you know after a few months of a surgery I'll have one glass of wine and then all of a sudden I found myself going to 2 three four you know and then

they will become either more sensitive is still not known the entire biology but they will become either not only more sensitive but more more attracted to that type of stimulus I can't help but ask about OIC monjaro and glp1 glucagon like peptide one um analogues which are really out of all the rage right now at least for discussion but many many many millions of people are now taking this for treatment of diabetes and for weight loss um my understanding is that glp1 acts at the level of the brain the hypothalamus to reduce hunger but also

at the level of the gut to give the sensation of more gastric distension is there any knowledge of whether or not glp1 interacts with the neurop Pod cells and this pathway that you're describing given what these neuropodia complimentary question and uh in fact when I got into uh studying in this field uh 15 years ago uh the study among scientists in this area uh glucagon like peptide was already very uh popular uh in the study in fact in this area it was people were very focused on on the study of this peptide and they were

very focused on the study of this peptide because it was one of the most potent um stimulators of insulin release in the pancreas uh after gastric bass surgery it will actually increase its amount in uh circulating levels uh and there were already like uh some uh studies suggesting that the the effect of this gluc glucagon like peptide it was actually not through the circulation but more in a localized uh action onto nerve fibers especially of the vus nerve so there was already like someone going um discussion about this uh and certainly some of these enteroendocrine

cells these um neuroendocrine cells particularly at least in uh in animals I think it's more distal and uh in the digestive tract that they do release this glucagon like peptide um one in response to primarily like all of the macronutrients but primarily sugar and then these glucagon Li peptide one will act on specific receptors of the nerve Terminals and then will trigger some of the behaviors is also thought that uh it acts at the level of the uh the brain stem and what it will uh potentiate is the reduction of uh appetite so I say

that this is a complimentary question because what is happening in the first few milliseconds is the actual choice and the actual feeling of how you feel about food and what is happening in the minutes two hours later is the amount how much you can eat right and when you should stop because after four hours you're going to come back and feel again the tickling of the gut because the gut starts uh to churn again and it starts to call for food remember it has to fit uh two giant organisms the host itself but also the

microbes that are inside right so it has to H keep uh so to speak that that hunger going every 4 hours or so right so that's why the hormones are more acting on the cyclical uh circadian way but the transmitters are acting in this very fast uh responsive way of uh the precise stimul stimuli in a specific uh regions of the gastrointestinal tract so these neuroendocrine cells are releasing glp1 or responding to glp1 they're releasing uh glp1 they're releasing glp1 to shut down transiently shut down hunger and probably there is some interaction between the cells

that they are they are having you know the technical term is autoc cring or they are having like power cring between the cells you know neuromodulation but primarily let's say they respond to the stimulus and release gp1 onto the nerve fiber right I have a theory uh for which I have no direct data but I'd like your thoughts on um having spoken to a lot of people that work on nutrition but also gut bra brain axis today and U microbiome in previous episodes that one of the key things that a human learns somewhat unconsciously but

also consciously is the relationship between a given food which macronutrients it contains the ratios of you know carbohydrate protein and fat the taste of that food the amount of that food translated into to calories but also physical volume and then the micronutrients why do I say this well there are a growing number of studies showing that the ingestion of Highly processed food leads to the intake of excess calories or more calories than if one consumes Foods in their more natural form single ingredient Foods or two ingredient foods are very different than a food that has

a bunch of different things in it and it seems to me that if we were to look back into our Evolution um sure people were making stews soups and things for a long time um presumably the sandwich came about through a either desire for convenience or taste or both uh you know putting Meats protein in between two pieces of bread something of that sort um by definition of a sandwich maybe some vegetables in there as well some cheese but that what this whole pathway along the gut is trying to do it seems is to deconstruct

what's coming in what's here and shaping choices as you mentioned about food Choice including the amount of food to further consume and whether or not to return to that food or to avoid it and at the extremes it seems pretty straightforward and this is a very classically described case right you you go and you have the um you know the kungpow shrimp or you have the lentil soup at a given place and a few hours later you don't feel right start some sweating some gastric distress and you develop a pretty broad aversion to that food

or maybe the entire meal maybe the restaurant maybe even that entire type of Cuisine depending on how um how much of a lumper or versus a splitter you are as we say in science right how much you you make uh kind of large large bin decisions or fine bin decisions um this is nerd speak for saying you know do you do you go back to the same restaurant but order something different or do you just decide to never go back again but that's a pretty extreme case right the other extreme would be you eat a

food it's delicious you feel wonderful the the restaurant the people it's wonderful and you crave more of that food okay there's all the contextual stuff too but what we really are talking about here is how one navigates this whole landscape of what to put into one's body in terms of nutrition and trying to understand how that's impacting everything from how we feel right away how it tastes whether or not we conceive it as good or bad for us whether or not we think it's impacting our body composition and health in ways that we want or

don't want I mean it's pretty complex stuff right this is at least as complex as going to the Metropolitan Museum of Art and looking at a painting and trying to evaluate whether or not you really like that painting or not in fact it's probably much more complicated than that but it's what we do and I'm beginning to get the the asense again no pun intended that this pathway that we call the gut brain axis is really it's a six sense of a very elaborate kind so you just touch on a on an entire realm of

a topic which is one of my favorite topics because at some point you know uh we as scientists we travel we travel the world and it started to become very obvious to me that wherever I went we solve this issue of food in a very similar way whether it's a tortilla or two pieces of bread which is another way of a tortilla uh you have your carbs and then you add a little bit of meat or a mushroom and now you have your protein or fish or chicken or fish your chicken the the carnivores will

say Mushrooms not a protein the vegans will say mushroom beans lentil great protein we're not here to to resolve that debate um do as you choose and then you add the lettuce or the vegetables and here's the first stop in that com the first uh stop in that in that discussion because this is fascinating there is some recent work showing that if you remove the protein from a diet the animal swallows that that that meal ER the gut evaluates that there is no protein in there and it stops eating that meal wow so this is

like um ordering the vegetarian Taco yeah or burrito or sandwich and then avoiding that particular taco or sandwich thereafter because it lacks protein because it lacks protein okay so foods that lack animal-based proteins are tend to be avoided going forward so here's the second part of that no and in fact if the protein is low not completely absent if the protein is low the animal consumes more of the diet because it's trying to compensate for the lack of protein and obviously if it has sugars or fats that are more pleasurable it keeps eating that that

that meal right I see if the protein is completely absent the animal avoids that diet unless unless the diet is very rich in uh dietary fibers and the study that uh that I saw uh which I thought it was fascinating is that because somehow the microorganisms in the digestive tract if they have enough highly digestible fiber now they turn on the ability to synthesize essential amino acids really yes so our gut meaning the neurons in our gut are essentially waiting for hoping we give them a Consciousness proteins from animal sources that's correct if those animal

proteins arrive in the form of meat fish eggs Etc the cells signal to the brain craving more of those Foods until satiety is reached but in the absence of that protein the animal quickly learns the person quickly learns to avoid that particular food unless there's fiber in it in which case these gut cells are able to now synthesize the essential amino acids microorganisms excuse me the microorganisms of the gut here we're talking about the microbiome now can synthesize the essential amino acids that ordinarily would come from the meat chicken fish or eggs that's right so

