Learn. Share. Evolve…

0:00:00 Welcome to the Huberman Lab Podcast, where we discuss science and science-based tools
0:00:04 for everyday life.
0:00:06 I’m Andrew Huberman, and I’m a professor of neurobiology and ophthalmology at Stanford
0:00:14 School of Medicine.
0:00:15 My guest today is Dr. Diego Borquez.
0:00:18 Dr. Diego Borquez is a professor of medicine and neurobiology at Duke University.
0:00:23 He did his training in gastrointestinal physiology and nutrition and later neuroscience, and
0:00:28 by combining that unique training and expertise, he is considered a pioneer and leader in so-called
0:00:33 gut sensing or the gut brain axis.
0:00:36 Now, when most people hear the words “gut brain axis,” they immediately think of the
0:00:40 so-called microbiome, which is extremely important, but that is not the topic of Dr. Borquez’s
0:00:45 expertise.
0:00:46 Dr. Borquez focuses on the actual sensing that occurs within one’s gut, just as one
0:00:51 would sense light with their eyes or sound waves with their ears for hearing.
0:00:56 Our gut contains receptors that respond to specific components of food, including amino
0:01:01 acids, fats, sugars, and other aspects of food, including temperature, acidity, and other
0:01:07 micronutrients that are contained in food that give our gut the clear picture of what
0:01:12 is happening at the level of the types and qualities of food that we ingest and then
0:01:16 communicate that below our conscious detection to our brain in order to drive specific patterns
0:01:21 of thinking, emotion, and behavior.
0:01:24 And of course, everybody has heard of our so-called gut sense or our ability to believe
0:01:29 or feel certain things based on perceptions that are below or somehow different from conventional
0:01:35 language.
0:01:36 Today, Dr. Borquez teaches us about all aspects of gut sensing, how it occurs at the level
0:01:41 of specific neurons and neural circuits, how the brain responds to that, how specific
0:01:45 foods and components of food impact not just our feeling of digestion or feeling good or
0:01:50 bad about what we ate, but indeed, how we feel overall, how safe we feel, how excited
0:01:55 we feel, whether or not we feel depressed or sad, angry or happy.
0:02:00 Today’s discussion, I promise you, is unique among all discussions of neuroscience, at
0:02:04 least that I’ve heard previously, in that it combines two seemingly disparate fields,
0:02:09 nutrition and neuroscience.
0:02:10 Indeed, today’s discussion gets into how different foods and food combinations impact
0:02:15 how we feel and what we crave and what we tend to avoid.
0:02:18 We also get to hear the absolutely extraordinary story of Dr. Borquez’s upbringing in the
0:02:23 Amazon jungle and how his knowledge and intuition about plants has influenced his science and
0:02:29 how the incredible science that his laboratory is doing relates to all of us and our ability
0:02:34 to better tap into our gut sense.
0:02:37 Before we begin, I’d like to emphasize that this podcast is separate from my teaching
0:02:40 and research roles at Stanford.
0:02:42 It is, however, part of my desire and effort to bring zero cost to consumer information
0:02:46 about science and science related tools to the general public.
0:02:50 In keeping with that theme, I’d like to thank the sponsors of today’s podcast.
0:02:54 Our first sponsor is Juve.
0:02:56 Juve makes medical grade red light therapy devices.
0:02:58 Now, if there’s one thing that I’ve consistently emphasized on this podcast, it’s the incredible
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0:06:46 And now for my discussion with Dr. Diego Borcas.
0:06:49 Great to have you here.
0:06:54 Thank you for having me, Andrew.
0:06:56 I am super excited to learn from you today, as I know everyone else is.
0:07:02 And if they don’t realize why, soon they will, which is that you work on one of the more
0:07:08 fascinating aspects of us, which is our gut, our gut sensing, the gut brain axis, which
0:07:18 I think most people don’t realize is nearby, but separate from the so-called microbiome.
0:07:26 So we’re not talking about the microbiome, a very interesting and important topic, of
0:07:30 course, but we are going to talk about this thing that we call our gut sense and how it
0:07:37 impacts everything from our cravings to our brain health and our cognition.
0:07:44 So once again, welcome.
0:07:47 And I just want to kick things off by asking you to educate us, explain what is this gut
0:07:54 brain axis that we hear about, and what’s going on in our gut besides digestion?
0:08:01 Well, Andrew, thank you so much for having me here, thrilled to be here.
0:08:07 I knew that since we met a few years ago that we will have this ongoing conversation and
0:08:14 a great conversation, the gut and the brain, people call it an axis because traditionally
0:08:21 thought to be an imaginary line that was connected through hormones.
0:08:26 So since 1902, when the first hormone secretion was reported by Bayleys and Starling, it was
0:08:40 known that when we eat, then hormones, these molecules in the gut are released and then
0:08:47 they will enter the bloodstream and then eventually will have a cause in distant organs.
0:08:54 And for the next hundred or so years, the field focused on the hormones.
0:09:00 And as a consequence, there was no direct line of communication between the gut and
0:09:07 the brain.
0:09:08 But as often I say, you don’t say or we don’t say the nose brain axis or the eye brain axis,
0:09:16 and all of the organs are in sync, working in sync.
0:09:20 So in the gut, there are also some sensory cells that are able to detect the outside
0:09:28 world and then quickly communicate that information to the brain.
0:09:33 And I say the outside world because the gut is the only organ that passes throughout our
0:09:39 body, but it is still exposed to the outside.
0:09:44 If you think about it, if you will swallow a marble, it still has a chance to get out.
0:09:50 Please don’t do that, anybody.
0:09:54 But it is still exposed to the surface.
0:09:57 You’re right.
0:09:58 I never thought about the gut as the organ that is in contact with the outside world,
0:10:02 unlike our heart, which is not in direct contact with the outside world or our liver or our
0:10:06 pancreas, but the gut is.
0:10:08 The gut is.
0:10:10 And if you think about it, it is just separated by some compartments that have all of these
0:10:16 valves and the epiglottis, the gastrosophageal junction, the pylorus, the iliocecal junction,
0:10:27 the rectum.
0:10:28 So these are the sequences of valves of chambers with valves between them that food passes
0:10:35 through, air passes through, and within each, as I understand it, there are different functions
0:10:40 related to digestion.
0:10:42 But I think where you’re taking us is that there are different modes of sensing what’s
0:10:46 coming through and signaling to the brain and other organs what’s going on in the outside
0:10:53 world by what’s sensed coming through that passage.
0:10:55 Is that correct?
0:10:56 That’s correct.
0:10:57 And if we think about it, when we swallow something, literally we have to trust our gut.
0:11:07 Because that’s why we use this phrase, trust your gut, right?
0:11:10 Because after that, there’s not much that you can do, at least in regular humans, that
0:11:15 you can do consciously to expel something that perhaps is poisonous or toxic, right?
0:11:23 It is the gut that has to make the distinction.
0:11:27 And then usually accommodate things for absorption or let them pass through digestion and then
0:11:33 ultimately they will be secreted, right?
0:11:35 So if you could describe for us the architecture that is the cells that respond to things in
0:11:44 the gut and where they send that information and how they send that information.
0:11:49 What is this thing that we call gut sensing made up of?
0:11:53 What’s the parts list?
0:11:55 So the parts list has been evolving recently and while some of the elements we have known
0:12:02 for a while.
0:12:05 But in general, what we’re talking about, because it’s an external surface, it is lined
0:12:10 by a single layer of cells that are called epithelial cells.
0:12:15 And essentially these cells are exposed to the outside world, but they also are like
0:12:20 attached in like a little membrane and they are the ones that interface with the inside
0:12:25 of the body.
0:12:27 So in the stomach we have an stratified epithelium for instance that is thicker so it can survive
0:12:34 digestion chemicals and other things like harsh environment.
0:12:38 And in the intestine we have a little bit more of a more delicate epithelial layer.
0:12:45 And we think this epithelial layer, there are several different cell types.
0:12:49 And one of those is the so-called endocrine cell.
0:12:53 To put it in more simple terms, is a gut endocrine cell or a gut cell that releases hormones.
0:12:59 The term was coined in 1938 by a German physician, his name was Frederick Vater.
0:13:08 And at that time it was a major advancement in our understanding of physiology because
0:13:14 he came up with the idea that the organs were not only communicating to organs.
0:13:19 In fact there were cells within the organs that were communicating to other organs through
0:13:23 the release of some of these endocrine factors, these neuromodulators or these neuropeptides
0:13:29 that we know as hormones.
0:13:31 And so he named the diffuse endocrine system of the gut and then he came up with his word
0:13:37 enteroendocrine cell.
0:13:39 And these cells are dispersed at a ratio roughly speaking like 1 to 1000 epithelial cells throughout
0:13:45 the digestive tract.
0:13:48 And we thought for the longest time that these cells were not connecting directly to the
0:13:53 nervous system, that they will release these neuromodulators and the neuromodulators through
0:13:57 diffusion will act on receptors into some of the nerve terminals.
0:14:02 And that is true, that is a very well-established system.
0:14:06 But in 2015 we made an observation that some of these cells, anywhere from 1/3 to 2/3 of
0:14:11 these cells, it depends on the type of systems that you use to identify, they were contacting
0:14:17 directly the nervous system.
0:14:20 And that brought up a new dimension of how it is that the gut could be communicating to
0:14:26 the brain, because as you know in the brain the synapses are the ones that are most predominant.
0:14:32 However, there is a lot of neuromodulation from endocrine functions in the brain too.
0:14:38 So in the gut, this was not well described.
0:14:43 There had been historically a few examples that these cells may be making synaptic contacts,
0:14:49 but they had not been studied.
0:14:52 And perhaps one of the main reasons why they hadn’t been studied is because the tools were
0:14:56 not there.
0:14:57 And I will recall in the 1990s with the advancement of green fluorescence protein as one of the
0:15:06 main molecules to tag cells.
0:15:09 Now all of a sudden there was a revolution in biology, because you could identify the
0:15:13 cells, you can take them out, you can do a transcriptomic analysis to see what genes
0:15:17 they express, you could co-culture them, you can modify their genome, and then you can
0:15:23 start to interrogate what is their contribution to the entire body.
0:15:26 I’ll just interrupt you for a second just to make sure that I and everyone else is
0:15:29 on board.
0:15:30 So if I understand correctly, it’s long been known that there are cells that are in these
0:15:36 layers of the gut in the intestine.
0:15:40 And it’s long been appreciated that as food passes through, these cells somehow can sense
0:15:45 the chemical constituents of the food as it gets broken down, and then release hormones
0:15:50 into the bloodstream that could influence the brain, those hormones could travel and influence
0:15:55 things far away.
0:15:56 In fact, for those that don’t know, endocrine generally means signaling at a distance between
0:16:01 cells, so between gut and brain or gut and liver, it can also mean local effects.
0:16:06 So hormone endocrine effects can also be local.
0:16:09 But if I also understand you correctly, it was only about 15 years ago when you mentioned
0:16:16 green fluorescent protein, we should probably just tell the tale in a few sentences.
0:16:20 This is an amazing story in biology where if you’ve ever seen fluorescing jellyfish,
0:16:26 that’s because they express a gene for so-called green fluorescent protein, and biologists
0:16:31 have hijacked that gene sequence and put it into mice, and now actually other organisms
0:16:37 as well, which allows you to see individual cells and cell types.
0:16:41 So these cells release hormones, the hormones influence the brain and other organs.
0:16:46 And now I think you’re going to tell us that they also are able to make direct communication
0:16:52 lines with other organs as well.
0:16:55 Correct.
0:16:57 So maybe here is fitting how it is that I got into starting the system.
0:17:03 And as you know, between the ’90s and the early 2000s, there was an explosion in tools
0:17:09 to study the brain and neural circuitry and the connection of neurons and each one of
0:17:15 the neurons.
0:17:16 Because up until the 1990s, the tools were limited, electrophysiology, behavior.
0:17:23 And then not only we had a green fluorescence protein, we had optogenetics.
0:17:29 We had rabies modified to be able to trace how it is that neurons connect at one synapse,
0:17:39 which was a dream.
0:17:40 I think that in fact, that was the dream of Francis Crick when he was at the South.
0:17:44 He talked about having the way to control.
0:17:46 For those who don’t know, Crick I was a co-recipient of the Nobel Prize for the discovery of the
0:17:51 structured DNA, but then later in his career, developed an obsession for neuroscience.
0:17:56 And yeah, he daydreamed out loud about having tools to visualize individual connections in
0:18:02 the nervous system.
0:18:03 And as Diego is pointing out, scientists have hijacked the rabies virus, which hops
0:18:09 between neurons, labeled the rabies virus with things that glow fluorescent.
0:18:14 And in doing so, we now understand a lot about what Crick dreamed for, which was the ability
0:18:20 to see different specific connections in the nervous system.
0:18:24 Yes.
0:18:26 So then you could isolate the cells.
0:18:29 And then you could do sequencing technology to see what are the genes that these cells
0:18:32 are expressing.
0:18:34 And then you can start to understand the makeup of the cells.
0:18:38 In 2009, Hans Kleber is a scientist in the Netherlands, did a beautiful experiment.
0:18:45 He discovered these factors that will trigger a receptor of the stem cells in the intestinal
0:18:50 epithelium and will form literally a mini gut in a dish.
0:18:55 These cells will be all lined up and then they will have a lumen.
0:18:58 And I remember seeing some of these papers coming out when I was a PhD student and I
0:19:04 was already starting the gut.
0:19:06 So it was inspiring to see all of the things that all of a sudden you could do.
0:19:12 So when I began studying the cells, immediately by isolating the cells and simply observing
0:19:18 the cells in the native tissue of these mice models, it quickly became evident that some
0:19:29 of the cells had a very peculiar anatomy.
0:19:33 Some of them had these very prominent arms at the base, like literally like in the Sistine
0:19:39 Chapel, Adam reaching out to God, right, like with a hand.
0:19:44 The cells will have that type of anatomical features and even ending with a little hand
0:19:51 at the end of that arm.
0:19:54 And obviously, I immediately thought, like, why would a cell that it is supposed to react
0:20:00 to food and release hormones into the bloodstream or just in the vicinity will invest so much
0:20:07 energy into developing an arm, right?
0:20:11 So then I started to look, well, perhaps it is because it’s providing a bridge directly
0:20:15 into the vasculature, into the vessels to put the hormones into the bloodstream, right,
0:20:21 grown, like I couldn’t find that direct connection.
0:20:25 So then I started to study, perhaps they were associated with the nervous system.
0:20:30 And that’s how we made some of the first observations that some of them with the arm
0:20:37 or without the arm, they will have a more intimate relationship with nerve fibers.
0:20:44 And that, of course, opened up a bunch of new questions.
0:20:50 But the first thing that we had to do, it was to come up with a name for this food.
0:20:58 And it kind of became organic.
0:20:59 And I want to highlight this because I think that as we go through the discovery trajectory,
0:21:05 we don’t realize the need to also engineer language.
0:21:09 How we go about language is we start to attach words that we already knew and we start to
0:21:15 put them together to describe something that knew that we’re observing, right?
0:21:20 And I say this because at the very beginning with my mentor, we will start to call these
0:21:24 little feet.
0:21:25 First we call them axon, which is like the term for like the long extending branches
0:21:30 of the neurons, the main branches of the neurons.
0:21:33 So we will call them axon-like because they look like a baby axon.
0:21:38 But then we call them also like pseudopod because it was like a pod, but it was pseudo.
0:21:45 And at some point we, and it was coming from like some cells in the kidneys that they are
0:21:50 called podia or something like that.
0:21:54 So it was axon-like, pseudopod-like, basal process to describe that it was on the base.
0:21:59 So at some point it became so long that we couldn’t fit it in an abstract, right?
0:22:02 Yeah, it’s a bit of a mouthful.
0:22:04 So we began thinking about it and then eventually I came up with the term, I thought like, “Neuropod.”
0:22:11 And I remember pitching it to my mentor and he said like, “Let me think about the weekend.”
0:22:15 And then on a Monday he came in and he said like, “You know, it has a ring to it.
0:22:18 I think that we should use it.”
0:22:20 But essentially the thought was that if these cells are contacting, then perhaps they are
0:22:27 passing information directly onto the nervous system.
0:22:31 And that is very different than just spewing neuromodulators in the vicinity and hoping
0:22:39 that some of those catch the nervous system, right?
0:22:42 And like I said, while that still exists, and I think that is just like matter of space
0:22:47 and time.
0:22:48 Like they modulate these terminals in a different space and time, the hormones, but the neurotransmission
0:22:56 is directly and more precise in space and time.
