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

00:00:00.000 | - Welcome to the Huberman Lab Podcast,

00:00:02.240 | where we discuss science

00:00:03.660 | and science-based tools for everyday life.

00:00:05.900 | - I'm Andrew Huberman,

00:00:10.320 | and I'm a professor of neurobiology and ophthalmology

00:00:13.600 | at Stanford School of Medicine.

00:00:15.400 | My guest today is Dr. Diego Borges.

00:00:18.040 | Dr. Diego Borges is a professor of medicine

00:00:20.600 | and neurobiology at Duke University.

00:00:22.880 | He did his training in gastrointestinal physiology

00:00:25.520 | and nutrition and later neuroscience.

00:00:27.960 | And by combining that unique training and expertise,

00:00:30.680 | he is considered a pioneer and leader

00:00:33.160 | in so-called gut sensing or the gut-brain axis.

00:00:36.600 | Now, when most people hear the words gut-brain axis,

00:00:39.160 | they immediately think of the so-called microbiome,

00:00:41.880 | which is extremely important,

00:00:43.280 | but that is not the topic of Dr. Borges' expertise.

00:00:46.600 | Dr. Borges focuses on the actual sensing

00:00:49.600 | that occurs within one's gut,

00:00:51.260 | just as one would sense light with their eyes

00:00:53.640 | or sound waves with their ears for hearing.

00:00:56.240 | Our gut contains receptors

00:00:57.880 | that respond to specific components of food,

00:01:00.080 | including amino acids, fats, sugars,

00:01:03.560 | and other aspects of food, including temperature,

00:01:05.880 | acidity, and other micronutrients that are contained in food

00:01:09.560 | that give our gut the clear picture

00:01:11.800 | of what is happening at the level of the types

00:01:14.280 | and qualities of food that we ingest,

00:01:16.120 | and then communicate that below our conscious detection

00:01:18.920 | to our brain in order to drive specific patterns

00:01:21.840 | of thinking, emotion, and behavior.

00:01:24.680 | And of course, everybody has heard of our so-called gut sense

00:01:27.680 | or our ability to believe or feel certain things

00:01:30.920 | based on perceptions that are below

00:01:33.560 | or somehow different from conventional language.

00:01:36.520 | Today, Dr. Borges teaches us

00:01:38.160 | about all aspects of gut sensing,

00:01:40.280 | how it occurs at the level of specific neurons

00:01:42.640 | and neural circuits, how the brain responds to that,

00:01:45.160 | how specific foods and components of food impact

00:01:47.920 | not just our feeling of digestion

00:01:49.880 | or feeling good or bad about what we ate,

00:01:51.960 | but indeed how we feel overall, how safe we feel,

00:01:54.960 | how excited we feel, whether or not we feel depressed

00:01:57.760 | or sad, angry, or happy.

00:02:00.080 | Today's discussion, I promise you, is unique

00:02:02.520 | among all discussions of neuroscience,

00:02:04.360 | at least that I've heard previously,

00:02:06.040 | in that it combines two seemingly disparate fields,

00:02:08.720 | nutrition and neuroscience.

00:02:11.160 | Indeed, today's discussion gets into how different foods

00:02:13.960 | and food combinations impact how we feel

00:02:16.360 | and what we crave and what we tend to avoid.

00:02:18.820 | We also get to hear the absolutely extraordinary story

00:02:21.860 | of Dr. Borges' upbringing in the Amazon jungle

00:02:24.960 | and how his knowledge and intuition about plants

00:02:27.600 | has influenced his science

00:02:29.200 | and how the incredible science that his laboratory is doing

00:02:32.040 | relates to all of us and our ability

00:02:34.480 | to better tap into our gut sense.

00:02:37.180 | Before we begin, I'd like to emphasize that this podcast

00:02:39.920 | is separate from my teaching and research roles at Stanford.

00:02:42.560 | It is, however, part of my desire and effort

00:02:44.620 | to bring zero cost to consumer information about science

00:02:47.280 | and science-related tools to the general public.

00:02:50.000 | In keeping with that theme,

00:02:51.240 | I'd like to thank the sponsors of today's podcast.

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00:06:46.140 | And now for my discussion with Dr. Diego Borges.

00:06:49.500 | Dr. Diego Borges, great to have you here.

00:06:54.020 | - Thank you for having me, Andrew.

00:06:55.740 | - I am super excited to learn from you today,

00:07:00.340 | as I know everyone else is.

00:07:02.260 | And if they don't realize why, soon they will,

00:07:06.780 | which is that you work on one of the more fascinating aspects

00:07:10.140 | of us, which is our gut, our gut sensing,

00:07:15.140 | the gut brain axis,

00:07:17.540 | which I think most people don't realize is nearby,

00:07:21.940 | but separate from the so-called microbiome.

00:07:25.960 | So we're not talking about the microbiome,

00:07:28.020 | a very interesting and important topic, of course,

00:07:31.120 | but we are going to talk about this thing

00:07:34.580 | that we call our gut sense

00:07:37.140 | and how it impacts everything from our cravings

00:07:40.320 | to our brain health and our cognition.

00:07:43.100 | So once again, welcome.

00:07:47.180 | And I just want to kick things off by asking you

00:07:50.580 | to educate us, explain, you know,

00:07:53.580 | what is this gut brain axis that we hear about

00:07:56.880 | and what's going on in our gut besides digestion?

00:08:00.920 | - Well, Andrew, thank you so much for having me here.

00:08:06.220 | Thrilled to be here.

00:08:07.260 | I knew that since we met a few years ago

00:08:11.860 | that we will have this ongoing conversation

00:08:14.460 | and a great conversation.

00:08:15.720 | The gut and the brain, you know,

00:08:19.340 | people call it an axis because traditionally

00:08:21.980 | it's thought to be an imaginary line

00:08:24.260 | that was connected through hormones.

00:08:26.760 | So since 1902, when the first hormone secreting

00:08:31.020 | was reported by Bayleys and Stout,

00:08:36.020 | and it was known that when we eat,

00:08:41.020 | then hormones, these molecules in the gut are released

00:08:47.420 | and then they will enter the bloodstream

00:08:49.240 | and then eventually will have a cause in distant organs.

00:08:53.000 | And for the next hundred or so years,

00:08:57.100 | the field focused on the hormones.

00:09:00.660 | And as a consequence, there was no direct line

00:09:04.380 | of communication between the gut and the brain.

00:09:08.180 | But as often I say, you don't, you don't say,

00:09:11.220 | or we don't say the nose brain axis, right?

00:09:13.620 | Like, or the eye brain axis, right?

00:09:15.880 | And all of the organs are in sync, working in sync.

00:09:20.700 | So in the gut, there are also some sensory cells

00:09:25.700 | that are able to detect the outside world

00:09:28.900 | and then quickly communicate that information to the brain.

00:09:33.380 | And I say the outside world,

00:09:35.680 | because the gut is the only organ

00:09:38.380 | that passes throughout our body,

00:09:40.700 | but it is still exposed to the outside.

00:09:44.140 | If you think about it, if you will swallow a marble,

00:09:48.260 | it still has a chance to get out.

00:09:50.380 | - Please don't do that anybody.

00:09:53.360 | - But it is still exposed to the surface.

00:09:57.180 | - You're right, I never thought about the gut

00:09:58.820 | as the organ that is in contact with the outside world.

00:10:02.500 | Unlike our heart, which is not in direct contact

00:10:04.800 | with the outside world, or our liver, our pancreas,

00:10:07.500 | but the gut is.

00:10:08.660 | - The gut is, and if you think about it,

00:10:11.740 | it is just separated by some compartments

00:10:15.940 | that have all of these valves.

00:10:18.140 | And the epiglottis, the gastroesophageal junction,

00:10:23.140 | the pylorus, the ileocecal junction, the rectum.

00:10:28.420 | - So these are the sequences of valves,

00:10:30.820 | of chambers with valves between them

00:10:33.620 | that food passes through, air passes through.

00:10:37.660 | And within each, as I understand it,

00:10:39.740 | there are different functions related to digestion.

00:10:42.620 | But I think where you're taking us is that

00:10:44.660 | there are different modes of sensing what's coming through

00:10:48.140 | and signaling to the brain and other organs

00:10:51.860 | what's going on in the outside world

00:10:53.380 | by what's sensed coming through that passage.

00:10:55.740 | Is that correct?

00:10:56.580 | - That's correct, and if we think about it,

00:11:00.140 | the, when we swallow something,

00:11:04.060 | literally we have to trust our gut.

00:11:06.740 | Perhaps that's why we use this phrase, trust your gut.

00:11:09.620 | Because after that, there's not much that you can do,

00:11:13.620 | at least in regular humans, that you can do consciously

00:11:17.540 | to expel something that perhaps is poisonous or toxic.

00:11:22.540 | It is the gut that has to make that distinction.

00:11:26.940 | And then usually accommodate things for absorption,

00:11:30.100 | or let them pass through digestion,

00:11:32.460 | and then ultimately they will be secreted, right?

00:11:35.420 | - So if you could describe for us the architecture

00:11:40.420 | that is the cells that respond to things in the gut

00:11:44.940 | and where they send that information

00:11:47.340 | and how they send that information.

00:11:49.100 | What is this thing that we call gut sensing made up of?

00:11:53.220 | What's the parts list?

00:11:54.800 | - So the parts list has been evolving recently.

00:11:59.680 | And while some of the elements we have known for a while,

00:12:04.080 | but in general, what we're talking about,

00:12:07.240 | because it's an external surface,

00:12:09.400 | it is lined by a single layer of cells

00:12:12.960 | that are called epithelial cells.

00:12:15.640 | And essentially these cells are exposed

00:12:17.640 | to the outside world,

00:12:19.200 | but they also are like attached in like a little membrane.

00:12:22.760 | And they are the ones that interface

00:12:25.200 | with the inside of the body.

00:12:27.120 | So in the stomach, we have a stratified epithelium,

00:12:30.860 | for instance, that is thicker,

00:12:32.960 | so it can survive digestion, chemicals,

00:12:35.840 | and other things like harsh environment.

00:12:37.880 | And in the intestine,

00:12:38.720 | we have a little bit more delicate epithelial layer.

00:12:43.720 | And within this epithelial layer,

00:12:46.760 | there are several different cell types.

00:12:49.040 | And one of those is the so-called enteroendocrine cell.

00:12:53.240 | To put it in more simple terms,

00:12:54.960 | is a gut endocrine cell,

00:12:56.680 | or a gut cell that releases hormones.

00:12:59.480 | The term was coined in 1938 by a German physician.

00:13:04.480 | His name was Friedrich Feter.

00:13:06.840 | And at that time, it was a major advancement

00:13:11.280 | in our understanding of physiology,

00:13:12.960 | because he came up with the idea

00:13:15.360 | that the organs were not only communicating to organs.

00:13:19.220 | In fact, there were cells within the organs

00:13:21.520 | that were communicating to other organs

00:13:23.600 | through the release of some of these endocrine factors,

00:13:27.120 | these neuromodulators,

00:13:28.360 | or these neuropeptides that we know as hormones.

00:13:31.000 | And so he named the diffuse endocrine system of the gut,

00:13:35.160 | and then he came up with this word enteroendocrine cell.

00:13:39.000 | And these cells are dispersed

00:13:40.960 | at a ratio of roughly speaking,

00:13:42.760 | like one to 1,000 epithelial cells

00:13:45.480 | throughout the digestive tract.

00:13:47.300 | And we thought for the longest time

00:13:50.360 | that these cells were not connecting directly

00:13:53.160 | to the nervous system,

00:13:54.080 | that they will release these neuromodulators,

00:13:56.120 | and the neuromodulators through diffusion

00:13:58.360 | will act on receptors into some of the nerve terminals.

00:14:02.400 | And that is true.

00:14:03.240 | That is a very well-established system.

00:14:05.880 | But in 2015, we made an observation

00:14:08.240 | that some of these cells,

00:14:09.800 | anywhere from 1/3 to 2/3 of these cells,

00:14:12.360 | it depends on the type of systems

00:14:15.320 | that you use to identify it,

00:14:16.960 | they were contacting directly the nervous system.

00:14:20.320 | And that brought up a new dimension

00:14:23.200 | of how it is that the gut could be communicating

00:14:26.640 | to the brain, because as you know,

00:14:28.000 | in the brain, the synapses are the ones

00:14:30.680 | that are most predominant.

00:14:32.600 | However, there is a lot of neuromodulation

00:14:34.880 | from endocrine functions in the brain too.

00:14:38.800 | So in the gut, this was not well-described.

00:14:43.200 | There had been historically a few examples

00:14:46.320 | that these cells may be making synaptic contacts,

00:14:48.920 | but they had not been studied.

00:14:50.960 | And perhaps one of the main reasons

00:14:53.920 | why they hadn't been studied

00:14:55.160 | is because the tools were not there.

00:14:57.720 | And if you recall, in the 1990s,

00:15:02.120 | with the advancement of green fluorescence protein

00:15:04.400 | as one of the main molecules to tag cells,

00:15:09.400 | now all of a sudden, there was a revolution in biology

00:15:11.880 | because you could identify the cells,

00:15:13.360 | you can take them out,

00:15:14.280 | you can do a transcriptomic analysis

00:15:16.800 | to see what genes they express,

00:15:19.080 | you could co-culture them, you can modify their genome,

00:15:22.400 | and then you can start to interrogate

00:15:23.920 | what is their contribution to the entire body.

00:15:26.560 | - I'll just interrupt you for a second

00:15:27.760 | just to make sure that I and everyone else is on board.

00:15:30.600 | So if I understand correctly,

00:15:32.080 | it's long been known that there are cells

00:15:35.260 | that are in these layers of the gut and the intestine,

00:15:39.800 | and it's long been appreciated that as food passes through,

00:15:43.840 | these cells somehow can sense the chemical constituents

00:15:46.640 | of the food as it gets broken down,

00:15:49.120 | and then release hormones into the bloodstream

00:15:52.200 | that could influence the brain,

00:15:53.960 | those hormones could travel and influence things far away.

00:15:56.240 | In fact, for those that don't know,

00:15:57.440 | endocrine generally means signaling

00:15:59.680 | at a distance between cells.

00:16:01.440 | So between gut and brain or gut and liver,

00:16:03.720 | it can also mean local effects.

00:16:06.120 | So hormones, endocrine effects can also be local.

00:16:08.960 | But if I also understand you correctly,

00:16:13.040 | it was only about 15 years ago

00:16:15.400 | when you mentioned green fluorescent protein,

00:16:17.840 | we should probably just tell the tale in a few sentences.

00:16:20.280 | This is an amazing story in biology,

00:16:22.420 | where if you've ever seen fluorescing jellyfish,

00:16:26.400 | that's because they express a gene

00:16:28.040 | for so-called green fluorescent protein,

00:16:31.120 | and biologists have hijacked that gene sequence

00:16:33.620 | and put it into mice,

00:16:35.520 | and now actually other organisms as well,

00:16:38.240 | which allows you to see individual cells and cell types.

00:16:41.120 | So these cells release hormones,

00:16:43.160 | the hormones influence the brain and other organs,

00:16:46.800 | and now I think you're gonna tell us

00:16:48.040 | that they also are able to make direct communication lines

00:16:52.800 | with other organs as well.

00:16:54.580 | - Correct.

00:16:55.420 | So maybe here is feeling how it is

00:16:58.400 | that I got into studying the system.

00:17:02.640 | And as you know, between the '90s and the early 2000s,

00:17:07.540 | there was an explosion in tools to study the brain

00:17:11.480 | and neural circuitry and the connection of neurons

00:17:14.320 | and each one of the neurons.

00:17:16.360 | Because up until the 1990s,

00:17:18.640 | the tools were limited, electrophysiology, behavior.

00:17:22.740 | But then not only we had green fluorescent protein,

00:17:27.000 | we had optogenetics,

00:17:29.200 | we had a rabies modified to be able to trace

00:17:34.200 | and how it is that neurons connect at one synapse,

00:17:39.000 | which was a dream.

00:17:40.480 | I think that in fact, that was the dream of Francis Crick.

00:17:43.120 | When he was at Salk,

00:17:44.320 | he talked about having the way to control.

00:17:46.640 | - For those that don't know,

00:17:47.460 | Crick was a co-recipient to the Nobel Prize

00:17:50.320 | for the discovery of the structured DNA,

00:17:52.160 | but then later in his career,

00:17:54.140 | developed an obsession for neuroscience.

00:17:56.120 | And yeah, he daydreamed out loud about having tools

00:18:00.260 | to visualize individual connections in the nervous system.

00:18:02.960 | And as Diego is pointing out,

00:18:05.600 | scientists have hijacked the rabies virus,

00:18:09.320 | which hops between neurons,

00:18:11.000 | labeled the rabies virus with things that glow fluorescent.

00:18:14.680 | And in doing so,

00:18:15.800 | we now understand a lot about what Crick dreamed for,

00:18:19.080 | which was the ability to see

00:18:21.280 | different specific connections in the nervous system.

00:18:24.200 | - Yes.

00:18:25.040 | So then you could isolate the cells

00:18:29.160 | and then you could do sequencing technology

00:18:31.120 | to see like what are the genes

00:18:32.480 | that these cells are expressing.

00:18:34.160 | And then you can start to understand

00:18:35.880 | the makeup of the cells.

00:18:38.420 | In 2009, Hans Clevers, a scientist in the Netherlands,

00:18:43.420 | did a beautiful experiment.

00:18:45.240 | Like he discovered these factors

00:18:47.600 | that will trigger a receptor of the stem cells

00:18:50.040 | in the intestinal epithelium

00:18:51.280 | and will form literally a mini gut in a dish.

00:18:55.360 | You know, these cells will be all lined up

00:18:57.600 | and then they will have a lumen.

00:18:58.640 | And I remember like seeing some of these papers coming out

00:19:01.880 | when I was a PhD student and I was already studying the gut.

00:19:06.240 | So it was inspiring to see like all of the things

00:19:08.880 | that all of a sudden you could do, right?

00:19:11.880 | So when I began studying the cells,

00:19:14.580 | immediately by isolating the cells

00:19:17.220 | and simply observing the cells in the native tissue

00:19:22.220 | of these mice models,

00:19:25.620 | it quickly became evident that some of the cells

00:19:30.140 | had a very peculiar anatomy.

00:19:33.180 | Some of them had these very prominent arms at the base,

00:19:36.660 | like literally like in the Sistine Chapel,

00:19:40.580 | Adam reaching out to God, right?

00:19:42.460 | Like with a hand.

00:19:43.380 | These cells will have that type of anatomical features

00:19:48.540 | and even ending with a little hand at the end of the arm.

00:19:52.980 | And obviously I immediately thought like,

00:19:56.100 | why would a cell that it is supposed to react to food

00:20:01.700 | and release hormones into the bloodstream

00:20:04.740 | or just in the vicinity will invest so much energy

00:20:08.700 | into developing an arm, right?

00:20:11.360 | So then I started to look, well,

00:20:12.860 | perhaps it is because it's providing a bridge

00:20:14.860 | directly into the vasculature, into the vessels

00:20:18.240 | to put the hormones into the bloodstream, right?

00:20:21.360 | Grown, like I couldn't find that direct connection.

00:20:25.340 | So then I started to study,

00:20:26.980 | perhaps they were associated with the nervous system

00:20:29.860 | and that's how we made some of the first observations

00:20:33.100 | that some of them with the arm or without the arm,

00:20:38.100 | they will have a more intimate relationship

00:20:41.380 | with nerve fibers.

00:20:44.100 | And that of course, open up a bunch of new questions.

00:20:49.100 | But the first thing that we had to do,

00:20:53.660 | it was to come up with a name for this food.

00:20:57.820 | And it kind of became organic.

00:20:59.500 | And I wanna highlight these because I think that

00:21:01.460 | as we go through the discovery trajectory,

00:21:05.340 | we don't realize the need to also engineer language.

00:21:08.900 | How we go about languages,

00:21:11.140 | we start to attach words that we already knew

00:21:14.660 | and we start to put them together to describe something

00:21:17.300 | that new that we're observing, right?

00:21:19.860 | And I say this because at the very beginning with my mentor,

00:21:22.900 | we will start to call these little feet.

00:21:25.060 | First, we call them axon,

00:21:27.220 | which is like the term for like

00:21:29.500 | the long extending branches of the neurons,

00:21:31.580 | the main branches of the neurons.

00:21:33.340 | So we will call them axon-like

00:21:35.340 | because they look like a baby axon.

00:21:37.780 | But then we call them also like pseudopod

00:21:41.100 | because it was like a pod, but it was pseudo.

00:21:44.620 | And at some point we,

00:21:46.060 | and it was coming from like some cells in the kidneys

00:21:50.100 | that they are called podia or something like that.

00:21:54.380 | So it was axon-like, pseudopod-like basal process

00:21:57.340 | to describe that it was on the base.

00:21:59.020 | So at some point it became so long

00:22:00.460 | that we couldn't fit it in an abstract, right?

00:22:02.180 | - Yeah, it's a bit of a mouthful.

00:22:04.140 | - So we began thinking about it

00:22:05.460 | and then eventually I came up with the term.

00:22:07.380 | I thought like, "Ah, Neuropod."

00:22:09.420 | And I remember pitching it to my mentor

00:22:12.980 | and I said like, "Let me think about the weekend."

00:22:15.100 | And then on a Monday he came in and he said like,

00:22:17.300 | "You know, it has a ring to it.

00:22:18.780 | "I think that we should use it."

00:22:20.460 | But essentially the thought was that

00:22:23.780 | if these cells are contacting,

00:22:26.260 | then perhaps they are passing information directly

00:22:29.300 | onto the nervous system.

00:22:31.660 | And that is very different

00:22:33.060 | than just spewing neuromodulators in the vicinity

00:22:38.060 | and hoping that some of those catch the nervous system.

00:22:42.580 | And like I said, while that still exists,

00:22:44.740 | and I think that is just like matter of space and time.

00:22:48.780 | Like they modulate these terminals

00:22:51.700 | in a different space and time, the hormones,

00:22:54.260 | but the neurotransmission is directly

00:22:57.820 | and more precise in space and time.

00:23:00.540 | - Could I just interrupt for a moment, please?

