How to Enhance Your Gut Microbiome for Brain & Overall Health

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

00:00:02.260 | where we discuss science and science-based tools

00:00:04.900 | for everyday life.

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

00:00:10.060 | and I'm a professor of neurobiology and ophthalmology

00:00:12.620 | at Stanford School of Medicine.

00:00:14.500 | Today, we are going to discuss the gut and the brain,

00:00:17.860 | and we are going to discuss how your gut influences

00:00:20.700 | your brain and your brain influences your gut.

00:00:24.140 | As many of you probably know,

00:00:25.860 | there is a phenomenon called your gut feeling,

00:00:28.640 | which tends to be something that you seem to know

00:00:31.460 | without really knowing how you know it.

00:00:33.920 | That's one version of the gut feeling.

00:00:35.920 | The other is that you sense something in your actual gut,

00:00:39.800 | in your body, and that that somehow drives you to think

00:00:44.420 | or feel or act in a particular way,

00:00:46.520 | maybe to move towards something

00:00:48.120 | or to move away from something.

00:00:50.280 | Now, today, we aren't going to focus so much

00:00:52.200 | on the psychology of gut feelings,

00:00:54.840 | but on the biology of gut feelings

00:00:57.280 | and how the gut and brain interact,

00:00:59.100 | because indeed your gut is communicating to your brain

00:01:01.580 | both directly by way of neurons, nerve cells,

00:01:05.080 | and indirectly by changing the chemistry of your body,

00:01:08.340 | which permeates up to your brain

00:01:09.980 | and impacts various aspects of brain function.

00:01:12.940 | But it works in the other direction too.

00:01:14.820 | Your brain is influencing your entire gut.

00:01:18.000 | And when I say entire gut, I don't just mean your stomach,

00:01:20.280 | I mean your entire digestive tract.

00:01:22.420 | Your brain is impacting things

00:01:23.740 | like how quickly your food is digesting,

00:01:26.280 | the chemistry of your gut.

00:01:28.020 | If you happen to be stressed or not stressed,

00:01:30.360 | whether or not you are under a particular social challenge

00:01:33.640 | or whether or not you're particularly happy

00:01:35.280 | will in fact adjust the chemistry of your gut

00:01:38.040 | and the chemistry of your gut in turn

00:01:40.300 | will change the way that your brain works.

00:01:42.740 | I'll put all that together for you

00:01:44.240 | in the context of what we call the gut microbiome.

00:01:47.200 | The gut microbiome are the trillions of little bacteria

00:01:50.820 | that live all the way along your digestive tract

00:01:54.040 | and that strongly impact the way that your entire body works

00:01:57.800 | at the level of metabolism, immune system,

00:02:00.340 | and brain function.

00:02:01.720 | And of course, we will discuss tools,

00:02:03.680 | things that you can do in order to maintain

00:02:06.400 | or improve your gut health.

00:02:08.440 | Because as you'll also soon see,

00:02:10.680 | gut health is immensely important

00:02:13.080 | for all aspects of our wellbeing

00:02:15.560 | at the level of our brain, at the level of our body.

00:02:18.520 | And there are simple actionable things that we can all do

00:02:21.240 | in order to optimize our gut health

00:02:23.740 | in ways that optimize our overall nervous system functioning.

00:02:26.960 | So we will be sure to review those today.

00:02:29.780 | This episode also serves as a bit of a primer

00:02:32.340 | for our guest episode that's coming up next week

00:02:34.980 | with Dr. Justin Sonnenberg from Stanford University.

00:02:38.320 | Dr. Sonnenberg is a world expert in the gut microbiome

00:02:42.440 | and so we will dive really deep into the gut microbiome

00:02:45.800 | in all its complexity.

00:02:47.480 | We'll make it all very simple for you.

00:02:49.000 | We will also talk about actionable tools in that episode.

00:02:51.740 | This episode is a standalone episode

00:02:53.760 | so you'll get a lot of information and tools,

00:02:55.820 | but if you have the opportunity to see this episode first,

00:02:58.360 | I think it will serve as a nice primer

00:03:00.160 | for the conversation with Dr. Sonnenberg.

00:03:02.860 | Before we begin, I'd like to emphasize that this podcast

00:03:05.440 | is separate from my teaching and research roles at Stanford.

00:03:08.200 | It is however, part of my desire and effort

00:03:10.260 | to bring zero cost to consumer information about science

00:03:12.920 | and science related tools to the general public.

00:03:15.760 | In keeping with that theme,

00:03:16.840 | I'd like to thank the sponsors of today's podcast.