0:23:00 Could I just interrupt for a moment, please?
0:23:02 So hormone signaling, endocrine signaling, generally is slower than the forms of communication
0:23:10 directly between neurons, right?
0:23:14 Could be on the order of seconds, sure.
0:23:16 But typically on the orders of minutes or hours, whereas neural communication on the
0:23:22 order of milliseconds.
0:23:25 So if I understand correctly, these, what you decide to call neuropod cells, and thank
0:23:30 you for shortening the name from the other description, line the gut.
0:23:36 Are we talking about everything from esophagus down to the stomach to the intestine, or is
0:23:42 it just at the level of the stomach and intestine?
0:23:45 Where does it exist?
0:23:46 So this is where the conversation becomes expansive, because these neuropods or cosines
0:23:53 of these neuropods.
0:23:55 So these neuropods are simply a specialized neuroepithelial cells, meaning that are electrically
0:24:01 excitable, that they can discharge electricity.
0:24:04 But they are, these type of cells are in every single epithelial cell or epithelial layer
0:24:10 of the body, because that’s how the body creates a representation of the world through sensor
0:24:16 cells that are equipped to detect the outside world, meaning that they can be exposed to
0:24:22 fluctuations in temperature, fluctuations in pH, fluctuations in concentrations.
0:24:28 And then they quickly can generate a chemo electrical code that they pass it on to the
0:24:33 nervous system.
0:24:34 And then ultimately the brain integrates that and says like, oh, my belly is feeling good,
0:24:39 but I’m feeling cold in the skin, right?
0:24:42 And that is thanks to all of these neuropathelial cells that they are even in tasting, so to
0:24:48 speak, they are the cerebrospinal fluid inside of the spinal cord and the ventricles.
0:24:54 They are inside of the inner ears, the taste, the taste buds.
0:24:58 So it is, and in fact, there’s a beautiful book from the seventies from some Japanese
0:25:04 scientists, Fujita Kanon Kobayashi, who called these cells para neurons.
0:25:11 And their whole concept is that there was not such a discrete distinction between an
0:25:16 entire neuron that lives inside of the brain or the central nervous system and a neuropathelial
0:25:22 or a neuroendocrine cell that lives exposed to the outside, simply that there is a continuum
0:25:28 of adaptation so that the organism can bring the information from outside inside of into
0:25:34 the body to be able to process it and then process it and then guide behavior.
0:25:40 So based on the way you describe it, we have these neuropod cells that line our gut, and
0:25:47 we also have these similar cell types in the other organs of the body, and these cells
0:25:52 are responding to the chemical constituents of what we eat as the food is broken down.
0:25:59 Also to the temperature of the environment, to the pH, that is how relatively basic or
0:26:07 acidic something is that we ate, and presumably to other features in our environment as well.
0:26:14 And all of that information is activating these cells to some degree or another, and
0:26:19 then we’re releasing hormones into our body as a consequence, but also there’s a direct
0:26:24 line to the brain, and we’re not necessarily aware of all of this happening, right?
0:26:30 I mean, until you describe it, I think most of us have not been aware that this is happening.
0:26:34 And we probably shouldn’t be aware, as I often say, if you and I are having a conversation,
0:26:41 we probably shouldn’t be aware of the macrophage and the spleen that is chasing this bacterium
0:26:45 that got inside of the lettuce that we swallowed at lunch, right?
0:26:49 Like, just do your thing so we can keep communicating, right?
0:26:52 Except maybe don’t eat more of that lettuce, right?
0:26:55 Which is the…
0:26:56 That’s right.
0:26:57 Okay, so you discovered these neuropod cells.
0:27:01 That’s right.
0:27:02 And you…
0:27:03 Or I describe them.
0:27:04 Yeah.
0:27:05 And you had in hand some tools to selectively label them.
0:27:09 What did that reveal about their connectivity with…
0:27:12 You’re referring to it as the nervous system, which I love because a resounding theme on
0:27:16 this podcast, as I always say, brain and spinal cord and all the connections to the body and
0:27:20 back again is the nervous system.
0:27:22 But what did you discover in terms of the connections with the brain proper?
0:27:27 Here is where the tools started to make a big difference.
0:27:31 All of a sudden you could see the resolution of a receptor inside of a cell using certain
0:27:36 type of microscopes, right?
0:27:38 So I remember that one of the first questions that I will always get drill on, you know
0:27:43 how these laugh meetings can get intense, right?
0:27:47 Like when I would bring data and show you just very simple immunohistochemistry, meaning
0:27:52 labeling to see how the cells were interacting with the nervous system.
0:27:58 Because then I will show some of the images.
0:28:01 Then the other scientists will say, well, you know, yeah, those are nice images.
0:28:05 But remember that contact does not mean connection.
0:28:10 And then I went thinking about that.
0:28:11 Like at the very beginning I thought that it was silly semantics, you know.
0:28:16 But I specifically remember that there was one time I was running and I was thinking like
0:28:20 how do you demonstrate connection between two cells?
0:28:23 And then I thought that since we had the ability to identify these cells by fluorescence, we
0:28:27 could isolate them based on their fluorescence.
0:28:31 And what will happen if we put them in front of a sensory neuron and then just record them
0:28:37 inside of a microscope, right, over time?
0:28:41 And I thought maybe they will get close to each other and then we can go and do some
0:28:45 more labeling and show that they are contacting or connecting.
0:28:49 But much to our surprise, we actually saw that in real time, when you isolate them from
0:28:56 the mouse and you put them in a dish, they both look like these round circles.
0:29:00 But after a few hours, not only they get close to each other, but they recapitulate the circuitry
0:29:05 in the dish.
0:29:06 Literally, they form like two brains in a dish, right, like the gut and the brain in
0:29:11 a dish.
0:29:12 Amazing.
0:29:13 Yeah, and that was an eye opener, you know.
0:29:17 I still remember it was somewhere, I think it was like June 27, 2012, when I saw that
0:29:21 experiment because it opened my eyes to so many different things.
0:29:27 One was that these cells are not static.
0:29:30 Because since we have been seeing them for decades, just in slices or fixed tissue, we
0:29:37 had lost the notion that this thing is constantly moving, right?
0:29:41 The cells are actually moving.
0:29:42 The cells are actually moving.
0:29:43 So these cells line the gut, meaning they’re along the walls of the gut, any intestine.
0:29:48 They reach a hand into the gut to sense whatever chemicals are there.
0:29:53 Yeah.
0:29:54 They have little cilia, little hair or microbioli that is literally like little hair that is
0:29:59 exposed to the lumen, you know.
0:30:01 So the lumen, folks, is the cavity, the empty cavity of the gut, not empty, but the internal
0:30:08 part.
0:30:09 And so they’re sensing the chemicals there and you’re saying they can move, okay?
0:30:13 And they’re sending a process, by the way, folks, anytime you don’t know whether or not
0:30:17 something is a dendrite or an axon, just call it a process.
0:30:21 You’ll get it right.
0:30:22 A process up to the brain.
0:30:25 And underneath that will connect to the nervous system.
0:30:27 I see.
0:30:28 So through a series of stations.
0:30:30 Yeah.
0:30:31 Okay.
0:30:32 Amazing.
0:30:33 So what we’re talking about here is Diego’s discovery of a pathway from the gut to the
0:30:40 brain that essentially allows sensing of what’s happening in the gut to inform feelings,
0:30:46 that’s correct.
0:30:47 Yeah.
0:30:48 So that was the first experiment like showing in addition, right?
0:30:53 The next experiment was, well, does it happen in the mouse?
0:30:57 And then through a series of, I have a friend neuroscientist that she calls these rabies
0:31:01 gymnastics because you have to put in some genes and make things work.
0:31:06 Then we demonstrated that these cells, that the virus will be capable of infecting these
0:31:12 cells specifically, instead of infecting the other epithelial cells, it will infect these
0:31:16 neuro epithelial cells because rabies likes neurons.
0:31:21 And then it will jump from that cell into a nerve fiber.
0:31:26 And these rabies can only jump one connection, right?
0:31:30 And what it was surprising is that the fluorescence from that rabies will show up in the brain
0:31:37 stem and in the bodies of the cells that are in the Nodos ganglia, which is this cluster
0:31:42 where the cell bodies of the neurons of the Bego’s nerve are located, right?
0:31:47 Underneath the neck, meaning that there was just one stop between the surface of the intestine
0:31:58 and the brain stem.
0:32:00 The two cells were connecting that space.
0:32:06 So obviously the information, that was the anatomical basis for the information to travel
0:32:11 very rapidly up into the brain and rapidly in the subconscious, right?
0:32:17 Like we’re not necessarily aware of it, although I’ve read that there are some instances in
0:32:22 which people become more aware of it, either in a typical fashion or with meditation and
0:32:32 other things like people can become aware.
0:32:34 Yes, people definitely can become more aware of their so-called interoception.
0:32:38 What’s going on at the level of their heartbeat frequency or their gut sensing if they spend
0:32:43 time on it.
0:32:44 Some people, as you mentioned, develop an almost pathologic sense of interoception such
0:32:49 that they have trouble navigating normal life because they’re so aware of what’s going on
0:32:53 inside their body.
0:32:54 This is actually an interesting issue in the field of psychiatry.
0:32:57 My colleagues in psychiatry at Stanford tell me that some people with a lot of anxiety,
0:33:02 for instance, are so aware of their heartbeat that it becomes disruptive and distracting
0:33:09 to them.
0:33:10 So it’s not always the case that it’s better to become more aware of your internal processing.
0:33:15 Sometimes it can be deleterious, other times it can be good for us.
0:33:19 Some people are very unaware of what’s happening in their body and they need to develop more
0:33:22 awareness of that.
0:33:24 I feel like as long as we’re talking about rabies, we should have a little bit of fun
0:33:27 and explain to people something about rabies viruses because what we’ve been talking about
0:33:31 is the use of viruses as experimental tools in order to take a virus, basically a attach
0:33:42 or put something in so that whatever cell is infected by it glows a certain color so
0:33:45 you can see the cells and visualize the circuitry.
0:33:48 But as long as we’re talking about rabies, I feel like it’s such a word that has such
0:33:53 salience.
0:33:54 The rabies virus, which exists in nature, is amazing because I don’t know if it has
0:34:01 a consciousness, but it essentially propagates between animals by way of the animals that
0:34:05 have it bite.
0:34:06 They become more aggressive.
0:34:09 They bite a target animal.
0:34:13 The virus gets in, it’s picked up by the nerve terminals and is carried back from one cell
0:34:19 to the next across synaptic connections, synapses, the little gaps between neurons.
0:34:24 And what Dr. Diego Borquez has been telling us is that scientists have engineered the
0:34:31 rabies virus so that it only jumps one station and then stops.
0:34:35 You can do this by modifying the coat protein.
0:34:36 There’s a bunch of fun virology that can be done to do that.
0:34:40 But what I find amazing about rabies virus, and there’s a great book by the way called
0:34:44 “Rabid,” which is essentially a history of the study of rabies, is that once it travels
0:34:52 from the site of the bite up to the brain, what does it do?
0:34:56 It changes the brain to make the now infected animal or person more aggressive so that then
0:35:02 they go bite somebody else.
0:35:05 So I mean, in some ways, the viruses have a sort of unconscious genius to them, right?
0:35:10 What’s the best way to get from one animal to the next?
0:35:14 Well, there are a number of different ways, but one way is to just make that animal more
0:35:17 aggressive so it goes and bites things.
0:35:19 Yeah, make that.
0:35:20 Wild, right?
0:35:21 Make that animal work for you, right?
0:35:22 Make the animal work for you, right?
0:35:24 It’s almost exploitive, right?
0:35:25 It exploits a certain circuitry in the nervous system.
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0:36:59 Okay.
0:37:00 So you identify these, you said described, but you, I’ll say discovered because that’s
0:37:06 what happened.
0:37:07 You discovered these, these cells, you label their connections, you see that there’s just
0:37:12 two stations between these cells or one station really between these cells and the brain.
0:37:18 And so now these cells can sense chemicals in the gut that are the consequence of the
0:37:23 breakdown of food and send that information directly to the brain.
0:37:26 What does the brain do with that information?
0:37:28 All right.
0:37:29 So here it comes, the key experiment and this was building obviously on the work of other
0:37:34 scientists that had already described that the gut had some receptors for sugars for specifically
0:37:41 for glucose, for other nutrients around this area in the early 2000s, when we were starting
0:37:46 to be able to identify some of these cells, then it quickly became obvious that these
0:37:54 cells, these enteroendocrine cells throughout the lining of the stomach intestine colon,
0:38:02 they had multiple receptors for multiple nutrients, you know, like we have the macronutrients
0:38:07 for instance, sugars, fats, proteins, but within them we have, you know, a repertoire
0:38:13 of molecules, you know, multiple lipids, multiple types of sugars and so on and so forth.
0:38:19 And these cells, depending on their location, they will express a different type of receptors
0:38:24 or a combination of those receptors.
0:38:27 And I said that depending on the location, because when we’re eating, let’s say an apple,
0:38:31 you know, the apple is going to be partially undigested by the time that it enters in testing,
0:38:35 but by the time that it gets to the colon, most of those nutrients have been absorbed
0:38:39 and perhaps only fibers are surviving to feed off most of the microbes that live in
0:38:43 the colon, right?
0:38:45 So the gut has evolved to mirror and to become a velcro to the molecules that will be in
0:38:55 that specific space, so it will detect.
0:38:58 So it will detect sugars more in the proximal intestine, but fibers or fermented by products
0:39:06 more in the distal intestine or in the colon, like short chain fatty acids, butyrate, propionate
0:39:13 and so on and so forth, you know.
0:39:14 What other kinds of nutrients do these neuropod cells detect from food?
0:39:18 So you mentioned sugars, you mentioned fermentation, presumably short and long chain fatty acids?
0:39:26 Yes.
0:39:27 The short answer is that I think that in due time, we are going to realize that they detect
0:39:33 just about every single thing that we put on our mouths every day, you know, that they
0:39:38 have some either a specific receptor that is dedicated to it or a combination of receptors
0:39:43 to be able to detect some of these compounds.
0:39:47 And not only the chemical compounds, but also an area that I think is going to be fascinating
0:39:51 in the future is the mechanical extension plus the adjustment in temperature as the
0:39:58 chimes starts to flow from the mouth into the colon.
0:40:04 Like for instance, I heard this from a bioengineer and not long ago that was engineering an artificial
0:40:10 gut and a stomach, and he shared with me a piece of information that I was not aware
0:40:16 of that the sofas has to adjust the temperature of the food very rapidly within seconds into
0:40:24 physiological temperature of the inside of the body.
0:40:27 Like so we are having hot coffee within couple of seconds, it has to be at the physiological
0:40:32 temperature of the body by the time that it gets into the stomach, right?
0:40:36 And all of that happens in very rapidly in the sofas, right?
0:40:40 So if I understand correctly, these neuropod cells have a variety of different receptors
0:40:44 depending on where they are located along the trajectory from the mouth to the rectum.
0:40:52 And some are sensing sugar, some are sensing temperature, some are sensing pH, so relative
0:40:58 acidity.
0:41:00 Some are sensing amino acids, presumably, I mean I’ve heard it said and I believe there’s
0:41:06 a researcher down in Australia who has been very bullish on the theory that we are not
0:41:13 exclusively but we are predominantly amino acid foraging machines because we need amino
0:41:19 acids for all sorts of important biological processes.
0:41:24 And these cells are essentially evaluating how much sugar, how much leucine, how much
0:41:31 short chain fatty acid, how much, you know, essential fatty acids of different kinds and
0:41:36 then making changes to the gut itself but then presumably signaling that information
0:41:40 elsewhere in the body.
0:41:42 So here I’m going to give you something that will get your gut churning, so to speak.
0:41:49 So these cells have to make sense not only of the molecule that are being adjusted, meaning
0:41:55 the chemistry of the molecule, let’s say it is glucose, it has to make sense, a little
0:41:58 bit of the taste, is it sweet, right, is it bitter.
0:42:02 Then it has to take into account how much of the molecule is absorbed inside of the cell,
0:42:08 right?
0:42:09 So that’s a second layer of integration.
0:42:11 And once the cell has eaten that molecule, so to speak, then that molecule will be digested
0:42:17 inside of the cell to release ATP or some other compound, ATP, for energy, for instance.
0:42:26 That has also have to be taken into account, for instance, in glucose.
0:42:31 Glucose activates the TAS-1R3, which is a sweet taste receptor.
0:42:35 Then the glucose is absorbed by some of the sodium glucose transporters, which are active
0:42:38 transporters.