00:23:02.620 | So hormone signaling, endocrine signaling,

00:23:06.420 | generally is slower than the forms of communication

00:23:10.900 | directly between neurons, right?

00:23:13.140 | Could be on the order of seconds, sure,

00:23:16.260 | but typically on the orders of minutes or hours.

00:23:19.380 | Whereas neural communication on the order of milliseconds.

00:23:24.180 | - Correct.

00:23:25.020 | - So if I understand correctly,

00:23:26.900 | these, what you decided to call neuropod cells,

00:23:29.820 | and thank you for shortening the name

00:23:32.100 | from the other description, line the gut.

00:23:36.620 | Are we talking about everything from esophagus

00:23:38.980 | down to the stomach, to the intestine,

00:23:42.300 | or is it just at the level of the stomach and intestine?

00:23:44.780 | Where does it exist?

00:23:47.060 | - This is where the conversation becomes expansive

00:23:49.980 | because these neuropods, or cousins of these neuropods,

00:23:54.980 | so these neuropods are simply

00:23:56.380 | a specialized neuroepithelial cells,

00:23:59.300 | meaning that are electrically excitable,

00:24:02.020 | that they can discharge electricity,

00:24:04.700 | but they are, these type of cells

00:24:06.740 | are in every single epithelial cell,

00:24:09.340 | or epithelial layer of the body,

00:24:11.700 | because that's how the body creates a representation

00:24:14.820 | of the world, through sensor cells

00:24:17.380 | that are equipped to detect the outside world,

00:24:20.980 | meaning that they can be exposed

00:24:22.460 | to fluctuations in temperature,

00:24:24.020 | fluctuations in pH, fluctuations in concentrations,

00:24:27.740 | and then they quickly can generate a chemo-electrical code

00:24:32.420 | that they pass it on to the nervous system,

00:24:34.220 | and then ultimately the brain integrates that

00:24:36.460 | and says like, ooh, my belly's feeling good,

00:24:39.460 | but I'm feeling cold in the skin, right?

00:24:42.700 | And that is thanks to all of these neuropithelial cells

00:24:45.700 | that they are even in tasting, so to speak,

00:24:49.020 | the cerebrospinal fluid inside of the spinal cord

00:24:52.860 | and the ventricles, they are inside of the inner ears,

00:24:55.940 | the taste pads.

00:24:58.460 | So it is, and in fact, there's a beautiful book

00:25:01.660 | from the '70s from some Japanese scientists,

00:25:05.740 | Fujita Kannon Kobayashi,

00:25:07.220 | who called these cells paraneurons,

00:25:11.060 | and their whole concept is that there was not

00:25:13.500 | such a discrete distinction between a neuron

00:25:17.380 | that lives inside of the brain or the central nervous system

00:25:20.500 | and a neuropithelial or a neuroendocrine cell

00:25:24.220 | that lives exposed to the outside,

00:25:26.620 | simply that there is a continuum of adaptation

00:25:29.340 | so the organism can bring the information from outside

00:25:33.540 | inside into the body to be able to process it

00:25:36.860 | and then process it and then guide behavior.

00:25:40.140 | - So, based on the way you describe it,

00:25:41.980 | we have these neuropod cells that line our gut,

00:25:46.260 | and we also have these similar cell types

00:25:50.340 | in the other organs of the body,

00:25:52.300 | and these cells are responding to the chemical constituents

00:25:55.780 | of what we eat as the food is broken down,

00:25:58.860 | also to the temperature of the environment,

00:26:01.780 | to the pH, that is how relatively basic or acidic

00:26:08.280 | something is that we ate,

00:26:10.120 | and presumably to other features

00:26:12.300 | in our environment as well,

00:26:14.160 | and all of that information is activating these cells

00:26:17.660 | to some degree or another,

00:26:19.080 | and then we're releasing hormones

00:26:21.600 | into our body as a consequence,

00:26:23.360 | but also there's a direct line to the brain,

00:26:25.900 | and we're not necessarily aware of all of this happening,

00:26:30.000 | right, I mean, until you describe it,

00:26:31.320 | I think most of us have not been aware

00:26:33.380 | that this is happening.

00:26:34.480 | - And we probably shouldn't be aware,

00:26:36.040 | you know, like as I often say,

00:26:38.160 | if you and I are having a conversation,

00:26:41.360 | we probably shouldn't be aware of the macrophage

00:26:43.680 | in the spleen that is chasing this bacterium

00:26:45.600 | that got inside of the lettuce

00:26:47.120 | that we swallowed at lunch, right,

00:26:49.080 | like you just do your thing

00:26:50.260 | so we can keep communicating, right?

00:26:52.520 | - Except maybe you don't eat more of that lettuce, right,

00:26:55.560 | which is the-- - That's right.

00:26:57.600 | - Okay, so you discovered these neuropod cells.

00:27:01.000 | - That's right. - And you--

00:27:02.440 | - Or I described them, yeah. - You described them, yeah.

00:27:04.600 | And you had in hand some tools to selectively label them.

00:27:08.960 | What did that reveal about their connectivity with,

00:27:12.720 | you're referring to it as the nervous system,

00:27:14.280 | which I love because a resounding theme on this podcast

00:27:17.120 | is I always say, you know, brain and spinal cord

00:27:19.000 | and all the connections to the body and back again

00:27:21.640 | is the nervous system, but what did you discover

00:27:23.960 | in terms of the connections with the brain proper?

00:27:27.080 | - Here is where the tools started to make a big difference.

00:27:30.560 | You know, all of a sudden you could see

00:27:33.240 | the resolution of a receptor inside of a cell

00:27:36.080 | using certain type of microscopes, right?

00:27:38.720 | So I remember that one of the first questions

00:27:41.160 | that I will always get, drill on,

00:27:43.160 | you know how these laugh meetings can get intense, right,

00:27:47.000 | like when I would bring data

00:27:48.200 | and showing just very simple immunohistochemistry,

00:27:52.000 | meaning labeling, to see how the cells were interacting

00:27:54.800 | with the nervous system.

00:27:56.280 | As an eye will show some of the images,

00:28:00.880 | then the other scientists will say,

00:28:02.800 | well, you know, yeah, those are nice images,

00:28:05.240 | but remember that contact does not mean connection.

00:28:10.240 | And then I went thinking about that,

00:28:11.720 | like at the very beginning,

00:28:12.640 | I thought that it was silly semantics, you know,

00:28:15.080 | but I specifically remember that there was one time

00:28:18.640 | I was running and I was thinking like,

00:28:20.640 | how do you demonstrate connection between two cells?

00:28:23.600 | And then I thought that since we had the ability

00:28:25.400 | to identify these cells by fluorescence,

00:28:27.360 | we could isolate them based on their fluorescence.

00:28:31.240 | And what will happen if we put them

00:28:32.880 | in front of a sensory neuron

00:28:35.840 | and then just record them inside of a microscope, right,

00:28:38.880 | over time.

00:28:39.720 | And I thought maybe they will get close to each other

00:28:44.000 | and then we can go and do some more labeling

00:28:46.160 | and show that they are contacting or connecting.

00:28:49.720 | But much to our surprise,

00:28:50.960 | we actually saw that in real time,

00:28:53.120 | when you isolate them from the mouse

00:28:56.560 | and you put them in a dish,

00:28:57.520 | they both look like these round circles.

00:29:00.720 | But after a few hours,

00:29:01.920 | not only they get close to each other,

00:29:03.560 | but they recapitulate the circuitry in the dish.

00:29:06.920 | Literally they form like two brains in a dish, right?

00:29:09.600 | Like it's the gut and the brain in a dish.

00:29:12.160 | Yeah, and that was an eye opener.

00:29:16.400 | I still remember it was somewhere,

00:29:18.840 | I think it was like June 27, 2012,

00:29:21.280 | when I saw that experiment,

00:29:22.360 | because it opened my eyes to so many different things.

00:29:27.160 | One, it was that these cells are not static.

00:29:29.400 | Because since we have been seeing them for decades,

00:29:34.040 | just in slices or fixed tissue,

00:29:37.000 | and we have lost the notion

00:29:38.920 | that this thing is constantly moving, right?

00:29:40.920 | - The cells are actually moving.

00:29:41.760 | - The cells are actually moving.

00:29:43.440 | - So these cells line the gut,

00:29:44.800 | meaning they're along the walls of the gut.

00:29:47.120 | - Yeah. - The intestine.

00:29:48.040 | - Yeah, the intestine.

00:29:48.880 | - They reach a hand into the gut

00:29:51.800 | to sense whatever chemicals are there.

00:29:53.880 | - Yeah, they have little cilia, little hair, or microvilli,

00:29:57.160 | that is literally like little hair

00:29:59.000 | that is exposed to the lumen, you know?

00:30:01.240 | - So the lumen, folks, is the cavity,

00:30:04.080 | the empty cavity of the gut.

00:30:05.440 | Not empty, but you know, the internal part.

00:30:09.000 | And so they're sensing the chemicals there,

00:30:10.680 | and you're saying they can move, okay?

00:30:12.960 | And they're sending a process.

00:30:16.000 | By the way, folks,

00:30:16.840 | anytime you don't know whether or not

00:30:17.720 | something is a dendrite or an axon,

00:30:19.640 | just call it a process.

00:30:21.080 | You'll get it right.

00:30:22.680 | A process up to the brain.

00:30:25.320 | - Underneath that will connect to the nervous system.

00:30:27.960 | - I see, so through a series of stations.

00:30:30.960 | - Yeah. - Okay.

00:30:31.800 | Amazing.

00:30:34.080 | So what we're talking about here is Diego's discovery

00:30:38.000 | of a pathway from the gut to the brain

00:30:41.620 | that essentially allows sensing

00:30:43.240 | of what's happening in the gut to inform feelings,

00:30:47.120 | decisions. - That's correct.

00:30:48.280 | - Yeah, so that was the first experiment

00:30:50.720 | like showing in a dish, right?

00:30:52.920 | The next experiment was, well, does it happen in the mouse?

00:30:57.040 | And then through a series of,

00:30:58.960 | I have a friend, neuroscientist,

00:31:00.280 | that she calls these rabies gymnastics

00:31:02.560 | because you have to put in some genes and make things work.

00:31:05.880 | Then we demonstrated that these cells,

00:31:09.420 | that the virus will be capable

00:31:11.160 | of infecting these cells specifically.

00:31:13.580 | Instead of infecting the other epithelial cells,

00:31:16.160 | it will infect these neuropithelial cells

00:31:18.160 | because rabies likes neurons.

00:31:20.200 | And then it will jump from that cell into a nerve fiber.

00:31:24.980 | And these rabies can only jump one connection, right?

00:31:30.060 | And what was surprising is that the fluorescence

00:31:34.840 | from the rabies will show up in the brainstem

00:31:37.880 | and in the bodies of the cells

00:31:39.720 | that are in the notos ganglia,

00:31:41.240 | which is this cluster where the cell bodies

00:31:44.120 | of the neurons of the vagus nerve

00:31:46.920 | are located right underneath the neck.

00:31:49.200 | Meaning that there was just one stop

00:31:53.600 | between the surface of the intestine and the brainstem.

00:31:58.600 | The two cells were connecting that space, you know?

00:32:05.440 | So obviously the information,

00:32:07.720 | that was the anatomical basis for the information

00:32:11.200 | to travel very rapidly up into the brain.

00:32:15.440 | And rapidly in the subconscious, right?

00:32:17.320 | Like we're not necessarily aware of it.

00:32:19.920 | Although I've read that there are some instances

00:32:22.480 | in which people become more aware of it,

00:32:25.200 | either in a typical fashion or with meditation

00:32:30.200 | and other things that people can become aware.

00:32:34.560 | - Yes, people definitely can become more aware

00:32:36.800 | of their so-called interoception.

00:32:38.440 | What's going on at the level of their heartbeat frequency

00:32:41.400 | or their gut sensing if they spend time on it.

00:32:44.160 | Some people, as you mentioned,

00:32:45.680 | develop an almost pathologic sense of interoception

00:32:49.580 | such that they have trouble navigating normal life

00:32:51.880 | because they're so aware

00:32:53.080 | of what's going on inside their body.

00:32:54.720 | This is actually an interesting issue

00:32:55.960 | in the field of psychiatry.

00:32:57.640 | My colleagues in psychiatry at Stanford tell me

00:32:59.880 | that some people with a lot of anxiety, for instance,

00:33:03.160 | are so aware of their heartbeat

00:33:05.840 | that it becomes disruptive and distracting to them.

00:33:09.900 | So it's not always the case

00:33:11.640 | that it's better to become more aware

00:33:13.360 | of your internal processing.

00:33:14.800 | Sometimes it can be deleterious.

00:33:17.520 | Other times it can be good for us.

00:33:19.720 | Some people are very unaware

00:33:20.760 | of what's happening in their body

00:33:21.880 | and they need to develop more awareness of that.

00:33:24.340 | I feel like as long as we're talking about rabies,

00:33:26.280 | we should have a little bit of fun

00:33:27.560 | and explain to people something about rabies viruses

00:33:30.560 | because what we've been talking about

00:33:31.680 | is the use of viruses as experimental tools

00:33:36.680 | in order to take a virus,

00:33:39.620 | basically attach or put something in

00:33:43.200 | so that whatever cell is infected by it

00:33:44.800 | glows a certain color so you can see the cells

00:33:46.880 | and visualize the circuitry.

00:33:48.480 | But as long as we're talking about rabies,

00:33:49.800 | I feel like it's such a word that has such salience.

00:33:53.560 | The rabies virus, which exists in nature,

00:33:55.820 | is amazing because it's,

00:33:59.400 | I don't know if it has a consciousness,

00:34:01.760 | but it essentially propagates between animals

00:34:04.480 | by way of the animals that have it bite.

00:34:07.160 | They become more aggressive.

00:34:09.340 | They bite a target animal.

00:34:13.260 | The virus gets in, it's picked up by the nerve terminals

00:34:16.740 | and is carried back from one cell to the next

00:34:19.700 | across synaptic connections, right?

00:34:21.940 | Synapses, the little gaps between neurons.

00:34:24.440 | And what Dr. Diego Borges has been telling us

00:34:28.920 | is that scientists have engineered the rabies virus

00:34:32.180 | so that it only jumps one station and then stops.

00:34:34.920 | You can do this by modifying the coat protein.

00:34:36.700 | There's a bunch of fun virology that can be done to do that.

00:34:40.220 | But what I find amazing about rabies virus,

00:34:42.900 | and there's a great book, by the way, called "Rabid,"

00:34:45.140 | which is essentially a history of the study of rabies,

00:34:50.040 | is that once it travels from the site of the bite

00:34:53.980 | up to the brain, what does it do?

00:34:56.500 | It changes the brain to make the now infected animal

00:35:00.480 | or person more aggressive

00:35:02.100 | so that then they go bite somebody else.

00:35:05.060 | So, I mean, in some ways that the viruses

00:35:07.420 | have a sort of kind of unconscious genius to them, right?

00:35:10.260 | What's the best way to get from one animal to the next?

00:35:13.960 | Well, there are a number of different ways,

00:35:15.820 | but one way is to just make that animal more aggressive

00:35:18.140 | so it goes and bites things.

00:35:19.500 | - Yeah, make the animal work for you, right?

00:35:22.140 | - Make the animal work for you, right.

00:35:24.140 | It's almost exploitive, right?

00:35:26.300 | It exploits a certain circuitry in the nervous system.

00:35:28.820 | I'd like to take a brief break

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00:36:59.860 | - Okay, so you identified these, you said described,

00:37:04.140 | but I'll say discovered 'cause that's what happened.

00:37:07.260 | You discovered these cells, you label their connections,

00:37:11.060 | you see that there's just two stations between these cells,

00:37:14.900 | or one station really between these cells and the brain.

00:37:18.100 | And so now these cells can sense chemicals in the gut

00:37:22.340 | that are the consequence of the breakdown of food

00:37:24.740 | and send that information directly to the brain.

00:37:26.660 | What does the brain do with that information?

00:37:29.580 | - All right, so here comes the key experiment.

00:37:32.580 | And this was building obviously on the work

00:37:34.540 | of other scientists that had already described

00:37:36.900 | that the gut had some receptors for sugars,

00:37:40.820 | specifically for glucose, for other nutrients.

00:37:43.580 | Around this area in the early 2000s,

00:37:45.860 | when we were starting to be able to identify

00:37:48.740 | some of these cells,

00:37:50.260 | then it quickly became obvious that these cells,

00:37:55.260 | these enteroendocrine cells,

00:37:57.420 | throughout the lining of the stomach, intestine, colon,

00:38:02.140 | they had multiple receptors for multiple nutrients.

00:38:05.980 | Like we have the macronutrients, for instance,

00:38:08.180 | sugars, fats, proteins,

00:38:09.900 | but within them we have a repertoire of molecules,

00:38:14.580 | multiple lipids, multiple types of sugars,

00:38:17.660 | and so on and so forth.

00:38:18.980 | And these cells, depending on their location,

00:38:21.460 | they will express different type of receptors

00:38:24.740 | or a combination of those receptors.

00:38:26.980 | And I said that depending on the location,

00:38:28.700 | because when we're eating, let's say an apple,

00:38:31.180 | the apple is gonna be partially undigested

00:38:33.420 | by the time that it enters the intestine,

00:38:35.100 | but by the time that it gets to the colon,

00:38:37.020 | most of those nutrients have been absorbed

00:38:39.180 | and perhaps only fibers are surviving

00:38:41.100 | to feed off most of the microbes

00:38:43.260 | that live in the colon, right?

00:38:44.860 | So the gut has evolved to mirror

00:38:49.860 | and to become a Velcro to the molecules

00:38:53.700 | that will be in that specific space.

00:38:56.940 | So it will detect.

00:38:58.260 | So it will detect sugars more in the proximal intestine,

00:39:03.260 | but fibers or fermented by-products

00:39:06.420 | more in the distal intestine or in the colon,

00:39:08.740 | like short-chain fatty acids, butyrate, propionate,

00:39:11.860 | and so on and so forth, you know.

00:39:14.340 | - What other kinds of nutrients

00:39:15.660 | do these neuropod cells detect from food?

00:39:18.420 | So you mentioned sugars,

00:39:19.540 | you mentioned fermentation,

00:39:22.540 | presumably short and long-chain fatty acids.

00:39:26.980 | - Yes, the short answer is that,

00:39:29.100 | I think that in due time,

00:39:31.780 | we are gonna realize that they detect

00:39:33.780 | just about every single thing

00:39:35.060 | that we put on our mouths every day, you know,

00:39:37.780 | that they have some either,

00:39:39.020 | and a specific receptor that is dedicated to it,

00:39:41.500 | or a combination of receptors

00:39:43.900 | to be able to detect some of these compounds.

00:39:47.380 | And not only the chemical compounds,

00:39:49.220 | but also an area that I think

00:39:50.900 | that is gonna be fascinating in the future

00:39:52.620 | is the mechanical extension

00:39:54.340 | plus the adjustment in temperature

00:39:57.860 | as the chyme starts to flow

00:39:59.500 | from the mouth into the colon.

00:40:03.820 | Like for instance, I heard this from a bioengineer

00:40:07.180 | not long ago that was engineering

00:40:09.580 | artificial gut and stomach.

00:40:12.060 | And he shared with me a piece of information

00:40:15.740 | that I was not aware of,

00:40:16.860 | that the esophagus has to adjust

00:40:20.100 | the temperature of the food very rapidly within seconds

00:40:23.460 | into physiological temperature of the inside of the body.

00:40:27.740 | Like, so if we're having hot coffee,

00:40:29.920 | within a couple of seconds,

00:40:30.900 | it has to be at the physiological temperature of the body

00:40:33.220 | by the time that it gets into the stomach, right?

00:40:35.980 | And all of that happens in very rapidly.

00:40:38.940 | - Amazing. - In the esophagus, right?

00:40:40.220 | - So if I understand correctly,

00:40:41.660 | these neuropod cells have a variety of different receptors,

00:40:45.060 | depending on where they are located

00:40:47.180 | along the trajectory from the mouth to the rectum.

00:40:50.700 | - That's correct.

00:40:51.540 | - And some are sensing sugar,

00:40:53.660 | some are sensing temperature,

00:40:55.380 | some are sensing pH, so relative acidity.

00:41:00.380 | Some are sensing amino acids, presumably.

00:41:04.700 | I mean, I've heard it said,

00:41:05.980 | and I believe there's a researcher down in Australia

00:41:09.380 | who has been very bullish on the theory

00:41:11.460 | that we are not exclusively,

00:41:14.740 | but we are predominantly amino acid foraging machines,

00:41:18.640 | because we need amino acids

00:41:20.420 | for all sorts of important biological processes.

00:41:23.020 | And these cells are essentially evaluating how much sugar,

00:41:27.940 | how much leucine, how much short-chain fatty acid,

00:41:32.740 | how much essential fatty acids of different kinds,

00:41:35.900 | and then making changes to the gut itself,

00:41:38.300 | but then presumably signaling that information

00:41:40.620 | elsewhere in the body.

00:41:42.180 | So here I'm gonna give you something

00:41:45.260 | that will get your gut churning, so to speak.

00:41:48.820 | So these cells have to make sense

00:41:52.380 | not only of the molecule that had been adjusted,

00:41:54.900 | meaning the chemistry of the molecule.

00:41:56.500 | Let's say it's glucose, it has to make sense

00:41:58.300 | a little bit of the taste.

00:41:59.640 | Is it sweet, right, is it bitter?

00:42:02.460 | Then it has to take into account

00:42:04.500 | how much of the molecule is absorbed inside of the cell.

00:42:09.020 | So that's the second layer of integration.

00:42:10.880 | Then once the cell has eaten that molecule, so to speak,

00:42:15.460 | then that molecule will be digested inside of the cell

00:42:19.260 | to release ATP or some other compound.

00:42:23.060 | ATP is for energy, for instance.

00:42:25.940 | That has also have to be taken into account.

00:42:29.020 | For instance, in glucose.

00:42:31.380 | Glucose activates the TAS1R3,

00:42:33.060 | which is a sweet taste receptor.

00:42:34.900 | Then the glucose is absorbed

00:42:36.100 | by some of the sodium glucose transporters,

00:42:37.980 | which are active transporters.