wow so I'm I'm an omnivore I love meat high quality meat but I also love vegetables fruits and starches of certain kinds but I have friends who are vegetarian vegan many of them eat a vegetarian vegan diet that includes a lot of fiber and you're saying that the fiber itself can trigger the gut microbiome to synthesize the essential amino acids that ordinarily would come from meat but you also said if I recall that if there's a small amount of protein so not zero protein but a small amount of protein in there then We crave more

of that food in order to try and get compens protein very interesting because this is the first thing that to me squares the argument based on the observation that or the hypothesis that we are essentially amino acid foraging machines and that complete proteins in the form of meat fish chicken eggs Etc you know there are those that argue those are the quote unquote best forms of protein right the most complete forms but there are many vegetarians and vegans who seem to thrive on a vegetarian vegan diet and you're telling me that perhaps their body is

their gut microbiome is compensating for the lack of whole animal protein that's right but the people who are trying to limit their meat intake are what hungrier in general so you're better off either indulging it or avoiding it but not having a small amount of it is that the idea the the idea is that uh the the the body or the gut will be able to detect that and then we'll try to compensate right I see and this I I actually learned um recently from a friend Laura dubal at Colombia who works uh does some

beautiful work on mosquitoes and how it is that they they feed on uh blood she came for the gastronauts uh uh series is she from Leslie V Vel yeah and what I learned is that when the mosquitoes are not reproducing they can leave off ATP which is the energy molecule right uh but they cannot lay X they need the protein in order to be able to lay eggs otherwise the mosquitoes cannot lay the egg you know so this leaves us with a picture of the gut sensing cells these neurop pod cells as exquisitely sensitive to

amino acid content in our Foods um which makes perfect sense and it has not been published or demonstrated yet sure we're now in the realm of of new incoming data we want to highlight this bracket it bold face and underline it as we're now at The Cutting Edge of what's may be coming um that's right right observation um but nonetheless very interesting but there is this fairly long-standing hypothesis that we are foraging for essential amino acids because they are the building blocks of so many important things in the brain and body and in fact there

is evidence on that and Professor Steven Simpson in Australia uh in uh the uh in nutrition uh Research Institute at Sydney University he is uh main proponent of these protein leverage hypothesis you know that and in fact protein is the most suting uh macronutrient so that that has been established and that's why uh normally we have focused on sugars and fats but we have neglected a little bit of on the protein because it's not as pleasurable as the sugars or fats but what is fascinating is that is the most suting um nutrient and as you

know it's like the most limiting and also like even commercially is the most expensive right yeah I certainly have had the experience of um at one time in my life really enjoying and even craving sweet Foods desserts and sugars and things of that sort and I noticed that over time if I eat sufficient amounts of meat chicken eggs fish and which is not to say that I consume excess amounts of them that my sugar Cravings go way way down that's just my personal experience but I know it's an experience that family members of mine and

others share as well but I promise you that this was a a fun um a fun topic right I couldn't uh we couldn't stop at like just layer number one layer number two is that in agriculture we have this instinct to plant plants that a complement each other like for instance a classic um especially native among native communities is called like the three Marys uh I believe is a a um pumpkins or some type of fibers with corn carbohydrates and Bings so in purely plant-based diets there's an effort to get the fiber the sugar and

the amino acids that's right and I grew up uh in a in a farm my my parents had farms and I remember when they will plant they will also like throw in there the the beans and the beans will wrap around the the corn and it just seem like so natural and that's what you will do because that what you learn to do but if you think about it it's an instin that we have developed even agriculturally probably in the subconscious to cultivate them in such a way or perhaps the plants taught us how to

cultivate cultivate them in such a way that now when we put them in the plate it just makes sense ER at the nutritional level because if you think about it every time that we go to eat how is it that we arrange that plate right there is some rice which is very deficient in in some essential amino acids but is rich in carbohydrates right it has some beans right uh and then there's some lettuce you know and sometimes we have like for omnivores people will put meat or you will put other types of protein in

there right and certainly it varies by culture time of year food availability and things of that sort as long as we're talking about um your upbringing um you have a fascinating story um so maybe we could could discuss that for a few minutes uh where were you born uh I was born in the Amazonia of Ecuador a small town called el Cho in Ecuador uh is on the slopes of um the Eastern slopes of uh the Andes on the way to the Amazonia uh in the Napo Province uh coincidentally was like through the path from

where uh Francisco the Orana in uh 1542 march on its way to the discovery of the the Amazon actually passed through a a trail that later on reading I realized that uh Native people had all of these Trails between the Amazonia and the Andes and the coastal line for thousands of years so you grew up in a very rural yes uh the uh oil had been detected in the 1920s in Ecuador uh it was first explorer in 1964 in uh the first uh ER oil um um well was uh in a town called lag Wago

which now is only like three or four hours from the town where I grew up but at that time it was like eight hours the roads were not good and the first road passed through it uh in uh 1974 uh I was born in 1983 but I remember that we used to have like a a giant um a diesel T engine that will give us a light electricity only from uh 7 to 900 p.m. you know uh I remember when my father bought the the first uh a um color television in the in the town

and then neighbors will come to the our living room and then we will watch movies wow and this was in the 80s that was in the 80s right um such an interesting upbringing so um did you eat a purely vegetarian diet or you ate Meats as well where did those meats come from if you did primarily from a cattle uh goats ship so how do you go from the Amazon to a study of nutrition and ultimately Neuroscience um yeah uh that's the question right like the deeper I go the more I question I used to

think that oh it was very simple you know like when I was um uh specifically when I was 11 years old uh my father he was born in 1932 uh by 19 he lost uh his father my grandfather when he was six years old then he was giv away and he had to go and like build his his his life uh he was a very successful entrepreneur but in the process he had uh made a lot of uh a lot of friends and acquaintances so when I was 11 years old I remember specifically that a

friend of of his who was in the Special Forces stopped by uh our home because that was the main road that we go into the Amazon jungle where the uh folks in the special forces in the in the military will will be trained and he stopped by and said like hey roio like what are you going to do with Diego you know like I think that is about time that you know I think that you should send him to the military school and I remember in a matter of like literally a couple of weeks or

three weeks I had given the taken the tests and um I was accepted into the military school and then uh I ended up in a military school and this was the at that time it was the premier uh military school in the in the country that alone it was uh with years you start to understand the context in which you you developed uh because it was a it was a very interesting context for for a child like just to give you an idea uh these these uh this school had the first and the only zoo

in the country so from my uh classroom I would literally look at the at the at the Lions and then I think that was by the second year that I was in the school second or third year that became that because the the the city start to grow and then the the military school is wrong and then they separated the higher education for Military Officers they separated them and they put them in a different place but that Zoo actually became the first zoo of the capital of Kiton wait so you had a zoo with lions

at your school yes and you said you could could see the lions from your classroom and they could see you presumably probably know yeah well I assume they could see you uh lion vision is pretty good I don't know what the resolution is but I'm guessing that their Vision yeah they they definitely use their old faction but they are uh sight sight based Hunters as well so but I I have a specifically uh one memory like climbing up I think was like from the because we had an Olympic pool and we had all of these

events um they they they the the soccer field uh was the the field where the uh national team will go and train on because they didn't have their own their own um H training grounds later on they had their own training grounds so but that was something that you just grow into it right like but you it was with the years and now especially like that I get to reflect on it I was extremely fortunate uh through that experience and that education and now I'm I'm I'm here sharing some of the story and hopefully uh