0:42:40 And these transporters depolarize the cell.
0:42:43 And then once glucose gets inside of the cell, glucose enters the TCA cycle, it’s catabolized,
0:42:48 and then produces ATP.
0:42:49 And the ATP further activates another voltage-gated channel, further depolarizing the cell.
0:42:59 And then the cell releases, in turn, a transmitter, for instance, glutamate, that very rapidly
0:43:05 tells the vagus nerve within milliseconds, you know, “I got sugar.”
0:43:10 And it tells it in two phases, because that glutamate will activate two different type
0:43:14 of receptors, ionotropic, which are very fast, and metapotropic, which are a little
0:43:19 bit more delayed.
0:43:22 But then the metabolism of that glucose that produces the ATP and further depolarizes the
0:43:27 cell, we believe that it will cause the release of the hormone, of the neuropeptide.
0:43:33 So then the neuropeptide comes on top of that and gives you that full experience of what
0:43:38 it means to consume sugar, right?
0:43:43 So that happens at the level of one cell and at the level of one molecule.
0:43:48 So imagine, like, all of the computation that the gut has to be making for each one of the
0:43:52 molecules throughout the digestive tract.
0:43:54 So if I stand back from this picture, what I get is there are very interesting cell types
0:44:02 that line our gut that are evaluating all of the not just macronutrients, proteins, fats,
0:44:08 and carbohydrates, but micronutrients within the food we eat, as well as some of the other
0:44:14 qualitative features, temperature, for instance, maybe even quality of the amino acids or the
0:44:20 sugars, you know, simple versus complex sugars, et cetera.
0:44:25 If we could just further zoom out for a moment and take a human perspective on this at the
0:44:30 level of experience.
0:44:33 I once heard you tell a story about someone you knew who changed their gut radically and
0:44:43 that changed their entire perceptual experience of food, including certain cravings.
0:44:49 Would you mind sharing that story?
0:44:50 Yes.
0:44:51 Thank you for bringing that story, Andrew.
0:44:54 That story is very personal to me.
0:44:56 I often say when I get on stage that we are constantly influenced by two things in life,
0:45:01 the food that we eat and the people that we meet, you know, like now I, we have known
0:45:05 each other, but now we meet in person and we are knowing other people, right?
0:45:10 And I remember that when I was starting my PhD in nutrition at North Carolina State University,
0:45:16 I was, so I didn’t grow up in the United States.
0:45:18 I grew up in Ecuador and I was invited to my first Thanksgiving celebration.
0:45:26 So I sat at dinner and, you know, as we began chatting with the people that were next to
0:45:31 each other, all of a sudden I was enthralled in this conversation of a woman telling me
0:45:38 this story about her experience with gastric bypass surgery for treating obesity.
0:45:45 So gastric bypass surgery was begun to be developed by surgeons in the ’60s.
0:45:53 And by the ’90s, it had become a mainstream type of surgery for the treatment of chronic
0:45:59 obesity.
0:46:01 So she told me that there were primarily three things that happened.
0:46:04 She said, well, within six months of the surgery, I had lost about 40% of body weight, you know?
0:46:10 She said, like, I was about 300 pounds, you do the math, you know?
0:46:14 So it was a significant amount.
0:46:19 She said, within one week of the surgery, my diabetes was gone.
0:46:23 She said, I did not need more insulin shots.
0:46:26 So I had the same reaction that you’re having.
0:46:29 I was like, you know, I don’t know much about diabetes, but I know that it’s a major health
0:46:35 burden, right?
0:46:38 But the thing that really caught my eye was when she said, but since you’re studying nutrition,
0:46:43 I want you to answer this to me.
0:46:45 She said, why is it that before the surgery, I could not even look at sonyside up eggs?
0:46:49 She said, just looking at the yolk will make me queasy, you know?
0:46:54 But after the surgery, not only I can eat sonyside up eggs, I actually have a craving
0:47:00 for the yolk.
0:47:01 She said, every time we go on Saturday to a restaurant for breakfast, I will take the
0:47:05 toast and I will actually clean the plate of the yolk.
0:47:08 So how is it that rewiring the gut?
0:47:12 After my perception of flavor, after my cravings and my mind to get the yolk, she said.
0:47:18 And even inverted her sense of what was aversive versus apetitive.
0:47:24 And I guess for those of us that don’t know, meaning me, I understand the gastric bypass
0:47:29 surgery involves the removal of a portion of the gut.
0:47:33 How much gut tissue do they actually take?
0:47:35 Is it centimeters, inches?
0:47:39 The gut’s a long distance.
0:47:41 So what do they do for gastric bypass?
0:47:43 In simple terms, the most, the classic surgery is called a ruin Y gastric bypass surgery,
0:47:52 which involves a reduction of the stomach and short cutting the connection of the stomach
0:48:01 to the intestine.
0:48:02 So you will cut, you know, one third, which will be the duodenum, one third of that will
0:48:07 be cut, and then that portion will be reconnected to the stomach, meaning that you’re short
0:48:14 circuiting the gut.
0:48:16 And the whole idea was, at the very beginning, it was like, well, if we reduce the surface
0:48:21 that is exposed to food, then we can reduce body weight by the simply reduction of surface
0:48:29 that is exposed to the food that is absorbed, right?
0:48:33 And what it became very clear is that well before the body weight changes got taken place,
0:48:39 there was already like some dramatic changes in physiology, like the hormones, the neuropeptides
0:48:45 that were released from the intestine in response to nutrients, you know, it will change very
0:48:50 rapidly.
0:48:52 Then as I mentioned, the food choices will change, diabetes will be resolved.
0:48:57 So then it became obvious that it was not necessarily just the reduction in the surface
0:49:04 of the gut.
0:49:05 So that’s one of the main surgeries.
0:49:07 The other one, as I understand, is vertical isleaf gastrectomy.
0:49:13 And this vertical isleaf gastrectomy is simply a reduction in the size of the stomach.
0:49:19 So now the stomach is very tiny, and the idea is that it will accumulate less, it could
0:49:24 call less food, and then the food will go very rapidly into the intestine.
0:49:28 And what is becoming very obvious is that there is a rapid change in the sensory function
0:49:34 of the gastrointestinal tract.
0:49:36 So the gut seems to rapidly shift, perhaps become more, so to speak, in general terms,
0:49:42 more sensitive to the presence of nutrients, right?
0:49:46 Interesting.
0:49:47 So this woman that you met at Thanksgiving had gastric bypass surgery, and presumably,
0:49:53 I think it’s fair to assume, a good number of these neuropod cells that sense different
0:49:57 nutrients were removed.
0:50:00 And as a consequence, she completely shifted her craving of a particular food.
0:50:06 And is there any sense whether or not, no pun intended, the lack of sensing of what was
0:50:13 in sunny side egg yolks was somehow related to a shift in appetite or something else,
0:50:21 whereas it merely a qualitative, albeit a dramatic qualitative shift in what she craved.
0:50:29 So two contextual pieces of information.
0:50:33 So I remember leaving that dinner, and I was like, whoa, this is major, you know, like
0:50:38 I’m sure that people have written about this or done research.
0:50:42 And I realized that it was very little was known.
0:50:45 Even gastroenterologists knew very little about this.
0:50:49 The first clinical report that the alteration in food choices was common in these patients
0:50:56 came out, I believe, in 2011.
0:50:59 And then later on, scientists replicated that even in rats or in mice, we have done it in
0:51:05 the laboratory, and consistently, they changed their food preferences, their food choices.
0:51:13 So in recent years, we have been starting that system.
0:51:22 And I will tell you that in 2022, this is another important contextual piece that we
0:51:27 have gotten, have not gotten to it.
0:51:30 So after we found and we described that these cells were connecting to the nervous system
0:51:37 and that they were sending information up to the brain very rapidly, the challenge was,
0:51:42 well, if this is a sense, what behavior is affecting, right?
0:51:46 How is it that is affecting the responses of the organism?
0:51:50 And that took a little bit of a technical hurdle, and here is where optogenetics comes
0:51:56 in.
0:51:57 Yeah, please explain for me what optogenetics is, at least at a top contour level.
0:52:02 Yeah.
0:52:03 Optogenetics, in 2005, Professor Carl Diceroth, Ed Boyden, and other scientists had been
0:52:14 able to make this dream of an experiment, which was isolate the genes that encode for
0:52:20 these opsins that are sensitive to specific wavelengths of light and put them into neurons.
0:52:26 And now by turning that light, they could make the neuron activate.
0:52:31 And ultimately, then later on, they went on to describe that that could be used to control
0:52:35 specific cells that are regulating behavior, and then by that, define what cells are orchestrating
0:52:41 certain type of behaviors like movement, foot intake, thirst, anxiety, so on and so forth.
0:52:48 So in 2014, we began trying to adapt that technology to the gut.
0:52:56 Very quickly, we realized that the way that light was brought into the brain was through
0:53:02 a fiber optic cable that was rigid, and in the brain, it helps that it’s actually rigid.
0:53:11 But in the gut, it doesn’t help because the gut is constantly moving and so on and so
0:53:14 forth.
0:53:15 So it’s not compatible for running those experiments.
0:53:18 And here’s where I usually say, we really don’t know what is going on because some forces
0:53:23 like move around us.
0:53:25 And in 2017, Professor Polina Nikeva from MIT came to give a talk at Duke, and she reached
0:53:32 out to me, and literally she came, and as we were chatting, she said, like Diego, I see
0:53:37 that you’re working in this interface of the gut and the brain, and I have this fiber optic
0:53:42 that is flexible, you know, will you have any use for it?
0:53:47 So with that fiber optic, that made a big difference to study interrogate the function
0:53:51 of these cells to behavior.
0:53:54 So when we were able to put those options, the light sensitive proteins inside of these
0:54:00 neuropods, now when we turn the light on to shut off these cells very rapidly, we found
0:54:10 something very interesting.
0:54:12 So normally, animals, when you give them the choice between a suitor, which is the void
0:54:17 of caloric value.
0:54:18 So like aspartame or stevia or something.
0:54:25 And you give them sugar, table sugar, the animal invariably will go to sugar.
0:54:33 They prefer sugar.
0:54:34 They prefer sugar, you know.
0:54:36 If they have never seen sugar, it will take them a little bit more time, but regularly,
0:54:42 by the second day, is within 90 seconds that they detect what is sugar.
0:54:48 So they’re drinking out of one tube, they get some water with stevia, they drink out
0:54:52 of another tube, water with sugar, and they invariably prefer the water with sugar.
0:54:57 That’s correct.
0:54:59 And people have described this phenomenon for a while, and in fact, in 2007, there was
0:55:05 an elegant experiment done by Professor Ivan Deraujo at Duke University, in which the sweet
0:55:14 taste receptors were, or the taste receptors were genetically erased.
0:55:20 And the animals were not capable of distinguishing the sweetener from the water, but they could
0:55:27 still distinguish sugar from water, meaning that there was something else that was detecting
0:55:34 that sugar.
0:55:35 So just to make sure people are on board, an experiment where sensing of sweet taste
0:55:41 at the level of the mouth is eliminated does not disrupt the preference for sugar water,
0:55:49 which means that there’s something going on below the depth of consciousness that causes
0:55:57 mammals, presumably us included, to prefer things that have sugar.
0:56:02 Yes.
0:56:03 And then Professor Tony Esclafani, he had been studying these behaviors, and he went
0:56:09 in so far to suggest that perhaps the sodium glucose transporters are some of the ones
0:56:14 that are detecting the sugar as it enters the intestine, and that’s what is causing
0:56:18 the behavior.
0:56:21 So we began working on the system, and we wondered, could these cells be the ones that are guiding
0:56:28 that behavior?
0:56:29 And around the time that we published this work, Professor Charles Zucker at Columbia,
0:56:36 so far they’re advanced that area by building on the previous work and demonstrating that
0:56:43 there were a population of neurons in the brainstem that were integrating this information
0:56:48 from the gut, and by that the gut and the brain were guiding this behavior.
0:56:55 And it is true that from the earliest of ages, we crave sugar, or at least if we are exposed
0:57:03 to the taste of sugar, it tends to drive seeking of more sugar, and you can see that in babies
0:57:09 even.
0:57:10 Correct.
0:57:11 And as I usually say, I call it instinctively because our mother doesn’t have to teach us
0:57:16 a Diego that is glucose, you know.
0:57:21 It may present us in some ways, but at the end of the day, I have to go and get my glucose,
0:57:25 get my amino acids, right?
0:57:27 Because eating is very simple.
0:57:28 We are just trying to solve this issue of getting our carbons, getting our nitrogen,
0:57:33 getting our phosphorus, our potassium, our sodium, and our chloride in so many different
0:57:38 ways, shape or forms, right?
0:57:40 So I went back to the experiment, the key experiment.
0:57:44 So when we were able to put these options and bring the light and shut off these cells
0:57:49 very rapidly, when we had presented the animal with the choice of sweetener over sugar, then
0:57:56 all of a sudden the animal became blind to the solutions.
0:58:00 It couldn’t discern between the stevia, so to speak, or the sweetener from the actual
0:58:07 sugar.
0:58:08 And the entire manipulation, the experimental manipulation that is, is occurring at the
0:58:13 level of the gut.
0:58:14 The intestine, that’s right.
0:58:15 Right after the stomach, it’s like just a small portion of the intestine.
0:58:19 So if we make an attempt to transfer this to the human real world experience, if I have
0:58:29 some ice cream, it tastes sweet.
0:58:33 I like it.
0:58:34 And now I’m thinking about it, and I’m craving it just a little bit.
0:58:37 I don’t have a huge craving for sweets, but I do like some of them.
0:58:43 So eating ice cream, it tastes sweet.
0:58:46 The tendency is to crave more.
0:58:48 That’s correct.
0:58:49 You eat a lot of ice cream before you’re truly full.
0:58:53 And most people self-regulate, or their parents regulate for them by limiting the number of
0:58:57 scoops or something.
0:59:00 And that sweet taste is part of the motivator.
0:59:05 But what you’re saying is that as the ice cream enters the gut, there are neuropod cells
0:59:11 there that are also sensing the sugar and signaling to the brain.
0:59:16 And the brain is responding to pursue more of that sweet, containing substance.
0:59:23 That’s correct.
0:59:24 And it’s happening below our awareness.
0:59:26 It is independent from the sweet taste of the ice cream.
0:59:30 Correct.
0:59:31 The conscious sweet taste.
0:59:32 The conscious sweet taste, whichever you think about it, it’s not fully conscious.
0:59:39 What we detect of the world is just a very tiny little portion, even sight.
0:59:45 We think we are looking for light, but I don’t know what is happening behind my back.
0:59:49 I trust that everything is going OK.
0:59:54 So when we shut off the cells, the animal, and as I usually say, it became blind to the
1:00:02 sugars, because it’s kind of like akin to having turned off the cells that are able
1:00:09 to detect light, the wavelength of light for us to be able to discern color.
1:00:17 And it’s not that the animal is losing its memory, because then if you remove the light
1:00:21 and now the cells are functional again, then the animal again is able to distinguish one
1:00:26 solution over the other.
1:00:30 And then we did a couple more experiments in there.
1:00:32 And what happens if we do the reverse, if we turn on the cells now?
1:00:38 And the fascinating thing is that when we turn on the cells, now the mouse will eat
1:00:43 the sweetener, as if it will be sugar.
1:00:46 Interesting.
1:00:47 So the activation of these cells makes the crave non-caloric sweetener or low-calorie
1:00:54 sweetener as if it were sugar, but is it blinding them to the difference between sugar
1:01:01 and low-calorie sweetener?
1:01:04 So here’s another piece of information.
1:01:06 We will offer them water and we will turn on the cells.
1:01:10 The animal will drink the water as if it will be sugar, like it will be appetizing.
1:01:15 Even though it’s just plain water.
1:01:17 And what is becoming very obvious is that the gut has this sense at the most basic level.
1:01:26 What the senses are doing is calculating a couple of things.
1:01:31 One is the salience of the stimulus is like how intense is the stimulus.
1:01:39 And the other one is the valence of the stimulus is a pleasurable or painful, so to speak in
1:01:46 like broad terms.
1:01:48 And I say this because on the pain side, Professor David Julius, Professor Holly Ingram, Jim
1:01:57 Byra at UCSF, they have done some beautiful work demonstrating that there are these serotonin
1:02:03 releasing cells, specifically in the colon, they have focus in the colon, that they couple
1:02:09 to nerve fibers of the spinal cord and when they are activated, now all of a sudden they
1:02:16 drive what we call in the clinical realm, visceral hypersensitivity.