00:42:40.540 | And these transporters depolarize the cell.

00:42:43.500 | And then once glucose gets inside of the cell,

00:42:45.780 | glucose enters the TCA cycle,

00:42:47.500 | is catabolized, and then produces ATP.

00:42:49.500 | And the ATP further activates

00:42:52.180 | another voltage-gated channel,

00:42:56.220 | further depolarizing the cell.

00:42:59.460 | And then the cell releases, in turn, a transmitter.

00:43:03.820 | For instance, glutamate that very rapidly tells

00:43:06.140 | the vagus nerve within milliseconds, you know, I got sugar.

00:43:09.620 | And it tells it in two phases

00:43:11.660 | because that glutamate will activate

00:43:13.660 | two different type of receptors,

00:43:15.340 | ionotropic, which are very fast,

00:43:17.740 | and metabotropic, which are a little bit more delayed.

00:43:21.420 | But then the metabolism of that glucose

00:43:25.260 | that produces the ATP and further depolarizes the cell,

00:43:28.820 | we believe that it will cause the release

00:43:31.420 | of the hormone, of the neuropeptide.

00:43:33.420 | So then the neuropeptide comes on top of that

00:43:36.260 | and gives you that full experience

00:43:38.140 | of what it means to consume sugar, right?

00:43:41.980 | So that happens at the level of one cell

00:43:45.700 | and at the level of one molecule.

00:43:48.060 | So imagine, like, all of the computation

00:43:49.980 | that the gut has to be making

00:43:51.700 | for each one of the molecules

00:43:52.940 | throughout the digestive tract.

00:43:54.500 | - So if I stand back from this picture,

00:43:57.820 | what I get is there are very interesting cell types

00:44:02.740 | that line our gut that are evaluating

00:44:05.380 | all of the, not just macronutrients,

00:44:08.140 | proteins, fats, and carbohydrates,

00:44:09.580 | but micronutrients within the food we eat,

00:44:12.220 | as well as some of the other qualitative features,

00:44:15.900 | temperature, for instance,

00:44:17.140 | maybe even quality of the amino acids

00:44:19.980 | or the sugars, you know,

00:44:22.060 | simple versus complex sugars, et cetera.

00:44:24.380 | If we could just further zoom out for a moment

00:44:28.620 | and take a human perspective on this

00:44:30.540 | at the level of experience.

00:44:33.500 | I once heard you tell a story

00:44:35.220 | about someone you knew

00:44:38.100 | who changed their gut radically

00:44:42.620 | and that changed their entire perceptual experience

00:44:46.340 | of food, including certain cravings.

00:44:48.860 | Would you mind sharing that story?

00:44:50.500 | - Yes, thank you for bringing that story, Andrew.

00:44:54.100 | That story is very personal to me.

00:44:56.740 | I often say when I get on stage

00:44:58.460 | that we are constantly influenced

00:45:00.060 | by two things in life,

00:45:01.100 | the food that we eat and the people that we meet,

00:45:03.060 | you know, like now we have known each other,

00:45:06.100 | but now we meet in person

00:45:07.140 | and we are knowing other people, right?

00:45:10.060 | And I remember that when I was starting my PhD

00:45:13.860 | in nutrition at North Carolina State University,

00:45:16.100 | I was, so I didn't grow up in the United States,

00:45:18.900 | I grew up in Ecuador,

00:45:21.020 | and I was invited to my first Thanksgiving celebration.

00:45:26.020 | So I sat at dinner and, you know,

00:45:28.900 | as we began chatting with the people

00:45:31.300 | that were next to each other,

00:45:33.340 | all of a sudden I was enthralled in this conversation

00:45:37.500 | of a woman telling me this story

00:45:39.220 | about her experience with gastric bypass surgery

00:45:43.300 | for treating obesity.

00:45:45.780 | So gastric bypass surgery was begun

00:45:48.340 | to be developed by surgeons in the '60s.

00:45:53.180 | And by the '90s, it had become a mainstream type of surgery

00:45:57.460 | for the treatment of chronic obesity.

00:46:01.020 | So she told me that there were primarily

00:46:02.860 | three things that happened.

00:46:04.020 | She said, well, within six months of the surgery,

00:46:07.700 | I had lost about 40% of body weight.

00:46:10.500 | You know, she said, like, I was about 300 pounds,

00:46:13.220 | you do the math, you know?

00:46:14.540 | So it was a--

00:46:16.300 | - Significant amount.

00:46:17.140 | - Yeah, significant amount.

00:46:19.020 | She said, within one week of the surgery,

00:46:22.220 | my diabetes was gone, she said.

00:46:23.860 | I did not need more insulin shots.

00:46:26.580 | So I had the same reaction that you're having.

00:46:29.580 | I was like, that, you know,

00:46:31.220 | I don't know much about diabetes,

00:46:32.980 | but I know that it's a major health burden, right?

00:46:36.580 | But the thing that really caught my eye was when she said,

00:46:41.260 | but since you're studying nutrition,

00:46:43.300 | I want you to answer this to me.

00:46:45.140 | She said, why is it that before the surgery,

00:46:47.660 | I could not even look at sunny-side-up eggs, she said.

00:46:50.420 | Just looking at the yolk would make me queasy, you know?

00:46:54.860 | But after the surgery, not only I can eat sunny-side-up eggs,

00:46:58.980 | I actually have a craving for the yolk, she said.

00:47:00.980 | Every time we go on Saturday to a restaurant for breakfast,

00:47:04.580 | I will take the toast

00:47:05.420 | and I will actually clean the plate of the yolk.

00:47:08.460 | So how is it that rewiring the gut

00:47:11.700 | altered my perception of flavor,

00:47:14.580 | altered my cravings and my mind to get the yolk, she said.

00:47:18.780 | - And even inverted her sense

00:47:20.340 | of what was aversive versus appetitive.

00:47:23.740 | And I guess for those of us that don't know, meaning me,

00:47:27.980 | I understand the gastric bypass surgery

00:47:29.700 | involves the removal of a portion of the gut.

00:47:33.780 | How much gut tissue do they actually take?

00:47:35.860 | Is it centimeters, inches?

00:47:39.260 | I mean, the gut's a long distance.

00:47:41.140 | So what do they do for gastric bypass?

00:47:43.460 | - In simple terms, the classic surgery

00:47:48.020 | is called Roux-en-Y gastric bypass surgery,

00:47:52.420 | which involves a reduction of the stomach

00:47:56.260 | and shortcutting the connection of the stomach

00:48:01.060 | to the intestine.

00:48:01.900 | So you will cut one third, which will be the duodenum,

00:48:06.940 | one third of that will be cut

00:48:09.980 | and then that portion will be reconnected to the stomach,

00:48:13.220 | meaning that you're short-circuiting the gut.

00:48:16.420 | And the whole idea was, at the very beginning,

00:48:18.700 | was like, well, if we reduce the surface

00:48:21.260 | that is exposed to food,

00:48:23.260 | then we can reduce body weight

00:48:25.660 | by the simply reduction of surface

00:48:29.220 | that is exposed to the food that is absorbed, right?

00:48:32.660 | And what it became very clear is that

00:48:35.060 | well before the body weight changes got taken place,

00:48:39.740 | there was already like some dramatic changes in physiology,

00:48:43.060 | like the hormones, the neuropeptides

00:48:45.380 | that were released from the intestine

00:48:47.740 | in response to nutrients, you know,

00:48:49.860 | it will change very rapidly.

00:48:52.060 | Then, as I mentioned, the food choices will change,

00:48:54.580 | diabetes will be resolved.

00:48:56.340 | So then it became obvious that it was not necessarily

00:49:00.540 | just the reduction in the surface of the gut.

00:49:05.300 | So that's one of the main surgeries.

00:49:07.180 | The other one, as I understand,

00:49:09.340 | is vertical sleeve gastrectomy.

00:49:12.900 | And this vertical sleeve gastrectomy

00:49:14.860 | is simply a reduction in the size of the stomach.

00:49:19.660 | So now the stomach is very tiny

00:49:21.460 | and the idea is that it will accumulate less,

00:49:24.060 | it could hold less food,

00:49:25.380 | and then the food will go very rapidly into the intestine.

00:49:28.340 | And what is becoming very obvious

00:49:30.540 | is that there is a rapid change

00:49:32.820 | in the sensory function of the gastrointestinal tract.

00:49:36.060 | So the gut seems to rapidly shift,

00:49:39.580 | perhaps become more, so to speak in general terms,

00:49:42.700 | more sensitive to the presence of nutrients, right?

00:49:45.900 | - Interesting.

00:49:46.740 | So this woman that you met at Thanksgiving

00:49:48.820 | had gastric bypass surgery.

00:49:51.480 | And presumably, I think it's fair to assume,

00:49:55.460 | a good number of these neuropod cells

00:49:57.260 | that sense different nutrients were removed.

00:50:00.620 | And as a consequence,

00:50:02.180 | she completely shifted her craving of a particular food.

00:50:05.980 | And is there any sense whether or not, no pun intended,

00:50:10.300 | the lack of sensing of what was in sunny side egg yolks

00:50:17.180 | was somehow related to a shift in appetite or something else

00:50:20.980 | or is it merely a qualitative,

00:50:25.020 | albeit a dramatic qualitative shift in what she craved?

00:50:28.220 | - So two contextual pieces of information.

00:50:33.380 | So I remember leaving that dinner and I was like,

00:50:35.780 | whoa, this is major, you know?

00:50:37.900 | Like I'm sure that people have written about this

00:50:40.540 | or done research.

00:50:41.500 | And I realized that it was very little was known.

00:50:45.180 | Even gastroenterologists knew very little about this.

00:50:49.140 | The first clinical report that the alteration in food choices

00:50:54.140 | was common in these patients came out, I believe, in 2011.

00:50:58.540 | And then later on, scientists replicated that

00:51:02.780 | even in rats or in mice.

00:51:05.020 | We have done it in the laboratory

00:51:06.380 | and consistently they change their food preferences,

00:51:10.180 | their food choices.

00:51:13.820 | So in recent years we have been studying that system.

00:51:18.820 | And I will tell you that in 2022,

00:51:25.500 | this is another important contextual piece

00:51:27.540 | that we have not gotten to it.

00:51:30.260 | So after we found and we described that the cells

00:51:35.260 | were connecting to the nervous system

00:51:37.620 | and that they were sending information

00:51:39.260 | up to the brain very rapidly, the challenge was,

00:51:42.620 | well, if this is a sense, what behavior is affecting, right?

00:51:46.580 | Like how is it that is affecting

00:51:47.940 | the responses of the organism?

00:51:50.340 | And that took a little bit of a technical hurdle.

00:51:53.740 | And here is where optogenetics comes in.

00:51:56.780 | - Yeah, please explain for people what optogenetics is,

00:52:00.140 | at least at a top contour level.

00:52:02.060 | - Yeah, so optogenetics in 2005,

00:52:05.380 | Professor Karl Deisseroth, Ed Boyden

00:52:10.380 | and other scientists had been able to make this dream

00:52:15.380 | of an experiment, which was isolate the genes

00:52:19.580 | that encode for these opsins that are sensitive

00:52:22.020 | to specific wavelengths of light

00:52:24.380 | and put them into neurons.

00:52:26.180 | And now by turning that light,

00:52:28.660 | they could make the neuron activate.

00:52:31.060 | And then ultimately then later on,

00:52:32.980 | they went on to describe that that could be used

00:52:34.860 | to control specific cells that are regulating behavior.

00:52:38.580 | And then by that define what cells are orchestrating

00:52:41.860 | certain type of behaviors like movement,

00:52:44.340 | food intake, thirst, anxiety, so on and so forth.

00:52:48.820 | So in 2014, we began trying to adapt

00:52:52.860 | that technology to the gut.

00:52:54.820 | Very quickly, we realized that the way that was,

00:52:59.700 | that light was brought into the brain

00:53:01.660 | was through a fiber optic cable that was rigid.

00:53:05.980 | And in the brain, it helps that it's actually rigid.

00:53:10.980 | But in the gut, it doesn't help

00:53:12.740 | because the gut is constantly moving and so on and so forth.

00:53:15.060 | So it's not compatible for running those experiments.

00:53:18.220 | And here's where I usually say like,

00:53:20.580 | we really don't know what is going on

00:53:21.980 | because some forces like move around us.

00:53:25.300 | And in 2017, Professor Polina Nikeva from MIT

00:53:29.620 | came to give a talk at Duke and she reached out to me.

00:53:34.140 | And literally she came and as we were chatting,

00:53:36.180 | she said like, "Diego, I see that you're working

00:53:38.820 | "in this interface of the gut and the brain.

00:53:41.180 | "And I have this fiber optic that is flexible.

00:53:44.940 | "Will you have any use for it?"

00:53:47.020 | So with that fiber optic, that made a big difference

00:53:49.980 | to study interrogate the function of these cells to behavior.

00:53:53.460 | So when we were able to put those opsins,

00:53:57.500 | the light sensitive proteins inside of these neuropods,

00:54:01.500 | now when we turn the light on

00:54:03.860 | to shut off these cells very rapidly,

00:54:06.980 | we found something very interesting.

00:54:12.420 | So normally animals, when you give them the choice

00:54:14.820 | between a suriner, which is devoid of caloric value.

00:54:18.900 | - So like a aspartame or splenda or stevia or something.

00:54:23.660 | - Yeah. - Yep.

00:54:24.500 | - And you give them sugar, table sugar,

00:54:29.540 | the animal invariably will go to sugar.

00:54:33.540 | - They prefer sugar.

00:54:34.380 | - They prefer sugar.

00:54:35.420 | If they have never seen sugar,

00:54:38.260 | it will take them a little bit more time,

00:54:39.980 | but regularly by the second day is within 90 seconds

00:54:44.980 | that they detect what is sugar.

00:54:48.140 | - So they're drinking out of one tube,

00:54:50.340 | they get some water with stevia,

00:54:51.700 | they drink out of another tube, water with sugar,

00:54:53.860 | and they invariably prefer the water with sugar.

00:54:57.420 | - That's correct.

00:54:58.700 | And people have described this phenomenon for a while.

00:55:03.700 | And in fact, in 2007, there was an elegant experiment

00:55:07.180 | done by Professor Ivan de Araujo at Duke University,

00:55:11.580 | in which the sweet taste receptors were,

00:55:15.540 | or the taste receptors were genetically erased.

00:55:20.540 | And the animals were not capable of distinguishing

00:55:24.420 | the sugar, the sweetener from the water,

00:55:27.180 | but they could still distinguish sugar from water,

00:55:31.460 | meaning that there was something else

00:55:33.820 | that was detecting that sugar.

00:55:35.500 | - So just to make sure people are on board,

00:55:38.340 | an experiment where sensing of sweet taste

00:55:41.220 | at the level of the mouth is eliminated

00:55:44.140 | does not disrupt the preference for sugar water.

00:55:48.900 | - Correct.

00:55:49.740 | - Which means that there's something going on

00:55:52.020 | below the depth of consciousness

00:55:55.280 | that causes mammals, presumably us included,

00:55:59.780 | to prefer things that have sugar.

00:56:01.700 | - Yes.

00:56:03.460 | And then Professor Tony Sclafani,

00:56:06.580 | he had been studying these behaviors,

00:56:08.740 | and he went in so far to suggest

00:56:10.420 | that perhaps the sodium glucose transporters

00:56:13.580 | are some of the ones that are detecting the sugar

00:56:16.180 | as it enters the intestine,

00:56:17.460 | and that's what is causing the behavior.

00:56:19.460 | So we began working on the system,

00:56:23.140 | and we wonder, could these cells

00:56:26.160 | be the ones that are guiding that behavior?

00:56:29.540 | And around the time that we published this work,

00:56:32.540 | Professor Charles Zucker at Columbia

00:56:36.100 | also further advanced that area

00:56:38.840 | by building on the previous work

00:56:41.540 | and demonstrated that there were population of neurons

00:56:45.660 | in the brainstem that were integrating this information

00:56:48.700 | from the gut, and by that the gut and the brain

00:56:53.520 | were guiding this behavior.

00:56:55.740 | - And it is true that from the earliest of ages

00:56:58.420 | we crave sugar, or at least if we are exposed

00:57:03.260 | to the taste of sugar,

00:57:04.540 | it tends to drive seeking of more sugar.

00:57:08.180 | I mean, you can see that in babies even.

00:57:10.360 | - Correct.

00:57:11.240 | And as I usually say, I call it instinctively

00:57:14.380 | because our mother doesn't have to teach us,

00:57:17.180 | hey, Diego, that is glucose, you know.

00:57:19.920 | It may present us in some ways,

00:57:22.820 | but at the end of the day I have to go and get my glucose,

00:57:25.660 | get my amino acids right.

00:57:27.340 | Because eating is very simple.

00:57:29.340 | We're just trying to solve this issue

00:57:31.020 | of getting our carbons, getting our nitrogen,

00:57:33.180 | getting our phosphorous, our potassium,

00:57:34.920 | our sodium, and our chloride

00:57:37.780 | in so many different ways, shapes, or forms, right?

00:57:40.560 | So I went back to the experiment, the key experiment.

00:57:43.920 | So when we were able to put these options

00:57:46.720 | and bring the light and shut off these cells very rapidly,

00:57:50.780 | when we had presented the animal

00:57:52.340 | with a choice of sweetener over sugar,

00:57:55.560 | then all of a sudden the animal became blind

00:57:59.720 | to the solutions.

00:58:00.620 | It couldn't discern between this tibia,

00:58:04.960 | so to speak, or the sweetener, from the actual sugar.

00:58:08.340 | - And the entire manipulation,

00:58:09.720 | the experimental manipulation that is,

00:58:12.060 | is occurring at the level of the gut.

00:58:14.580 | - The intestine, that's right.

00:58:15.660 | Right after the stomach.

00:58:16.660 | It's like just a small portion of the intestine.

00:58:19.740 | - So if we make an attempt to transfer this

00:58:23.500 | to the human real world experience,

00:58:25.760 | if I have some ice cream, it tastes sweet.

00:58:32.260 | I like it, and now I'm thinking about it,

00:58:35.900 | and I'm craving it just a little bit.

00:58:37.900 | I don't have a huge craving for sweets,

00:58:39.760 | but I do like some of them.

00:58:43.120 | - So eating ice cream, it tastes sweet.

00:58:45.960 | The tendency is to crave more.

00:58:47.920 | - That's correct.

00:58:48.740 | - Right, and you have to eat a lot of ice cream

00:58:49.880 | before you're truly full.

00:58:51.520 | - Yeah.

00:58:53.120 | - And most people self-regulate

00:58:54.560 | or their parents regulate for them

00:58:56.760 | by limiting the number of scoops or something.

00:58:59.060 | And that sweet taste is part of the motivator,

00:59:04.880 | but what you're saying is that

00:59:07.500 | as the ice cream enters the gut,

00:59:09.840 | there are neuropod cells there

00:59:11.800 | that are also sensing the sugar

00:59:14.200 | and signaling to the brain,

00:59:15.780 | and the brain is responding to pursue more

00:59:20.500 | of that sweet containing substance.

00:59:23.640 | - That's correct.

00:59:24.480 | - And it's happening below our awareness.

00:59:26.600 | It is independent from the sweet taste of the ice cream.

00:59:30.060 | - Correct.

00:59:31.120 | - The conscious sweet taste.

00:59:32.280 | - The conscious sweet taste.

00:59:34.120 | Whichever you think about it,

00:59:35.940 | it's not fully conscious, right?

00:59:39.600 | What we detect of the world

00:59:41.680 | is just a very tiny little portion, right?

00:59:44.040 | Even sight.

00:59:45.600 | We think we are looking for light,

00:59:47.120 | but I don't know what is happening behind my back.

00:59:49.680 | I trust that everything is going okay, right?

00:59:52.360 | So when we shut off these cells,

00:59:57.260 | the animal, as I usually say,

01:00:00.600 | became blind to the sugars

01:00:03.840 | because it's kind of akin to having turned off

01:00:08.320 | the cells that are able to detect light,

01:00:11.560 | the wavelength of light,

01:00:13.360 | for us to be able to discern color, right?

01:00:17.240 | And it's not that the animal is losing its memory

01:00:19.600 | because then if you remove the light

01:00:21.520 | and now the cells are functional again,

01:00:23.340 | then the animal, again, is able to distinguish

01:00:26.360 | one solution over the other.

01:00:28.080 | And then we did a couple more experiments in there,

01:00:32.280 | and what happens if we do the reverse,

01:00:35.560 | if we turn on the cells now?

01:00:38.120 | And the fascinating thing

01:00:39.400 | is that when we turn on the cells,

01:00:40.900 | now the mouse will eat the sweetener

01:00:44.760 | as if it will be sugar.

01:00:46.600 | - Interesting.

01:00:47.440 | So the activation of these cells

01:00:48.880 | makes them crave non-caloric sweetener

01:00:54.040 | or low-calorie sweetener as if it were sugar.

01:00:56.940 | But is it blinding them to the difference

01:00:59.880 | between sugar and low-calorie sweetener?

01:01:04.240 | - So here's another piece of information.

01:01:06.320 | If we will offer them water

01:01:08.080 | and we will turn on the cells,

01:01:10.360 | the animal will drink the water

01:01:12.080 | as if it will be sugar, like it will be appetizing.

01:01:15.160 | - Even though it's just plain water.

01:01:16.440 | - Yes, and what is becoming very obvious

01:01:18.840 | is that the gut has this sense,

01:01:23.840 | at the most basic level,

01:01:26.440 | what the senses are doing

01:01:28.600 | is calculating a couple of things.

01:01:31.480 | One is the salience of the stimulus,

01:01:36.480 | is like how intense is the stimulus,

01:01:39.480 | and the other one is the valence of the stimulus.

01:01:42.600 | Is it pleasurable or painful,

01:01:45.840 | so to speak, in broad terms?

01:01:48.080 | And I say this because on the pain side,

01:01:51.100 | Professor David Julius, Professor Holly Ingram,

01:01:57.360 | Jim Byra at UCSF, they have done some beautiful work

01:02:01.240 | demonstrating that there are these serotonin-releasing cells

01:02:05.560 | specifically in the colon, they have focus in the colon,

01:02:08.480 | that they couple to nerve fibers of the spinal cord,

01:02:13.480 | and when they are activated,

01:02:15.460 | now all of a sudden they drive what we call

01:02:18.560 | in the clinical realm visceral hypersensitivity.