through that inspiring some people uh especially young people that would like to go and chase their dreams you know so you you went to military school in Ecuador yeah you graduated and you decided to go to to uh yeah so I was allowed to become a so in the military school they will select uh the top uh Cadets um like I think was the top 10% and they will select them and they will put them through a special training um so you have essentially didn't have like what was a normal summer vacation you know I

will go into a military training uh ER so for me it was going to be very not easy but relatively straightforward to transition into officers Academy right like do four more years like West Point here and then like become an officer right in fact I I had a reserved officer degree when I graduated but two years before graduating a friend man who uh he prefer other types of uh careers he said like you're not going to become a military right you're not going to go into the military and he said you should probably study something

that will help your parents and then I said what will that be and he said like uh perhaps agriculture uh and I didn't think at that time it didn't dawn on me uh that uh you know people can study for agriculture and agriculture is like the base of food um er for all of us right and then I said where and then he mentioned for the first time this University in zamorano which was founded with some uh uh some funds that were donated by um the founder of the Standard fruit company which eventually became I

think chikita banana Zam zamurai and that is an oasis that is in Honduras outside of tusi Alpa so it's a boarding school you wear uniform so it was kind of like military it's very strict uh you cannot accumulate more than uh 12 de merits otherwise uh they will send you home how do you get a Dem Merit um hey you show up uh two minutes late to uh work in the morning at 6:00 a.m. in the field and then you just get to two minutes late one De Mer 12 of those you're out two demerits

two demerits you're out yeah you get a we used to get a um they they will check your room so for instance a guest like you if you will go there like they will give you a every Wednesday they they had at seven they will check your room but like very meticulously right and if they found a little bit of a dust on the window or something to the merits um and you're going home if you accumulate enough you will go home right wow um so it really forms character right and then do you do

that with your kids no I think that I have become do they make their beds they do make their beds yeah okay but that's that was the context and it was then where I learned about two things one is where this idea of getting a PhD because I noticed that most of the leaders will have a PhD most of the leaders in the university and I realized in the United States is one of the training runs main training runs for phds and the other one was nutrition I was a little bit more King on perhaps

going into a Veterinary um uh school and then uh I had an experience in a a dairy farm in uh California where I learned the value of uh nutrition there was more prophylactic rather than uh a paliative or like treating the the cow right um and that kind of convinced me like to look for a uh training in nutrition and then a friend of mine uh the late uh AEL gernat he was able to connect me with um some uh some friends and my mentor at uh North Carolina State University and that's where I ended

up doing my PhD nutrition you know and that's where like the career be became and then maybe another detailing there is that that I uh I was so excited about taking uh that's where I took my first physiology class and all of a sudden I realized that in a way the body was like a machine right like obviously is a limited way of thinking but the body was like a machine and one of the professors was um a neuroscientist uh and I took two physiologies two human physiologies with uh with him and I was just

thrilled by when he will explain how is it that in the synaptic terminal there were these vesicles that had like these proteins that will walk that vesicle in the preoptic active Zone and that's how we make movement you know or something like that um and I guess I kept that in the background of my head and when I had the opportunity to work in the gut uh I applied that so you were Enchanted by the nervous system yes yeah as as I was too I I'm um nothing to me is more um spectacular than the

realization that we are made up of these little tiny cells many different types but that the neurons essentially govern our entire experience of life it's just amazing um well that's quite a journey from uh the Amazon to uh well this table and and much and much more of course um thank you for sharing that uh so you grew up in a uh let's call it a plr environment the Amazon at least from the pictures I've seen very um let's talk about plant Botanicals and um the idea that maybe plants for lack of a better way

to put it have a certain intelligence or a composition that is not random with respect to our interactions with them right uh you described how agriculture in some places has evolved to include and ensure the different macronutrients and essential amino acid intake even in the absence of animal proteins you said the pumpkin or the squash the corn and the beans um what are your thoughts on Plants perhaps from the Amazon but elsewhere um too and their capacity to have things in them um chemicals that can be uh good for us at the level of the

gut but perhaps at the level of the the brain or other organs as well yeah how do you think about plants these days so the first thing you you you mentioned there like uh intelligence right I mean I don't know like if that exact terminology applies but I I do like this word wisdom because it's reflected uh experience right and I said reflected experience because somehow we are uh going over the experience and plants have been many more Millions years of age on Earth than any other animal right therefore they have had way more time

to actually experience the ground so to think that they they don't know what is going on um I think it's a little bit uh perhaps naive is the word I went to um the the the main Court of the uh these Mayan um ruins of kopan at the junction between Honduras and uh Guatemala uh this was a very special city of the of the Mayans and in the main Court you see like all of the EST Stellas which are like the main uh stones of the of the kings of several dynasties and at the top

of one of the uh the the the stairs of on these pyramids there is this giant uh SAA uh tree which is like 650 years old something like that so that tree was there before the spers uh landed in there when the um Mayans perhaps were still celebrating things or perhaps right after right so imagine how much information that a organism has in there and we will be able to just tap somehow into that information like climate uh fluxuations organisms interactions movements I mean like so many different things right like that right now I don't

think that we even have the the language of being able to understand at the organismic uh level of how much information that is stor in one single one of those organisms but then think about uh a um uh a chloroplast for instance or like one of the photosynthetic uh organel inside of the the the cells uh how is it that they have been shaped for hundreds of years in those organisms right um and I think that perhaps in the future uh this is more of a Sci-Fi right now but perhaps in the future we we

will be able to harvest that type of wisdom we will be able to understand a lot about the uh about the the place or the Earth that we live in that's Point number one uh Point number two is that this plants have been interacting and we have been interacting with plants for hundreds of years right and obviously we are a consequence of the environment right like here driving in in La uh or driving in a major uh City uh for some of us is just like second nature right but if you go into a jungle

then all of a sudden it will not be the same thing right but for somebody that has been in the jungle for hundreds of years now all of a sudden they are able to describe with such a sensitivity of like how it is that the the the jungle is uh the makeup of the Jungle is in there I've seen uh Native people walking through the jungle without shoes and right before for stepping on a leaf stopping and then pointing out like look underneath that leaf and then like lifting it out and then a tarantula right

there like how do you even uh make sense of that like I don't have the sensory acuity or the wisdom to be able to figure that out uh but they do right and certainly that is a is is just a level of um sensory perception that uh I am not equipped with uh but I do think that there's quite a bit of that interaction in there to learn and then of course not only for food but also for medicine for textiles uh and for many other uh functions uh these plants have been part of the

ecosystem of how these people navigate uh their world all the way from making a canoe to uh making a backpack to carry a fish from the river into the house right so how do you think we evolved food choices and flavor preferences I imagine humans you know um that existed long before us being hungry the gut starts rumbling and there are all these plants everywhere and some nuts and some berries and things and so they had presumably no choice but to consume them and decide at the level of the the mouth like that's bitter no

that's not good maybe eventually cook those and see if that changes the relationship yeah I'm thinking raw Acorn versus cooked Acorn you know yeah um but that ultimately there was a lot of trial and error and that these neurop pod cells which surely existed for a very long time prior to us played a key role in Discerning what's in these plants barks Roots nuts berries we're setting aside Meats for the moment and other animal proteins and making decisions about what's nutritious what is safe what is not safe and that's a pretty complex process given that

some things might taste okay go down okay but then you run into serious trouble later but given the critical importance of ingesting sufficient amounts of macronutrients and the need for micronutrients to survive on a day-to-day basis much less reproduce propagate one imagines that you know this is like almost as essential as breathing you know and that and that this path of in our nervous system of the neurop Pod cells to the brain for sake of decision making of yum yuck or me is perhaps one of the most important core functions of the nervous system once

you get past the elements that control breathing heart rate um you know temperature regulation things of that sort I see it is some among the senses it's at least as important as vision and perhaps more in terms of making sure that we survive from dayto day that's correct and uh here's where I think that is a large vacuum in biology uh if I will be with my biological my training in biology if I would put my my hat of the training in biology I wouldn't be able to explain much of like how is it that

we figure it out because uh even if you just go to a Botanical Garden here uh in you know in the city I will be really hard to figure out um you know what plant is for what right yeah what safe to e what safe to eat not you know uh maybe like the Coti you are able to figure that out by touch right so from the biological perspective I think that there is quite a bit in there to explore and to learn there is some very interesting work from the anthropological perspective so anthropologists and