00:03:19.720 | Our first sponsor is Athletic Greens.

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00:03:26.040 | I've been using Athletic Greens,

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00:04:05.480 | for my gut microbiome.

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00:06:55.960 | Okay, let's talk about the gut and the brain

00:06:58.360 | and how your gut and your brain communicate

00:07:00.360 | in both directions.

00:07:02.100 | Because as I mentioned before,

00:07:03.600 | your gut is communicating all the time with your brain

00:07:07.300 | and your brain is communicating all the time with your gut.

00:07:10.360 | And so the two are in this ongoing dance with one another

00:07:14.040 | that ordinarily is below your conscious detection.

00:07:17.180 | Although you're probably familiar with the experience

00:07:19.340 | of every once in a while getting a stomach ache

00:07:21.700 | or of eating something that doesn't agree with you

00:07:23.740 | or conversely eating something

00:07:25.420 | that you find particularly delicious.

00:07:27.840 | And that sensation or that experience rather

00:07:30.800 | being a whole body experience.

00:07:32.760 | Your mind is excited about what you're eating or just ate.

00:07:35.740 | Your gut is excited about what you're eating or just ate.

00:07:39.160 | And it seems to be a kind of unified perception

00:07:42.040 | of both brain and body.

00:07:44.080 | Today, we're going to talk about how that comes about

00:07:46.280 | in the negative sense.

00:07:47.640 | Like, you know, when you meet someone you really dislike

00:07:50.520 | or when you have a stomach ache and in the positive sense,

00:07:52.840 | when you interact with somebody that you really, really like

00:07:54.920 | and you'd like to spend more time with them, for instance,

00:07:57.160 | or when you eat something that you really, really like

00:07:59.880 | and you'd like to spend more time with that food,

00:08:01.800 | so to speak.

00:08:03.060 | Now, the gut and the brain represent

00:08:05.600 | what we call a biological circuit.

00:08:08.200 | Meaning they include different stations.

00:08:10.880 | So station A communicates with station B,

00:08:13.600 | which communicates with station C and so on.

00:08:16.200 | And as I mentioned earlier, it is bi-directional.

00:08:18.480 | It's a two-way street between gut and brain.

00:08:21.240 | I want to make the important point at the outset

00:08:24.000 | that when I say the word gut, when I refer to the gut,

00:08:27.400 | I'm not just referring to the stomach.

00:08:30.480 | Most of us think that the gut equates to the stomach

00:08:33.720 | because we think of having a gut or not having a gut

00:08:36.960 | or having a gut feeling of some sort.

00:08:39.760 | But in the context of gut-brain signaling

00:08:43.200 | and the related microbiome,

00:08:45.780 | the gut includes the entire digestive tract.

00:08:49.500 | That's right, from start to finish,

00:08:51.240 | the entire digestive tract.

00:08:53.040 | So much so that today we're going to talk about,

00:08:55.740 | for instance, the presence of neurons, nerve cells

00:08:58.800 | that reside in your gut,

00:09:00.420 | that communicate to specific locations in the brain

00:09:03.600 | and cause the release of specific neurochemicals,

00:09:06.240 | such as the neurochemical dopamine or serotonin,

00:09:09.480 | that can motivate you to seek more of a particular food

00:09:12.760 | or type of interaction or behavior,

00:09:14.960 | or to avoid particular foods, interactions, and behaviors.

00:09:18.520 | And some of those neurons, many of those neurons, in fact,

00:09:21.580 | reside in your intestines, not in your stomach.

00:09:24.680 | They can be in the small intestine or the large intestine.

00:09:27.540 | In fact, you actually have taste receptors and neurons

00:09:31.120 | located all along your digestive tract.

00:09:33.800 | You have neurons that are located all along your digestive

00:09:36.420 | tract, and they are communicating to your brain

00:09:39.420 | to impact what you think, what you feel, and what you do.

00:09:42.780 | Okay, so for the gut-brain axis,

00:09:44.300 | we need to deal with the brain part,

00:09:45.880 | and then we need to deal with the gut part.

00:09:48.040 | Let's just quickly talk about the brain part,

00:09:49.840 | because there, the word brain is also a bit of a misnomer

00:09:53.560 | in that when we say the gut-brain axis,

00:09:55.900 | it does include the brain,

00:09:57.180 | but it includes a lot of other things as well.

00:10:00.280 | So as many of you probably know by now,

00:10:02.660 | if you're listeners of this podcast, and if you don't,

00:10:04.780 | that's fine, your nervous system includes your brain

00:10:09.120 | and your spinal cord, and those together constitute

00:10:11.640 | what's called the central nervous system.