01:02:22.940 | So they are responsible for triggering

01:02:26.000 | the hypersensitivity of the nerve fibers,

01:02:28.100 | the colonic nerve fibers,

01:02:30.200 | because they detect noxious stimuli,

01:02:33.800 | and then ultimately they gate that noxious stimuli

01:02:36.960 | and pass it on to the nerve fiber in broad terms

01:02:41.960 | as a painful stimulus.

01:02:43.960 | - So is this Irritable Bowel Syndrome?

01:02:47.040 | - It is, we could call it as the biological basis

01:02:50.320 | of what could degenerate into Irritable Bowel Syndrome

01:02:53.800 | and so on and so forth, or this chronical GI,

01:02:59.000 | they call them disorders of gut-brain interactions

01:03:03.000 | in the clinic.

01:03:04.200 | - I'd like to take a brief break

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01:04:04.000 | - As a neuroscientist, I was trained to think

01:04:05.720 | about the neural retina, the light-sensing tissue

01:04:08.400 | at the back of the eye, the cochlea,

01:04:11.220 | the essentially mechanosensory cells in the inner ear

01:04:16.220 | that respond to sound waves, not directly,

01:04:20.360 | but through a number of different transducers

01:04:23.040 | and this kind of thing, and then, of course,

01:04:25.160 | we are all familiar with the skin

01:04:26.800 | and that it responds to pressure, light touch,

01:04:28.480 | tickle, itch, et cetera.

01:04:30.360 | What I'm understanding, based on what you're telling me,

01:04:33.800 | is that all along the pathway from our mouth to our rectum,

01:04:37.760 | we have sensory cells that are evaluating

01:04:40.640 | the chemical constituents of the foods that we eat,

01:04:43.560 | emitting broad, kind of maybe even crude,

01:04:48.560 | slow signals in the form of hormones

01:04:50.540 | to change our appetite, our feelings of well-being,

01:04:53.920 | maybe our feelings of not well-being,

01:04:56.340 | but also sending direct signals to the brain

01:05:01.100 | to drive certain types of thinking, emotions, and behavior.

01:05:06.100 | What sorts of thoughts, emotions, and behaviors

01:05:10.220 | are foods known to evoke through this pathway from the gut?

01:05:15.140 | Because the story about your friend

01:05:18.140 | that had the gastric bypass

01:05:19.520 | and then changed the relationship completely

01:05:21.720 | to the craving of or the aversion to Sunnyside eggs

01:05:26.720 | indicates that it's a pretty crude,

01:05:29.220 | as I'm describing a system to begin with,

01:05:31.020 | but it ultimately converges

01:05:32.860 | on pretty fine-scale decision-making.

01:05:34.780 | You order this and you avoid that.

01:05:37.780 | You really like this and you really are almost nauseous

01:05:41.060 | at the thought of something else.

01:05:42.260 | That's pretty high-level decisions.

01:05:43.740 | It might not seem like it to most,

01:05:45.540 | but it's impacting significant behavior

01:05:50.240 | or impacting behavior at a significant level.

01:05:53.260 | - That's correct.

01:05:54.140 | And when I think about that specific example

01:05:59.200 | is that after there has been

01:06:03.120 | this rewiring of the intestine,

01:06:07.160 | then now the intestine is very sensitive,

01:06:10.940 | so to speak, to the stimuli.

01:06:12.840 | And when those lipids from the yolk

01:06:14.840 | start to enter the intestine,

01:06:17.080 | if that sensitivity has changed,

01:06:18.880 | meaning it could have changed

01:06:20.120 | in how fast it reacts to the stimulus

01:06:23.580 | or how fast it communicates to the stimulus

01:06:26.580 | and how sensitive it is to the saliency

01:06:31.080 | or the strength of the stimulus,

01:06:34.000 | it could communicate that, ooh,

01:06:35.920 | what it used to be repulsive

01:06:38.240 | with a tiny little bit amount,

01:06:40.040 | now it is actually pleasurable

01:06:42.320 | with a tiny little bit of amount.

01:06:45.080 | And here's a clear example.

01:06:46.840 | So it has been very well,

01:06:48.360 | I will say that it has been documented in the clinic

01:06:53.240 | that patients that undergo gastric bypass surgery,

01:06:56.520 | they're actually more prone.

01:06:57.880 | I think that it goes from like two to seven-fold

01:07:02.880 | the likelihood that they will develop alcoholism.

01:07:08.240 | - Really?

01:07:09.120 | - Yes, because now the way that they describe it is like,

01:07:14.120 | well, either before I didn't like wine,

01:07:18.440 | and then now after a few months of the surgery,

01:07:22.600 | I'll have one glass of wine,

01:07:24.160 | and then all of a sudden I found myself

01:07:25.760 | going to two, three, four,

01:07:27.800 | and then they will become either more sensitive.

01:07:31.120 | It's still not known the entire biology,

01:07:33.080 | but they will become either not only more sensitive,

01:07:35.440 | but more attracted to that type of stimulus.

01:07:38.920 | - I can't help but ask about ozempic, Munjaro,

01:07:42.720 | and GLP-1, glucagon-like peptide-1 analogs,

01:07:47.720 | which are really kind of all the rage right now,

01:07:52.400 | at least for discussion,

01:07:53.800 | but many, many, many millions of people

01:07:56.000 | are now taking this for treatment of diabetes

01:07:58.380 | and for weight loss.

01:08:00.080 | My understanding is that GLP-1

01:08:03.280 | acts at the level of the brain, the hypothalamus,

01:08:05.320 | to reduce hunger, but also at the level of the gut

01:08:07.980 | to give the sensation of more gastric distension.

01:08:11.820 | Is there any knowledge of whether or not

01:08:14.840 | GLP-1 interacts with the neuropod cells

01:08:17.280 | and this pathway that you're describing,

01:08:18.880 | given what these neuropod cells do for craving or aversion?

01:08:22.880 | - Yes, that's a complimentary question,

01:08:26.960 | and in fact, when I got into studying in this field

01:08:31.040 | 15 years ago, the study among scientists in this area,

01:08:36.520 | glucagon-like peptide was already very popular

01:08:40.100 | in the study.

01:08:40.940 | In fact, in this area, people were very focused

01:08:43.980 | on the study of this peptide,

01:08:46.180 | and they were very focused on the study of this peptide

01:08:48.620 | because it was one of the most potent stimulators

01:08:52.220 | of insulin release in the pancreas.

01:08:55.020 | After gastric bypass surgery,

01:08:58.260 | it will actually increase its amount in circulating levels,

01:09:03.740 | and there were already some studies suggesting

01:09:07.480 | that the effect of this glucagon-like peptide,

01:09:12.480 | it was actually not through the circulation,

01:09:15.800 | but more in a localized action onto nerve fibers,

01:09:20.800 | especially of the vagus nerve.

01:09:22.480 | So there was already some ongoing discussion about this,

01:09:27.480 | and certainly some of these enteroendocrine cells,

01:09:31.440 | these neuroendocrine cells, particularly,

01:09:34.860 | at least in animals, I think it's more distal

01:09:37.980 | and in the digestive tract,

01:09:40.940 | that they do release this glucagon-like peptide,

01:09:44.060 | one in response to primarily all of the macronutrients,

01:09:50.060 | but primarily sugar.

01:09:52.900 | And then these glucagon-like peptide one

01:09:58.140 | will act on specific receptors of the nerve terminals,

01:10:01.300 | and then will trigger some of the behaviors.

01:10:02.960 | It's also thought that it acts at the level of the brainstem.

01:10:07.760 | And what it will potentiate is the reduction of appetite.

01:10:12.260 | So I say that this is a complementary question

01:10:16.520 | because what is happening in the first few milliseconds

01:10:18.760 | is the actual choice and the actual feeling

01:10:21.600 | of how you feel about food.

01:10:23.800 | And what is happening in the minutes to hours later

01:10:26.560 | is the amount, how much you can eat, right?

01:10:30.040 | And when you should stop, because after four hours,

01:10:33.220 | you're gonna come back and feel again

01:10:35.660 | the tickling of the gut because the gut starts to churn again

01:10:39.820 | and it starts to call for food.

01:10:41.180 | Remember, it has to feed two giant organisms,

01:10:44.660 | the host itself, but also the microbes that are inside,

01:10:47.460 | right, so it has to keep, so to speak,

01:10:52.460 | that hunger going every four hours or so, right?

01:10:56.800 | So that's why the hormones are more acting

01:10:58.940 | on the cyclical, circadian way,

01:11:03.220 | but the transmitters are acting

01:11:06.220 | in this very fast, responsive way of the precise stimuli

01:11:11.220 | in specific regions of the gastrointestinal tract.

01:11:14.500 | - So these neuroendocrine cells are releasing GLP-1

01:11:19.700 | or responding to GLP-1?

01:11:21.340 | - They are releasing GLP-1.

01:11:23.380 | - They're releasing GLP-1 to shut down,

01:11:26.560 | transiently shut down hunger.

01:11:28.780 | And probably there is some interaction

01:11:30.480 | between these cells that they are having,

01:11:33.020 | you know, the technical term is autocrine,

01:11:35.460 | or they are having like paracrine between the cells,

01:11:38.220 | you know, neuromodulation.

01:11:39.420 | But primarily, let's say they respond to the stimulus

01:11:43.060 | and release GLP-1 onto the nerve fiber.

01:11:45.520 | - I have a theory for which I have no direct data,

01:11:49.180 | but I'd like your thoughts on,

01:11:51.060 | having spoken to a lot of people that work on nutrition,

01:11:53.340 | but also gut-brain access today

01:11:56.620 | and microbiome in previous episodes,

01:11:59.980 | that one of the key things that a human learns,

01:12:04.500 | somewhat unconsciously, but also consciously,

01:12:08.900 | is the relationship between a given food,

01:12:12.340 | which macronutrients it contains,

01:12:15.940 | the ratios of, you know, carbohydrate, protein, and fat,

01:12:19.900 | the taste of that food,

01:12:21.440 | the amount of that food translated into calories,

01:12:26.420 | but also physical volume,

01:12:28.100 | and then the micronutrients.

01:12:30.420 | Why do I say this?

01:12:31.260 | Well, there are a growing number of studies showing

01:12:33.540 | that the ingestion of highly processed food

01:12:35.740 | leads to the intake of excess calories,

01:12:38.420 | or more calories than if one consumes foods

01:12:41.100 | in their more natural form.

01:12:43.060 | Single ingredient foods or two ingredient foods

01:12:45.280 | are very different than a food

01:12:47.140 | that has a bunch of different things in it.

01:12:49.260 | And it seems to me that if we were to look back

01:12:51.980 | into our evolution,

01:12:53.580 | sure, people were making stews and soups and things

01:12:56.200 | for a long time.

01:12:57.780 | Presumably the sandwich came about

01:12:59.500 | through either desire for convenience or taste or both,

01:13:03.460 | you know, putting meats, protein,

01:13:05.060 | in between two pieces of bread, something of that sort.

01:13:07.820 | My definition of a sandwich.

01:13:10.540 | Maybe some vegetables in there as well, some cheese,

01:13:13.840 | but that what this whole pathway along the gut

01:13:17.860 | is trying to do, it seems,

01:13:19.620 | is to deconstruct what's coming in, what's here,

01:13:24.940 | and shaping choices, as you mentioned, about food choice,

01:13:28.880 | including the amount of food to further consume,

01:13:31.520 | and whether or not to return to that food or to avoid it.

01:13:34.560 | And at the extremes, it seems pretty straightforward.

01:13:38.200 | And this is a very classically described case, right?

01:13:40.560 | You go and you have the Kung Pao shrimp,

01:13:44.280 | or you have the lentil soup at a given place,

01:13:46.800 | and a few hours later, you don't feel right,

01:13:48.960 | start some sweating, some gastric distress,

01:13:51.440 | and you develop a pretty broad aversion to that food,

01:13:54.700 | or maybe even the entire meal, maybe the restaurant,

01:13:57.280 | maybe even that entire type of cuisine,

01:13:59.740 | depending on how much of a lumper

01:14:03.120 | versus a splitter you are, as we say in science, right?

01:14:05.520 | How much you make kind of large bin decisions

01:14:09.720 | or fine bin decisions.

01:14:11.000 | This is nerd speak for saying, you know,

01:14:13.600 | do you go back to the same restaurant

01:14:15.280 | but order something different,

01:14:16.360 | or do you decide to never go back again?

01:14:18.480 | But that's a pretty extreme case, right?

01:14:21.220 | The other extreme would be you eat a food,

01:14:23.980 | it's delicious, you feel wonderful,

01:14:25.760 | the restaurant, the people, it's wonderful,

01:14:28.040 | and you crave more of that food, okay?

01:14:29.720 | There's all the contextual stuff too.

01:14:31.600 | But what we really are talking about here

01:14:33.600 | is how one navigates this whole landscape

01:14:37.280 | of what to put into one's body in terms of nutrition,

01:14:42.280 | and trying to understand how that's impacting everything

01:14:46.120 | from how we feel right away, how it tastes,

01:14:49.020 | whether or not we conceive it as good or bad for us,

01:14:51.940 | whether or not we think it's impacting

01:14:53.460 | our body composition and health

01:14:55.620 | in ways that we want or don't want.

01:14:57.660 | I mean, it's pretty complex stuff, right?

01:15:00.220 | This is at least as complex as going

01:15:02.380 | to a Metropolitan Museum of Art

01:15:04.900 | and looking at a painting and trying to evaluate

01:15:08.160 | whether or not you really like that painting or not.

01:15:10.020 | In fact, it's probably much more complicated than that,

01:15:14.040 | but it's what we do.

01:15:15.140 | And I'm beginning to get the sense, again,

01:15:19.020 | no pun intended, that this pathway

01:15:21.620 | that we call the gut-brain axis is really,

01:15:25.980 | it's a sixth sense of a very elaborate kind.

01:15:30.720 | - So you just touched on an entire realm of a topic,

01:15:35.780 | which is one of my favorite topics,

01:15:37.740 | because at some point, as scientists, we travel the world.

01:15:42.200 | And it started to become very obvious to me

01:15:46.140 | that wherever I went, we solved this issue of food

01:15:51.140 | in a very similar way.

01:15:53.940 | Whether it's a tortilla or two pieces of bread,

01:15:56.980 | which is another way of a tortilla, you have your carbs.

01:16:01.980 | And then you add a little bit of meat or a mushroom,

01:16:06.420 | and now you have your protein.

01:16:08.060 | - Or fish or chicken.

01:16:10.180 | - Or fish or chicken.

01:16:11.980 | - The carnivores will say mushrooms, not a protein,

01:16:14.460 | and the vegans will say mushroom, beans,

01:16:16.180 | lentils, great protein.

01:16:17.060 | We're not here to resolve that debate.

01:16:19.500 | Do as you choose.

01:16:21.220 | - And then you add the lettuce or the vegetables.

01:16:26.220 | And here's the first stop in that discussion,

01:16:33.340 | because this is fascinating.

01:16:35.700 | There is some recent work showing that

01:16:39.580 | if you remove the protein from a diet,

01:16:44.220 | the animal swallows that meal,

01:16:46.740 | the gut evaluates that there is no protein in there,

01:16:52.660 | and it stops eating that meal.

01:16:55.100 | - Wow, so this is like ordering the vegetarian taco

01:17:00.100 | or burrito or sandwich,

01:17:02.700 | and then avoiding that particular taco or sandwich thereafter

01:17:07.700 | because it lacks protein.

01:17:11.980 | - Because it lacks protein.

01:17:13.220 | - Okay, so foods that lack animal-based proteins

01:17:16.100 | tend to be avoided going forward.

01:17:18.740 | - So here's the second part of that.

01:17:20.540 | And in fact, if the protein is low, not completely absent.

01:17:26.660 | If the protein is low, the animal consumes more of the diet

01:17:30.660 | because it's trying to compensate for the lack of protein.

01:17:33.960 | And obviously, if it has sugars or fats

01:17:35.640 | that are more pleasurable, it keeps eating that meal, right?

01:17:39.180 | - I see.

01:17:40.180 | - If the protein is completely absent,

01:17:41.860 | the animal avoids that diet.

01:17:45.020 | Unless that diet is very rich in dietary fibers.

01:17:50.980 | And the study that I saw,

01:18:00.260 | which I thought it was fascinating,

01:18:02.260 | is that because somehow the microorganisms

01:18:06.400 | in the digestive tract,

01:18:08.060 | if they have enough highly digestible fiber,

01:18:11.760 | now they turn on the ability

01:18:13.700 | to synthesize essential amino acids.

01:18:16.500 | - Really?

01:18:17.340 | - Yes.

01:18:18.160 | - So our gut, meaning the neurons in our gut,

01:18:22.580 | are essentially waiting for,

01:18:25.060 | hoping we'll give them a consciousness,

01:18:27.500 | proteins from animal sources.

01:18:31.780 | - That's correct.

01:18:32.620 | - If those animal proteins arrive

01:18:35.640 | in the form of meat, fish, eggs, et cetera,

01:18:38.140 | the cells signal to the brain craving more of those foods

01:18:42.980 | until satiety is reached.

01:18:44.920 | But in the absence of that protein,

01:18:47.160 | the animal quickly learns,

01:18:48.900 | the person quickly learns to avoid that particular food,

01:18:52.520 | unless there's fiber in it,

01:18:54.260 | in which case these gut cells are able

01:18:57.320 | to now synthesize the essential amino acids.

01:18:59.320 | - The microorganisms.

01:19:00.480 | - Excuse me, the microorganisms of the gut,

01:19:02.680 | here we're talking about the microbiome now,

01:19:05.060 | can synthesize the essential amino acids

01:19:08.080 | that ordinarily would come from the meat,

01:19:10.320 | chicken, fish, or eggs.

01:19:11.440 | - That's right.

01:19:12.400 | - So, wow.

01:19:13.800 | So I'm an omnivore.

01:19:17.100 | I love meat, high quality meat,

01:19:19.760 | but I also love vegetables, fruits,

01:19:22.200 | and starches of certain kinds.

01:19:25.440 | But I have friends who are vegetarian vegan.

01:19:27.680 | Many of them eat a vegetarian vegan diet

01:19:31.680 | that includes a lot of fiber.

01:19:34.200 | And you're saying that the fiber itself

01:19:36.280 | can trigger the gut microbiome

01:19:38.600 | to synthesize the essential amino acids

01:19:40.440 | that ordinarily would come from meat.

01:19:42.720 | But you also said, if I recall,

01:19:45.480 | that if there's a small amount of protein,

01:19:48.400 | so not zero protein,

01:19:50.720 | but a small amount of protein in there,

01:19:52.640 | then we crave more of that food

01:19:54.720 | in order to try and get that protein.

01:19:55.960 | - Compensate.

01:19:57.200 | - Very interesting,

01:19:58.040 | because this is the first thing that to me

01:20:00.840 | squares the argument based on the observation that,

01:20:04.560 | or the hypothesis that we are essentially

01:20:07.280 | amino acid foraging machines,

01:20:09.680 | and that complete proteins

01:20:11.400 | in the form of meat, fish, chicken, eggs, et cetera.

01:20:14.200 | You know, there are those that argue

01:20:15.200 | those are the quote-unquote best forms of protein, right?

01:20:18.040 | The most complete forms.

01:20:19.360 | But there are many vegetarians and vegans

01:20:21.080 | who seem to thrive on a vegetarian vegan diet.

01:20:24.360 | And you're telling me that perhaps their body is,

01:20:27.240 | their gut microbiome is compensating

01:20:28.880 | for the lack of whole animal protein.

01:20:31.800 | - That's right.

01:20:32.640 | - People who are trying to limit their meat intake

01:20:34.440 | are what, hungrier in general?

01:20:37.120 | So you're better off either indulging it or avoiding it,

01:20:41.120 | but not having a small amount of it.

01:20:43.000 | Is that the idea?

01:20:44.000 | - The idea is that the body or the gut

01:20:47.760 | will be able to detect that

01:20:49.160 | and then we'll try to compensate, right?

01:20:51.680 | - I see.

01:20:52.520 | - And these, I actually learned recently

01:20:55.440 | from a friend, Laura Duval at Columbia,

01:20:58.960 | who works, does some beautiful work on mosquitoes

01:21:01.960 | and how it is that they feed on blood.

01:21:04.560 | She came for the Gastronauts series.

01:21:08.440 | - Is she from Lesley-Valsal?

01:21:09.680 | - Yeah.

01:21:10.520 | - Valsal, sorry.

01:21:11.360 | - Yeah.

01:21:12.200 | And what I learned is that

01:21:13.120 | when the mosquitoes are not reproducing,

01:21:16.320 | they can live off ATP, which is the energy molecule, right?

01:21:21.040 | But they cannot lay eggs.

01:21:24.920 | They need the protein in order to be able to lay eggs.

01:21:30.720 | Otherwise, the mosquitoes cannot lay the egg, you know?

01:21:35.320 | - So this leaves us with a picture of the gut-sensing cells,

01:21:39.480 | these neuropod cells as exquisitely sensitive

01:21:43.760 | to amino acid content in our foods,

01:21:47.520 | which makes perfect sense to me.

01:21:48.360 | - And it has not been published or demonstrated yet.

01:21:51.120 | - Sure, we're now in the realm of new incoming data.

01:21:54.480 | - Incoming, yeah.

01:21:55.400 | - We wanna highlight this, bracket it,

01:21:57.400 | boldface and underline it as we're now at the cutting edge

01:21:59.840 | of what may be coming.

01:22:02.440 | - That's right.

01:22:03.280 | - Right, observation.

01:22:04.560 | But nonetheless, very interesting.

01:22:06.120 | But there is this fairly longstanding hypothesis

01:22:08.920 | that we are foraging for essential amino acids

01:22:11.440 | because they are the building blocks

01:22:12.680 | of so many important things in the brain and body.

01:22:15.120 | - And in fact, there is evidence on that.