ER ER botanists that were studying the plants um were exploring the jungles not only the Amazon uh but Borneo Sri Lanka and so on and so forth and studying the interaction of native people with the plants and if uh going through the literature that literature there is a pattern that emerges and like uh the native people they talk about how it is that they actually learned from the plants that the plants were the ones that were uh teach them you know so that's why I said from the biological perspective like how can we make reconcile

that uh I think that there is still quite a bit of uh to learn what does that mean to to learn from the plants I mean there's something that intuitively makes sense uh and when you say that I've heard about um you know looking at plants as teachers about the local environment you know when they're open right they're light sensing when they're closed um but you know in terms of trans ating some of that to you know how humans have learned to navigate given environments navigate meaning you sort of thrive in those environments um how

do we go about that does it mean taking plants grinding them up and figuring out the constituent parts or is that too reductionist is that going to leave us with a parts list that doesn't mean anything sort of like if I split out all the pieces of a a car or an airplane um in front of us it doesn't really tell us anything about that except what parts make up the thing that flies yes and that's why I said like this is more on the anthropological um studies that have uh you know especially from scientists

that have gone there learned the language leave with the natives as natives you know and then start to understand the dynamic of uh their culture and their interactions um then that's when like for instance uh how it is that they classify uh plants the way that they classify plants is like several levels more richer than our classification our our scientific classification by um the two name system or the variety right like for instance they take into account not only the the flavor but also the shape uh the location uh how they uh interact over the

year how they react over the year uh for instance there's this beautiful plant that um people call it a the lips plant I don't know if you have a very if you Google it you will see it uh it's like lips literally like lips it has like these red beautiful lips like uh the the the plant just looks like lips um and then people use it for uh pain for some rashes skin rashes and also like in some rituals and like most of these plants um the the way that the natives interact with the plants

is in a sacred uh level you know there is this respect for the plant right um so yeah I think that uh biologically I think that there is quite a bit in there to um understand and explore and Define I do agree with you that like just thinking about grinding it up and like just putting it in a in a tee perhaps is to uh reductionist it could be a beginning of a understanding but it is reductionist seems like nowadays in the field of bioed research and clinical research that there's a lot of interest in

uh plant-based psychedelics um you know LSD from Urgot and psilocybin mushroom um and so on and so forth iasa iboga um so it seems like science and plants have merged at that level in terms of clinical implications of course there are entire fields of plant biology that are extremely important I think most people probably don't realize this but a lot of what we understand about circadian rhythms grew nope pun intended out of our understanding of plant circadian rhythms first and then it was translated to mammals your beautiful work by Steve Kay and and others um

seeing the circadian rhythms in leaf opening and orientation of the whole plant and and other features of plants that are mirrored by the changes in um arousal level in in mammals including us which is why I'm always telling people to get sunlight in their eyes early in the day and to avoid bright light um in the evening and night time um so what are your thoughts on Plants as a source of medicine psychedelic or otherwise I think that uh well traditionally that's where medicine was um developed from I was at uh the Oxford uh botanical

gardens uh last year with the family and uh we went into the gardens and they have a beautiful garden was established in 1621 I think was the first uh Botanical Gardens in England and they have a beautiful uh medicinal plant collection and there was this very humble uh a um uh what little sign with a description in there uh that said in there that about 80% of medicine it still comes straight from Plants really yes uh and if you think about it uh it kind of makes sense right like because you know when we think

about like the the medicines that we have been able to develop which have been phenomenal for especially for certain chronic diseases uh but we don't have like a broad uh repertoire uh of it right um so I think that has been obviously a great Advance um in in our society that we have been able to identify the molecules uh synthesize the molecules package the molecules render them by available in a specific sites uh and I think that when we are able to couple that with the rest of the molecules that the plants through their I

keep saying their wisdom because somehow they develop their ability to have not only one molecule but like a combination of other things that will provide the full experience of of the plant right uh for instance uh Gera mattive you know it's not only caffeine right because it's very different than a shot of espresso you know if you take the whole thing uh it not only gives you energy but it gives you a full range of experience that is specific to the yamatic which is a is a leaf right yeah it's a distinctly different um sub

subjective experience than coffee and I I enjoy both coffee and espresso and yum mate you um were the one who introduced me to gu guayusa which is a is a causing of jate because jate is parensis WUSA is elix WUSA and it's not as bitter as mate but it has uh almost as much caffeine as coffee and it has antioxidants and other uh compounds um which give you this very smooth uh experience so natives in the in the in the Amazon they take uh a drink of a WUSA every morning uh around 4:00 a.m. between

4 and 6:00 a.m. they they wake up early they actually call it yes like Joo willink early yeah some people understand that joke he wakes up every morning3 A.M he post a picture of his of his Casio watch yep and he's already training 4:30 so no no guay Uso required for Joo and uh they call it the WIA opina Ura the hour of the WUSA and is a ritualistic uh drinking of the WUSA in the morning and where they talk as a family of the issues that they have had the the days before or the

week before like either with other communities within the family if they have to reprehend or repr uh one of the children or talk to them about like some mistakes that they're making and then they plan the the full day of activities uh by drinking uh WUSA and uh around 5:30 because they will boil the W USA right and they keep boiling the W USA and they just keep adding uh water to it uh and then around 5 5:30 then they will have what is called um the is a bowl of um CH and Cha is

this H Palm date uh very rich in lipids and fibers uh so they will have the WUSA because the WUSA they say that gives them energy it heals uh any any pain uh it shuts down appetite so they will eat at like 3 p.m. you know shuts down or modulates appetite as does your brma those one of the more potent effects actually of of mate and guayusa is a mild to moderate appetite suppression and then if you combine that to Cha which gives you the lipids and then it's like a full meal for until 3

p.m. and then you they go on a work in the in the fields interesting so they're essentially starting the day with hydration caffeine and then they what in some circles they call Fat fasting meaning consuming lipids in order to Stave off hunger I mean so highest density source of of of calories among the macro macronutrients and is a vegetable um based diet I guess right uh are they a healthy culture do they live a long time uh I am not uh and I should probably do more reading that I'm not well educated in what are

the um studies that have follow up uh on the ER you know and the healthy status of the communi but what I can tell you is that uh at least colloquially I will say that the diabetes those type of issues are not as prevalent but they do have obviously through like social exposure they have other things you know yeah fascinating um this morning ritual of um conversation about family and culture and what's needed planning the day um we had on this podcast as a guest Dr sain Panda who is um at the sulk Institute for

biological studies often known for his work on intermittent fasting Tim restricted feeding but also um has done beautiful circadian biology and he talked about um the use of Fireside Chats um not the sword on stage but you know uh gathering around fire at night um is something that has existed in many cultures where people reflect on the previous day and discuss issues social and work issues and sort of dissect what's happened and talk and um it's about um building and repairing relationships um sounds like in this is it a what is this group is it

a rural is this a yeah native Native Community because there are like about 70 or so communities that have been uh documented in uh in the Amazonia with their own language with their own traditions and many of them share the same uh type of traditions and if you think about it like a podcast is a one way of an evolution of that conversation right like where we can have this extended conversation and get this uh the more primordial things the ones that we have them in the prefrontal cortex right away and like discuss about like

well you know this discovers this identifications but then we get to the the part of like what does it mean for the whole Community yeah there's um doing there's reflecting and then there's um resting and recovering right and there is something about like leing that for the next uh generation right you know yeah passing on of lessons better learn from the mistakes and success of others if you can as you go forward very interesting um if we could I'd like to now return to the biology the nervous system absolutely um and thank you for that