1:02:23 So they are responsible for triggering the hypersensitivity of the nerve fibers, the
1:02:28 colonic nerve fibers, because they detect noxious stimuli and then ultimately they gate that
1:02:36 noxious stimuli and pass it on to the nerve fiber as in broad terms, as a painful stimulus.
1:02:44 So is this irritable bowel syndrome?
1:02:47 It is, we could call it as the biological basis of what could degenerate into irritable
1:02:52 bowel syndrome and so on and so forth, or these chronical GI, they call them disorders
1:03:00 of gut brain interactions in the clinic.
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1:04:04 As a neuroscientist, I was trained to think about the neural retina, the light sensing
1:04:08 tissue at the back of the eye, the cochlea, the essentially mechanosensory cells in the
1:04:15 inner ear that respond to sound waves, not directly, but through a number of different
1:04:22 transducers and this kind of thing, and then of course where you are all familiar with
1:04:26 the skin and that it responds to pressure like touch, tickle, itch, etc.
1:04:32 What I’m understanding based on what you’re telling me is that all along the pathway from
1:04:36 our mouth to our rectum, we have sensory cells that are evaluating the chemical constituents
1:04:42 of the foods that we eat, emitting broad, maybe even crude, slow signals in the form
1:04:49 of hormones to change our appetite, our feelings of well-being, maybe our feelings of not well-being,
1:04:58 but also sending direct signals to the brain to drive certain types of thinking, emotions
1:05:05 and behavior.
1:05:07 What sorts of thoughts, emotions and behaviors are foods known to evoke through this pathway
1:05:14 from the gut?
1:05:16 Because the story about your friend that had the gastric bypass and then changed the relationship
1:05:21 completely to the craving of or the aversion to sunny side eggs indicates that it’s a pretty
1:05:28 crude as I’m describing a system to begin with, but it ultimately converges on pretty
1:05:33 fine-scale decision making.
1:05:34 You order this and you avoid that.
1:05:38 You really like this and you really are almost nauseous at the thought of something else.
1:05:42 That’s pretty high level decisions.
1:05:43 It might not seem like it to most, but it’s impacting significant behavior or impacting
1:05:51 behavior at a significant level.
1:05:53 That’s correct.
1:05:56 When I think about that specific example is that after there has been this rewiring of
1:06:05 the intestine, then now the intestine is very sensitive, so to speak, to the stimuli.
1:06:13 When those lipids from the yolk start to enter the intestine, if that sensitivity has changed
1:06:18 meaning it could have changed in how fast it reacts to the stimulus or how fast it communicates
1:06:25 to the stimulus and how sensitive it is to the saliency or the strength of the stimulus,
1:06:34 it could communicate that what it used to be a repulsive with a tiny little bit of amount.
1:06:40 Now it is actually pleasurable with a tiny little bit of amount.
1:06:45 Here’s a clear example.
1:06:47 It has been very well, I will say that it has been documented in the clinic that patients
1:06:54 that undergone gastric bypass surgery, they’re actually more prone.
1:06:57 I think that it goes from like two to seven-fold the likelihood that they become, they will
1:07:06 develop alcoholism.
1:07:08 Really?
1:07:09 Yes, because now the way that they describe it is like, well, either before I didn’t like
1:07:17 mine, and then now after a few months of a surgery I’ll have one glass of wine, and then
1:07:24 all of a sudden I found myself going to two, three, four, and then they will become either
1:07:30 more sensitive.
1:07:31 It’s still not known the entire biology, but they will become either not only more sensitive,
1:07:35 but more attracted to that type of stimulus.
1:07:38 I can’t help but ask about Ozempic, Monjaro, and GLP-1, glucagon-like peptide-1 analogs,
1:07:49 which are really out of all the rage right now, at least for discussion, but many, many,
1:07:54 many millions of people are now taking this for treatment of diabetes and for weight loss.
1:08:00 My understanding is that GLP-1 acts at the level of the brain, the hypothalamus to reduce
1:08:05 hunger, but also at the level of the gut to give the sensation of more gastric distention.
1:08:11 Is there any knowledge of whether or not GLP-1 interacts with the neuropod cells and this
1:08:17 pathway that you’re describing, given what these neuropod cells do for craving or aversion?
1:08:23 Yes, that’s a complementary question.
1:08:27 In fact, when I got into studying in this field 15 years ago, the study among scientists
1:08:35 in this area, glucagon-like peptide was already very popular in the study.
1:08:40 In fact, in this area, people were very focused on the study of this peptide, and they were
1:08:46 very focused on the study of this peptide because it was one of the most potent stimulators
1:08:52 of insulin release in the pancreas.
1:08:56 After gastric bypass surgery, it will actually increase its amount in circulating levels,
1:09:03 and there were already some studies suggesting that the effect of this glucagon-like peptide,
1:09:12 it was actually not through the circulation, but more in a localized action onto nerve
1:09:20 fibers, especially of the vagus nerve.
1:09:22 There was already someone going discussion about this, and certainly some of these endocrine
1:09:30 cells, these neuroendocrine cells, particularly at least in animals, I think, is more distal
1:09:38 and in the digestive tract, that they do release this glucagon-like peptide, one in response
1:09:46 to primarily all of the macronutrients, but primarily sugar, and then these glucagon-like
1:09:57 peptide-1 will act on specific receptors of the nerve terminals and then will trigger
1:10:02 some other behaviors.
1:10:03 It’s also thought that it acts at the level of the brainstem, and what it will potentiate
1:10:09 is the reduction of appetite.
1:10:14 So I say that this is a complementary question because what is happening in the first few
1:10:18 milliseconds is the actual choice and the actual feeling of how you feel about food, and what
1:10:24 is happening in the minutes, two hours later, is the amount, how much you can eat and when
1:10:30 you should stop, because after four hours, you’re going to come back and feel again the
1:10:35 tickling of the gut, because the gut starts to churn again and starts to call for food.
1:10:41 Remember, it has to feed two giant organisms, the host itself, but also the microbes that
1:10:46 are inside, right?
1:10:48 So it has to keep, so to speak, that hangar going every four hours or so, right?
1:10:56 So that’s why the hormones are more acting on the cyclical circadian way, but the transmitters
1:11:05 are acting in this very fast, responsive way of the precise stimuli in specific regions
1:11:13 of the gastrointestinal tract.
1:11:15 So these neuroendocrine cells are releasing GLP1 or responding to GLP1?
1:11:21 They’re releasing GLP1.
1:11:23 They’re releasing GLP1 to shut down, transiently shut down, hunger.
1:11:28 And probably there is some interaction between the cells that they are having, you know,
1:11:33 the technical term is auto-cring, or they are having like power-cring between the cells,
1:11:38 you know, neuromodulation, but primarily, let’s say, they respond to the stimulus and
1:11:43 release GLP1 onto the nerve fiber.
1:11:46 I have a theory for which I have no direct data, but I’d like your thoughts on having
1:11:51 spoken to a lot of people that work on nutrition, but also gut-brain access today and microbiome
1:11:58 in previous episodes, that one of the key things that a human learns, somewhat unconsciously,
1:12:07 but also consciously, is the relationship between a given food, which macronutrients
1:12:14 it contains, the ratios of, you know, carbohydrate, protein and fat, the taste of that food, the
1:12:23 amount of that food translated into calories, but also physical volume, and then the micronutrients.
1:12:30 Why do I say this?
1:12:31 Well, there are a growing number of studies showing that the ingestion of highly processed
1:12:35 food leads to the intake of excess calories, or more calories, than if one consumes foods
1:12:41 in their more natural form.
1:12:43 Single-ingredient foods or two-ingredient foods are very different than a food that
1:12:47 has a bunch of different things in it.
1:12:49 And it seems to me that if we were to look back into our evolution, sure, people were
1:12:54 making stews and soups and things for a long time, presumably the sandwich came about through
1:12:59 either desire for convenience or taste or both, you know, putting meats, protein in
1:13:05 between two pieces of bread, something of that sort.
1:13:09 My definition of a sandwich, maybe some vegetables in there as well, some cheese, but that what
1:13:15 this whole pathway along the gut is trying to do, it seems, is to deconstruct what’s
1:13:23 coming in, what’s here, and shaping choices, as you mentioned, about food choice, including
1:13:29 the amount of food to further consume, and whether or not to return to that food or to
1:13:33 avoid it.
1:13:34 That’s correct.
1:13:35 And at the extremes, it seems pretty straightforward.
1:13:38 And this is a very classically described case, right?
1:13:40 You go and you have the, you know, the Kung Pao shrimp, or you have the lentil soup at
1:13:45 a given place, and a few hours later, you don’t feel right, start some sweating, some
1:13:50 gastric distress, and you develop a pretty broad aversion to that food, or maybe even
1:13:55 the entire meal, maybe the restaurant, maybe even that entire type of cuisine, depending
1:14:00 on how much of a lump or versus a splitter you are, as we say in science, right?
1:14:05 How much you make kind of large, large bin decisions or fine bin decisions.
1:14:12 This is nerd speak for saying, you know, do you go back to the same restaurant but order
1:14:15 something different, or do you just decide to never go back again?
1:14:18 But that’s a pretty extreme case, right?
1:14:21 The other extreme would be you eat a food, it’s delicious, you feel wonderful, the restaurant,
1:14:26 the people, it’s wonderful, and you crave more of that food, okay?
1:14:29 There’s all the contextual stuff too.
1:14:31 But what we really are talking about here is how one navigates this whole landscape of
1:14:38 what to put into one’s body in terms of nutrition, and trying to understand how that’s impacting
1:14:45 everything from how we feel right away, how it tastes, whether or not we conceive it as
1:14:50 good or bad for us, whether or not we think it’s impacting our body composition and health
1:14:55 in ways that we want or don’t want.
1:14:57 I mean, it’s pretty complex stuff, right?
1:15:00 This is at least as complex as going to Metropolitan Museum of Art and looking at a painting and
1:15:07 trying to evaluate whether or not you really like that painting or not.
1:15:10 In fact, it’s probably much more complicated than that.
1:15:14 But it’s what we do.
1:15:15 And I’m beginning to get the sense, again, no pun intended, that this pathway that we
1:15:21 call the gut brain axis is really, it’s a sixth sense of a very elaborate kind.
1:15:31 So you just touch on an entire realm of a topic, which is one of my favorite topics,
1:15:38 because at some point, you know, as scientists, we travel the world, and it started to become
1:15:44 very obvious to me that whatever I went, we sold this issue of food in a very similar
1:15:52 way, whether it’s a tortilla or two pieces of bread, which is another way of a tortilla,
1:16:00 you have your carbs.
1:16:03 And then you add a little bit of meat or a mushroom, and now you have your protein.
1:16:09 Or fish or chicken.
1:16:10 Or fish or chicken.
1:16:12 The carnivores will say mushrooms, not a protein.
1:16:14 The vegans will say mushroom, beans, lentils, great protein.
1:16:17 We’re not here to resolve that debate.
1:16:19 Do as you choose.
1:16:21 And then you add the lettuce or the vegetables.
1:16:28 And here’s the first stop in that discussion, because this is fascinating.
1:16:35 There is some recent work showing that if you remove the protein from a diet, the animal
1:16:44 swallows that meal, they got evaluates that there is no protein in there and stops eating
1:16:53 that meal.
1:16:54 Wow.
1:16:55 It’s like ordering the vegetarian taco or burrito or sandwich, and then avoiding that
1:17:05 particular taco or sandwich thereafter because it lacks protein.
1:17:12 Because it lacks protein.
1:17:13 Okay.
1:17:14 So foods that lack animal-based proteins tend to be avoided going forward.
1:17:18 So here’s the second part of that.
1:17:22 And in fact, if the protein is low, not completely absent.
1:17:27 If the protein is low, the animal consumes more of the diet because it’s trying to compensate
1:17:32 for the lack of protein.
1:17:34 And obviously, if it has sugars or fats that are more pleasurable, it keeps eating that
1:17:38 meal, right?
1:17:39 I see.
1:17:40 If the protein is completely absent, the animal avoids that diet, unless that diet is
1:17:50 very rich in dietary fibers.
1:17:56 And the study that I saw, which I thought it was fascinating, is that because somehow
1:18:05 the microorganisms in the digestive tract, if they have enough highly digestible fiber,
1:18:11 now they turn on the ability to synthesize essential amino acids.
1:18:16 Really?
1:18:17 Yes.
1:18:18 And our gut, meaning the neurons in our gut, are essentially waiting for, hoping, we’ll
1:18:26 give them a consciousness, proteins from animal sources.
1:18:31 That’s correct.
1:18:33 If those animal proteins arrive in the form of meat, fish, eggs, et cetera, the cells
1:18:39 signal to the brain craving more of those foods until satiety is reached.
1:18:45 But in the absence of that protein, the animal quickly learns, the person quickly learns to
1:18:50 avoid that particular food, unless there’s fiber in it, in which case these gut cells
1:18:56 are able to now synthesize the essential amino acids.
1:18:59 The microorganisms.
1:19:00 Excuse me.
1:19:01 The microorganisms of the gut, here we’re talking about the microbiome now, can synthesize the
1:19:06 essential amino acids that ordinarily would come from the meat, chicken, fish, or eggs.
1:19:11 That’s right.
1:19:12 So wow.
1:19:13 So I’m an omnivore.
1:19:17 I love meat, high-quality meat, but I also love vegetables, fruits, and starches of certain
1:19:24 kinds.
1:19:25 But I have friends who are vegetarian vegan.
1:19:29 Many of them eat a vegetarian vegan diet that includes a lot of fiber.
1:19:34 And you’re saying that the fiber itself can trigger the gut microbiome to synthesize the
1:19:39 essential amino acids that ordinarily would come from meat.
1:19:43 But you also said, if I recall, that if there’s a small amount of protein, so not zero protein,
1:19:50 but a small amount of protein in there, then we crave more of that food in order to try
1:19:55 and get that protein.
1:19:57 Very interesting because this is the first thing that to me squares the argument based
1:20:02 on the hypothesis that we are essentially amino acid foraging machines and that complete
1:20:10 proteins in the form of meat, fish, chicken, eggs, et cetera.
1:20:14 There are those that argue those are the “best forms of protein,” the most complete forms.
1:20:19 But there are many vegetarians and vegans who seem to thrive on a vegetarian vegan diet.
1:20:24 And you’re telling me that perhaps their gut microbiome is compensating for the lack of
1:20:30 whole animal protein.
1:20:31 But the people who are trying to limit their meat intake are, what, hungrier in general.
1:20:37 So you’re better off either indulging it or avoiding it, but not having a small amount
1:20:42 of it.
1:20:43 Is that the idea?
1:20:44 The idea is that the body or the gut will be able to detect that and they will try to
1:20:49 compensate.
1:20:52 And this I actually learned recently from a friend, Laura Dubal, at Columbia, who does
1:21:00 some beautiful work on mosquitoes and how it is that they feed on blood.
1:21:04 She came for the gastronauts series.
1:21:08 Is she from Leslie Volcel?
1:21:09 Yeah.
1:21:10 Volcel, so.
1:21:11 Yeah.
1:21:12 And what I learned is that when the mosquitoes are not reproducing, they can leave off ATP,
1:21:18 which is the energy molecule, right?
1:21:22 But they cannot lay eggs.
1:21:26 They need the protein in order to be able to lay eggs.
1:21:30 Otherwise, the mosquitoes cannot lay the egg.
1:21:35 So this leaves us with a picture of the gut-sensing cells, these neuropod cells, as exquisitely
1:21:43 sensitive to amino acid content in our foods, which makes perfect sense to me.
1:21:48 And it has not been published or demonstrated yet.
1:21:51 Sure.
1:21:52 We’re now in the realm of new incoming data.
1:21:55 We want to highlight this, bracket it, boldface and underline it as we’re now at the cutting
1:21:59 edge of what may be coming.
1:22:02 That’s right.
1:22:03 Right.
1:22:04 Observation.
1:22:05 But nonetheless, very interesting.
1:22:06 But there is this fairly long-standing hypothesis that we are foraging for essential amino acids
1:22:11 because they are the building blocks of so many important things in the brain and body.
1:22:15 And in fact, there is evidence on that.
1:22:18 Like Professor Steven Simpson in Australia at the Nutrition Research Institute at Sydney
1:22:26 University, he is a main proponent of these protein leverage hypotheses.
1:22:31 And in fact, protein is the most assiating macronutrient, so that has been established.
1:22:39 And that’s why normally we have focused on sugars and fats, but we have neglected a little
1:22:44 bit on the protein because it’s not as pleasurable as the sugars or fats.