01:22:16.840 | And Professor Stephen Simpson in Australia

01:22:20.920 | in the Nutrition Research Institute at Sydney University,

01:22:27.240 | he is a main proponent of this protein leverage hypothesis.

01:22:32.240 | And in fact, a protein is the most satiating macronutrient,

01:22:36.840 | so that has been established.

01:22:39.280 | And that's why normally we have focused on sugars and fats,

01:22:43.200 | but we have neglected a little bit on the protein

01:22:45.720 | because it's not as pleasurable as the sugars or fats.

01:22:49.360 | But what is fascinating is

01:22:50.680 | that it is the most satiating nutrient.

01:22:53.560 | And as you know, it's like the most limiting

01:22:55.960 | and also like even commercially

01:22:57.680 | is the most expensive right now.

01:22:59.400 | - Yeah, I certainly have had the experience

01:23:01.600 | of at one time in my life really enjoying

01:23:05.240 | and even craving sweet foods, desserts and sugars

01:23:08.320 | and things of that sort.

01:23:09.160 | And I noticed that over time,

01:23:11.240 | if I eat sufficient amounts of meat, chicken, eggs, fish,

01:23:15.920 | which is not to say that I consume excess amounts of them,

01:23:19.080 | that my sugar cravings go way, way down.

01:23:22.360 | That's just my personal experience,

01:23:23.920 | but I know it's an experience

01:23:25.120 | that family members of mine and others share as well.

01:23:28.240 | - But I promised you that this was a fun topic, right?

01:23:32.760 | I couldn't, we couldn't stop at like just layer number one.

01:23:36.200 | Layer number two is that in agriculture,

01:23:39.320 | we have this instinct to plant plants

01:23:42.640 | that complement each other.

01:23:45.920 | Like for instance, a classic,

01:23:48.360 | especially native, among native communities

01:23:50.840 | is called like the Three Marys.

01:23:54.520 | I believe it's pumpkins or some type of fibers

01:23:59.520 | with corn, carbohydrates and beans.

01:24:03.520 | - So in purely plant-based diets,

01:24:06.100 | there's an effort to get the fiber,

01:24:08.880 | the sugar and the amino acids.

01:24:11.560 | - That's right, and I grew up in a farm.

01:24:13.800 | My parents had farms and I remember when they would plant,

01:24:16.520 | they will also like throw in there the beans

01:24:18.320 | and the beans will wrap around the corn.

01:24:21.080 | And it just seemed like so natural

01:24:23.000 | and that's what you will do

01:24:24.000 | because that's what you learn to do.

01:24:25.320 | But if you think about it,

01:24:26.160 | it's an instinct that we have developed

01:24:28.500 | even agriculturally and probably in the subconscious

01:24:32.560 | to cultivate them in such a way,

01:24:34.880 | or perhaps the plants taught us

01:24:36.480 | how to cultivate them in such a way

01:24:39.360 | that now when we put them in the plate,

01:24:41.320 | it just makes sense at the nutritional level.

01:24:47.400 | Because if you think about it,

01:24:49.120 | every time that we go to eat,

01:24:50.540 | how is it that we arrange that plate, right?

01:24:53.280 | There is some rice,

01:24:54.120 | which is very deficient in some essential amino acids,

01:24:57.360 | but it's rich in carbohydrates, right?

01:24:59.720 | It has some beans, right?

01:25:02.040 | And then there's some lettuce, you know?

01:25:04.840 | And sometimes we have like for omnivores,

01:25:07.240 | people will put meat

01:25:08.080 | or you would put other types of protein in there, right?

01:25:11.080 | - And certainly it varies by culture, time of year,

01:25:13.400 | food availability and things of that sort.

01:25:15.800 | As long as we're talking about your upbringing,

01:25:19.260 | you have a fascinating story.

01:25:23.180 | So maybe we could discuss that for a few minutes.

01:25:27.040 | Where were you born?

01:25:28.580 | - I was born in the Amazonia of Ecuador,

01:25:30.980 | a small town called El Chaco in Ecuador.

01:25:34.460 | It's on the slopes of the eastern slopes of the Andes

01:25:39.000 | on the way to the Amazonia in the Napo province.

01:25:42.700 | Coincidentally, it was like through the path

01:25:46.340 | from where Francisco de Orellana in 1542

01:25:50.980 | marched on its way to the discovery of the Amazon.

01:25:54.380 | Actually passed through a trail that later on reading,

01:25:57.660 | I realized that a native people had all of these trails

01:26:00.920 | between the Amazonia and the Andes

01:26:03.660 | and the coastal line for thousands of years.

01:26:07.460 | - You grew up in a very rural place.

01:26:09.300 | - Yes, the oil had been detected in the 1920s in Ecuador.

01:26:17.820 | It was first explored in 1964 in the first oil well

01:26:22.820 | was in a town called Laguagrio,

01:26:30.920 | which now is only like three or four hours

01:26:33.000 | from the town where I grew up.

01:26:34.560 | But at that time it was like eight hours,

01:26:36.600 | the roads were not good.

01:26:38.360 | And the first road passed through it in 1974.

01:26:42.240 | I was born in 1983,

01:26:47.140 | but I remember that we used to have like a giant

01:26:50.220 | diesel engine that will give us a light,

01:26:55.760 | electricity only from seven to 9 p.m.

01:27:00.020 | I remember when my father bought the first

01:27:04.660 | color television in the town

01:27:09.640 | and then neighbors will come to our living room

01:27:12.340 | and then we will watch movies.

01:27:13.740 | - Wow, and this was in the '80s.

01:27:15.280 | - That was in the '80s, right?

01:27:16.640 | - Yeah, such an interesting upbringing.

01:27:19.020 | So did you eat a purely vegetarian diet

01:27:23.620 | or you ate meats as well?

01:27:25.220 | Where did those meats come from if you did?

01:27:27.160 | - Primarily from cattle, goats, sheep.

01:27:32.160 | - So how do you go from the Amazon

01:27:35.420 | to a study of nutrition and ultimately neuroscience?

01:27:40.180 | - Yeah, that's the question, right?

01:27:43.700 | Like the deeper I go, the more I question this.

01:27:46.100 | I used to think that, oh, it was very simple.

01:27:48.300 | Specifically when I was 11 years old,

01:27:54.940 | my father, he was born in 1932.

01:27:57.780 | He lost his father, my grandfather,

01:28:04.960 | when he was six years old and he was given away

01:28:07.620 | and he had to go and build his life.

01:28:11.720 | He was a very successful entrepreneur,

01:28:13.740 | but in the process, he had made a lot of friends

01:28:17.100 | and acquaintances.

01:28:19.000 | So when I was 11 years old, I remember specifically

01:28:23.020 | that a friend of his who was in the special forces

01:28:26.340 | stopped by our home because that was the main road

01:28:30.620 | that we go into the Amazon jungle

01:28:32.060 | where the folks in the special forces

01:28:34.360 | in the military will be trained.

01:28:36.860 | And he stopped by and said, "Hey, Rogelio,

01:28:38.900 | "what are you gonna do with Diego?

01:28:40.700 | "I think that it's about time that..."

01:28:43.160 | "I think that you should send him to the military school."

01:28:46.040 | And I remember in a matter of like,

01:28:47.800 | literally a couple of weeks or three weeks,

01:28:49.640 | I had taken the tests and I was accepted

01:28:54.100 | into the military school and then I ended up

01:28:56.380 | in a military school and this was the,

01:28:59.080 | at that time, it was the premier military school

01:29:01.420 | in the country.

01:29:02.780 | That alone, it was, with years, you start to understand

01:29:06.960 | the context in which you developed.

01:29:10.320 | And it was a very interesting context for a child.

01:29:14.500 | Like just to give you an idea,

01:29:16.100 | this school had the first and the only zoo in the country.

01:29:21.100 | So from my classroom, I would literally look at the lions

01:29:28.540 | and then I think that was by the second year

01:29:30.380 | that I was in the school, second or third year,

01:29:32.040 | that became, because the city started to grow

01:29:35.880 | and then the military school was wrong

01:29:38.860 | and then they separated the higher education

01:29:41.720 | for military officers, they separated them

01:29:44.300 | and they put them in a different place.

01:29:46.100 | But that zoo actually became the first zoo

01:29:48.160 | of the capital of Quito.

01:29:49.860 | - Wait, so you had a zoo with lions at your school?

01:29:52.860 | - Yes.

01:29:53.700 | - And you said you could see the lions

01:29:55.200 | from your classroom and they could see you, presumably.

01:29:58.080 | - I probably know them.

01:29:59.540 | - Well, I assume they could see you.

01:30:01.700 | Lion vision is pretty good.

01:30:02.940 | I don't know what the resolution is,

01:30:04.280 | but I'm guessing that their vision is, yeah.

01:30:06.380 | They definitely use their olfaction,

01:30:08.320 | but they are sight-based hunters as well.

01:30:11.880 | - But I have specifically one memory,

01:30:14.820 | like climbing up, I think it was like from the,

01:30:17.260 | because we had an Olympic pool

01:30:18.820 | and we had all of these events.

01:30:20.860 | The soccer field was the field

01:30:28.200 | where the national team will go and train on

01:30:31.300 | because they didn't have their own training grounds.

01:30:37.180 | Later on, they had their own training grounds.

01:30:39.680 | But that was something that you just grow into it, right?

01:30:42.420 | But it was with the years, and now especially,

01:30:45.520 | that I get to reflect on it.

01:30:46.820 | I was extremely fortunate through that experience

01:30:49.780 | and that education.

01:30:51.060 | And now I'm here sharing some of the story

01:30:53.820 | and hopefully through that, inspiring some people,

01:30:57.060 | especially young people that would like to go

01:30:59.700 | and chase their dreams.

01:31:01.200 | - So you went to military school in Ecuador.

01:31:04.200 | You graduated and you decided to go to school in the States.

01:31:09.200 | - So in the military school,

01:31:12.840 | they will select the top cadets.

01:31:15.800 | Like I think it was the top 10% and they will select them

01:31:19.380 | and they will put them through a special training.

01:31:22.540 | So you have essentially,

01:31:24.080 | I didn't have like what was a normal summer vacation.

01:31:27.820 | I would go into a military training.

01:31:32.860 | So for me, it was gonna be very, not easy,

01:31:35.360 | but relatively straightforward to transition

01:31:37.300 | into officer's academy, right?

01:31:39.500 | Like do four more years, like West Point here,

01:31:41.420 | and then like become an officer, right?

01:31:43.540 | In fact, I had a reservist officer degree when I graduated.

01:31:48.060 | But two years before graduating,

01:31:52.180 | a friend of mine who, he prefer other types of careers,

01:31:58.540 | he said like, "You're not gonna become a military, right?

01:32:02.180 | "You're not gonna go into the military."

01:32:03.960 | And he said, "You should probably study something

01:32:06.240 | "that will help your parents."

01:32:07.500 | And then I said, "What will that be?"

01:32:09.060 | And he said like, "Perhaps agriculture."

01:32:11.620 | And I didn't think at that time, it didn't dawn on me

01:32:16.060 | that people can study for agriculture

01:32:18.940 | and agriculture is like the base of food

01:32:21.940 | for all of us, right?

01:32:26.020 | And then I said, "Where?"

01:32:27.020 | And then he mentioned for the first time

01:32:28.720 | this university in Zamorano,

01:32:30.500 | which was founded with some funds

01:32:34.460 | that were donated by the founder

01:32:37.340 | of the Standard Fruit Company,

01:32:38.900 | which eventually became, I think, Chiquita Banana,

01:32:41.660 | Zamorano, right?

01:32:42.620 | And that is an oasis that is in Honduras,

01:32:45.620 | outside of Tegucigalpa.

01:32:47.620 | So it's a boarding school, you wear uniform.

01:32:49.640 | So it was kind of like military, it was very strict.

01:32:52.460 | You cannot accumulate more than 12 demerits,

01:32:56.420 | otherwise they will send you home.

01:32:58.820 | - How do you get a demerit?

01:33:01.020 | - You show up two minutes late to work

01:33:04.460 | in the morning at 6 a.m. in the field,

01:33:06.420 | and then you just get to--

01:33:07.260 | - Two minutes late, one demerit.

01:33:08.980 | 12 of those, you're out.

01:33:10.020 | - Two demerits.

01:33:10.860 | - Two demerits, you're out.

01:33:12.100 | - Yeah, you get a, we used to get a,

01:33:14.940 | they will check your room.

01:33:18.220 | So for instance, a guest like you,

01:33:19.540 | if you will go there, like they will give you,

01:33:21.620 | every Wednesday, they had at 7 p.m.,

01:33:24.040 | they will check your room,

01:33:25.620 | but like very meticulously, right?

01:33:27.600 | And if they found a little bit of a dust on the window

01:33:30.300 | or something, two demerits.

01:33:32.200 | - And you're going home.

01:33:33.980 | - If you accumulate enough, you will go home, right?

01:33:36.900 | - Wow.

01:33:38.220 | - So it really forms character, right?

01:33:40.260 | And then--

01:33:41.100 | - Do you do that with your kids?

01:33:41.920 | - No.

01:33:42.760 | (laughs)

01:33:43.600 | I think that I have become very--

01:33:44.420 | - Do they make their beds?

01:33:45.260 | - They do make their beds, yeah.

01:33:47.380 | But that was the context.

01:33:48.620 | And it was then where I learned about two things.

01:33:51.260 | One is where this idea of getting a PhD,

01:33:53.720 | because I noticed that most of the leaders

01:33:55.840 | will have a PhD, most of the leaders in the university.

01:33:58.980 | And I realized in the United States

01:34:00.760 | is one of the training grounds,

01:34:02.700 | main training grounds for PhDs.

01:34:04.220 | And the other one was nutrition.

01:34:06.500 | I was a little bit more keen on perhaps

01:34:08.620 | going into a veterinary school.

01:34:12.100 | And then I had an experience in a dairy farm in California

01:34:18.260 | where I learned the value of nutrition.

01:34:21.340 | There was more prophylactic

01:34:22.580 | rather than a palliative, like treating the cow, right?

01:34:27.240 | And that kind of convinced me

01:34:29.840 | to look for a training in nutrition.

01:34:33.840 | And then a friend of mine, the late Abel Garnath,

01:34:38.640 | he was able to connect me with some friends

01:34:42.260 | and my mentor at North Carolina State University.

01:34:45.840 | And that's where I ended up doing my PhD in nutrition.

01:34:48.320 | And that's where the career became.

01:34:51.500 | And then maybe another detail in there

01:34:53.320 | is that I was so excited about taking,

01:34:57.720 | that's where I took my first physiology class.

01:35:00.440 | And all of a sudden I realized that in a way,

01:35:04.280 | the body was like a machine, right?

01:35:05.760 | Leg obviously is a limited way of thinking,

01:35:07.400 | but the body was like a machine.

01:35:09.240 | And one of the professors was a neuroscientist.

01:35:12.700 | And I took two physiologists,

01:35:15.200 | two human physiologists with him.

01:35:17.960 | And I was just thrilled by when he will explain

01:35:21.900 | how is it that in the synaptic terminal,

01:35:24.100 | there were these vesicles that had like these proteins

01:35:27.460 | that will walk the vesicle in the presynaptic active zone.

01:35:30.580 | And that's how we make movement, you know,

01:35:32.340 | or something like that.

01:35:33.540 | And I guess I kept that in the background of my head.

01:35:36.460 | And when I had the opportunity to work in the gut,

01:35:39.060 | I applied that.

01:35:40.880 | - So you were enchanted by the nervous system.

01:35:43.220 | - Yes.

01:35:44.060 | - As I was too.

01:35:47.940 | Nothing to me is more spectacular than the realization

01:35:52.940 | that we are made up of these little tiny cells,

01:35:56.020 | many different types,

01:35:56.880 | but that the neurons essentially govern

01:35:59.580 | our entire experience of life.

01:36:02.100 | That's just amazing.

01:36:03.440 | Well, that's quite a journey from the Amazon to,

01:36:08.900 | well, this table and much more, of course.

01:36:12.260 | Thank you for sharing that.

01:36:15.100 | So you grew up in a, let's call it a plant rich environment,

01:36:19.100 | the Amazon, at least from the pictures I've seen are very.

01:36:22.780 | Let's talk about plants, botanicals,

01:36:26.020 | and the idea that maybe plants,

01:36:30.340 | for lack of a better way to put it,

01:36:31.600 | have a certain intelligence or a composition

01:36:36.600 | that is not random with respect

01:36:39.460 | to our interactions with them, right?

01:36:42.900 | You described how agriculture in some places

01:36:46.140 | has evolved to include and ensure

01:36:49.020 | the different macronutrients

01:36:50.940 | and essential amino acid intake,

01:36:53.020 | even in the absence of animal proteins.

01:36:54.860 | Is it the pumpkin or the squash, the corn and the beans?

01:36:58.220 | What are your thoughts on plants,

01:37:02.460 | perhaps from the Amazon, but elsewhere too,

01:37:05.780 | and their capacity to have things in them,

01:37:08.260 | chemicals that can be good for us

01:37:12.220 | at the level of the gut,

01:37:13.260 | but perhaps at the level of the brain

01:37:15.820 | or other organs as well?

01:37:17.300 | Yeah, how do you think about plants these days?

01:37:19.060 | - So the first thing you mentioned there,

01:37:21.220 | like intelligence, right?

01:37:23.300 | I mean, I don't know if that exact terminology applies,

01:37:26.780 | but I do like this word wisdom

01:37:28.660 | because it's reflective experience, right?

01:37:31.580 | And I say reflective experience

01:37:32.700 | because somehow we are going over the experience.

01:37:37.340 | And plants have been many more millions years

01:37:42.140 | of age on earth than any other animal, right?

01:37:47.140 | Therefore, they have had way more time

01:37:52.060 | to actually experience the ground.

01:37:54.540 | So to think that they don't know what is going on,

01:37:58.300 | I think is a little bit perhaps naive is the word.

01:38:03.180 | I went to the main court of these Mayan rulers

01:38:08.180 | in these Mayan ruins of Copan

01:38:13.180 | at the junction between Honduras and Guatemala.

01:38:16.900 | This was a very special city of the Mayans.

01:38:21.260 | And in the main court, you see like all of these stelas,

01:38:24.060 | which are like the main stones

01:38:26.780 | of the kings of several dynasties.

01:38:30.460 | And at the top of one of the stairs on these pyramids,

01:38:36.500 | there is this giant ceiba tree,

01:38:41.460 | which is like 650 years old, something like that.

01:38:46.460 | So that tree was there before the Spaniards landed in there

01:38:50.660 | when the Mayans perhaps were still celebrating things

01:38:54.740 | or perhaps right after, right?

01:38:57.820 | So imagine how much information that organism has in there.

01:39:01.140 | And we will be able to just tap somehow

01:39:04.580 | into that information, like climate, fluctuations,

01:39:09.580 | organisms, interactions, movements.

01:39:13.900 | I mean, like so many different things, right?

01:39:15.700 | Like that right now, I don't think that we even have

01:39:18.380 | the language of being able to understand

01:39:21.500 | at the organismic level of how much information

01:39:24.980 | that is stored in one single one of those organisms.

01:39:28.340 | But then think about a chloroplast, for instance,

01:39:32.820 | or like one of the photosynthetic organelles

01:39:36.820 | inside of the cells.

01:39:39.780 | How is it that they have been shaped

01:39:41.900 | for hundreds of years in those organisms, right?

01:39:44.700 | And I think that perhaps in the future,

01:39:48.500 | this is more of a sci-fi right now,

01:39:53.500 | but perhaps in the future we will be able

01:39:55.580 | to harvest that type of wisdom.

01:39:57.340 | We will be able to understand a lot about the place

01:40:01.900 | or the earth that we live in.

01:40:04.140 | That's point number one.

01:40:05.420 | Point number two is that these plants

01:40:09.660 | have been interacting and we have been interacting

01:40:11.860 | with plants for hundreds of years, right?

01:40:15.340 | And obviously we are a consequence of the environment,

01:40:18.140 | like here driving in LA or driving in a major city

01:40:23.140 | for some of us is just like second nature, right?

01:40:28.780 | But if you go into a jungle,

01:40:30.540 | then all of a sudden it will not be the same thing, right?

01:40:33.100 | But for somebody that has been in the jungle

01:40:35.140 | for hundreds of years,

01:40:37.020 | now all of a sudden they are able to describe

01:40:39.420 | with such a sensitivity of like how it is

01:40:43.060 | that the jungle is, the makeup of the jungle is in there.

01:40:47.980 | I've seen native people walking through the jungle

01:40:51.060 | without shoes and right before stepping on a leaf,

01:40:55.180 | stopping and then pointing out like,

01:40:57.620 | look underneath that leaf and then lifting it out

01:40:59.900 | and then a tarantula right there.

01:41:01.540 | Like, how do you even make sense of that?

01:41:05.540 | Like, I don't have the sensory acuity

01:41:07.580 | or the wisdom to be able to figure that out.

01:41:10.260 | But they do, right?

01:41:12.700 | And certainly that is just a level of sensory perception

01:41:17.340 | that I am not equipped with.

01:41:19.980 | But I do think that there's quite a bit

01:41:23.020 | of that interaction in there to learn.

01:41:25.660 | And then of course, not only for food,

01:41:27.940 | but also for medicine, for textiles

01:41:30.220 | and for many other functions.

01:41:32.820 | These plants have been part of the ecosystem

01:41:36.660 | of how these people navigate their world

01:41:39.940 | all the way from making a canoe

01:41:42.500 | to making a backpack to carry a fish

01:41:45.780 | from the river into the house, right?

01:41:47.620 | - How do you think we evolved food choices

01:41:50.780 | and flavor preferences?

01:41:52.780 | I imagine humans, you know, that existed long before us,

01:41:57.740 | being hungry, the gut starts rumbling

01:42:02.500 | and there are all these plants everywhere,

01:42:05.180 | some nuts and some berries and things.

01:42:06.740 | And so they had presumably no choice,

01:42:09.420 | but to consume them and decide at the level of the mouth,

01:42:14.140 | like, that's bitter, nope, that's not good.

01:42:16.900 | Maybe eventually cook those

01:42:19.100 | and see if that changes the relationship.

01:42:20.700 | Yeah, I'm thinking raw acorn versus cooked acorn, you know?