Voyage Through uh some of your background um in Ecuador fascinating I um due for a mug of guayusa um sometimes I'll mix the two the loose leaf yerba mate and the guayusa um and as you said what's how does he feel I really like it um most of the time it's loose leaf yamate or cobu yamate um it's um but sometimes I'll mix in the GU guayusa leaves um and what I do like as you mentioned is you can continue to pour water over them for many hours and it tastes different as the time goes

on and my guess is you're extracting different things from it in different concentrations as time goes on I realize it's not a precise science you know it's it's interesting today we're talking about very precise neurons and methods of tracing neurons and spe sensing of specific Amino acids and lipids at the level of the gut then we're also going to um more macroscopic uh View kind of a broader scale view of the plants having many things that um need to coexist in um in certain ratios that the plants have evolved to create for us um so

we're sort of straddling both both ends of the of the Continuum and if I could fit in their story I not long ago I visited a a friend a native friend in um a in a nearby by town and he produces some of the best uh chocolate uh what I say in the planet you know because actually um uh the plants of theobroma cacao it was recently documented there was a paper in science not long ago that it was domesticated in Ecuador in near uh where I grew up uh and uh they have done some

tracing and genetic tracing and um so he produces some of the the best chocolate like literally like he harvested in there and then he roasted grinded and then he prepared uh for us in there and he the Swiss are saying well the belgians right are claim the best chocolate but now we know e Ecuador is the place for the best chocolate I think I just got a lot of Swiss and belgians angry at me for saying that but um it is do they have a very dark variety I like the extreme dark varieties you know

95% even even 100% chocolate if it comes from a really quality Source can be absolutely delicious it's like milk straight from the cow right like and what he did is like he said like uh Diego you you have to try it um with W USA and he mix uh the chocolate with WUSA as a as a drink a like as a drink boy like that will give you wings you know guayusa hot chocolate yes and uh and it's a very smooth experience right like you're mixing this tea which is for energy with uh chocolate you

know of the best quality so we're not talking about eating chocolate and drinking tea we're talking about about melting the the chocolate in the in the GU in the guayusa it was something like Wonder hour kind yeah know of course I couldn't sleep until like 3:00 a.m. I think right there's something to do maybe this is why these um these groups drink the guayusa so early in the day that's right yeah and I have to imagine I would need caffeine at 4:00 a.m. 5 a.m. otherwise I'd be falling back asleep so yeah um so back

in the gut and nervous system um in particular within the brain we haven't talked about the brain so much so the information from the gut is is sent via these neurop pod cells up to you you mentioned the noo ganglion such a a cool name for a brain um an a ganglion in this instance is an aggregate of neurons so it's a like a batch of neurons that then send a connection into the brain what what brain areas do they send to um and maybe we could describe these by name but also by function what

what they generally resp are responsible for and uh probably should be prefaced with ultimately will go to the entire brain right everything ultimately connects to everything it's like Google Maps everything connects to everything but but what are some of the primary uh recipients of that information the um first hubs into of sensor integration are in the brain stem you know um and for instance the nucleus tractus solitarius is in a specific region within the the brain the Cal is one area and and NTS for those that don't know is involved in regulating hunger and appetite

that's correct um other functions perhaps but like for instance um that seems to be an area of sensory integration for nutrients and when we say drives hunger or appetite sensory integration for nutrients I mean what would be great is if you know people could understand you know the the language of the nervous system is chemical and electrical so when these neurons are active um we tend to Crave certain foods you know seek them literally go to the refrigerator among the different choices go to that thing and select that and put it into our mouth so

so presumably it's driving um reward systems motor systems I mean it um what we call hunger and appetite is really a kind of a a domino effect of a lot of different brain circuits do we know whether or not the um uh nucleus tractus solitus um projects to the areas of the brain involved in dopamine release and craving uh yes uh and there has been some elegant work uh from several different uh neuroscientists in this area like tracking the the circuitry uh from there onto many other uh different areas the hypothalamus for instance very basic

behavioral fun functions um and the the stum where there is dopam dopamine release and then there is this pleasurable sensation and reward uh there is several other areas in there that are involved in this uh sensory integration uh there is quite a bit of work still to be done from specifically from uh the neurop pods there is like some evidence that they are connecting directly to um or there are if you put two papers together is obvious that there connecting to like some of these areas of dopamine release uh basal ganglia in the in the

in the brain um and that's why they're causing this reinforcing uh effect like in the lateral hypothalamus and uh other other areas I do think that ultimately um there is quite a bit of a gap in like different regions of the digestive tract like we today we just talk about the esophagus right like the esophagus I think that is still there is a little bit of work uh perhaps I think that Steve liberis has worked in that in that area another great neuros scientist uh doing some uh very fine detailed work in sensory biology uh

in esophagus uh there is quite a bit of Mis lack of uh precise biology in how it is that the esophagus specific cells of the esophagus are inated or like making sense of the environment and same thing for the stomach and how it is that ultimately each one of those regions are fitting into different regions of uh the brain uh even then how each one of these valves I'm fascinated by the each one of the valves that we talked earli on like um the gastroesophagal uh sphincter or the pyos or the oscal junction yeah we

should um illustrate for people I'm not an expert in the gut by by any means but what Dr borquez is referring to is that you know the gut as it extends from the mouth to the rectum is not just a series of tubes of different uh diameters uh but rather they have valves Chambers and these sphincters that cut off you know everyone hears the word sphincter and they always think oh you know anal sphincter and then they ah you know it's like you know Elementary School uh Middle School humor but but sphincters are they they

literally can close and open to varying extent um in order to allow um passage or prohibit passage from one compartment to the next such that the um certain things can take place over time in one one region like the esophagus or within the stomach or you know before passing to other um other Chambers and so I hear you saying that critical processing is happening at each of these Chambers the sphincters are determining how long that processing occurs and that distinct sets of neurop pod cells are likely detecting distinct of qualities and quantities within the food

chemical qualities and quantities within the food and relaying that to the brain that's correct and here's something that since we're getting into the future of uh of this area uh and while there is not direct published evidence yet I think that is going to be a a fun area um so the gut as the brain also generates these electrical patterns those electrical patterns um change depending on fasting versus feeding and circadian rhythms probably can realize jetl the God is asking you for a burger at 3:00 a.m. and your brain is telling the God you know