1:22:49 But what is fascinating is that it’s the most assiating and nutrient.
1:22:53 And as you know, it’s like the most limiting and also like even commercially, it’s the
1:22:57 most expensive right now.
1:22:59 Yeah.
1:23:00 I certainly have had the experience of, at one time in my life, really enjoying and
1:23:05 even craving sweet foods, desserts and sugars and things of that sort.
1:23:09 And I noticed that over time, if I eat sufficient amounts of meat, chicken, eggs, fish, which
1:23:16 is not to say that I consume excess amounts of them, that my sugar cravings go way, way
1:23:22 down.
1:23:23 That’s just my personal experience, but I know it’s an experience that family members
1:23:25 of mine and others share as well.
1:23:27 But I promise you that this was a fun topic, right?
1:23:33 We couldn’t stop at like just layer number one.
1:23:36 Layer number two is that in agriculture, we have this instinct to plant, plants that complement
1:23:44 each other.
1:23:45 Like, for instance, a classic, especially among native communities is called like the
1:23:51 Three Marys.
1:23:54 I believe it’s pumpkins on some type of fibers with corn, carbohydrates and beans.
1:24:03 So in purely plant-based diets, there’s an effort to get the fiber, the sugar and the
1:24:10 amino acids.
1:24:11 That’s right.
1:24:12 And I grew up in a farm, my parents had farms.
1:24:15 And I remember when they would plant, they will also like throw in there the beans and
1:24:18 the beans will wrap around the corn.
1:24:21 And it just seemed like so natural and that’s what you will do because that’s what you learn
1:24:24 to do.
1:24:25 But if you think about it, it’s an instinct that we have developed even agriculturally,
1:24:29 probably in the subconscious, to cultivate them in such a way, or perhaps the plants taught
1:24:36 us how to cultivate them in such a way that now when we put them in the plate, it just
1:24:42 makes sense at a nutritional level.
1:24:46 Because if you think about it, every time that we go to eat, how is it that we arrange
1:24:52 that plate, right?
1:24:53 There is some rice, which is very deficient in some essential amino acids, but it’s reaching
1:24:58 carbohydrates.
1:24:59 It has some beans, right?
1:25:02 And then there are some lettuce.
1:25:05 And sometimes if we have, like for omnivores, people would put meat or you would put other
1:25:09 types of protein in there, right?
1:25:11 And certainly it varies by culture, time of year, food availability and things of that
1:25:15 sort.
1:25:16 As long as we’re talking about your upbringing, you have a fascinating story.
1:25:23 So maybe we could discuss that for a few minutes.
1:25:27 Where were you born?
1:25:28 I was born in the Amazonia of Ecuador, a small town called El Chaco in Ecuador.
1:25:33 It’s on the slopes of, the eastern slopes of the Andes, on the way to the Amazonia,
1:25:41 in the Naples province.
1:25:43 Coincidentally, it was like through the path from where Francisco de Orejana in 1542 marched
1:25:51 on its way to the discovery of the Amazon.
1:25:53 It actually passed through a trail that later on reading, I realized that native people had
1:26:00 all of these trails between the Amazonia and the Andes and the coastal line for thousands
1:26:06 of years.
1:26:07 So you grew up in a very rural place?
1:26:10 Yes.
1:26:11 The oil had been detected in the 1920s in Ecuador.
1:26:17 It was first explored in 1964 in the first oil well was in a town called La Guagrio,
1:26:31 which now is only like three or four hours from the town where I grew up.
1:26:34 But at that time, it was like eight hours, the roads were not good.
1:26:38 And the first road passed through it in 1974, I was born in 1983.
1:26:47 But I remember that we used to have like a giant diesel engine that will give us a light
1:26:55 electricity only from 7 to 9 p.m., I remember when my father bought the first color television
1:27:08 in the town and then neighbors will come to our living room and then we will watch movies.
1:27:13 Wow.
1:27:14 And this was in the 80s.
1:27:15 That was in the 80s, right?
1:27:16 Yeah.
1:27:17 Such an interesting upbringing.
1:27:19 So did you eat a purely vegetarian diet or did you eat meats as well, where did those
1:27:25 meats come from if you did?
1:27:27 Primarily from cattle, goat’s ship.
1:27:32 So how do you go from the Amazon to a study of nutrition and ultimately neuroscience?
1:27:40 Yeah, that’s the question, right?
1:27:43 Like the deeper I go, the more I question this, I used to think that, oh, it was very
1:27:47 simple, you know, like when I was specifically, when I was 11 years old, my father, he was
1:27:55 born in 1932, by 19, he lost his father, my grandfather, when he was six years old and
1:28:06 he was given away and he had to go and like build his life.
1:28:11 He was a very successful entrepreneur.
1:28:13 But in the process, he had made a lot of friends and acquaintances.
1:28:19 So when I was 11 years old, I remember specifically that a friend of his who was in the Special
1:28:25 Forces stopped by our home because that was the main road that we go into the Amazon jungle
1:28:32 where the folks in the Special Forces in the military will be trained.
1:28:36 And he stopped by and said, like, hey, Rogelio, what are you going to do with Diego?
1:28:40 You know, like, I think that is about time that, you know, I think that you should send
1:28:44 him to the military school.
1:28:46 And I remember in a matter of like literally a couple of weeks or three weeks, I had given
1:28:50 the, taken the tests and I was accepted into the military school and then I ended up in
1:28:56 military school.
1:28:57 And this was the, at that time, it was the premier military school in the country.
1:29:03 That alone, it was, with years, you started to understand the context in which you developed.
1:29:10 Because it was a very interesting context for a child.
1:29:14 Like, just to give you an idea, this school had the first and the only zoo in the country.
1:29:23 So from my classroom, I would literally look at the lions and then I think that was by
1:29:29 the second year that I was in the school, second or third year.
1:29:32 That became that because the city started to grow and then the military school was wrong.
1:29:39 And then they separated the higher education for military officers.
1:29:43 They separated them and they put them in a different place.
1:29:46 But that zoo actually became the first zoo of the capital of Quito.
1:29:49 Wait, so you had a zoo with lions at your school.
1:29:52 Yes.
1:29:53 And you said you could see the lions in your classroom.
1:29:56 And they could see you presumably.
1:29:57 I probably know them.
1:29:59 Yeah.
1:30:00 Well, I assume they could see you.
1:30:01 Lion vision is pretty good.
1:30:02 I don’t know what the resolution is, but I’m guessing that their vision is, yeah.
1:30:06 They definitely use their olfaction, but they are site-based hunters as well.
1:30:12 But I have specifically one memory like climbing up.
1:30:15 I think it was like from the because we had an Olympic pool and we had all of these events.
1:30:24 The soccer field was the field where the national team will go and train on because they didn’t
1:30:32 have their own training grounds.
1:30:37 Later on, they had their own training grounds.
1:30:39 But that was something that you just growing to it, right?
1:30:42 But it was with the years and now especially that I get to reflect on it.
1:30:46 I was extremely fortunate through that experience and that education.
1:30:51 And now I’m here sharing some of the story.
1:30:53 And hopefully through that inspiring some people, especially young people, that would
1:30:59 like to go and chase their dreams.
1:31:01 So you went to military school in Ecuador.
1:31:04 You graduated and you decided to go to school in the state.
1:31:11 So in the military school, they will select the top cadets like I think was the top 10%.
1:31:18 And they will select them and they will put them through a special training.
1:31:22 So you have essentially didn’t have like what was a normal summer vacation, you know, I
1:31:27 will go into military training.
1:31:32 So for me, it was going to be very not easy, but relatively straightforward to transition
1:31:37 into officers academy, right?
1:31:39 Like do four more years like West Point here and then like become an officer, right?
1:31:43 In fact, I had a reserves officer degree when I graduated.
1:31:49 But two years before graduating, a friend of mine, who he prefer other types of careers,
1:31:58 he said like, you’re not going to become a military, right?
1:32:02 You’re not going to go into the military.
1:32:04 And he said, you should probably study something that will help your parents.
1:32:07 And then I said, what will that be?
1:32:09 And he said, like, perhaps agriculture.
1:32:13 And I didn’t think at that time, he didn’t don on me that, you know, people can study
1:32:18 for agriculture.
1:32:19 And agriculture is like the base of food for all of us, right?
1:32:26 And then I said, where?
1:32:27 And then he mentioned for the first time, this university in Zamorano, which was founded
1:32:31 with some funds that were donated by the founder of the Standard Fruit Company, which eventually
1:32:39 became, I think, Chiquita Banana, Zamzemoran.
1:32:43 And that is an oasis that is in Honduras, outside of Tegucigalpa.
1:32:47 So it’s a boarding school, you wear a uniform.
1:32:49 So it was kind of like military, it’s very strict.
1:32:52 You cannot accumulate more than 12 demerits, otherwise, they will send you home.
1:32:58 How do you get a demerit?
1:33:01 You show up two minutes late to work in the morning at 6 a.m. in the field, and then you
1:33:07 just get two.
1:33:08 Two minutes late, one demerit, 12 of those, you’re out.
1:33:10 Two demerits.
1:33:11 Two demerits, you’re out.
1:33:12 And you get a, we used to get a, they will check your room.
1:33:18 So for instance, I guess like you, if you will go there, like they will give you every
1:33:21 Wednesday, they had at 7 p.m., they will check your room, but like very meticulously, right?
1:33:27 And they found a little bit of dust on the window or something to the demerits.
1:33:32 And you’re going home.
1:33:34 If you accumulate enough, you will go home, right?
1:33:38 So it really forms character, right?
1:33:40 Did you do that with your kids?
1:33:42 No.
1:33:43 I think that I have become very-
1:33:44 Do they make their beds?
1:33:45 They do make their beds, yeah.
1:33:47 But that was the context, and it was then where I learned about two things.
1:33:51 One is where this idea of getting a PhD, because I noticed that most of the leaders will have
1:33:56 a PhD, most of the leaders in the university, and I realized in the United States is one
1:34:01 of the training grounds, main training grounds for PhDs.
1:34:04 And the other one was nutrition.
1:34:06 I was a little bit more keen on perhaps going into veterinary school.
1:34:13 And then I had an experience in a dairy farm in California, where I learned the value of
1:34:20 nutrition.
1:34:21 It was more prophylactic rather than a palliative, like treating the cow, right?
1:34:28 And that kind of convinced me to look for a training in nutrition.
1:34:34 And then a friend of mine, Abel Gornath, he was able to connect me with some friends
1:34:42 and my mentor at North Carolina State University.
1:34:46 And that’s where I ended up doing my PhD in nutrition, and that’s where the career became.
1:34:51 And then maybe another detail in there is that I was so excited about taking, that’s
1:34:57 where I took my first physiology class.
1:35:00 And all of a sudden, I realized that in a way, the body was like a machine, right?
1:35:05 Like obviously it’s a limited way of thinking, but the body was like a machine.
1:35:09 And one of the professors was a neuroscientist.
1:35:13 And I took two human physiologists with him.
1:35:18 And I was just thrilled by when he will explain how is he that in the synaptic terminal, there
1:35:24 were these vesicles that had like these proteins that will walk the vesicle in the presynaptic
1:35:29 active zone.
1:35:30 And that’s how we make movement, you know, or something like that.
1:35:34 And I guess I kept that in the background of my head.
1:35:36 And when I had the opportunity to work in the gut, I applied that.
1:35:40 So you were enchanted by the nervous system?
1:35:43 Yes.
1:35:44 Yeah.
1:35:45 As I was too, nothing to me is more spectacular than the realization that we are made up of
1:35:54 these little tiny cells, many different types, but that the neurons essentially govern our
1:36:00 entire experience of life.
1:36:02 That’s just amazing.
1:36:04 Well, that’s quite a journey from the Amazon to, well, this table and much more, of course.
1:36:13 Thank you for sharing that.
1:36:15 So you grew up in a, let’s call it a plant rich environment, the Amazon, at least from
1:36:20 the pictures I’ve seen.
1:36:22 Let’s talk about plants, botanicals.
1:36:26 And the idea that maybe plants, for lack of a better way to put it, have a certain intelligence
1:36:34 or a composition that is not random with respect to our interactions with them, right?
1:36:43 You described how agriculture in some places has evolved to include and ensure the different
1:36:49 macronutrients and essential amino acid intake, even in the absence of animal proteins.
1:36:55 The pumpkin or the squash, the corn and the beans.
1:37:00 What are your thoughts on plants, perhaps from the Amazon, but elsewhere, too, and their
1:37:06 capacity to have things in them, chemicals that can be good for us at the level of the
1:37:12 gut, but perhaps at the level of the brain or other organs as well?
1:37:17 How do you think about plants these days?
1:37:19 So the first thing you mentioned there like intelligence, right?
1:37:22 I mean, I don’t know like if that exact terminology applies, but I do like this word wisdom because
1:37:28 it’s reflected experience, right?
1:37:31 And I said reflected experience because somehow we are going over the experience.
1:37:38 And plants have been many more millions years of age on Earth than any other animal, right?
1:37:49 And therefore they have had way more time to actually experience the ground.
1:37:55 So to think that they don’t know what is going on, I think it’s a little bit perhaps naïve
1:38:02 is the word.
1:38:03 I went to the main court of these Mayan ruins of Copan, the junction between Honduras
1:38:15 and Guatemala.
1:38:17 This was a very special city of the Mayans.
1:38:21 And in the main court, you see like all of these stellas, which are like the main stones
1:38:26 of the kings of several dynasties.
1:38:30 And at the top of one of the stairs on these pyramids, there is this giant seiva tree, which
1:38:41 is like 650 years old, something like that.
1:38:47 So that tree was there before the Spaniards landed in there when the Mayans perhaps were
1:38:53 still celebrating things, or perhaps right after, right?
1:38:57 So imagine how much information that the organism has in there.
1:39:02 And we will be able to just tap somehow into that information, like climate, floctuation,
1:39:10 organisms, interactions, movements, I mean, like so many different things, right?
1:39:15 Like that right now, I don’t think that we even have the language of being able to understand
1:39:21 at the organismic level of how much information that is stored in one single one of those
1:39:27 organisms.
1:39:28 But then think about a chloroplast, for instance, or like one of the photosynthetic organelles
1:39:36 inside of the cells.
1:39:39 How is it that they have been shaped for hundreds of years in those organisms, right?
1:39:46 And I think that perhaps in the future, this is more of a sci-fi right now, but perhaps
1:39:54 in the future, we will be able to harvest that type of wisdom, we will be able to understand
1:39:58 a lot about the place or the earth that we live in.
1:40:04 That’s point number one.
1:40:06 Point number two is that these plants have been interacting, and we have been interacting
1:40:11 with plants for hundreds of years, right?
1:40:15 And obviously, we are a consequence of the environment, right?
1:40:18 Like here, driving in a L.A. or driving in a major city for some of us is just like second
1:40:27 nature, right?
1:40:28 But if you go into a jungle, then all of a sudden it will not be the same thing, right?
1:40:33 But for somebody that has been in the jungle for hundreds of years, now all of a sudden
1:40:38 they are able to describe with such a sensitivity of like how it is that the jungle is, the
1:40:45 makeup of the jungle is in there.
1:40:47 I’ve seen native people walking through the jungle without shoes, and right before stepping
1:40:53 on a leaf, stopping and then pointing out like, look underneath that leaf, and then
1:40:59 I’m lifting it out, and then a tarantula right there, like how do you even make sense of
1:41:05 that?
1:41:06 Like I don’t have the sensory acuity or the wisdom to be able to figure that out, but
1:41:11 they do, right?
1:41:13 And certainly that is just a level of sensory perception that I am not equipped with, but
1:41:21 I do think that there’s quite a bit of that interaction in there to learn.
1:41:25 And then of course, not only for food, but also for medicine, for textiles, and for many
1:41:31 other functions.
1:41:34 These plants have been part of the ecosystem of how these people navigate their world all
1:41:40 the way from making a canoe to making a backpack to carry a fish from the river into the house,
1:41:47 right?
1:41:48 So how do you think we evolved food choices and flavor preferences?
1:41:52 I imagine humans that existed long before us, being hungry, the gut starts rumbling,
1:42:03 and there are all these plants everywhere, some nuts and some berries and things.
1:42:06 And so they had presumably no choice but to consume them and decide at the level of the
1:42:13 mouth, like that’s bitter, nope, that’s not good, maybe eventually cook those and see
1:42:19 if that changes the relationship, I’m thinking raw acorn versus cooked acorn.