01:42:24.980 | But that ultimately there was a lot of trial and error

01:42:28.260 | and that these neuropod cells,

01:42:30.540 | which surely existed for a very long time prior to us,

01:42:33.820 | played a key role in discerning what's in these plants,

01:42:39.820 | barks, roots, nuts, berries,

01:42:43.060 | we're setting aside meats for the moment

01:42:45.380 | and other animal proteins

01:42:47.220 | and making decisions about what's nutritious,

01:42:50.380 | what is safe, what is not safe.

01:42:52.700 | And that's a pretty complex process

01:42:55.100 | given that some things might taste okay, go down okay,

01:42:58.740 | but then you run into serious trouble later.

01:43:01.780 | But given the critical importance

01:43:04.100 | of ingesting sufficient amounts of macronutrients

01:43:07.500 | and the need for micronutrients

01:43:09.500 | to survive on a day-to-day basis,

01:43:11.420 | much less reproduce and propagate,

01:43:14.040 | one imagines that, you know,

01:43:17.500 | this is like almost as essential as breathing, you know?

01:43:22.180 | And that this path in our nervous system

01:43:25.100 | of the neuropod cells to the brain

01:43:26.700 | for sake of decision-making of yum, yuck, or meh

01:43:31.700 | is perhaps one of the most important core functions

01:43:36.540 | of the nervous system

01:43:37.620 | once you get past the elements that control breathing,

01:43:42.180 | heart rate, you know, temperature regulation,

01:43:45.500 | things of that sort.

01:43:46.660 | I see it as among the senses,

01:43:50.100 | it's at least as important as vision

01:43:53.140 | and perhaps more in terms of making sure

01:43:55.740 | that we survive from day-to-day.

01:43:58.480 | - That's correct.

01:43:59.320 | And here's where I think there is a large vacuum in biology.

01:44:03.100 | If I will be with my biological,

01:44:07.980 | my training in biology,

01:44:10.740 | if I would put my hat of the training in biology,

01:44:13.820 | I wouldn't be able to explain much

01:44:16.500 | of like how is it that we figure it out

01:44:18.540 | because even if you just go to a botanical garden here

01:44:22.860 | in, you know, in the city,

01:44:24.920 | it would be really hard to figure out, you know,

01:44:29.120 | what plant is for what, right?

01:44:31.420 | - Yeah, what's safe to eat, what's not.

01:44:32.260 | - What is safe to eat, what is not.

01:44:33.080 | - Do you need to cook it or not?

01:44:34.740 | - You know, maybe like the cacti,

01:44:37.440 | you are able to figure that out by touch, right?

01:44:40.260 | So from the biological perspective,

01:44:41.780 | I think that there is quite a bit in there

01:44:43.320 | to explore and to learn.

01:44:45.080 | There is some very interesting work

01:44:47.880 | from the anthropological perspective.

01:44:50.440 | So anthropologists and botanists

01:44:54.900 | that were studying the plants

01:44:56.380 | were exploring the jungles, not only the Amazon,

01:45:01.140 | but Borneo, Sri Lanka, and so on and so forth,

01:45:04.700 | and studying the interaction

01:45:06.100 | of native people with the plants.

01:45:08.140 | And if going through the literature,

01:45:10.660 | that literature, there is a pattern that emerges

01:45:13.860 | and like the native people,

01:45:16.100 | they talk about how it is that they actually learn

01:45:18.600 | from the plants, that the plants were the ones

01:45:20.960 | that will teach them, you know?

01:45:23.680 | So that's why I said from the biological perspective,

01:45:26.160 | like, how can we make reconcile that?

01:45:28.680 | I think that there is still quite a bit to learn.

01:45:31.520 | - What does that mean to learn from the plants?

01:45:34.240 | I mean, there's something that intuitively makes sense.

01:45:37.480 | When you say that, I've heard about, you know,

01:45:41.320 | looking at plants as teachers, about the local environment,

01:45:44.440 | you know, when they're open, right, they're light sensing,

01:45:47.140 | when they're closed, but, you know,

01:45:51.540 | in terms of translating some of that to, you know,

01:45:55.480 | how humans have learned to navigate given environments,

01:45:58.860 | navigate meaning sort of thrive in those environments.

01:46:02.120 | How do we go about that?

01:46:04.140 | Does it mean taking plants, grinding them up,

01:46:07.060 | and figuring out the constituent parts?

01:46:09.600 | Or is that too reductionist?

01:46:11.380 | Is that gonna leave us with a parts list

01:46:13.060 | that doesn't mean anything?

01:46:14.160 | Sort of like if I splayed out all the pieces of a car

01:46:16.940 | or an airplane in front of us,

01:46:19.420 | it doesn't really tell us anything about that,

01:46:21.780 | except what parts make up the thing that flies.

01:46:25.100 | - Yes, and that's why I said, like,

01:46:26.980 | this is more on the anthropological studies that have,

01:46:31.980 | you know, especially from scientists that have gone there,

01:46:34.300 | learned the language, live with the natives as natives,

01:46:38.300 | you know, and then start to understand the dynamic

01:46:41.020 | of their culture and their interactions.

01:46:43.800 | Then that's when, like, for instance,

01:46:46.600 | how it is that they classify plants.

01:46:48.960 | The way that they classify plants is like

01:46:51.560 | several levels more richer than our classification,

01:46:56.040 | our scientific classification by the two-name system

01:47:00.880 | or the variety, right?

01:47:01.840 | Like, for instance, they take into account

01:47:03.280 | not only the flavor, but also the shape,

01:47:07.160 | the location, how they interact over the year,

01:47:11.600 | how they react over the year.

01:47:13.960 | For instance, there is this beautiful plant

01:47:16.080 | that people call it the lips plant.

01:47:21.080 | I don't know if you have, but if you Google it,

01:47:23.680 | you will see it.

01:47:25.200 | - Looks like lips?

01:47:26.280 | - Literally like lips.

01:47:27.480 | It has, like, these red, beautiful lips, like the plant.

01:47:31.680 | It just looks like lips.

01:47:32.980 | And then people use it for pain, for some rashes,

01:47:37.640 | skin rashes, and also, like, in some rituals.

01:47:40.960 | And, like, most of these plants,

01:47:43.680 | the way that the natives interact with the plants

01:47:46.200 | is in a sacred level.

01:47:48.280 | You know, there is this respect for the plant, right?

01:47:51.820 | So, yeah, I think that biologically,

01:47:57.160 | I think that there is quite a bit in there

01:47:58.720 | to understand and explore and define.

01:48:03.080 | I do agree with you that, like,

01:48:04.440 | just thinking about grinding it up

01:48:06.320 | and, like, just putting it in a tea,

01:48:08.320 | perhaps is too reductionist.

01:48:10.700 | It could be a beginning of understanding,

01:48:13.840 | but it is reductionist.

01:48:15.480 | - Seems like nowadays, in the field of biomedical research

01:48:19.040 | and clinical research, that there's a lot of interest

01:48:22.500 | in plant-based psychedelics.

01:48:24.780 | You know, LSD from ergot and psilocybin,

01:48:31.160 | mushroom, and so on and so forth, ayahuasca.

01:48:36.260 | Iboga.

01:48:37.100 | So it seems like science and plants

01:48:40.320 | have merged at that level

01:48:42.600 | in terms of clinical implications.

01:48:44.000 | Of course, there are entire fields of plant biology

01:48:46.200 | that are extremely important.

01:48:47.180 | I think most people probably don't realize this,

01:48:49.020 | but a lot of what we understand about circadian rhythms

01:48:51.960 | grew, no pun intended,

01:48:55.880 | out of our understanding of plant circadian rhythms first,

01:48:59.240 | and then it was translated to mammals.

01:49:01.040 | You know, beautiful work by Steve Kay and others,

01:49:04.400 | seeing the circadian rhythms in leaf opening

01:49:07.620 | and the orientation of the whole plant

01:49:09.620 | and other features of plants

01:49:11.140 | that are mirrored by the changes

01:49:14.020 | in arousal level in mammals, including us,

01:49:17.780 | which is why I'm always telling people

01:49:18.940 | to get sunlight in their eyes early in the day

01:49:20.740 | and to avoid bright light in the evening and nighttime.

01:49:24.580 | So what are your thoughts on plants as a source of medicine,

01:49:30.500 | psychedelic or otherwise?

01:49:33.100 | - I think that, well, traditionally,

01:49:35.160 | that's where medicine was developed from.

01:49:38.760 | I was at the Oxford Botanical Gardens

01:49:42.920 | last year with the family,

01:49:44.360 | and we went into the gardens,

01:49:46.820 | and they have a beautiful garden.

01:49:48.120 | It was established in 1621.

01:49:49.840 | I think it was the first botanical gardens in England,

01:49:53.760 | and they have a beautiful medicinal plant collection,

01:49:57.360 | and there was this very humble,

01:50:02.080 | what are we, little sign with a description in there

01:50:05.640 | that said in there that about 80% of medicine

01:50:09.520 | still comes straight from plants.

01:50:12.160 | - Really?

01:50:13.000 | - Yes, and if you think about it,

01:50:15.720 | it kind of makes sense, right?

01:50:17.120 | Because when we think about the medicines

01:50:19.840 | that we have been able to develop,

01:50:21.000 | which have been phenomenal,

01:50:22.600 | especially for certain chronic diseases,

01:50:24.900 | but we don't have a broad repertoire of it, right?

01:50:32.160 | So I think that has been, obviously,

01:50:36.000 | a great advance in our society

01:50:39.320 | that we have been able to identify the molecules,

01:50:41.720 | synthesize the molecules, package the molecules,

01:50:45.720 | render them bioavailable in specific sites,

01:50:48.840 | and I think that when we are able to couple that

01:50:51.400 | with the rest of the molecules that the plants,

01:50:53.840 | through their, I keep saying, their wisdom,

01:50:56.220 | because somehow they develop their ability

01:50:58.680 | to have not only one molecule,

01:51:00.800 | but like a combination of other things

01:51:03.200 | that will provide the full experience of the plant, right?

01:51:07.720 | For instance, yerba mate, it's not only caffeine, right?

01:51:12.720 | Because it's very different than a shot of espresso.

01:51:16.880 | If you take the whole thing, it not only gives you energy,

01:51:20.600 | but it gives you a full range of an experience

01:51:23.120 | that is specific to the yerba mate,

01:51:25.000 | which is a leaf, right?

01:51:26.920 | - Yeah, it's a distinctly different subjective experience

01:51:31.600 | than coffee, and I enjoy both,

01:51:33.880 | coffee and espresso and yerba mate.

01:51:36.880 | You were the one who introduced me to guayusa.

01:51:40.760 | - Guayusa, yeah, which is a cousin of yerba mate,

01:51:44.680 | because yerba mate is Ilex paragensis,

01:51:47.400 | guayusa is Ilex guayusa.

01:51:50.080 | And it's not as bitter as mate,

01:51:52.880 | but it has almost as much caffeine as coffee,

01:51:56.440 | and it has antioxidants and other compounds,

01:52:00.320 | which give you these very smooth experience.

01:52:03.800 | So natives in the Amazon,

01:52:06.560 | they take a drink of guayusa every morning around 4 a.m.,

01:52:11.560 | between 4 and 6 a.m.

01:52:14.600 | - But they wake up early.

01:52:15.840 | - They actually call it, yes.

01:52:17.200 | - It was like Jocko Willink early.

01:52:18.880 | - Yeah.

01:52:19.720 | - Some people understand that joke.

01:52:20.840 | He wakes up every morning and he posts a picture

01:52:23.480 | of his Casio watch, yep, and he's already training 4.30,

01:52:26.720 | so no guayusa required for Jocko.

01:52:29.480 | - And they call it the guaysa upina ura,

01:52:35.440 | the hour of the guayusa,

01:52:40.960 | and is a ritualistic drinking of the guayusa in the morning,

01:52:45.960 | and where they talk as a family

01:52:48.560 | of the issues that they have had the days before

01:52:52.000 | or the weeks before, like either with other communities,

01:52:54.800 | within the family, if they have to reprehend

01:52:57.160 | or reprimand one of the children,

01:52:59.360 | or talk to them about some mistakes that they're making,

01:53:02.360 | and then they plan the full day of activities

01:53:05.800 | by drinking guayusa, and around 5.30,

01:53:11.680 | because they will boil the guayusa, right,

01:53:14.000 | and they keep boiling the guayusa,

01:53:15.360 | and they just keep adding water to it,

01:53:17.800 | and then around 5, 5.30,

01:53:19.880 | then they will have what is called a bowl of chonta,

01:53:24.880 | and chonta is this palm date,

01:53:33.160 | very rich in lipids and fibers,

01:53:36.400 | so they will have the guayusa,

01:53:38.840 | because the guayusa, they say, that gives them energy,

01:53:41.760 | it heals any pain, it shuts down appetite,

01:53:46.760 | so they will eat at like 3 p.m.,

01:53:49.040 | you know, shuts down or modulates appetite.

01:53:51.480 | - As does yerba mate.

01:53:52.680 | That's one of the more potent effects, actually,

01:53:54.760 | of mate and guayusa,

01:53:56.840 | is a mild to moderate appetite suppression.

01:54:00.120 | - And then if you combine that to chonta,

01:54:02.440 | which gives you the lipids,

01:54:04.360 | and then it's like a full meal until 3 p.m.,

01:54:06.860 | and then they go and work in the fields.

01:54:09.520 | - Interesting, so they're essentially starting the day

01:54:11.560 | with hydration, caffeine, and then they,

01:54:13.640 | what in some circles they call fat fasting,

01:54:16.300 | meaning consuming lipids in order to stave off hunger.

01:54:20.060 | I mean, it's the highest density source of calories

01:54:23.800 | among the macronutrients.

01:54:25.360 | - And it's a vegetable-based diet, I guess you're right.

01:54:29.580 | - Are they a healthy culture?

01:54:31.800 | Do they live a long time?

01:54:33.400 | - I am not, and I should probably do more reading that,

01:54:38.400 | I'm not well-educated in what are the studies

01:54:42.220 | that have follow-up on the health status of the communities.

01:54:47.220 | But what I can tell you is that, at least colloquially,

01:54:52.000 | I will say that diabetes, those type of issues,

01:54:55.520 | are not as prevalent.

01:54:57.500 | But they do have, obviously, through social exposure,

01:55:00.800 | they have other things.

01:55:02.120 | - Fascinating, this morning ritual of conversation

01:55:08.520 | about family and culture and what's needed

01:55:11.200 | and planning the day.

01:55:12.300 | We had on this podcast as a guest, Dr. Sachin Panda,

01:55:16.380 | who is at the Salk Institute for Biological Studies,

01:55:19.460 | often known for his work on intermittent fasting,

01:55:21.400 | time-restricted feeding,

01:55:22.240 | but also has done beautiful circadian biology.

01:55:25.200 | And he talked about the use of fireside chats,

01:55:28.980 | not the sort on stage, but gathering around fire at night

01:55:34.940 | is something that has existed in many cultures

01:55:36.900 | where people reflect on the previous day and discuss issues.

01:55:41.020 | Social and work issues and sort of dissect what's happened

01:55:44.600 | and talk and it's about building

01:55:48.900 | and repairing relationships.

01:55:51.400 | Sounds like in this, is it, what is this group?

01:55:55.100 | Is it a rural, is this a--

01:55:56.720 | - Yeah, native community.

01:55:58.760 | Because there are like about 70 or so communities

01:56:03.160 | that have been documented in the Amazonia

01:56:06.760 | with their own language, with their own traditions.

01:56:09.060 | And many of them share the same type of traditions.

01:56:13.600 | And if you think about it,

01:56:14.440 | like a podcast is one way of an evolution

01:56:17.360 | of that conversation, right?

01:56:18.560 | Like where we can have this extended conversation

01:56:20.680 | and get these, the more primordial things,

01:56:23.960 | the ones that we have them in the prefrontal cortex

01:56:26.240 | right away and like discuss about like,

01:56:27.880 | well, you know, this discovers these identifications.

01:56:30.840 | But then we get to the part of like,

01:56:33.880 | what does it mean for the whole community?

01:56:36.360 | - Yeah, there's doing, there's reflecting,

01:56:39.700 | and then there's resting and recovering, right?

01:56:42.860 | - And there is something about like,

01:56:44.300 | living that for the next generation, right?

01:56:46.740 | - Yeah, passing on of-- - Passing on.

01:56:49.180 | - Lessons, but better learn from the mistakes

01:56:51.860 | and successes of others if you can as you go forward.

01:56:55.940 | Very interesting.

01:56:57.040 | If we could, I'd like to now return to the biology,

01:57:01.940 | the nervous system. - Absolutely.

01:57:03.980 | And thank you for that voyage through

01:57:06.360 | some of your background in Ecuador.

01:57:08.640 | Fascinating.

01:57:09.480 | I do for a mug of guayusa.

01:57:13.000 | Sometimes I'll mix the two,

01:57:14.040 | the loose leaf yerba mate and the guayusa.

01:57:17.680 | And as you said, what's-- - How does it feel?

01:57:19.480 | - I really like it.

01:57:20.960 | Most of the time it's loose leaf yerba mate

01:57:23.600 | or cold brew yerba mate.

01:57:25.060 | But sometimes I'll mix in the guayusa leaves.

01:57:29.220 | And what I do like, as you mentioned,

01:57:31.920 | is you can continue to pour water over them for many hours

01:57:34.680 | and it tastes different as the time goes on.

01:57:37.040 | And my guess is you're extracting different things from it

01:57:39.680 | in different concentrations as time goes on.

01:57:42.000 | I realize it's not a precise science.

01:57:44.160 | It's interesting, today we're talking about

01:57:45.920 | very precise neurons and methods of tracing neurons

01:57:49.580 | and sensing of specific amino acids and lipids

01:57:53.480 | at the level of the gut.

01:57:54.320 | And then we're also going to more macroscopic view,

01:57:58.000 | a kind of broader scale view of the plants

01:58:01.600 | having many things that need to coexist

01:58:04.360 | in certain ratios that the plants have evolved

01:58:08.000 | to create for us.

01:58:09.600 | So we're sort of straddling both ends of the continuum.

01:58:14.120 | - And if I could fit in there a story,

01:58:16.400 | not long ago, I visited a friend, a native friend

01:58:19.480 | in a nearby town and he produces some of the best chocolate,

01:58:24.480 | what I will say in the planet,

01:58:29.660 | because actually the plants of Theobroma cacao,

01:58:34.660 | it was recently documented, there was a paper in Science

01:58:38.240 | not long ago that it was domesticated in Ecuador

01:58:41.640 | in near where I grew up and they have done some tracing

01:58:46.340 | and genetic tracing.

01:58:47.280 | And so he produces some of the best chocolate,

01:58:50.880 | like literally he harvested in there

01:58:53.440 | and then he roasted, grinded,

01:58:56.120 | and then he prepared it for us in there.

01:58:58.880 | And the Swiss are saying, or the Belgians, right?

01:59:01.460 | I claim the best chocolate, but now we know Ecuador

01:59:04.400 | is the place for the best chocolate.

01:59:05.740 | I think I just got a lot of Swiss and Belgians angry at me

01:59:08.080 | for saying that, but do they have a very dark variety?

01:59:12.040 | I like the extreme dark varieties, 95%.

01:59:15.800 | Even a hundred percent chocolate,

01:59:17.100 | if it comes from a really quality source

01:59:19.860 | can be absolutely delicious.

01:59:21.620 | - It's like milk straight from the cow, right?

01:59:24.260 | And what he did is like, he said like,

01:59:26.500 | Diego, you have to try it with guayusa.

01:59:31.160 | And he mixed the chocolate with guayusa.

01:59:34.280 | - As a drink?

01:59:36.240 | - Like as a drink.

01:59:37.440 | Boy, like that will give you wings, you know?

01:59:40.320 | - Guayusa hot chocolate.

01:59:41.840 | - Yes, and it's a very smooth experience, right?

01:59:46.640 | Like you're mixing this tea, which is for energy,

01:59:49.920 | with chocolate, you know, of the best quality.

01:59:53.520 | - So we're not talking about eating chocolate

01:59:54.980 | and drinking tea, we're talking about melting the chocolate

01:59:57.920 | in the guayusa.

02:00:00.440 | - It was something like one of a kind, you know?

02:00:03.760 | Then of course I couldn't sleep until like 3 a.m., I think.

02:00:06.120 | - Right, there's something to do.

02:00:07.220 | Maybe this is why these groups drink the guayusa

02:00:11.000 | so early in the day.

02:00:12.100 | - That's right.

02:00:12.940 | - Yeah, and I have to imagine I would need caffeine

02:00:15.820 | at 4 a.m., 5 a.m., otherwise I'd be falling back asleep.

02:00:22.640 | - So back in the gut and nervous system,

02:00:26.560 | in particular within the brain,

02:00:27.960 | we haven't talked about the brain so much.

02:00:29.760 | - We kind of haven't talked.

02:00:30.640 | - So the information from the gut

02:00:32.080 | is sent via these neuropod cells up to,

02:00:35.720 | you mentioned the no-dose ganglion,

02:00:37.800 | such a cool name for a brain.

02:00:40.740 | And a ganglion in this instance is an aggregate of neurons,

02:00:44.280 | so it's like a batch of neurons,

02:00:46.680 | that then send a connection into the brain.

02:00:49.440 | What brain areas do they send it to?

02:00:52.900 | And maybe we could describe these by name,

02:00:54.480 | but also by function, what they generally are responsible for.

02:00:58.340 | - And probably should be prefaced with,

02:01:01.620 | ultimately will go to the entire brain.

02:01:04.060 | - Right, everything ultimately connects to everything.

02:01:05.980 | It's like Google Maps, everything connects to everything.

02:01:08.180 | But what are some of the primary recipients

02:01:10.860 | of that information?

02:01:11.700 | - Some of the first hubs of sensor integration

02:01:16.700 | are in the brainstem.

02:01:20.900 | You know, and for instance, the nucleus tractus solitarius

02:01:25.700 | is in a specific region within the brain.

02:01:28.500 | The caudal is one area.

02:01:31.100 | - And NTS, for those that don't know,

02:01:33.100 | is involved in regulating hunger and appetite.