can you please go to sleep right um so these electrical patterns these electrical waves that are going into um that are uh being propagated by the gastrointestinal tract there are like several different cells like the ENT neurons are coordinating these these cells there are also these uh in interstitial cells of kahal so uh Santiago ramoni kahal uh the greatest neurobiologist of all time that's right it was named after after him he actually has I think it's like in the second volume of his classic uh book on the uh histology of the nervous system one of

the last figures talks about like the inovation of the v in the in the intestine so I'm beautiful for those that don't know kahal um shared the Nobel Prize with Camilo Gogi in 1906 they together um developed tools and and mapped the uh structure of the nervous system and and it's fair to say that kahal had Supernatural levels of insight into the nervous system he looked at the nervous systems of so many different animals um in dead specimens the the um the the joke even though it's not funny is that many animal species entered his

laboratory very few walked out um but by looking at fixed specimens under the microscope and then drawing them in you know select elements within them essentially came up with most of the major hypotheses about how the nervous system works not just its structure but neuroplasticity the failure of of mamalian central nervous system neurons to regenerate this is why after traumatic brain injury or stroke there's often loss of function that doesn't recover sometimes it recovers but um and that people who have injuries younger and can recover certain functions everything from the direction of electrical flow through

the nervous system all from looking at tissue that was not alive no electrophysiology no behavioral experiments just just raw but incredible Supernatural seemingly levels of intuition and insight amazing yes there is a some quote in uh one of his books that when he got invited to uh one of of his friends to England I I don't remember remember he was a he was a famous neuroscientist at the time in the late 1800s that who had helped him to expose um his work to other audiences you know and invited him to to England so he said

in there that it took like three months to go to that podcast right like it was a three-month trip trip so he said that he brought his um microscope with him with him and in the in the room he will be able to do some of these uh uh observations yeah peculiar guy also known for carrying a very heavy iron umbrella in order to do physical exercise on the way to the lab he was a he was a very very fit physical specimen also um reportedly reportedly I don't know which uh pick it pick which

one um a pretty Gruff person not terribly Pleasant uh to be around ran a tight ship um but in any event um so the cells of the gut are named after some of them are named after kahal interstitial cells ofal there you just got a a waltz into um uh into some Neuroscience history but critical history so they they have this emanating uh electricity right and uh so far these uh and it seems like the the sprinters modulate the emanation of this electricity oh like a like an instrument it it's um and you probably think

like that because the intestine and maybe here we get a little bit even deeper into this and I uh read some work from a philosopher uh in the UK who was and I'm going to paraphrase it very largely you know so please don't quote me but it's some something along the lines that uh if we are what we eat the place where food becomes us and we become food is should be the intestine right because that is where food is actually absorbed right so that is a is a very fascinating Point number two is that

the food enters us at a frequency that it will modulate the entire body right therefore like the the body H through these electricity these electrical waves should be in sync with also the electricity of the entire uh nervous system so I think that here's where in the future I think that there's going to be a fascinating realm of understanding how it is that these waves of the body and the Brain uh are synchronized with each other uh because as we know like for instance sometimes um when we don't uh we're hungry we become hungry you

know like uh we become irritated by the fact that we don't uh have food and perhaps is this dissonance in the emanation of the electrical waves between the digestive tract and uh the nervous system so I think that that is that's just like one of the one of the Realms um of how it is that the brain is connected to the gut at a more uh organ to organ level to be able to make us function ultimately right because um that's how we are integrating the outside world the food into our entire system so we

can maintain the entire organism well certainly our level of alertness is linked to our level of anticipation and a lot of our food anticipation um impacts our levels of arousal AKA alertness so as you mentioned in the we're di we're a dial species so in the middle of the night it's unusual to get hungry right A lot of these pathways are shut down digestion is happening at different rates and um typically our appetite is greater during the day than it is in the middle of the night that's right um but in addition to that you

know it makes good sense to me that what is going on at the level of our gut is going to tell the brain did we get enough nutrients from the previous day are we in a place of abundance um there's also the psychological aspect of gut sensing um and we haven't really touched on that what are your thoughts as both a scientist and a human with a with a gut brain axis on this notion of a kind of gut intuition you meet certain people and it sort of relaxes and warms you and you want to

get to know them more other people for whatever reason um you just feel like I don't know something doesn't feel quite right that we can sense things at the level of the body that inform our brain um and no one really understands that process yet but we do know that the vagus nerve which is a you know multi- uh pronged pathway big pathway it's probably its own major branch of the nervous system really um is is sending bidirectional communication between brain and body and presumably when we're around somebody or something that doesn't quote unquote feel

right the Vegas is involved um a few interesting things in in that area uh I mean in the work of uh Carl Yun talks talks about it about the subconscious and how it is that we're accumulating all of these experiences that we have been uh passing through in life is not that they are not a store anymore it's just that they are back in the subconscious right and then ultimately they become part of this so-called intuition right like we have this G feeling that uh and [Music] um if we analyze um some of the languages

I think that I've in past people have told me in so many different languages that uh there is this phrase for God feelings in so many like for instance in I think Portuguese is free of the barriga you know like cold in the in the in the stomach you get a cold uh in Spanish we call it a pre sentimento like a preeing you know or pre yeah pre sensation or feeling it will be more feeling if you translate that as if it arrives first yes before you're able to articulate it right so uh there

is this storage in the entire body that gives you like a depending on the context it gives you a certain type of uh feeling right and that's why we talk about uh intuition uh there's also like this this other aspect of um how it is that food synchronizes that intuition uh it seems to synchronize that intuition among two or more people because if you think about it we have this ritualistic way of uh serving something when we we we commonly say or colloquially say let's go for a cup of coffee and often what we mean

is let's go and talk about business the future resolve an any issue but we're talking about the cup of coffee and we have to share and people I think that there are some psychologist that have run some of these uh studies in which they say that if um the food that that we eat is more alike we are more likely to to connect at least on the moment right so there is this aspect and that's why we share you know the food interesting so is the idea that it's the actual chemical constituents of the food

that's creating a a common experience that then allows people to bond more readily or is it that the um the specific constituents of the food are actually driving bonding per se I mean it yeah and we go back to if we are what we eat then if we eat the same thing we should be more alike to each other right that's why you know like in communities uh you share the food in fact uh in like if you go into certain uh specific uh communities you pass around uh the food you pass around the the

drinks you know and is a it's very common to share right yeah and certainly in romantic bonding um there are many factors of course but um the kind of uh more basic functions of food sex and sleep represent the common places of bonding initially right and conversation of course and values Etc right not to dismiss any of those they're essential as well but in terms of you know um feelings of safety that's right feelings of um communing with somebody right the these very basic biological functions yeah and in business too right like people there has

been a studying like behavioral uh Economist they talk about how it is that business are more likely to happen when they are like made over a food or launch or things like that right like there's this synchronicity in the decision making and here is a a third uh dimension on this area that it has not been uh well explored but I suspected in the near future it will begin to be explored I read a while ago a very elegant paper from uh Walter Canon uh so you may want to expand on uh who Walter Canon

was but uh one of the uh found figures of the study of physiology yeah autonomic phy physiology right uh chair of physiology at Harvard uh 1920s 1930s uh author of the wisdom of the body you know uh he has a paper or he published a paper I believe in the 1930s it's called voodo death um Voodoo death and I remember when I found that title I was like oh this is something to sit down and dissect you know yeah good title good title if you want somebody to read it good title and he essentially the