1:42:25 But that ultimately there was a lot of trial and error and that these neural pod cells,
1:42:30 which surely existed for a very long time prior to us, played a key role in discerning
1:42:36 what’s in these plants, barks, roots, nuts, berries, we’re setting aside meats for the
1:42:44 moment and other animal proteins and making decisions about what’s nutritious, what is
1:42:50 safe, what is not safe.
1:42:53 And that’s a pretty complex process, given that some things might taste okay, go down
1:42:58 okay, but then you run into serious trouble later.
1:43:02 But given the critical importance of ingesting sufficient amounts of macronutrients and the
1:43:07 need for micronutrients to survive on a day to day basis, much less reproduce and propagate,
1:43:16 one imagines that this is almost as essential as breathing.
1:43:22 And that this path in our nervous system of the neural pod cells to the brain for sake
1:43:27 of decision making of yum, yuck, or meh is perhaps one of the most important core functions
1:43:36 of the nervous system.
1:43:37 Once you get past the elements that control breathing, heart rate, temperature regulation,
1:43:45 things of that sort, I see it as among the senses, it’s at least as important as vision
1:43:53 and perhaps more in terms of making sure that we survive from day to day.
1:43:58 That’s correct.
1:43:59 And here’s where I think that is a large vacuum in biology.
1:44:03 If I would be with my biological, my training in biology, if I would put my hat of the training
1:44:13 in biology, I wouldn’t be able to explain much of like, how is it that we figure it
1:44:18 out because even if you just go to a botanical garden here in the city, it would be really
1:44:25 hard to figure out what plant is for what, right?
1:44:31 Yeah.
1:44:32 What’s safe to eat?
1:44:33 What’s safe to eat?
1:44:34 Do you need to cook it or not?
1:44:36 Maybe like the cacti, you’re able to figure that out by touch, right?
1:44:40 So from the biological perspective, I think that there is quite a bit in there to explore
1:44:43 and to learn.
1:44:45 There is some very interesting work from the anthropological perspective.
1:44:50 So anthropologists and botanists that were studying the plants were exploring the jungles,
1:44:59 not only the Amazon, but Borneo, Sri Lanka, and so on and so forth, and studying the interaction
1:45:06 of native people with the plants.
1:45:08 And if going through the literature, that literature, there is a pattern that emerges
1:45:13 and like the native people, they talk about how it is that they actually learn from the
1:45:18 plants, that the plants were the ones that will teach them.
1:45:23 So that’s why I say from the biological perspective, like how can we make reconcile that?
1:45:28 I think that there is still quite a bit of to learn.
1:45:31 What does that mean to learn from the plants?
1:45:34 I mean, there’s something that intuitively makes sense.
1:45:37 When you say that, I’ve heard about looking at plants as teachers about the local environment,
1:45:44 when they’re open, right, they’re light sensing, when they’re closed.
1:45:50 But in terms of translating some of that to how humans have learned to navigate given
1:45:57 environments, navigate meaning thrive in those environments.
1:46:03 How do we go about that?
1:46:04 Does it mean taking plants, grinding them up and figuring out the constituent parts?
1:46:09 Or is that too reductionist?
1:46:11 Is that going to leave us with a parts list that doesn’t mean anything?
1:46:14 Sort of like if I played out all the pieces of a car or an airplane in front of us, it
1:46:19 doesn’t really tell us anything about that except what parts make up the thing that flies.
1:46:24 Yes, and that’s why I said this is more on the anthropological studies that have, especially
1:46:32 from scientists that have gone there, learned the language, live with the natives as natives
1:46:38 and then start to understand the dynamic of their culture and their interactions.
1:46:44 Then that’s when, for instance, how it is that they classify plants.
1:46:49 The way that they classify plants is like several levels more richer than our classification
1:46:55 or scientific classification by the two name system or the variety, right?
1:47:02 For instance, they take into account not only the flavor but also the shape, the location,
1:47:09 how they interact over the year, how they react over the year.
1:47:14 For instance, there is this beautiful plant, people call it the leaps plant.
1:47:21 I don’t know if you have, but if you Google it, you will see it.
1:47:24 It looks like lips.
1:47:26 Literally like lips.
1:47:27 It has this red, beautiful lips like the plant.
1:47:31 It just looks like lips.
1:47:34 Then people use it for pain, for some rashes, skin rashes and also some rituals.
1:47:42 Most of these plants, the way that the natives interact with the plants is in a sacred level.
1:47:48 There is this respect for the plant.
1:47:53 So yeah, I think that biologically, I think that there is quite a bit in there to understand
1:48:01 and explore and define.
1:48:03 I do agree with you that just thinking about grinding it up and just putting it in a teapot
1:48:08 perhaps is too reductionist.
1:48:10 This could be a beginning of understanding, but it is reductionist.
1:48:15 Seems like nowadays in the field of biomedical research and clinical research that there’s
1:48:21 a lot of interest in plant-based psychedelics, LSD from ergot and psilocybin, mushroom and
1:48:33 so on and so forth, ayahuasca, iboga.
1:48:38 So it seems like science and plants have merged at that level in terms of clinical implications.
1:48:44 Of course, they’re entire fields of plant biology that are extremely important.
1:48:47 I think most people probably don’t realize this, but a lot of what we understand about
1:48:50 circadian rhythms grew, no pun intended, out of our understanding of plant circadian rhythms
1:48:58 first and then it was translated to mammals, beautiful work by Steve Kay and others, seeing
1:49:04 the circadian rhythms in leaf opening and the orientation of the whole plant and other
1:49:10 features of plants that are mirrored by the changes in arousal level in mammals, including
1:49:17 us, which is why I’m always telling people to get sunlight in their eyes early in the
1:49:20 day and to avoid bright light in the evening and nighttime.
1:49:25 So what are your thoughts on plants as a source of medicine, psychedelic or otherwise?
1:49:33 I think that, well, traditionally that’s where medicine was developed from.
1:49:38 I was at the Oxford Botanical Gardens last year with the family and we went into the
1:49:46 gardens and they have a beautiful garden, it was established in 1621.
1:49:49 I think it was the first botanical gardens in England and they have a beautiful medicinal
1:49:56 plant collection.
1:49:57 And there was this very humble, what a little sign with a description in there that said
1:50:06 in there that about 80% of medicine still comes straight from plants.
1:50:12 Really?
1:50:13 Yes.
1:50:14 And if you think about it, it kind of makes sense, right?
1:50:17 Because when we think about the medicines that we have been able to develop, which have
1:50:21 been phenomenal, especially for certain chronic diseases, but we don’t have a broad repertoire
1:50:30 of it, right?
1:50:33 So I think that has been obviously a great advance in our society that we have been able
1:50:40 to identify the molecules, synthesize the molecules, package the molecules, render them
1:50:46 bioavailable in specific sites.
1:50:49 And I think that when we are able to couple that with the rest of the molecules that the
1:50:53 plants through their, I keep saying their wisdom, because somehow they develop their
1:50:58 ability to have not only one molecule, but like a combination of other things that will
1:51:04 provide the full experience of the plant, right?
1:51:07 For instance, a gerbamate, you know, it’s not only caffeine, right?
1:51:13 Because it’s very different than a shot of espresso, you know?
1:51:17 If you take the whole thing, it not only gives you energy, but it gives you a full range
1:51:22 of an experience that is specific to the gerbamate, which is a leaf, right?
1:51:26 Yeah.
1:51:27 It’s a distinctly different subjective experience than coffee, and I enjoy both coffee and espresso
1:51:35 and gerbamate.
1:51:37 You were the one who introduced me to…
1:51:39 Guayusa.
1:51:40 Guayusa.
1:51:41 Yeah.
1:51:42 It’s a causing of gerbamate, because gerbamate is elix paragensis.
1:51:47 Guayusa is elix guayusa, and it’s not as bitter as mate, but it has almost as much caffeine
1:51:55 as coffee, and it has antioxidants and other compounds, which give you this very smooth
1:52:03 experience.
1:52:04 So natives in the Amazon, they take a drink of guayusa every morning, around four in the
1:52:12 morning, between four and six a.m.
1:52:14 They wake up early.
1:52:15 They actually call it, yes.
1:52:17 It’s like Jaco willing early.
1:52:18 Yeah.
1:52:19 Some people understand that joke.
1:52:20 He wakes up every morning, and he posts a picture of his Casio watch, and he’s already
1:52:25 training 4.30.
1:52:26 So, no guayusa required for Jaco.
1:52:30 And they call it the guaysa upinaura, the hour of the guayusa, and it’s ritualistic drinking
1:52:44 of the guayusa in the morning, and where they talk as a family of the issues that they have
1:52:49 had the days before or the weeks before, like either with other communities within the family
1:52:55 if they have to represent or represent one of the children or talk to them about like
1:53:00 some mistakes that they’re making.
1:53:02 And then they plan the full day of activities by drinking guayusa, and around 5.30, because
1:53:12 they will boil the guayusa, right?
1:53:14 And they keep boiling the guayusa, and they just keep adding water to it.
1:53:18 And then around 5.30, then they will have what is called — it’s a bowl of chonta.
1:53:28 And chonta is this palm date, very rich in lipids and fibers.
1:53:37 So they will have the guayusa because the guayusa, they say that gives them energy.
1:53:41 It heals any pain, it shuts down appetite so they will eat at like 3 p.m., shuts down
1:53:50 or modulates appetite.
1:53:51 As does your brahmate.
1:53:52 It’s one of the more potent effects actually of mate in guayusa, is a mild to moderate
1:53:58 appetite suppression.
1:54:00 And then if you combine that to chonta, which gives you the lipids, and then it’s like a
1:54:05 full meal for until 3 p.m., and then they go and work in the fields.
1:54:09 Interesting.
1:54:10 They’re actually starting the day with hydration caffeine, and then they — what in some circles
1:54:14 they call fat fasting, meaning consuming lipids in order to stave off hunger.
1:54:19 Yes.
1:54:20 I mean, it’s the highest density source of calories among the macronutrients.
1:54:25 And it’s a vegetable-based diet, I guess, right?
1:54:30 Are they a healthy culture?
1:54:31 Do they live a long time?
1:54:33 I am not — I should probably do more reading that.
1:54:38 I’m not well-educated in what are the studies that have follow-up on the health status of
1:54:48 the communities.
1:54:49 But what I can tell you is that at least colloquially, I will say that diabetes, those type of issues
1:54:55 are not as prevalent.
1:54:57 But they do have, obviously, through social exposure, they have other things, you know?
1:55:03 Fascinating this morning ritual of conversation about family and culture and what’s needed
1:55:11 planning the day.
1:55:13 We had on this podcast, as a guest, Dr. Sachin Panda, who is at the Salk Institute for Biological
1:55:18 Studies, often known for his work on intermittent fasting, time-restricted feeding, but also
1:55:23 has done beautiful circadian biology.
1:55:25 And he talked about the use of fireside chats, not the sort on stage, but, you know, gathering
1:55:32 around fire at night is something that has existed in many cultures where people reflect
1:55:37 on the previous day and discuss issues, social and work issues, and sort of dissect what’s
1:55:44 happened and talk, and it’s about building and repairing relationships.
1:55:51 Sounds like in this — is it — what is this group?
1:55:55 Is it a rural?
1:55:56 It’s just a —
1:55:57 Native communities, because there are, like, about 70 or so communities that have been
1:56:04 documented in the Amazonia with their own language, with their own traditions, and many
1:56:09 of them share the same type of traditions.
1:56:12 And if you think about it, like, a podcast is one way of an evolution of that conversation,
1:56:18 right?
1:56:19 Like, where we can have this extended conversation and get these — the more primordial things,
1:56:24 the ones that we have them in the prefrontal cortex right away and, like, discuss about,
1:56:27 like, well, you know, these discoveries, these identifications, but then we get to the part
1:56:32 of, like, what does it mean for the whole community?
1:56:35 Mm-hmm.
1:56:36 Yeah, there’s doing, there’s reflecting, and then there’s resting and recovering, right?
1:56:43 And there is something about, like, living that for the next generation, right?
1:56:46 Mm-hmm.
1:56:47 You know?
1:56:48 Yeah, passing on of —
1:56:49 Passing on.
1:56:50 Lessons.
1:56:51 Lessons, but they’re all about the techniques and successes of others, if you can, as you
1:56:55 go forward.
1:56:56 Very interesting.
1:56:58 If we could, I’d like to now return to the biology, the nervous system.
1:57:02 Absolutely.
1:57:03 And thank you for that voyage through some of your background in Ecuador.
1:57:08 Fascinating.
1:57:09 I do for a mug of guayusa.
1:57:13 Sometimes I’ll mix the two, the loose leaf yerba, mate, and the guayusa.
1:57:17 And as you said, what’s —
1:57:18 How does it feel?
1:57:19 I really like it.
1:57:21 Most of the time, it’s loose leaf yerba mate or cobra yerba mate.
1:57:26 But sometimes I’ll mix in the guayusa leaves.
1:57:30 And what I do like, as you mentioned, is you can continue to pour water over them for many
1:57:34 hours, and it tastes different as the time goes on.
1:57:37 And my guess is you’re extracting different things from it in different concentrations
1:57:40 as time goes on.
1:57:41 I realize it’s not a precise science, you know?
1:57:44 It’s interesting.
1:57:45 Today, we’re talking about very precise neurons and methods of tracing neurons and sensing
1:57:50 of specific amino acids and lipids at the level of the gut.
1:57:54 And then we’re also going to more macroscopic view, a kind of broader scale view of the
1:58:01 plants, having many things that need to coexist in certain ratios that the plants have evolved
1:58:07 to create for us.
1:58:09 So we’re sort of straddling both ends of the continuum.
1:58:14 And if I could fit in their story, no long ago, I visited a friend, a native friend in
1:58:19 a nearby town, and he produces some of the best chocolate, what I will say, in the planet.
1:58:29 Because actually, the plants of Theobroma cacao, it was recently documented, there was
1:58:36 a paper in Science not long ago that it was domesticated in Ecuador, near where I grew
1:58:43 up, and they have done some tracing and genetic tracing.
1:58:48 So he produces some of the best chocolate, like literally he harvested in there, and
1:58:53 then he roasted, grinded, and then he prepared for us in there.
1:58:58 The Swiss are saying, or the Belgians, right, are claiming the best chocolate.
1:59:02 Now we know Ecuador is the place for the best chocolate.
1:59:05 I think I just got a lot of Swiss and Belgians angry at me for saying that, but do they have
1:59:11 a very dark variety?
1:59:12 I like the extreme dark varieties, you know, 95%.
1:59:16 Even 100% chocolate, if it comes from a really quality source, can be absolutely delicious.
1:59:21 It’s like milk straight from the cow, right?
1:59:24 And what he did is, he said like, Diego, you have to try it with Waiusa.
1:59:31 And he mixed the chocolate with Waiusa.
1:59:34 As a drink?
1:59:35 As a brew, like as a drink, boy, like that will give you wings, you know?
1:59:40 Waiusa hot chocolate.
1:59:41 Yes.
1:59:42 Okay.
1:59:43 Amazing.
1:59:44 It’s a very smooth experience, right?
1:59:46 Like you’re mixing this tea, which is for energy, with chocolate, you know, of the best
1:59:52 quality.
1:59:53 So we’re not talking about eating chocolate and drinking tea, we’re talking about melting
1:59:56 the chocolate in the Waiusa.
2:00:00 It was something like one or what kind, you know?
2:00:03 Of course, I couldn’t sleep until like 3 a.m., I think.
2:00:06 Right.
2:00:07 There’s something to do, or maybe this is why these groups drink the Waiusa so early
2:00:11 in the day.
2:00:12 That’s right.
2:00:13 Yeah.
2:00:14 And I would need caffeine at 4 a.m., 5 a.m., otherwise I would be falling back asleep.
2:00:22 So back in the gut and nervous system, in particular within the brain, we haven’t talked
2:00:28 about the brain so much.
2:00:29 We haven’t talked.
2:00:30 So the information from the gut is sent via these neuropod cells up to, you mentioned
2:00:36 the no-dose ganglion, such a cool name for a brain, a ganglion in this instance is an
2:00:43 aggregate of neurons.
2:00:44 So it’s like a batch of neurons that then send a connection into the brain.
2:00:49 What brain areas do they send it to, and maybe we could describe these by name, but also
2:00:54 by function, what they generally are responsible for.
2:00:58 And probably should be prefaced with, ultimately will go to the entire brain.
2:01:04 Right.
2:01:05 Everything ultimately connects to everything.
2:01:06 It’s like Google Maps, everything connects to everything.
2:01:08 But what are some of the primary recipients of that information?