02:01:35.420 | - That's correct.

02:01:36.260 | Other functions perhaps, but like for instance,

02:01:40.780 | that seems to be an area of sensory integration

02:01:43.580 | for nutrients.

02:01:45.420 | - And when we say drives hunger or appetite,

02:01:47.720 | sensory integration for nutrients,

02:01:49.280 | I mean, what would be great is if, you know,

02:01:51.660 | people could understand, you know,

02:01:53.160 | the language of the nervous system

02:01:54.380 | is chemical and electrical.

02:01:55.580 | So when these neurons are active,

02:01:58.060 | we tend to crave certain foods, you know, seek them,

02:02:01.100 | literally go to the refrigerator,

02:02:03.540 | among the different choices, go to that thing

02:02:06.340 | and select that and put it into our mouth.

02:02:09.780 | So presumably it's driving reward systems, motor systems.

02:02:16.660 | - I mean, what we call hunger and appetite

02:02:19.320 | is really a kind of a domino effect

02:02:23.000 | of a lot of different brain circuits.

02:02:24.680 | Do we know whether or not the nucleus tractus solitarius

02:02:29.680 | projects to the areas of the brain

02:02:31.960 | involved in dopamine release and craving?

02:02:34.680 | - Yes, and there has been some elegant work

02:02:38.240 | from several different neuroscientists in this area,

02:02:41.200 | like tracking the circuitry from there

02:02:45.440 | on to many other different areas.

02:02:48.340 | The hypothalamus, for instance,

02:02:50.400 | very basic behavioral functions.

02:02:52.580 | And the striatum, where there is dopamine release,

02:02:57.260 | and then there is this pleasurable sensation and reward.

02:03:01.900 | There are several other areas in there

02:03:03.940 | that are involved in this sensory integration.

02:03:06.900 | There is quite a bit of work still to be done

02:03:10.220 | from specifically from the neuropods.

02:03:13.300 | There is like some evidence that they are connecting

02:03:15.780 | directly to, or there are, if you put two papers together,

02:03:20.660 | it's obvious that they are connecting

02:03:22.300 | to like some of these areas of dopamine release,

02:03:25.300 | basal ganglia in the brain.

02:03:27.820 | And that's why they are causing this reinforcing effect

02:03:34.460 | like in the lateral hypothalamus and other areas.

02:03:38.540 | I do think that ultimately,

02:03:41.500 | there is quite a bit of a gap

02:03:43.380 | in like different regions of the digestive tract.

02:03:46.800 | Today, we just talked about the esophagus, right?

02:03:50.300 | Like the esophagus, I think that it's still,

02:03:52.380 | there is a little bit of work.

02:03:54.740 | Perhaps I think that Steve Liberlis

02:03:56.580 | has work in that area, another great neuroscientist,

02:04:01.140 | doing some very fine detail work

02:04:04.580 | in sensory biology in the esophagus.

02:04:08.260 | There is quite a bit of lack of precise biology

02:04:13.260 | in how it is that the esophagus,

02:04:16.900 | the specific cells of the esophagus are innervated

02:04:20.060 | or like making sense of the environment.

02:04:22.320 | Same thing for the stomach and how it is

02:04:24.420 | that ultimately each one of those regions

02:04:26.920 | are feeding into different regions of the brain.

02:04:29.820 | Even then, how each one of these valves,

02:04:34.780 | I'm fascinated by each one of the valves

02:04:36.900 | that we talked early on, like the gastroesophageal sphincter

02:04:41.900 | or the pylorus or the ileocecal junction.

02:04:47.140 | - Yeah, we should illustrate for people,

02:04:49.300 | I'm not an expert in the gut by any means,

02:04:51.540 | but what Dr. Borges is referring to

02:04:54.300 | is that the gut, as it extends from the mouth to the rectum,

02:04:59.300 | is not just a series of tubes of different diameters,

02:05:04.500 | but rather they have valves, chambers,

02:05:07.460 | and these sphincters that cut off,

02:05:09.420 | you know, everyone hears the word sphincter

02:05:10.700 | and they always think, "Oh, you know, anal sphincter."

02:05:12.420 | And then they, "Oh, you know, it's like, you know,

02:05:13.840 | "elementary school, middle school humor."

02:05:16.160 | But sphincters, they literally can close and open

02:05:19.740 | to varying extent in order to allow passage

02:05:24.360 | or prohibit passage from one compartment to the next,

02:05:27.680 | such that certain things can take place over time

02:05:31.020 | in one region, like the esophagus

02:05:33.700 | or within the stomach or, you know,

02:05:35.200 | before passing to other chambers.

02:05:37.820 | And so I hear you saying that critical processing

02:05:41.920 | is happening at each of these chambers.

02:05:44.360 | The sphincters are determining

02:05:45.660 | how long that processing occurs,

02:05:47.620 | and that distinct sets of neuropod cells

02:05:50.780 | are likely detecting distinct qualities

02:05:54.500 | and quantities within the food,

02:05:56.080 | chemical qualities and quantities within the food,

02:05:58.100 | and relaying that to the brain.

02:06:00.460 | - That's correct.

02:06:01.300 | And here's something that since we're getting

02:06:02.900 | into the future of this area,

02:06:05.160 | and while there is not direct published evidence yet,

02:06:11.700 | I think that is gonna be a fun area.

02:06:14.260 | So the gut as the brain

02:06:19.180 | also generates these electrical patterns.

02:06:22.100 | Those electrical patterns change

02:06:25.260 | depending on fasting versus feeding and circadian rhythms.

02:06:29.260 | Probably can realize jet lag.

02:06:32.020 | The gut is asking you for a burger at 3 a.m.,

02:06:34.420 | and your brain is telling the gut, you know,

02:06:37.260 | can you please go to sleep, right?

02:06:38.960 | So these electrical patterns,

02:06:43.300 | these electrical waves that are going into,

02:06:45.820 | that are being propagated by the gastrointestinal tract,

02:06:50.440 | there are like several different cells,

02:06:52.660 | like the enteric neurons are coordinating these cells.

02:06:57.900 | There are also these interstitial cells of Cajal.

02:07:02.660 | So Santiago Ramon Cajal.

02:07:05.580 | - The greatest neurobiologist of all time.

02:07:07.500 | - That's right, it was named after him.

02:07:10.220 | He actually has, I think it was like in the second volume

02:07:13.460 | of his classic book on the histology of the nervous system,

02:07:17.780 | one of the last figures talks about

02:07:19.260 | like the innervation of the villi in the intestine,

02:07:22.020 | some beautiful.

02:07:23.860 | - For those that don't know,

02:07:24.700 | Cajal shared the Nobel prize with Camillo Golgi in 1906.

02:07:28.660 | They together developed tools

02:07:31.420 | and mapped the structure of the nervous system.

02:07:34.460 | And it's fair to say that Cajal

02:07:36.980 | had supernatural levels of insight into the nervous system.

02:07:40.980 | He looked at the nervous systems

02:07:42.040 | of so many different animals in dead specimens.

02:07:46.620 | The joke, even though it's not funny,

02:07:51.420 | is that many animal species entered his laboratory,

02:07:54.340 | very few walked out.

02:07:56.040 | But by looking at fixed specimens under the microscope

02:07:58.580 | and then drawing them in select elements within them,

02:08:02.100 | essentially came up with most of the major hypotheses

02:08:05.180 | about how the nervous system works,

02:08:06.740 | not just its structure, but neuroplasticity,

02:08:09.300 | the failure of mammalian central nervous system neurons

02:08:12.320 | to regenerate.

02:08:13.160 | This is why after traumatic brain injury or stroke,

02:08:15.200 | there's often loss of function that doesn't recover.

02:08:17.260 | Sometimes it recovers.

02:08:18.300 | And that people who have injuries younger

02:08:21.340 | often can recover certain functions.

02:08:23.580 | Everything from the direction of electrical flow

02:08:27.000 | through the nervous system,

02:08:27.840 | all from looking at tissue that was not alive,

02:08:30.620 | no electrophysiology, no behavioral experiments,

02:08:32.940 | just raw, but incredible, supernatural,

02:08:37.940 | seemingly, levels of intuition and insight.

02:08:41.660 | Amazing.

02:08:42.620 | - Yes, there is some quote in one of his books

02:08:45.580 | that when he got invited to one of his friends to England,

02:08:50.260 | I don't remember, it was a famous neuroscientist

02:08:54.060 | at the time in the late 1800s

02:08:55.780 | who had helped him to expose his work to other audiences

02:09:00.780 | and invited him to England.

02:09:03.960 | So he said in there that it took like three months

02:09:06.660 | to go to that podcast, right?

02:09:08.620 | (laughs)

02:09:09.820 | It was a three-month trip.

02:09:11.460 | So he said that he brought his microscope.

02:09:15.820 | - With him. - With him.

02:09:17.020 | - Of course, that's very cool. - And in the room,

02:09:19.100 | he will be able to do some of these observations.

02:09:23.420 | - Yeah, peculiar guy,

02:09:24.380 | also known for carrying a very heavy iron umbrella

02:09:28.300 | in order to do physical exercise on the way to the lab.

02:09:31.060 | He was a very, very fit physical specimen.

02:09:34.260 | Also, reportedly, I don't know, pick which one,

02:09:39.260 | a pretty gruff person, not terribly pleasant to be around,

02:09:45.420 | ran a tight ship.

02:09:47.180 | But in any event, so the cells of the gut are named after,

02:09:51.180 | some of them are named after Cajal,

02:09:52.660 | interstitial cells of Cajal. - Cells of Cajal.

02:09:54.700 | - There, you just got a waltz

02:09:56.340 | into some neuroscience history, but critical history.

02:10:01.100 | - So they have this emanating electricity, right?

02:10:05.940 | And so far, these, and it seems like the sphincters

02:10:10.940 | modulate the emanation of this electricity.

02:10:14.460 | - Oh, like an instrument. - Yeah.

02:10:17.200 | And you probably think like that is because the intestine,

02:10:20.840 | and maybe here we get a little bit even deeper into these.

02:10:24.120 | And I read some work from a philosopher in the UK,

02:10:29.120 | who was, and I'm gonna paraphrase it very largely,

02:10:33.800 | so please don't quote me,

02:10:35.200 | but it's something along the lines

02:10:37.840 | that if we are what we eat,

02:10:40.320 | the place where food becomes us and we become food

02:10:43.240 | should be the intestine, right?

02:10:44.520 | Because that is where food is actually absorbed, right?

02:10:48.920 | So that is a very fascinating point.

02:10:51.760 | Number two is that the food enters us at a frequency

02:10:56.760 | that it will modulate the entire body, right?

02:11:00.560 | Therefore, like the body through this electricity,

02:11:06.200 | these electrical waves should be in sync

02:11:08.240 | with also the electricity of the entire nervous system.

02:11:11.440 | So I think that here's where in the future,

02:11:14.000 | I think that there's gonna be a fascinating realm

02:11:16.440 | of understanding how it is that these waves

02:11:19.520 | of the body and the brain are synchronized with each other.

02:11:24.520 | Because as we know, like for instance,

02:11:27.520 | sometimes when we don't, we are hungry,

02:11:31.440 | we become hangry, you know, like we become irritated

02:11:36.240 | by the fact that we don't have food,

02:11:38.120 | and perhaps it's this dissonance

02:11:40.480 | in the emanation of the electrical waves

02:11:42.640 | between the digestive tract and the nervous system.

02:11:45.760 | So I think that that is just like one of the realms

02:11:49.960 | of how it is that the brain is connected to the gut

02:11:55.360 | at a more organ to organ level

02:12:00.080 | to be able to make us function ultimately, right?

02:12:02.760 | Because that's how we are integrating the outside world,

02:12:07.760 | the food, into our entire system

02:12:09.960 | so we can maintain the entire organism.

02:12:12.960 | - Well, certainly our level of alertness

02:12:15.120 | is linked to our level of anticipation,

02:12:18.040 | and a lot of our food anticipation

02:12:20.760 | impacts our levels of arousal, aka alertness.

02:12:26.560 | So as you mentioned, we're a diurnal species,

02:12:30.000 | so in the middle of the night, it's unusual to get hungry,

02:12:32.560 | right, a lot of these pathways are shut down,

02:12:35.480 | digestion is happening at different rates,

02:12:37.480 | and typically our appetite is greater during the day

02:12:40.120 | than it is in the middle of the night.

02:12:42.120 | - That's right.

02:12:43.240 | - But in addition to that, it makes good sense to me

02:12:46.960 | that what is going on at the level of our gut

02:12:50.440 | is going to tell the brain,

02:12:53.080 | did we get enough nutrients from the previous day?

02:12:55.520 | Are we in a place of abundance?

02:12:58.400 | There's also the psychological aspect of gut sensing,

02:13:01.440 | and we haven't really touched on that.

02:13:03.720 | What are your thoughts as both a scientist

02:13:05.680 | and a human with a gut-brain axis

02:13:08.560 | on this notion of kind of gut intuition?

02:13:11.100 | You meet certain people, and it sort of relaxes

02:13:13.520 | and warms you, and you want to get to know them more.

02:13:15.520 | Other people, for whatever reason, you just feel like,

02:13:19.480 | I don't know, something doesn't feel quite right,

02:13:21.240 | that we can sense things at the level of the body

02:13:24.200 | that inform our brain,

02:13:25.840 | and no one really understands that process yet,

02:13:30.600 | but we do know that the vagus nerve,

02:13:32.560 | which is a multi-pronged pathway, big pathway,

02:13:37.560 | it's probably its own major branch

02:13:39.760 | of the nervous system, really,

02:13:41.760 | is sending bidirectional communication

02:13:44.160 | between brain and body,

02:13:45.920 | and presumably, when we're around somebody

02:13:48.680 | or something that doesn't quote-unquote feel right,

02:13:51.240 | the vagus is involved.

02:13:53.600 | - A few interesting things in that area.

02:13:59.240 | I mean, in the work of Carl Jung talks about it,

02:14:02.840 | about the subconscious and how it is

02:14:05.440 | that we are accumulating all of these experiences

02:14:07.760 | that we have been passing through in life

02:14:10.800 | is not that they are not a story anymore,

02:14:12.680 | it's just that they are back in the subconscious,

02:14:15.200 | and then, ultimately, they become part

02:14:16.880 | of this so-called intuition.

02:14:20.120 | We have this gut feeling that...

02:14:28.640 | We analyze some of the languages.

02:14:32.280 | I think that in the past,

02:14:34.560 | people have told me in so many different languages

02:14:36.920 | that there is this phrase for gut feelings in so many,

02:14:40.320 | like, for instance, I think in Portuguese,

02:14:42.280 | it's "frio de barriga," you know?

02:14:44.280 | Like, it's cold in the stomach.

02:14:48.280 | You get a cold.

02:14:49.320 | In Spanish, we call it a "presentimiento,"

02:14:53.800 | like a pre-feeling, you know?

02:14:56.720 | Or, yeah, pre-sensation or feeling.

02:14:59.640 | It would be more feeling if you translate that.

02:15:02.360 | - As if it arrives first.

02:15:04.480 | - Yes, before you're able to articulate it, right?

02:15:07.640 | So, there is this storage in the entire body

02:15:10.600 | that gives you, like, depending on the context,

02:15:13.560 | it gives you a certain type of feeling, right?

02:15:17.200 | And that's why we talk about intuition.

02:15:20.680 | There is also, like, this other aspect

02:15:24.520 | of how it is that food

02:15:29.200 | synchronizes that intuition.

02:15:34.680 | It seems to synchronize that intuition

02:15:39.640 | among two or more people.

02:15:41.960 | 'Cause if you think about it,

02:15:44.080 | we have this ritualistic way of serving something

02:15:48.800 | when we commonly say, or colloquially say,

02:15:52.200 | let's go for a cup of coffee.

02:15:54.440 | And often what we mean is let's go and talk about business,

02:15:56.920 | the future, resolve an issue.

02:15:59.200 | But we're talking about the cup of coffee

02:16:00.600 | and we have to share.

02:16:02.080 | And people, I think that there are some psychologists

02:16:04.040 | that have run some of these studies

02:16:06.720 | in which they say that if the food that we eat

02:16:10.560 | is more alike, we are more likely to connect,

02:16:13.280 | at least on the moment, right?

02:16:15.160 | So, there is this aspect.

02:16:16.680 | And that's why we share, you know, the food.

02:16:19.320 | - Interesting.

02:16:20.160 | So, is the idea that it's the actual chemical constituents

02:16:22.640 | of the food that's creating a common experience

02:16:25.640 | that then allows people to bond more readily?

02:16:28.200 | Or is it that the specific constituents of the food

02:16:33.200 | are actually driving bonding per se?

02:16:36.600 | I mean, it- - Yeah.

02:16:37.440 | And we go back to, if we are what we eat,

02:16:40.600 | then if we eat the same thing,

02:16:42.040 | we should be more alike to each other, right?

02:16:45.240 | That's why, you know, like in communities,

02:16:47.920 | you share the food.

02:16:48.960 | In fact, in like, if you go into certain specific communities

02:16:53.960 | you pass around the food, you pass around the drinks,

02:16:58.520 | you know, and it's very common to share, right?

02:17:02.280 | - Yeah, and certainly in romantic bonding,

02:17:04.880 | there are many factors, of course,

02:17:06.520 | but the kind of more basic functions of food, sex, and sleep

02:17:11.520 | represent the common places of bonding initially, right?

02:17:17.960 | And conversation, of course, and values, et cetera, right?

02:17:20.660 | Not to dismiss any of those, they're essential as well.

02:17:23.160 | But in terms of, you know, feelings of safety.

02:17:27.280 | - That's right.

02:17:28.120 | - Feelings of communing with somebody, right?

02:17:32.600 | These very basic biological functions.

02:17:35.880 | - Yeah, and in business too, right?

02:17:37.520 | Like people, there has been a study

02:17:39.760 | in like behavioral economists.

02:17:42.080 | They talk about how it is that business

02:17:44.040 | are more likely to happen when they are like made over food

02:17:47.080 | or launch or things like that, right?

02:17:48.600 | Like there's this synchronicity in the decision making.

02:17:51.280 | And here is a third dimension in this area

02:17:56.400 | that it has not been well explored,

02:17:59.600 | but I suspect that in the near future

02:18:01.720 | it will begin to be explored.

02:18:03.960 | I read a while ago a very elegant paper from Walter Cannon.

02:18:08.960 | So you may want to expand on who Walter Cannon was,

02:18:16.320 | but one of the founding figures

02:18:21.320 | of the study of physiology.

02:18:23.760 | - Yeah, autonomic physiology.

02:18:25.360 | - Autonomic physiology, right?

02:18:26.720 | Chair of physiology at Harvard in 1920s, 1930s.

02:18:30.980 | Author of "The Wisdom of the Body."

02:18:35.660 | He has a paper, or he published a paper,

02:18:40.520 | I believe in the 1930s.

02:18:44.160 | It's called "Voodoo Death."

02:18:47.040 | Voodoo Death.

02:18:49.760 | And I remember when I found that title,

02:18:51.560 | I was like, ooh, this is something to sit down and dissect.

02:18:56.360 | - Yeah, good title.

02:18:57.200 | - Good title.

02:18:58.020 | - If you want somebody to read it, good title.

02:19:00.080 | - And he essentially, the gist of it,

02:19:02.480 | let me see if I can do a little bit of justice,

02:19:06.080 | but obviously I will chop most of the details.

02:19:08.520 | But the gist of the paper is that

02:19:14.320 | in some observations, in some native tribes,

02:19:17.120 | I believe it was in Africa,

02:19:19.500 | that if young people, especially young, youngsters,

02:19:25.680 | if they were frightened by a shaman

02:19:34.000 | that they will not perform a certain thing,

02:19:36.920 | a certain task, right?

02:19:39.880 | They enter a level of psychosis, so to speak,

02:19:43.880 | that could cause death, like the custom spell, right?

02:19:48.880 | And that's why it's called Voodoo Death.

02:19:52.720 | What Cannon goes and describes is there is an activation

02:19:56.440 | of the vagus nerve and the peripheral nervous system

02:19:59.920 | that is a hyperactivation that is going

02:20:02.520 | through the sub-threshold level of consciousness.

02:20:05.560 | And in some of these tribes,

02:20:08.560 | at least that's what he explains that is happening.

02:20:12.000 | And I believe that he did some experiments in some animals.

02:20:16.080 | But what he was saying is that there's a hypertonic

02:20:18.320 | activation of the peripheral nervous system

02:20:20.480 | when there are these spells that are casted

02:20:24.400 | by a member of the tribe that is in a higher

02:20:27.560 | or more superior or more influential position.

02:20:31.480 | That if the other member,

02:20:34.880 | especially if it is paired with something, right?

02:20:37.280 | Like if you say, like, if you go outside

02:20:40.960 | and don't listen to what I just told you

02:20:43.520 | and you see a black cat, those two things match together

02:20:48.520 | and now you're hyperactivated, right?

02:20:50.640 | And become superstitious about it.

02:20:52.320 | But it is, what Walter Cannon goes to explain

02:20:55.280 | is there is a hyperactivation

02:20:56.760 | of the peripheral nervous system.

02:20:58.000 | Obviously, there's probably more details in there.

02:21:00.960 | But the paper really highlights an area of exploration

02:21:05.760 | that we don't know about.

02:21:06.680 | There's a threshold of subconsciousness

02:21:10.640 | of the nervous system, how it is driving us

02:21:12.720 | to have superstition, to drive instinctively

02:21:17.720 | to go and consume certain things

02:21:21.320 | or behave in certain ways, right?

02:21:24.400 | - Yeah, so it sounds like it's paired association learning

02:21:28.080 | through statements, cognition,

02:21:30.080 | but that's enacted through the vagus

02:21:31.800 | in order to control the organs of their periphery.

02:21:34.880 | That's nerd speak for if we hear and believe

02:21:38.240 | that certain events will cause certain changes

02:21:41.360 | in our physiology, they can, in some instances,

02:21:45.400 | become capable of that.

02:21:46.760 | Eat this food at this location and you'll get sick.

02:21:49.880 | Eat this food at this location, you'll feel better.

02:21:52.120 | - That's correct.

02:21:52.960 | - And it's learned association.