gist of it let me see if I can uh if I can do a little bit of justice but obviously I will chop most of the details but um the um the gist of the paper is that in some observations in some native tries I I believe it was in in Africa that if uh a young people especially young youngsters uh if they were uh frightened by a shaman that they will not perform a certain thing a certain task right uh they enter a level of psychosis so to speak that could cause death like the

cast an spell right um and uh that's why called Buu death what Canon goes and describes is there is an activation of uh the vus nerve and the peripheral nervous system that is a hyperactivation that is going through the subal level of Consciousness and that in some of these tribes uh that's what at least that's what he explains that is happening and I believe that he did some experiments in um in some animals but what he was saying is that there is a hypertonic activation of the peripheral nervous system when there are these uh spells

that are casted by a member of the tribe that is in a higher or more Superior more influential uh position that if the other a uh member uh especially if it is pair with something right like if you say like if you go outside and don't listen to what I just told you and you see a black cat those two things uh match together and now you're hyperactivated right and become superstitious about it but it is what Walter Canon goes to explain is there is a hyperactivation of the peripheral nervous system obviously there is probably

more details in there uh but the the the the paper um really highlights an area of exploration that we don't know about is a a threshold of subconsciousness of the nervous system how it is driving us to have Superstition to uh Drive instinctively to go and consume certain things things or behave in certain uh in certain ways right yeah so it's um it sounds like it's par Association learning through statements cognition but that's enacted through the Vegas in order to control the organs of their periphery that's nerd speak for um if we hear and believe

that certain events will cause certain changes in our physiology they can in some instances become capable of that eat this food on this at this location and you'll get sick eat this food at this location you'll feel better cor and it's learned Association there's not and ultimately it's physiological but um it sounds like it's subject to a lot of learning effects as long as we're talking about the Vegas I think it's a great opportunity um to just mention that a lot of people um understandably think that the Vegas nerve activation is always about calming of

the nervous system and indeed it's the N the Vegas is um placed under the umbrella of a parasympathetic um pathway but I think it's very important for people to know that both experimentally and clinically if the vagus nerve is stimulated you get exactly the opposite effect you get arousal effects this is um commonly known in Labs that do uh physiology of different kinds um it's in the clinical context people with depression are sometimes treated with vagal nerve stimulators and it certainly isn't driving more sedation more depression of the nervous system it drives alertness and arousal

so we have to I think make sure that we looked at the Vega system and describe the vagal pathway as one that can both induce states of calm of ease rest and digest as it's sometimes called but also states of arousal and alertness even fear and so I think of the Vegas as a super highway of a bunch of different Pathways with lots of inputs and outputs that's highly subject to learning and um indeed the Vegas can slow heart rate you know down through numbered things like long exhale breathing earlier we were talking about stress

modulation something my labs worked on extend your exhales that's that's the most basic way um physiological size two inhales followed by a full exhale to lungs empty um these are core physiological mechanisms known to activate the Vegas and lead to calming but the Vegas I I look at the Vegas as kind of a uh including both an accelerator of sorts accelerator based Pathways in terms of arousal and and breaks um and it and probably our basil level of vagal activation reflects sort of the RPM of our system how much are we are we calm or

are we humming at a higher level of activity such an interesting pathway such an interesting area of the nervous system and we don't really understand yet um even the the major branches and pathways are just now finally beginning to be understood it's it's we're we're we're on um we're on Virgin beaches yes and right now that I I hear you uh bringing up the coming for instance there is a branch of the vus that inates the ear the inner ear you know and that's why uh it is belief and I think there is a little

bit of evidence out there that how a certain music at a certain frequency will calm you down because it is immediately like brings uh the it starts to make the Vos vibrate at a certain frequency yeah and huming um has been linked to vasod dilation which is associated with a calming effect whereas activation of the sympathetic arm of the autonomic nervous system or the kind of what sometimes is referred to as fight or flight but it's involved in other things causes phasal constriction and if you think about it like in several uh religious practices there

is the humming right uh there is the uh singing there is the sound the sound plays a big role in running there is a certain frequency that makes you run uh make calms you more and makes you run uh better you know is that right yeah uh there is some evidence at least among Runners that they prefer a certain type of uh frequency for for the running right so a certain uh pace of running or breathing and the and the sound the specifically the sound the sound of their feet yeah no the sound of uh

the music like if you if you play a certain uh certain music right and probably the sound of their feet too right like it's just that it has not been explored right it's fascinating and you know so much of what I think about when I think about the nervous system is the fine grain processing of you know of color of light or what but when it comes to our feelings of well-being our levels of arousal sleep Etc it's the rather um I don't want to call them crude because they're really sophisticated they evolve to be

sophisticated but these um kind of macroscopic signals like light coming in in the morning has these you know long wavelength and short wavelength contrast that's what tells our brain it's morning that's right it's the orange red blue contrast even if there's cloud cover it's the it's the difference between those to um different qualities of light that says it's morning and when the sun is overhead you don't see that yellow blue or orange blue red blue contrast but you see it again at Sunset and it informs so um it sounds like the combination of specific chemicals

in the gut tell us this is good pursue more of this and maybe even the place where you found it is is a good place um as opposed to and the opposite is probably also true yes like that's an entire new domain of uh the the Digest the sensory system in the digestive tract that we haven't even be to uh um articulate it memory how do we remember like what was that first meal like in the ratat uh movie from when we were children right like it was very different like uh I still remember like

some of the very simple humble meals that my mother will make but it's just Priceless for me right uh I whenever I go home and it's like I I spec without asking sometimes my mother uh will prepare those for me and it's like it just brings you back when you were that age right yeah the memory system is tightly linked to taste and smell there's no question about it and then like the how it is that the gut triggers that uh those Sensations or further reinforces those Sensations we haven't even begin to articulate and when

I said articulate because we don't even have the language to refer to these things you know that's why at the very beginning we were talking of the in our conversation about the axis you know and uh that we don't say like the nose brain the nose brain axis right like we just went for what we had at that time and I do think that the language will continue to evolve for us to be able to articulate more precisely more richly more elegant more you know in so many different uh ways how it is that um

a the organs communicate with each other to make us who we are and in there um in one of our papers uh we quoted uh these uh beautiful passages from uh the book Memoirs of by stomach uh it was greeting in 1853 by a French by person by what it says in the first page by the minister of interior because all of those who eat May read or something like that and then on page 21 it goes to describe the dialogue between the gut and the brain and it says like that how it is that

the gut communicates to the brain with a rapidity uh through uh these two sets of electrical wires that communicate uh the arrivals of the day as we may eat uh with the Precision and rapidity to the brain uh so the brain will make its own uh feelings and um Impressions and then he said that uh when he talking from the perspective of the stomach it says like when I grew a morose like meaning I'm not working in digestion then the brain also grew irritable and petulant you angry angry it's so interesting to look at Human