2:01:12 Well, first hubs of sensory integration are in the brainstem, and for instance, the nucleus
2:01:24 tractus solitarius is in a specific region within the brain.
2:01:28 The caudal is one area.
2:01:31 And NTS, for those that don’t know, is involved in regulating hunger and appetite.
2:01:35 That’s correct.
2:01:37 Or functions perhaps, but like for instance, that seems to be an area of sensory integration
2:01:43 for nutrients.
2:01:44 And when we say drives hunger, appetite, sensory integration for nutrients, I mean, what would
2:01:50 be great is if people could understand the language of the nervous system is chemical
2:01:54 and electrical.
2:01:55 So when these neurons are active, we tend to crave certain foods, seek them literally,
2:02:01 go to the refrigerator, among the different choices, go to that thing and select that
2:02:08 and put it into our mouth.
2:02:10 So presumably it’s driving reward systems, motor systems.
2:02:16 I mean, what we call hunger and appetite is really a kind of a domino effect of a lot
2:02:23 of different brain circuits.
2:02:24 Do we know whether or not the nucleus tractus solitarus projects to the areas of the brain
2:02:31 involved in dopamine release and craving?
2:02:34 Yes.
2:02:35 And there has been some elegant work from several different neuroscientists in this area, like
2:02:42 tracking the circuitry from there on to many other different areas.
2:02:48 The hypothalamus, for instance, very basic behavioral functions and the striatum where
2:02:55 there is dopamine release and then there is this pleasurable sensation and reward.
2:03:02 There are several other areas in there that are involved in this sensory integration.
2:03:08 There is quite a bit of work still to be done from specifically from the neuropods.
2:03:13 There is some evidence that they are connecting directly to — or if you put two papers together
2:03:20 it’s obvious that they are connecting to some of these areas of dopamine release, basal
2:03:25 ganglia in the brain.
2:03:30 And that’s why they are causing this reinforcing effect, like in the lateral hypothalamus and
2:03:37 other areas.
2:03:38 I do think that ultimately, there is quite a bit of a gap in different regions of the
2:03:45 digestive tract.
2:03:48 Today we just talk about esophagus, right?
2:03:50 Like the esophagus, I think that there is a little bit of work.
2:03:53 Perhaps, I think that Steve Lieberlitz has worked in that area.
2:03:58 Another great neuroscientist doing some very fine, detailed work in sensory biology in
2:04:06 the esophagus.
2:04:08 There is quite a bit of lack of precise biology in how it is that the esophagus, specific
2:04:17 cells of the esophagus are innervated or like making sense of the environment.
2:04:22 Same thing for the stomach and how it is that ultimately each one of those regions are fitting
2:04:27 into different regions of the brain.
2:04:31 Even then, how each one of these valves — I’m fascinated by each one of the valves that
2:04:37 we talk early on, like the gastroesophageal sphincter or the pylorus or the iliocecal
2:04:46 junction.
2:04:47 Yeah.
2:04:48 We should illustrate for people.
2:04:49 I’m not an expert in the gut by any means.
2:04:51 But what Dr. Borges is referring to is that the gut, as it extends from the mouth to the
2:04:59 rectum, is not just a series of tubes of different diameters, but rather they have valves,
2:05:06 sphincters, and these sphincters that cut off — everyone hears the word sphincter and
2:05:10 they always think, “Oh, anal sphincter,” and then it’s like elementary school, middle
2:05:15 school humor.
2:05:16 But sphincters literally can close and open to varying extent in order to allow passage
2:05:24 or prohibit passage from one compartment to the next such that certain things can take
2:05:30 place over time in one region, like the esophagus or within the stomach or before passing to
2:05:35 other chambers.
2:05:38 And so I hear you saying that critical processing is happening at each of these chambers.
2:05:44 The sphincters are determining how long that processing occurs and that distinct sets of
2:05:49 neuropod cells are likely detecting distinct qualities and quantities within the food — chemical
2:05:56 qualities and quantities within the food — and relaying that to the brain.
2:06:00 That’s correct.
2:06:01 I think that since we’re getting into the future of this area, and while there is not
2:06:08 direct published evidence yet, I think that is going to be a fun area.
2:06:16 So the gut as the brain also generates these electrical patterns.
2:06:22 Those electrical patterns change depending on fasting versus feeding and circadian rhythms.
2:06:28 You probably cannot realize jet lag.
2:06:32 The gut is asking you for a burger at 3 a.m. and your brain is telling the gut, you know,
2:06:37 can you please go to sleep, right?
2:06:41 So these electrical patterns, these electrical waves that are going into — that are being
2:06:47 propagated by the gastrointestinal tract, there are like several different cells.
2:06:52 Like the enterica neurons are coordinating these cells.
2:06:58 There are also these interstitial cells of cahal.
2:07:02 So Santiago Ramon y Cahal.
2:07:05 The greatest neurobiologist of all time.
2:07:07 That’s right.
2:07:08 It was named after him.
2:07:10 He actually has, I think, in the second volume of his classic book on the histology of the
2:07:16 nervous system, one of the last figures talks about like the innervation of the villi in
2:07:21 the intestine.
2:07:22 So beautiful.
2:07:23 For those that don’t know, cahal shared the Nobel Prize with Camila Golgi in 1906.
2:07:28 They together developed tools and mapped the structure of the nervous system.
2:07:34 And it’s fair to say that cahal had supernatural levels of insight into the nervous system.
2:07:41 He looked at the nervous systems of so many different animals in dead specimens.
2:07:46 The joke, even though it’s not funny, is that many animal species entered his laboratory.
2:07:54 Very few walked out.
2:07:56 But by looking at fixed specimens under the microscope and then drawing them in, you
2:08:00 know, select elements within them, essentially came up with most of the major hypotheses
2:08:05 about how the nervous system works.
2:08:06 Not just its structure, but neuroplasticity.
2:08:09 The failure of mammalian central nervous system neurons to regenerate.
2:08:13 This is why after traumatic brain injury or stroke, there’s often loss of function that
2:08:16 doesn’t recover.
2:08:17 Sometimes it recovers.
2:08:19 And that people who have injuries younger often can recover certain functions.
2:08:23 Everything from the direction of electrical flow through the nervous system, all from
2:08:28 looking at tissue that was not alive.
2:08:30 No electrophysiology, no behavioral experiments, just raw, but incredible, supernatural seemingly
2:08:39 levels of intuition and insight.
2:08:41 Amazing.
2:08:42 Yes, there is some quote in one of his books that when he got invited to one of his friends
2:08:49 to England.
2:08:50 I don’t remember, he was a famous neuroscientist at the time in the late 1800s who had helped
2:08:57 him to expose his work to other audiences and invited him to England.
2:09:04 So he said in there that it took like three months to go to that podcast, right?
2:09:09 It was a three-month trip.
2:09:11 So he said that he brought his microscope with him.
2:09:16 With him.
2:09:17 And in the room, he will be able to do some of these observations.
2:09:22 Yeah.
2:09:23 A peculiar guy also known for carrying a very heavy iron umbrella in order to do physical
2:09:29 exercise on the way to the lab.
2:09:31 He was a very, very fit physical specimen.
2:09:34 So purportedly, I don’t know which one, a pretty gruff person, not terribly pleasant
2:09:44 to be around, ran a tight ship.
2:09:47 But in any event, so the cells of the gut are named after, some of them are named after
2:09:52 cajol, interstitial cells of cajol.
2:09:54 There you just got a waltz into some neuroscience history, but critical history.
2:10:01 So they have this emanating electricity, right?
2:10:06 And so far these, and it seems like the sphincters modulate the emanation of this electricity.
2:10:14 Oh, like an instrument.
2:10:16 Yeah.
2:10:17 And you probably think like that is because the intestine, and maybe here we get a little
2:10:22 bit even deeper into these, and I read some work from a philosopher in the UK who was
2:10:31 and I’m going to paraphrase it very largely.
2:10:33 So please don’t quote me, but it’s something along the lines that if we are what we eat,
2:10:40 the place where food becomes us and we become food, it should be the intestine, right?
2:10:44 Because that is where food is actually absorbed, right?
2:10:49 So that is a very fascinating point.
2:10:52 Number two is that the food enters us at a frequency that it will modulate the entire
2:10:59 body, right?
2:11:01 Therefore, like the body through these electricity, these electrical waves should be in sync with
2:11:08 also the electricity of the entire nervous system.
2:11:11 So I think that here’s where in the future, I think that there’s going to be a fascinating
2:11:15 realm of understanding how it is that these waves of the body and the brain are synchronized
2:11:23 with each other.
2:11:26 Because as we know, for instance, sometimes when we are hungry, we become angry, we become
2:11:35 irritated by the fact that we don’t have food and perhaps it’s this dissonance in the emanation
2:11:41 of the electrical waves between the digestive tract and the nervous system.
2:11:45 So I think that that is just like one of the realms of how it is that the brain is connected
2:11:54 to the gut at a more organ-to-organ level to be able to make us function ultimely, right?
2:12:03 Because that’s how we are integrating the outside world, the food, into our entire system
2:12:09 so we can maintain the entire organism.
2:12:12 Well, certainly our level of alertness is linked to our level of anticipation and a
2:12:18 lot of our food anticipation impacts our levels of arousal, aka alertness.
2:12:26 So as you mentioned, we’re a diurnal species, so in the middle of the night it’s unusual
2:12:31 to get hungry.
2:12:32 A lot of these pathways are shut down, digestion is happening at different rates and typically
2:12:38 our appetite is greater during the day than it is in the middle of the night.
2:12:43 But in addition to that, it makes good sense to me that what is going on at the level of
2:12:49 our gut is going to tell the brain, “Did we get enough nutrients from the previous day?
2:12:55 Are we in a place of abundance?”
2:12:58 There’s also the psychological aspect of gut sensing and we haven’t really touched
2:13:02 on that.
2:13:03 What are your thoughts as both a scientist and a human with a gut brain access on this
2:13:09 notion of a kind of gut intuition?
2:13:11 You meet certain people and it sort of relaxes and warms you and you want to get to know
2:13:15 them more.
2:13:16 Other people, for whatever reason, you just feel like something doesn’t feel quite right,
2:13:21 that we can sense things at the level of the body that inform our brain and no one really
2:13:28 understands that process yet.
2:13:30 But we do know that the vagus nerve, which is a multi-pronged pathway, big pathway, it’s
2:13:37 probably its own major branch of the nervous system, really, is sending bi-directional
2:13:43 communication between brain and body.
2:13:46 And presumably when we’re around somebody or something that doesn’t “feel right,” the
2:13:52 vagus is involved.
2:13:56 A few interesting things in that area, the work of Carl Jung talks about it, about the
2:14:03 subconscious and how it is that we’re accumulating all of these experiences that we have been
2:14:09 passing through in life.
2:14:10 It’s not that they are not a store anymore, it’s just that they are back in the subconscious
2:14:14 and then ultimately they become part of this so-called intuition.
2:14:20 We have this gut feeling that.
2:14:28 We analyze some of the languages.
2:14:34 In past, people have told me in so many different languages that there is this phrase for gut
2:14:39 feelings in so many, like for instance in, I think in Portuguese, it’s “frio de barrigo,”
2:14:43 you know, like cold in the stomach, you get a cold.
2:14:50 In Spanish, we call it “pre-sentimiento,” like a pre-feeling, or pre-sensation or feeling,
2:14:59 it will be more feeling if you translate that.
2:15:02 As if it arrives first, yes, before you’re able to articulate it, right?
2:15:07 So there is this storage in the entire body that gives you, depending on the context,
2:15:13 it gives you a certain type of feeling, right?
2:15:17 And that’s why we talk about intuition.
2:15:21 There’s also like this other aspect of how it is that food synchronizes that intuition.
2:15:36 It seems to synchronize that intuition among two or more people, because if you think about
2:15:43 it, we have this ritualistic way of serving something.
2:15:48 When we commonly say or colloquially say, “Let’s go for a cup of coffee,” and often
2:15:54 what we mean is, “Let’s go and talk about business, the future, resolve an A&E issue,”
2:15:59 but we’re talking about the cup of coffee and we have to share.
2:16:02 And people, I think that there are some psychologists that have run some of these studies in which
2:16:06 they say that if the food that we eat is more alike, we are more likely to connect at least
2:16:13 on the moment.
2:16:15 So there is this aspect, and that’s why we share the food.
2:16:19 Interesting.
2:16:20 So is the idea that it’s the actual chemical constituents of the food that’s creating
2:16:24 a common experience that then allows people to bond more readily, or is it that the specific
2:16:32 constituents of the food are actually driving bonding, per se?
2:16:36 Yeah, and if we go back to if we are what we eat, then if we eat the same thing, we should
2:16:42 be more alike to each other, right?
2:16:45 That’s why in communities, you share the food.
2:16:49 In fact, if you go into certain specific communities, you pass around the food.
2:16:56 You pass around the drinks, and it’s very common to share, right?
2:17:02 Yeah, and certainly in romantic bonding, there are many factors, of course, but the more
2:17:10 basic functions of food, sex, and sleep represent the common places of bonding initially, right?
2:17:18 And conversation, of course, and values, et cetera, right?
2:17:20 Not to dismiss any of those, they’re essential as well.
2:17:23 But in terms of feelings of safety, feelings of communing with somebody, right?
2:17:32 These very basic biological functions.
2:17:35 Yeah, and in business too, right, like people, there has been studying like behavioral economists.
2:17:42 They talk about how it is that business are more likely to happen when they are like made
2:17:45 over a food or launch or things like that, right?
2:17:48 Like there’s this synchronicity in the decision making.
2:17:52 And here is a third dimension in this area that it has not been well explored, but I
2:17:59 suspected in the near future it will begin to be explored.
2:18:03 I read a while ago a very elegant paper from Walter Cannon.
2:18:12 So you may want to expand on who Walter Cannon was, but one of the founding figures of the
2:18:22 study of physiology.
2:18:23 Yeah, autonomic physiology.
2:18:24 Autonomic physiology, right?
2:18:26 Yeah.
2:18:27 Physiology at Harvard, 1920s, 1930s, author of The Wisdom of the Body.
2:18:37 He has a paper, or he published a paper, I believe, in the 1930s.
2:18:43 It’s called Voodoo Death, and I remember when I found that title, I was like, “Ooh, this
2:18:52 is something to sit down and dissect.”
2:18:56 You know?
2:18:57 Yeah, good title.
2:18:58 Good title.
2:18:59 If you want somebody to read it.
2:19:00 Good title.
2:19:01 And he essentially, the gist of it, let me see if I can do a little bit of justice, but
2:19:06 obviously I will chop most of the details, but the gist of the paper is that in some
2:19:15 observations in some native tribes, I believe he was in Africa, that if a young people, especially
2:19:25 young youngsters, if they were frightened by a shaman, that they will not perform a certain
2:19:36 thing, a certain task, right?
2:19:39 The entire level of psychosis, so to speak, that could cause death, like the custom spell,
2:19:48 right?
2:19:49 And that’s why it’s called Voodoo Death.
2:19:52 What Canon goes and describes is that it’s an activation of the vagus nerve and the peripheral
2:19:59 nervous system that is a hyper activation that is going through the sub-tracial level
2:20:04 of consciousness, and that in some of these tribes, at least that’s what he explains that
2:20:11 is happening, and I believe that he did some experiments in some animals, but what he was
2:20:16 saying is that it’s a hypertonic activation of the peripheral nervous system when there
2:20:20 are these spells that are casted by a member of the tribe that is in a higher or more superior
2:20:28 or more influential position, that if the other member, especially if it is paired with
2:20:36 something, right?
2:20:37 Like if you say, like, if you go outside and don’t listen to what I just told you and you
2:20:43 see a black cat, those two things match together, now you’re hyper-activated, right, and become
2:20:51 superstitious about it.
2:20:52 But what Walter Canon goes to explain is that it’s a hyper-activation of the peripheral
2:20:57 nervous system.
2:20:58 Obviously, there’s probably more details in there, but the paper really highlights an
2:21:04 area of exploration that we don’t know about.
2:21:06 It is a threshold of subconsciousness of the nervous system, how it is driving us to have
2:21:13 superstition to drive instinctively to go and consume certain things or behave in certain
2:21:23 ways, right?
2:21:24 Yeah, so it sounds like it’s paired association learning through statements, cognition, but
2:21:30 that’s enacted through the vagus in order to control the organs of their periphery.
2:21:35 It’s nerd speak for if we hear and believe that certain events will cause certain changes
2:21:41 in our physiology, they can, in some instances, become capable of that.
2:21:46 Eat this food at this location and you’ll get sick.