00:10:14.240 | Your neural retinas, which are lining the back of your eyes

00:10:18.440 | and are the light sensing portion of your eyes,

00:10:22.340 | are also part of your central nervous system.

00:10:25.680 | So actually, your eyes are part of your brain.

00:10:27.780 | They're the only parts of your brain

00:10:28.940 | that are outside the cranial vault.

00:10:30.960 | So your retinas, your brain proper,

00:10:34.020 | and your spinal cord make up the central nervous system.

00:10:36.580 | The other parts of your nervous system

00:10:37.900 | constitute what's called the peripheral nervous system,

00:10:40.960 | which are the components of your nervous system

00:10:42.660 | that reside outside the retinas, brain, and spinal cord.

00:10:46.600 | Now, this is very important

00:10:47.720 | because today we're going to talk a lot

00:10:49.340 | about how the gut communicates with the brain,

00:10:52.120 | and it does that by way

00:10:53.700 | of peripheral nervous system components,

00:10:56.980 | meaning nerve cells that reside in the gut

00:10:59.460 | and elsewhere in the body that communicate to the brain

00:11:03.240 | and cross into the central nervous system

00:11:05.920 | to influence what you think and what you feel, okay?

00:11:08.760 | So that's the nervous system part

00:11:10.700 | of what we call the gut-brain axis.

00:11:13.360 | Brain, again, just being a shorthand

00:11:14.840 | for including all the elements I just described.

00:11:17.820 | Gut, as you now know,

00:11:19.020 | includes all the elements of the digestive tract.

00:11:21.520 | Let's talk about the architecture or the structure

00:11:24.620 | of the gut of your digestive system.

00:11:27.520 | Now, not surprisingly, your digestive system,

00:11:30.420 | AKA your gut, begins at your mouth and ends at your anus.

00:11:34.100 | And all along its length, there are a series of sphincters

00:11:37.960 | that cut off certain chambers of the digestive tract

00:11:41.300 | from the other chambers.

00:11:43.460 | Now, also along this tube that we call the digestive tract,

00:11:47.920 | there's great variation in the degree of acidity or pH,

00:11:52.100 | as it's sometimes called.

00:11:54.260 | That variation in acidity turns out to give rise

00:11:57.960 | to different little micro environments

00:12:00.520 | in which particular microbiota, micro bacteria,

00:12:04.280 | can thrive or fail to thrive.

00:12:07.480 | And so the way I'd like you to think

00:12:08.960 | about the digestive tract,

00:12:10.300 | this gut component of the gut-brain axis,

00:12:13.380 | is that it's not just one component.

00:12:15.620 | It's not just your stomach with a particular acidity

00:12:18.440 | and a bunch of microorganisms that work particularly well

00:12:22.400 | to make you feel good and make your digestive pathways

00:12:26.280 | work well.

00:12:27.120 | It's a series of chambers, little micro environments

00:12:30.340 | in which particular microbiota thrive

00:12:33.280 | and other microbiota do not.

00:12:35.740 | And certain behaviors that you undertake

00:12:38.600 | and certain experiences that you have

00:12:40.600 | will adjust those micro environments

00:12:43.080 | in ways that make particular microbiota, certain bacteria,

00:12:46.600 | more likely to thrive and others less likely to thrive.

00:12:50.000 | We'll talk about how that was set up for you

00:12:51.840 | early in life.

00:12:53.180 | Actually from the moment that you came into the world,

00:12:55.320 | that microbiome was being established.

00:12:57.680 | It was actually strongly impacted,

00:13:00.680 | depending on whether or not you were born by C-section

00:13:02.840 | or by vaginal birth.

00:13:04.960 | And it was strongly impacted by who handled you

00:13:07.920 | when you came into the world.

00:13:08.840 | Literally the hands that were on you,

00:13:10.800 | how much skin contact you had,

00:13:12.560 | whether or not you were a preemie baby or not,

00:13:14.840 | whether or not you had pets at home,

00:13:16.180 | whether or not you were allowed to play in the dirt,

00:13:17.800 | whether or not you were allowed to eat snails

00:13:19.240 | or whether or not you were kept

00:13:20.480 | in a very antiseptic environment.

00:13:22.360 | All of those experiences

00:13:23.760 | shaped these little micro environments

00:13:26.180 | and shaped what constitutes best or worst

00:13:29.000 | for those micro environments.

00:13:30.880 | So you have this long tube that we call the digestive tract

00:13:34.240 | and it's very, very long.