02:21:54.400 | And ultimately it's physiological,

02:21:56.400 | but it sounds like it's subject to a lot of learning effects.

02:22:00.180 | As long as we're talking about the vagus,

02:22:01.480 | I think it's a great opportunity to just mention

02:22:04.500 | that a lot of people understandably think

02:22:07.240 | that the vagus nerve activation

02:22:09.120 | is always about calming of the nervous system.

02:22:11.600 | And indeed, the vagus is placed under the umbrella

02:22:15.800 | of a parasympathetic pathway.

02:22:18.720 | But I think it's very important for people to know

02:22:21.200 | that both experimentally and clinically,

02:22:24.400 | if the vagus nerve is stimulated,

02:22:26.360 | you get exactly the opposite effect.

02:22:28.320 | You get arousal effects.

02:22:30.320 | This is commonly known in labs

02:22:32.840 | that do physiology of different kinds.

02:22:36.060 | It's in the clinical context,

02:22:37.460 | people with depression are sometimes treated

02:22:39.460 | with vagal nerve stimulators,

02:22:41.420 | and it certainly isn't driving more sedation,

02:22:43.420 | more depression of the nervous system.

02:22:45.380 | It drives alertness and arousal.

02:22:47.460 | So we have to, I think, make sure that we look

02:22:50.820 | at the vagus system and describe the vagal pathway

02:22:54.780 | as one that can both induce states of calm,

02:22:58.140 | of ease, rest, and digest,

02:22:59.820 | as it's sometimes called,

02:23:00.740 | but also states of arousal and alertness, even fear.

02:23:04.680 | And so I think of the vagus as a superhighway

02:23:07.820 | of a bunch of different pathways

02:23:09.220 | with lots of inputs and outputs

02:23:10.640 | that's highly subject to learning.

02:23:12.740 | And indeed, the vagus can slow heart rate,

02:23:16.020 | you know, down through a number of things

02:23:17.840 | like long exhale breathing.

02:23:19.540 | Earlier, we were talking about stress modulation,

02:23:21.500 | something my labs worked on.

02:23:23.280 | Extend your exhales, that's the most basic way.

02:23:26.900 | Physiological size, two inhales

02:23:28.380 | followed by a full exhale to lungs empty.

02:23:30.980 | These are core physiological mechanisms

02:23:33.180 | known to activate the vagus and lead to calming.

02:23:35.240 | But the vagus, I look at the vagus

02:23:37.620 | as kind of including both an accelerator of sorts,

02:23:42.140 | accelerator-based pathways in terms of arousal and breaks.

02:23:45.940 | And probably our basal level of vagal activation

02:23:50.480 | reflects sort of the RPM of our system.

02:23:52.660 | How much, are we calm?

02:23:54.900 | Are we humming at a higher level of activity?

02:23:57.660 | - Such an interesting pathway,

02:23:59.340 | such an interesting area of the nervous system.

02:24:01.020 | And we don't really understand yet.

02:24:04.260 | - No, because like-

02:24:05.100 | - Even the major branches and pathways

02:24:07.940 | are just now finally beginning to be understood.

02:24:11.480 | We're on virgin beaches.

02:24:16.980 | - Yes, and right now that I hear you

02:24:19.780 | bringing up the humming, for instance,

02:24:21.380 | there is a branch of the vagus

02:24:23.100 | that innervates the ear, the inner ear, you know?

02:24:27.100 | And that's why it is believed,

02:24:28.860 | and I think that there is a little bit of evidence out there

02:24:31.140 | that how it is certain music at a certain frequency

02:24:33.940 | will calm you down because it is immediately like,

02:24:36.940 | brings the, it starts to make the vagus vibrate

02:24:41.940 | at a certain frequency.

02:24:43.800 | - Yeah, and humming has been linked to vasodilation,

02:24:47.280 | which is associated with a calming effect,

02:24:49.700 | whereas activation of the sympathetic arm

02:24:52.340 | or the autonomic nervous system,

02:24:53.620 | or the kind of what sometimes is referred to

02:24:55.820 | as fight or flight, but it's involved in other things,

02:24:58.180 | causes vasoconstriction.

02:24:59.780 | - And if you think about it,

02:25:00.620 | like in several religious practices,

02:25:02.860 | there is the humming, right?

02:25:04.620 | There is the singing, there is the sound,

02:25:07.700 | the sound plays a big role.

02:25:09.460 | In running, there is a certain frequency

02:25:11.420 | that makes you run, calms you more

02:25:13.900 | and makes you run better, you know?

02:25:15.780 | - Is that right?

02:25:16.620 | - Yeah, there is some evidence, at least among runners,

02:25:19.580 | that they prefer a certain type of frequency

02:25:22.540 | for the running, right?

02:25:24.100 | So a certain pace of running or breathing.

02:25:27.260 | - And the sound, specifically the sound.

02:25:30.300 | - The sound of their feet.

02:25:31.300 | - Yeah, no, the sound of the music,

02:25:33.060 | like if you play a certain music, right?

02:25:36.660 | And probably the sound of their feet too, right?

02:25:38.540 | Like it's just, it has not been explored, right?

02:25:41.340 | - It's fascinating.

02:25:43.380 | And you know, so much of what I think about

02:25:45.660 | when I think about the nervous system

02:25:46.940 | is the fine grain processing of, you know,

02:25:49.900 | of color, of light or what,

02:25:51.460 | but when it comes to our feelings of wellbeing,

02:25:53.760 | our levels of arousal, sleep, et cetera,

02:25:56.660 | it's the rather, I don't want to call them crude

02:25:59.420 | because they're really sophisticated.

02:26:00.800 | They evolved to be sophisticated,

02:26:01.980 | but these kind of macroscopic signals

02:26:04.660 | like light coming in in the morning

02:26:07.180 | has these, you know, long wavelength

02:26:10.020 | and short wavelength contrast.

02:26:12.020 | That's what tells our brain it's morning.

02:26:14.740 | - That's right.

02:26:15.580 | - It's the orange, red, blue contrast.

02:26:17.260 | Even if there's cloud cover,

02:26:18.340 | it's the difference between those two

02:26:22.060 | different qualities of light that says it's morning.

02:26:25.200 | And when the sun is overhead,

02:26:26.600 | you don't see that yellow, blue,

02:26:28.560 | or orange, blue, red, blue contrast,

02:26:30.680 | but you see it again at sunset and it informs.

02:26:32.680 | So it sounds like the combination

02:26:35.620 | of specific chemicals in the gut tell us this is good.

02:26:38.800 | Pursue more of this.

02:26:39.640 | And maybe even the place where you found it is a good place

02:26:43.240 | as opposed to, and the opposite is probably also true.

02:26:45.840 | - Yes.

02:26:46.680 | Like that's an entire new domain of the digestive,

02:26:50.660 | the sensory system in the digestive tract

02:26:53.680 | that we haven't even begin to articulate yet.

02:26:56.680 | Memory.

02:27:00.600 | How do we remember, like what was that first meal?

02:27:03.640 | Like in the Ratatouille movie (laughs)

02:27:06.800 | from when we were children, right?

02:27:08.200 | Like it was very different, like I still remember

02:27:11.560 | like some of the very simple, humble meals

02:27:14.760 | that my mother would make,

02:27:15.880 | but it's just priceless for me, right?

02:27:19.100 | Whenever I go home, it's like I especially,

02:27:22.100 | without asking sometimes,

02:27:23.580 | my mother will prepare those for me

02:27:26.860 | and it's like, it just brings you back

02:27:30.060 | when you were that age, right?

02:27:32.300 | - Yeah, the memory system is tightly linked

02:27:34.100 | to taste and smell.

02:27:35.940 | There's no question about it.

02:27:37.220 | - And then like how it is that the gut triggers

02:27:39.720 | those sensations or farther reinforces those sensations.

02:27:44.620 | We haven't even begin to articulate.

02:27:46.860 | And when I said articulate,

02:27:48.140 | because we don't even have the language

02:27:50.020 | to refer to these things, you know?

02:27:52.660 | That's why at the very beginning we were talking

02:27:54.420 | over there in our conversations about the axis, you know?

02:27:57.820 | And that we don't say like the nose brain axis, right?

02:28:02.140 | Like we just went for what we had at that time.

02:28:05.700 | And I do think that the language will continue to evolve

02:28:08.100 | for us to be able to articulate more precisely,

02:28:11.860 | more richly, more elegant, more, you know,

02:28:15.260 | in so many different ways, how it is that

02:28:18.340 | the organs communicate with each other

02:28:23.340 | to make us who we are.

02:28:25.220 | And in there, in one of our papers,

02:28:29.060 | we quoted these beautiful passages

02:28:32.740 | from the book, "Memoirs of a Stomach."

02:28:37.240 | It was written in 1853--

02:28:41.340 | - By a French person?

02:28:43.660 | - By, what it says in the first page,

02:28:46.820 | by the minister of interior,

02:28:48.740 | because all of those who eat may read

02:28:52.060 | or something like that.

02:28:53.460 | And then on page 21, it goes to describe

02:28:55.900 | the dialogue between the gut and the brain.

02:28:58.140 | And it says like that, how it is that the gut

02:29:00.460 | communicates to the brain with a rapidity

02:29:03.900 | through these two sets of electrical wires

02:29:08.180 | that communicate the arrivals of the day,

02:29:12.260 | as we may eat, with a precision and rapidity

02:29:16.300 | to the brain, so the brain will make

02:29:19.140 | its own feelings and impressions.

02:29:22.700 | And then he said that when,

02:29:27.500 | he's talking from the perspective of the stomach,

02:29:30.060 | it says like, when I grew morose,

02:29:33.980 | like meaning I'm not working in digestion,

02:29:37.180 | then the brain also grew irritable and petulant.

02:29:40.900 | - Hangry. - Hangry.

02:29:42.460 | - It's so interesting to look at human experience

02:29:45.500 | from the directionality of gut to brain

02:29:47.960 | rather than brain to gut.

02:29:50.180 | - That's right.

02:29:51.380 | - And as I do from time to time,

02:29:55.780 | pay attention to what's happening in the landscape

02:29:58.580 | of wellness and mental health and physical health,

02:30:01.980 | a lot of what you see out there

02:30:06.480 | in terms of highly educated people

02:30:09.580 | who have thought very deeply about how to navigate

02:30:12.580 | decision-making in lots of different domains of life

02:30:15.340 | and to do it in a way that really honors

02:30:17.140 | our own individual preferences and needs.

02:30:20.780 | People like Martha Beck,

02:30:22.020 | I don't know if you've heard of her,

02:30:22.980 | but she exists in the, she has triple degreed from Harvard,

02:30:26.120 | but has talked a lot about learning to sense one's way

02:30:32.220 | into and through decisions through intuition

02:30:36.620 | that is more of the body

02:30:38.460 | and is more of particular brain circuits

02:30:42.060 | than our analytic, like pros and cons lists,

02:30:46.340 | because pros and cons lists,

02:30:47.620 | and obviously important metrics like objective metrics,

02:30:50.640 | like, oh, is this the right salary, the right location,

02:30:52.900 | the right, all the things that matter for decision-making,

02:30:56.620 | and we're trained in that in school in the United States

02:30:59.860 | and in many areas of the world as well, of course,

02:31:03.980 | and that's critical,

02:31:05.180 | but that there's this other training,

02:31:06.620 | there's this other learning of self

02:31:08.260 | that can be extremely useful,

02:31:09.460 | and it almost always comes back to body first,

02:31:13.480 | then to cognition and decision-making,

02:31:15.460 | and I feel like modern humans are trying to learn

02:31:18.980 | how to run the analysis of life decision-making

02:31:23.580 | through this, I guess, more ancient axis,

02:31:28.460 | so the, again, the intelligence of these,

02:31:30.740 | what used to be called more primitive systems,

02:31:33.080 | but I don't think they're primitive at all,

02:31:34.820 | and talking with you today,

02:31:35.860 | it's clear to me that these are highly sophisticated systems,

02:31:39.100 | just as sophisticated as any forebrain pathway

02:31:41.780 | involved in analyzing, say, like probability or something.

02:31:45.980 | - And that's why I like to highlight

02:31:47.820 | the example of having a nice meal

02:31:54.140 | and having a nice conversation at the same time.

02:31:58.100 | You know, if you go to a nice restaurant

02:31:59.820 | and you have a nice meal

02:32:00.900 | while you're having a nice conversation,

02:32:03.340 | and you pay attention to it,

02:32:05.600 | then it brings humility to your body

02:32:07.780 | to know how much your body's doing

02:32:10.600 | for you to be able to just express a tiny little bit

02:32:13.820 | and having some sort of highly intellectual,

02:32:17.340 | sophisticated conversation

02:32:19.420 | while you're able to put in the precise amount

02:32:22.940 | of lettuce inside of your mouth

02:32:25.060 | and chew it in the right way,

02:32:27.220 | and adjust it with a little bit of water

02:32:29.940 | and maybe a little bit of wine

02:32:31.520 | and understand what is cleansing your palate

02:32:33.620 | and like, you know, putting down the napkin

02:32:37.020 | and so on and so forth

02:32:38.940 | without going to the restroom

02:32:40.340 | every time that you feel like going to it, right?

02:32:43.300 | There is an entire sophistication of the body

02:32:46.420 | just to have something like as simple

02:32:48.100 | as a catch-up conversation, you know?

02:32:51.580 | - Do you think that our ability

02:32:53.020 | to sense into gut sensing more,

02:32:56.160 | to really hear and respond to the signals

02:33:01.100 | from the gut is something that we can learn

02:33:03.740 | even as adults, simply by paying more attention?

02:33:06.620 | - Yes, and I think that here's the concept

02:33:09.460 | that usually, you know,

02:33:12.060 | that when we talk about topics like meditation,

02:33:15.940 | you know, is that self-care,

02:33:17.300 | and that self-care is listening to your own body, right?

02:33:20.660 | How it is that the body is feeling.

02:33:23.180 | Like, I don't know, you know,

02:33:24.620 | I grew up in a, my mother will tell me like,

02:33:27.700 | or, you know, family will tell you,

02:33:29.940 | if you feel like going to the restroom

02:33:31.840 | to pee for a bio break, don't hold it for too long

02:33:36.740 | because it might be bad, right?

02:33:38.100 | Like, and I think that just learning that part

02:33:40.420 | of like listening to the body is an essential aspect.

02:33:43.980 | It's just that we're not constantly doing it

02:33:46.220 | over learning about how we are moving our career forward.

02:33:49.980 | - Yeah, so much of what we're taught

02:33:51.540 | in order to be high-achieving and forward-moving in life

02:33:56.100 | in modern culture is about learning

02:33:59.140 | to override the signals from the body,

02:34:01.540 | but it seems that learning to listen

02:34:04.420 | to the signals from the body

02:34:05.580 | is key to being a healthy human being.

02:34:08.340 | - Yes, and here I have an example.

02:34:10.460 | Years ago, I used to run quite a bit,

02:34:13.020 | and I remember that after I had run a marathon,

02:34:18.500 | I took a break for like a few weeks,

02:34:21.660 | and then I got back on the trail and I began running,

02:34:24.420 | and I was like, you know,

02:34:25.420 | I don't need to warm up for three or four weeks

02:34:27.860 | up to like get back into speed, right?

02:34:30.340 | And I remember that I started to feel like

02:34:32.860 | that my right, the soul of my right foot

02:34:36.980 | was a little bit like bothering me,

02:34:38.500 | like almost imperceptible.

02:34:41.300 | And I was like, no, you just have to keep going, you know?

02:34:45.740 | My wife Elaine told me like, you know,

02:34:47.900 | you should pay attention, take a break, you know?

02:34:50.020 | And I just kept running.

02:34:51.340 | And I remember specifically that one time I went to run

02:34:54.100 | and said like, I can put in 80 miles

02:34:56.980 | that I think that I was running at like seven minutes,

02:34:59.180 | 7.15 a mile or something like that.

02:35:01.980 | And I began running.

02:35:03.860 | And then I, after a mile, I was feeling pumped, you know?

02:35:07.300 | I had two miles, three miles, I was like,

02:35:09.660 | and then I usually will go and do four miles

02:35:12.140 | and then turn around and come back.

02:35:14.220 | I got on mile four and I felt crack,

02:35:18.380 | and I could not walk anymore.

02:35:20.700 | There was a hair fracture

02:35:23.780 | that is almost imperceptible in an X-ray,

02:35:26.460 | but boy, you cannot move your foot anymore.

02:35:29.420 | I had to limp for four miles all the way back to the car

02:35:32.700 | because I didn't even have my phone.

02:35:35.500 | And I never forgot that for next time,

02:35:39.220 | you gotta pay attention to your body, you know?

02:35:40.820 | Your body is simply telling you

02:35:42.340 | like something is a little bit off,

02:35:45.900 | just don't keep pushing it, you know?

02:35:47.860 | And I specifically remember because I kept running

02:35:50.460 | and I couldn't, I had to literally limp

02:35:53.660 | all the way back to the car, you know?

02:35:55.980 | - Well, Diego, I must say that among the many things

02:36:00.540 | that you've shared with us today and taught us

02:36:02.740 | about the gut and its ability to influence the brain

02:36:05.980 | and the incredible things that are happening

02:36:07.820 | at the level of biology and physiology of the gut,

02:36:10.580 | chief among them is the message

02:36:16.200 | that we should all pay more attention

02:36:18.900 | to our sensing at the level of our gut.

02:36:21.820 | And nowadays we hear so much about the gut microbiome

02:36:24.800 | such that fortunately,

02:36:25.960 | I think most people are starting to appreciate

02:36:27.620 | that the gut microbiome is vital for all aspects of health

02:36:31.820 | and that there are things that we can do

02:36:32.900 | to feed that microbiome, fiber intake,

02:36:34.780 | fermented food intake and so forth.

02:36:36.980 | But clearly based on what you've told us today

02:36:39.900 | that even just paying a little bit more attention

02:36:42.680 | to what our gut is telling us at the level of feeling good,

02:36:47.680 | feeling less good,

02:36:50.000 | 'cause the signs and signals are subtle, I realize,

02:36:54.920 | can really help us make better decisions

02:36:57.400 | and help us decide not just what foods to eat or not eat,

02:37:01.700 | how much to eat or not eat,

02:37:03.060 | but also how to navigate higher order decisions,

02:37:07.120 | if you will, about who to spend time with,

02:37:10.280 | what to do, what not to do,

02:37:11.880 | moving along the decision tree of life.

02:37:15.120 | And along those lines,

02:37:17.240 | I want to thank you for making the decision

02:37:19.200 | to come here today.

02:37:20.740 | I certainly am happy that we decided to do it.

02:37:24.180 | It's something that's been a long time coming.

02:37:26.020 | I really see you as one of the true pioneers in this area

02:37:28.500 | of trying to dissect the understanding

02:37:31.380 | of the gut brain axis,

02:37:32.660 | heal the brain through the gut,

02:37:34.340 | understand and modulate our emotions

02:37:37.180 | at the level of gut sensing.

02:37:38.820 | And while there are other researchers in this area,

02:37:41.860 | I refer to you as a pioneer

02:37:44.240 | because you've really undergone this incredible trajectory

02:37:47.260 | from the Amazon through nutrition science into neuroscience.

02:37:51.240 | And now we're getting a little bit

02:37:52.860 | into psychological science.

02:37:54.280 | And I'm excited for what comes next.

02:37:56.260 | I only ask one thing,

02:37:58.280 | which is that as you make these discoveries,

02:38:01.400 | that you come back and talk to us about them

02:38:03.700 | so that we can learn more about your incredible work.

02:38:07.240 | - So, Andrew, I want to say a few things.

02:38:10.020 | The first thing is that I feel deeply honored

02:38:12.440 | by your invitation.

02:38:14.120 | And thank you so much for the opportunity.

02:38:17.200 | I am just simply a representative

02:38:20.560 | of the people that work with me

02:38:25.040 | and work with us.

02:38:28.200 | You know, I'm just an ambassador

02:38:30.440 | and they get the majority of the credit

02:38:33.280 | for their dedication to help us understand

02:38:37.160 | a little bit more of the body

02:38:40.320 | and how it has helped us to navigate the world

02:38:42.800 | that we live in.

02:38:44.240 | So I want to thank you for the opportunity.

02:38:47.740 | I want to thank the people that have made this possible.

02:38:51.280 | Also, like the people that are along the way

02:38:53.960 | or the institutions that are along the way

02:38:56.560 | have helped fund these endeavor.

02:39:01.560 | You know, my home institution at Duke,

02:39:05.600 | I'm deeply grateful because my career has developed there.

02:39:09.600 | And some of my mentors, Roger Little, Andrew Muir,

02:39:13.640 | and the people that have helped me along the way.

02:39:16.560 | And then finally, I want to thank you and your team

02:39:21.560 | and congratulate you for the work that you do

02:39:25.000 | and that you have created this window

02:39:27.560 | for us to come and share with the public

02:39:30.440 | some of the, a little bit of the work that we do.

02:39:34.800 | Perhaps some of that is obviously is based on evidence.

02:39:39.800 | Some portion of that is thinking about the future,

02:39:44.540 | but I do think that through maintaining the dialogue

02:39:48.560 | with the public, that we can continue to understand

02:39:51.680 | the world that we live in.

02:39:52.720 | And for that, I have to thank you

02:39:54.300 | for having created this platform.

02:39:57.880 | - Well, it's a labor of love

02:39:59.320 | and I'm honored to be able to do it.

02:40:02.240 | And in no small part, because I get to sit down

02:40:05.120 | and have beautiful, intimate conversations

02:40:08.280 | about biology and life with you.

02:40:10.860 | So thank you so much.

02:40:12.260 | - Thank you.

02:40:13.200 | - Thank you for joining me for today's discussion

02:40:15.080 | about sensing with the gut and the gut brain axis

02:40:18.280 | with Dr. Diego Borges.

02:40:19.820 | To learn more about Dr. Borges' research

02:40:21.960 | and also to see a link to his fabulous podcast

02:40:24.440 | called "The Gastronauts," please see the show note captions.

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02:41:59.720 | Thank you once again for joining me for today's discussion

02:42:02.120 | with Dr. Diego Borges.

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02:42:08.080 | [upbeat music]

02:42:10.660 | you

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

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