2:21:50 Eat this food at this location and you’ll feel better, and it’s learned association.
2:21:54 And ultimately, it’s physiological, but it sounds like it’s subject to a lot of learning
2:21:59 effects.
2:22:00 As long as we’re talking about the vagus, I think it’s a great opportunity to just mention
2:22:04 that a lot of people understandably think that the vagus nerve activation is always
2:22:09 about calming of the nervous system.
2:22:11 And indeed, the vagus is placed under the umbrella of a parasympathetic pathway, but
2:22:19 I think it’s very important for people to know that both experimentally and clinically,
2:22:24 if the vagus nerve is stimulated, you get exactly the opposite effect.
2:22:28 You get arousal effects.
2:22:30 This is commonly known in labs that do physiology of different kinds.
2:22:36 It’s in the clinical context, people with depression are sometimes treated with vagal
2:22:40 nerve stimulators, and it certainly isn’t driving more sedation, more depression of
2:22:44 the nervous system.
2:22:45 It drives alertness and arousal.
2:22:47 So we have to, I think, make sure that we look at the vagus system and describe the
2:22:53 vagal pathway as one that can both induce states of calm, of ease, rest and digest,
2:22:59 as it’s sometimes called, but also states of arousal and alertness, even fear.
2:23:04 And so I think of the vagus as a superhighway of a bunch of different pathways with lots
2:23:09 of inputs and outputs that’s highly subject to learning.
2:23:13 And indeed, the vagus can slow heart rate down through a number of things like long exhale
2:23:18 breathing.
2:23:19 Earlier, we were talking about stress modulation, something my labs worked on, extend your exhales.
2:23:25 That’s the most basic way.
2:23:27 Exhaust size, two inhales followed by a full exhale to lungs empty.
2:23:31 These are core physiological mechanisms known to activate the vagus and lead to calming.
2:23:35 But the vagus, I look at the vagus as kind of a, including both an accelerator of sorts,
2:23:42 accelerator based pathways in terms of arousal and breaks.
2:23:46 And probably our basal level of vagal activation reflects sort of the RPM of our system.
2:23:52 So much, are we, are we calm or are we humming at a higher level of activity?
2:23:57 Such an interesting pathway, such an interesting area of the nervous system, and we don’t
2:24:01 really understand yet.
2:24:03 No, because like that.
2:24:05 The major branches and pathways are just now finally beginning to be understood.
2:24:12 We’re on, we’re on virgin beaches.
2:24:16 Yes.
2:24:17 Right now that I hear you bringing up the humming, for instance, there is a branch of
2:24:22 the vagus that innervates the ear, the inner ear.
2:24:27 And that’s why it is believed, and I think there is a little bit of evidence out there
2:24:31 that how it is certain music at a certain frequency will calm you down, because it is
2:24:35 immediately like brings the, it starts to make the vagus vibrate at a certain frequency.
2:24:43 Yeah.
2:24:44 And humming has been linked to vasodilation, which is associated with a calming effect,
2:24:49 whereas activation of the sympathetic arm or the autonomic nervous system, or the kind
2:24:54 of, what sometimes is referred to as fight or flight, but it’s involved in other things,
2:24:58 causes vasoconstriction.
2:24:59 And if you think about it, like in several religious practices, there is the humming,
2:25:04 right?
2:25:05 There is the singing, there is the sound, the sound plays a big role in running.
2:25:10 There is a certain frequency that makes you run, make, calms you more and makes you run
2:25:14 better.
2:25:15 Is that right?
2:25:16 Yeah.
2:25:17 There is some evidence, at least among runners, that they prefer a certain type of frequency
2:25:22 for the running, right?
2:25:24 So a certain pace of running or breathing.
2:25:27 And they sound, specifically the sound.
2:25:30 The sound of their feet.
2:25:31 Yeah.
2:25:32 No, the sound of the music.
2:25:33 Like if you play a certain music, right?
2:25:36 And probably the sound of their feet too, right?
2:25:38 Like it’s just that it has not been explored, right?
2:25:41 It’s fascinating.
2:25:43 And you know, so much of what I think about when I think about the nervous system is the
2:25:47 fine grain processing of, you know, of color, of light or what.
2:25:51 But when it comes to our feelings of well-being, our levels of arousal, sleep, et cetera, it’s
2:25:56 the rather, I don’t want to call them crude because they’re really sophisticated.
2:26:00 They evolved to be sophisticated, but these kind of macroscopic signals like light coming
2:26:05 in in the morning has these, you know, long wavelength and short wavelength contrast.
2:26:12 That’s what tells our brain it’s morning.
2:26:14 That’s right.
2:26:15 So orange, red, blue contrast, even if there’s cloud cover, it’s the difference between those
2:26:20 two different qualities of light that says it’s morning.
2:26:25 And when the sun is overhead, you don’t see that yellow, blue or orange, blue, red, blue
2:26:30 contrast.
2:26:31 But you see it again at sunset and in informed.
2:26:32 So it sounds like the combination of specific chemicals in the gut tell us, this is good.
2:26:39 Pursue more of this.
2:26:40 And maybe even the place where you found it is a good place as opposed to, and the opposite
2:26:44 is probably also true.
2:26:46 Yes.
2:26:47 Like that’s an entire new domain of the digestive, the sensory system in the digestive tract
2:26:53 that we haven’t even begin to articulate yet memory.
2:27:00 How do we remember like what was that first meal?
2:27:03 Like in the Ratatouille movie from when we were children, right?
2:27:08 Like it was very different.
2:27:09 Like I still remember like some of the very simple, humble meals that my mother will make,
2:27:16 but it’s just priceless for me, right?
2:27:19 Whenever I go home, it’s like, without asking, sometimes my mother will prepare those for
2:27:26 me.
2:27:27 And it’s like, it just brings you back when you were that age, right?
2:27:31 Yeah.
2:27:32 The memory system is tightly linked to taste and smell.
2:27:36 There’s no question about it.
2:27:37 And then like how it is that they got triggers that those sensations or farther reinforces
2:27:43 those sensations.
2:27:44 We haven’t even begin to articulate.
2:27:46 And when I said articulate, because we don’t even have the language to refer to these things.
2:27:51 You know, that’s why at the very beginning we were talking over there in our conversations
2:27:55 or the axis, you know, and that we don’t say like the nose brain and the nose brain
2:28:01 axis, right?
2:28:02 Like we just went for what we had at that time.
2:28:05 And I do think that the language will continue to evolve for us to be able to articulate
2:28:10 more precisely, more richly, more elegant, more, you know, in so many different ways,
2:28:17 how it is that the organs communicate with each other to make us who we are.
2:28:25 And in there, in one of our papers, we quoted these beautiful passages from the book Memoirs
2:28:35 of a Stomach.
2:28:38 It was written in 1853 by a French person, by what it says in the first page, by the
2:28:47 minister of interior, because all of those who it may read or something like that.
2:28:53 And then on page 21, it goes to describe the dialogue between the gut and the brain.
2:28:58 And it says like that.
2:28:59 How it is that the gut communicates to the brain with a rapidity through these two sets
2:29:06 of electrical wires that communicate the arrivals of the day as we may eat with a precision
2:29:15 and rapidity to the brain.
2:29:18 So the brain will make its own feelings and impressions.
2:29:24 And then he said that when, he’s talking from the perspective of the stomach, it says like
2:29:30 when I grew more rows, like meaning I’m not working in digestion, then the brain also
2:29:38 grew irritable and petulant.
2:29:40 I agree.
2:29:41 I agree.
2:29:42 It’s so interesting to look at human experience from the directionality of gut to brain rather
2:29:48 than brain to gut.
2:29:50 That’s right.
2:29:51 And as I do from time to time, pay attention to what’s happening in the landscape of wellness
2:29:59 and mental health and physical health, a lot of what you see out there in terms of highly
2:30:07 educated people who have thought very deeply about how to navigate decision making in lots
2:30:14 of different domains of life and to do it in a way that really honors our own individual
2:30:19 preferences and needs.
2:30:21 Well, like Martha Beck, I don’t know if you’ve heard of her, but she’s triple-degreed from
2:30:25 Harvard, but has talked a lot about learning to sense one’s way into and through decisions,
2:30:35 through intuition that is more of the body and is more of particular brain circuits than
2:30:42 our analytic, like pros and cons lists, because pros and cons lists and obviously important
2:30:49 metrics, like objective metrics, like, oh, is this the right salary, the right location,
2:30:52 the right, you know, all the things that matter for decision making, and we’re trained in
2:30:57 that in school, in the United States and in many areas of the world as well, of course,
2:31:04 and that’s critical, but that there’s this other training, there’s this other learning
2:31:07 of self that can be extremely useful, and it almost always comes back to body first,
2:31:13 then to cognition and decision making, and I feel like modern humans are trying to learn
2:31:18 how to run the analysis of life decision making through this, I guess, more ancient axis.
2:31:28 So, again, the intelligence of these, what used to be called more primitive systems,
2:31:33 but I don’t think they’re primitive at all, and talking with you today, it’s clear to
2:31:36 me that these are highly sophisticated systems, just as sophisticated as any forebrained pathway
2:31:41 involved in analyzing, say, like probability or something.
2:31:46 And that’s why I like to highlight the example of having a nice meal and having a nice conversation
2:31:55 at the same time.
2:31:57 You know, if you go to a nice restaurant and you have a nice meal while you’re having a
2:32:01 nice conversation and you pay attention to it, then it brings humility to your body to
2:32:07 know, like, how much your body is doing for you to be able to just express a tiny little
2:32:13 bit and having some sort of, like, highly intellectual, sophisticated conversation.
2:32:19 While you’re able to put in the precise amount of letters inside of your mouth and chew it
2:32:25 in the right way, like, adjusted with a little bit of water and maybe a little bit of wine
2:32:31 and understand what is cleansing your palate and, like, you know, putting down the napkin
2:32:36 and so on and so forth without going to the restaurant every time that you feel like going
2:32:42 to it, right?
2:32:43 There is an entire sophistication of how the body, just to have something like a simple
2:32:48 as a catch-up conversation, you know.
2:32:51 Do you think that our ability to sense into gut-sensing more, to really hear and respond
2:33:00 to the signals from the gut is something that we can learn even as adults simply by paying
2:33:05 more attention?
2:33:06 Yes, and I think that here’s the concept that usually, you know, that when we talk about
2:33:14 topics like meditation, you know, it’s that self-care and that self-care is listening to
2:33:19 your own body, right?
2:33:20 How it is that the body is feeling, like, I don’t know, you know, I grew up in, my mother
2:33:26 will tell me, like, or, you know, family will tell you.
2:33:30 If you feel like going to the restroom to pee for a bio-break, don’t hold it for too long
2:33:36 because it may be bad, right?
2:33:38 Like, and I think that just learning that part of, like, listening to the body is an
2:33:42 essential aspect.
2:33:43 It’s just that we’re not constantly doing it over learning about how we are moving our
2:33:48 career forward, you know.
2:33:49 Yes, so much of what we’re taught in order to be high-achieving and forward-moving in
2:33:55 life in modern culture is about learning to override the signals from the body, but it
2:34:01 seems that learning to listen to the signals from the body is key to being a healthy human
2:34:07 being.
2:34:08 Yes, and here I have an example.
2:34:10 A year ago, I used to run quite a bit, and I remember that after I had run a marathon,
2:34:18 I took a break for, like, a few weeks, and then I got back on the trail and I began running,
2:34:24 and I was like, “You know, I don’t need to warm up for three or four weeks up to, like,
2:34:28 get back into speed,” right?
2:34:30 And I remember that I started to feel like that my right, the soul of my right foot was
2:34:37 a little bit, like, bothering me, like, almost imperceptible.
2:34:41 And I was like, “No, you just have to keep going,” you know.
2:34:45 My wife Elaine told me, like, “You know, you should pay attention, take a break,” you
2:34:49 know, and I just kept running, and I remember specifically that one time I went to run and
2:34:54 I was like, “I can put in eight miles,” and I think that I was running at, like, seven
2:34:59 minutes, seven, fifteen, a mile or something like that, and I began running, and then after
2:35:05 a mile, I was feeling pumped, you know, two miles, three miles, I was like, “And then
2:35:10 I usually will go and do four miles and then turn around and come back.”
2:35:14 I got on mile four, and I fell crack, and I could not walk anymore.
2:35:21 There was a hair fracture.
2:35:24 That is almost imperceptible in the next ray, but, boy, you cannot move your foot anymore.
2:35:29 I had to limp for four miles all the way back to the car because I didn’t even have my phone.
2:35:35 And I never forgot that for next time, you got to pay attention to your body, you know.
2:35:41 Your body is simply telling you, like, something is a little bit off.
2:35:45 Just don’t keep pushing it, you know.
2:35:48 And I specifically remember because I kept running, and I couldn’t, I had to literally
2:35:53 limp all the way back to the car, you know.
2:35:55 Well, Diego, I must say that among the many things that you’ve shared with us today and
2:36:01 taught us about the gut and its ability to influence the brain, and the incredible things
2:36:07 that are happening at the level of biology and physiology of the gut, chief among them
2:36:13 is the message that we should all pay more attention to our sensing at the level of our
2:36:20 gut.
2:36:21 So nowadays, we hear so much about the gut microbiome such that, fortunately, I think
2:36:26 most people are starting to appreciate that the gut microbiome is vital for all aspects
2:36:30 of health and that there are things that we can do to feed that microbiome, fiber intake,
2:36:34 fermented food intake, and so forth.
2:36:37 But clearly, based on what you’ve told us today, that even just paying a little bit more
2:36:42 attention to what our gut is telling us at the level of feeling good, feeling less good
2:36:49 because the signs and signals are subtle, I realize, can really help us make better decisions
2:36:57 and help us decide not just what foods to eat or not eat, how much to eat or not eat,
2:37:03 but also how to navigate higher order decisions, if you will, about who to spend time with,
2:37:10 what to do, what not to do, moving along the decision tree of life.
2:37:15 And along those lines, I want to thank you for making the decision to come here today.
2:37:20 I certainly am happy that we decided to do it.
2:37:24 It’s something that’s been a long time coming.
2:37:26 I really see you as one of the true pioneers in this area of trying to dissect the understanding
2:37:31 of the gut brain axis, heal the brain through the gut, understand and modulate our emotions
2:37:36 at the level of gut sensing.
2:37:39 And while there are other researchers in this area, I refer to you as a pioneer because
2:37:44 you’ve really undergone this incredible trajectory from the Amazon through nutrition science
2:37:49 into neuroscience.
2:37:51 And now we’re getting a little bit into psychological science, and I’m excited for what comes next.
2:37:56 I only ask one thing, which is that as you make these discoveries, that you come back
2:38:02 and talk to us about them so that we can learn more about your incredible work.
2:38:07 So Andrew, I want to say a few things.
2:38:10 The first thing is that I feel deeply honored by your invitation, and thank you so much
2:38:15 for the opportunity.
2:38:17 I am just simply a representative of the people that work with me and work with us.
2:38:28 I’m just an ambassador, and they get the majority of the credit for their dedication to help
2:38:36 us understand a little bit more of the body and how it is helped us to navigate the world
2:38:42 that we live in.
2:38:44 So I want to thank you for the opportunity.
2:38:47 I want to thank the people that have made this possible.
2:38:51 Also the people that are along the way or the institutions that are along the way have
2:38:58 helped fund this endeavor.
2:39:04 My home institution at Duke, I’m deeply grateful because my career has developed there.
2:39:09 And some of my mentors, Roger Little, Andrew Muir, and the people that have helped me along
2:39:15 the way.
2:39:16 Finally, I want to thank you and your team, and congratulate you for the work that you
2:39:24 do and that you have created this window for us to come and share with the public a little
2:39:31 bit of the work that we do.
2:39:35 Perhaps some of that is obviously based on evidence.
2:39:42 Some portion of that is thinking about the future, but I do think that through maintaining
2:39:47 the dialogue with the public that we can continue to understand the world that we live in.
2:39:52 And for that, I have to thank you for having created this platform.
2:39:57 Well, it’s a labor of love and I’m honored to be able to do it in no small part because
2:40:04 I get to sit down and have beautiful intimate conversations about biology and life with
2:40:10 you.
2:40:11 So thank you so much.
2:40:12 Thank you.
2:40:13 Thank you for joining me for today’s discussion about sensing with the gut and the gut brain
2:40:17 axis with Dr. Diego Borquez.
2:40:19 To learn more about Dr. Borquez’s research and also to see a link to his fabulous podcast
2:40:24 called The Gastronauts, please see the show note captions.
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