Experience from the directionality of gut to brain rather than brain to gut um that's right and and you know as I do from time to time you know pay attention to what's happening in the landscape of wellness and mental health and physical health a lot of what um you see out there in terms of you know Highly Educated people um who have thought very deeply about how to navigate decisionmaking and lots of different domains of life and to do it in a way that really honors the our own individual preferences and needs needs um people

like Martha Beck I don't know if you've heard of her but she exists in the she has triple degreed from Harvard um but has uh talked a lot about um learning to sense one's way into and through decisions through intuition that is more of the body and is more of particular brain circuits than our analytic like you know pros and cons lists um you know because pros and cons lists and obviously important metrics like OB Ive metrics like oh is this the right salary the right location the right you know dem you know all the

all the things that matter for decision- making and we're trained in that in in school in in the United States and in many many areas of the world as well of course um and that's critical but that there's this other training there's this other learning of self that can be extremely useful and it almost always comes back to body first then to cognition and decision-making and I feel like uh modern humans are are trying to learn how to um run the the analysis of Life decision-making through uh this I guess more ancient axis so the

again the intelligence of these what used to be called more primitive systems but I don't think they're primitive at all and talking with you today it's clear to me that these are highly sophisticated systems just as sophisticated as any forbrain pathway involved in um analyzing say like probability or something and that's why I like to highlight uh um the example of having a nice meal and having a nice conversation at the at the at the same time you know if you go to a nice restaurant and you have a nice meal while you're having a

nice conversation and you pay attention to it then it brings humility to your body to know like how much your body is doing for you to be able to just Express a tiny little bit and having like some sort of like highly intellectual sophisticated conversation while you're able to put in the precise amount of lettuce inside of your mouth and chew it in the right way and like adjust it with a little bit of water and maybe a little bit of wine and understand what is cleansing your pette and like you know putting down the

the napkin and so on and so forth uh without going to the restroom every time that you feel like going to it right there is an entire sophistication of of the body just to have something like as simple as a catchup convers ation you know do you think that our ability to sense into gut sensing more um to really hear and respond to the signals from the gut is something that we can learn even as adults simply by paying more attention yes and I think that here's the the concept that I usually uh you know

that uh when we talk about topics like meditation you know is that self-care and that self self-care is listening to your own uh body right how it is that the body is feeling like uh I don't know you know I grew up in a my mother will tell me like or you know family will tell you if you feel like going to the restroom uh and uh to pee for a bio break don't hold it for too long because it might be bad right like and I think that just learning that part of like listening

to to the body is an essential aspect it's just that we're not constantly doing it over learning about how we are moving our career forward yeah so much of what we're taught in order to um be high achieving and forward moving in life um in modern culture is about learning to override the signals from the body but it seems that um learning to listen to the signals from the body is is key to being a healthy human being yes and here I have an example uh years ago I used to run quite a bit um

and I remember that after I had ran a marathon uh I took a a break for like a few weeks and then I got back on the on the trail and I began running and I was like you know I don't need to warm up for three or four weeks up to like get back into speed right and I remember that I started to feel like um that my right uh the soul of my right food was a little bit like bothering me like but like almost imperceptible and I was like no you know you

just can't you just have to keep going you know and my wife elain told me like H you know you should pay attention take a break you know and I just kept running and I remember specifically that one time I went to run and say like I can put I can put in 80 miles that I think that I was running at like 7 Minutes 7:15 a mile or something like that and uh I began running it and I I after a mile I was feeling pumped you know uh two miles three miles I was

like and then I usually will go and do four miles and then turn around and come back I got a mile mile four and I fell crack and I couldn't not walk anymore uh there was a hair fracture that is almost imperceptible in an x-ray but Bo that you cannot move your foot anymore I had to limp for four miles all the way back to the car uh because I didn't even have my phone and I H never forgot that uh for next time um you got to pay attention to your body you know your

body is simply telling you like uh something is a little bit off just don't keep pushing it you know and I I specifically remember because I kept running and and I couldn't I had to literally limp all the way back to the car you know well Diego um I must say that among the many things that you've shared with us today and taught us about the gut and its ability to influence the brain um and the incredible things that are happening at the level of biology and physiology of the gut um Chief among them is

the message that we should all pay more attention to our sensing at the level of our gut and nowadays we hear so much about the gut microbiome such that fortunately I think most people are starting to appreciate that the gut microbiome is vital for all aspects of health and that there are things that we can do to feed that microbiome fiber intake fermented food intake and so forth but clearly based on what you've told us today that even just paying a little bit more attention to what our gut is telling us at the level of

feeling Good Feeling less good because the signs and signals are subtle I realize can really help us make better decisions and help us um decide not just what foods to eat or not eat how much to eat or not eat but um also how to navigate higher order decisions if you will um about who to spend time with what to do what not to do moving along the decision tree of life and along those lines I I want to thank you for making the decision to come here here today uh I certainly um am happy

that we decided to do it it's something that's been a long time coming I really see you as one of the true Pioneers in this area of trying to dissect the understanding of the gut brain axis heal the brain through the gut understand and modulate our emotions uh at the level of gut sensing and while there are other researchers in this area um I refer to you as a Pioneer because you've really undergone this incredible trajectory from the Amazon through nutrition science into neuroscience and now we're getting a little bit into psychological science and I'm

excited for what comes next I only ask uh one thing which is that as you make these discoveries that you come back and talk to us about them uh so that uh we can learn more about your incredible work so Andrew I want to say h a few things the first thing is that I I feel deeply honored by uh your invitation and thank you so much for uh the opportunity I I am just simply uh representative of uh the people that uh work uh with me and uh work uh with us you know I'm

just an an ambassador and they get the majority of the credit for their dedication to help us understand a little bit more uh of uh the body and how it is help us to navigate the world that we live in so I want to thank uh you for the opportunity I want to thank uh the people that have made this possible also like um the people that are along the way or the institutions that are along the way uh have a help fund this um Endeavor you know my home institution I du I'm deeply grateful

because my career has developed there uh and uh some of my mentors Roger little Andrew mure and the people that have helped me along the way and then finally I want to thank uh you uh and your your team uh and congratulate you for uh the work that you do and that you have created this uh window for uh us to come and share with the public uh some of the a little bit of the the work that we do uh perhaps uh some of that is uh is obviously is based on uh evidence uh

some portion of that is thinking about the future uh but I do think that through maintaining the dialogue with the public uh that we can continue to understand the world that we live in and for that I I have to thank you for uh having creating this platform well it's a labor of love and I'm uh honored to uh be able to do it and um in no small part because I get to sit down and have uh beautiful intimate conversations about biology and life with you so thank you so much thank you thank you

for joining me for today's discussion about sensing with the gut and the gut brain axis with Dr Diego B to learn more about Dr bz's research and also to see a link to his fabulous podcast called the gastronauts please see the show note captions if you're learning from and or enjoying this podcast please subscribe to our YouTube channel that's a terrific zeroc cost way to support us in addition please follow the podcast on both Spotify and apple and on both Spotify and apple you can leave us up to a five-star review please also check out

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science-based tools some of which overlaps with the content of the hubman Lab podcast but much of which is distinct from the content of the hubman Lab podcast again that's hubman lab on all social media channels if you're not already following our newsletter the neural network newsletter is the hubman lab zeroc cost monthly newsletter that includes podcast summaries as well as protocols in the form of 1 to three page PDFs the protocols cover topics such as how to improve and even optimize your sleep how to regulate dopamine deliberate cold exposure deliberate heat exposure we have a

foundational Fitness protocol that includes everything including schedules and sets and Reps and cardiovascular training we also have a neuroplasticity and learning super protocol again all of which is available zero cost you go to hubman lab.com go to the menu tab scroll down to newsletter and enter your email and I should mention that we do not share your email with anybody thank you once again for joining me for today's discussion with Dr Diego borquez and last but certainly not least thank you for your interest in science [Music]