00:13:36.360 | In fact, if we were to splay it out,

00:13:38.600 | we were to take all the curves and turns

00:13:40.840 | out of the intestine, we would find that it is very long.

00:13:43.900 | It's approximately nine meters long.

00:13:46.920 | Now the structure of that digestive tract

00:13:48.680 | turns out to be very important

00:13:50.280 | in terms of gut brain signaling.

00:13:52.260 | Once again, it's a tube and the hollow of that tube

00:13:56.060 | is called the lumen, L-U-M-E-N.

00:13:59.180 | But the walls of the tube are not necessarily smooth,

00:14:02.440 | at least not for significant portions

00:14:04.440 | of the digestive tract.

00:14:06.120 | For much of the digestive tract,

00:14:09.000 | there are bumps and grooves that look very much

00:14:11.780 | like the folds in the brain,

00:14:13.100 | but these bumps and grooves are made up of other tissues.

00:14:15.960 | They're made up of what's called a mucosal lining.

00:14:17.940 | So there's a lot of mucus there.

00:14:20.080 | And if we were to look really closely,

00:14:22.360 | what we'd find is that there are little hairy

00:14:24.520 | like cellular processes that we call microvilli

00:14:29.040 | that are able to push things along the digestive tract.

00:14:32.620 | The microbiota reside everywhere along the lumen

00:14:38.120 | of the digestive tract, starting at the mouth

00:14:41.160 | and all the way to the other end.

00:14:43.000 | And they reside within those microvilli

00:14:45.840 | and they reside within the lumen.

00:14:48.080 | And if we were to look really closely

00:14:51.080 | at the bumps and grooves along the digestive tract,

00:14:54.280 | what we would find is that there are little niches,

00:14:56.960 | little areas in which particular things

00:14:59.880 | can grow and reside best.

00:15:02.400 | Now that might sound kind of gross,

00:15:03.640 | but it actually is a good thing,

00:15:05.300 | especially if what's growing and residing there

00:15:08.040 | are microbacterial organisms that are good for your gut

00:15:12.500 | and that signal good things to your brain.

00:15:14.240 | And we will talk about what that signaling looks like

00:15:16.400 | and how that's done and accomplished in just a few moments.

00:15:19.200 | But I want you to get a clear mental picture of your gut,

00:15:22.280 | something that we don't often see.

00:15:23.960 | And often when we think about the gut,

00:15:25.540 | again, we just think about the hollow of the stomach,

00:15:27.760 | food going in there and getting digested,

00:15:29.780 | but it's far more complex

00:15:31.100 | and actually far more interesting than that.

00:15:33.120 | Now I've been referring to the gut microbiome

00:15:35.340 | and to the microbiota and these bacteria.

00:15:38.280 | Let me define those terms a little bit more specifically

00:15:40.760 | just to avoid any confusion.

00:15:43.920 | The microbiota are the actual bacteria.

00:15:46.900 | The microbiome is used to refer to the bacteria,

00:15:50.140 | but also all the genes that those bacteria make,

00:15:52.800 | because it turns out that they make some important genes

00:15:54.680 | that actually impact all of us.

00:15:56.600 | You have loads and loads of these little microbiota,

00:16:01.840 | these bacteria.

00:16:03.360 | In fact, right now you are carrying with you

00:16:06.020 | about two to three kilograms.

00:16:08.160 | So that's more than six pounds of these microbiota,

00:16:11.760 | these bacteria.

00:16:13.080 | And if we were to look at them under a microscope,

00:16:14.880 | what we would see is these are relatively simple

00:16:17.480 | little organisms, some remain stationary.

00:16:19.820 | So they might plop down into the mucosal lining,

00:16:22.920 | or they might hang out on a particular microvilli,

00:16:25.400 | or they might be in one of those little niches

00:16:28.120 | and others can move about.

00:16:30.120 | But they basically fill the entire lumen,

00:16:32.960 | they surround and kind of coat the surface of the microvilli,

00:16:37.300 | and they're tucked up into any of those little niches

00:16:40.660 | that are available to them to tuck into.

00:16:43.180 | If you were to take the head of a pin

00:16:46.820 | and look at it under the microscope,

00:16:49.160 | you could fit many, many hundreds, if not thousands or more

00:16:53.220 | of these little microbacteria.

00:16:55.460 | And the reason I say many, many thousands or more,

00:16:58.400 | I'm giving a kind of broad range there,

00:17:00.260 | is that they do vary in size.

00:17:02.080 | And again, they vary as to whether or not they can move

00:17:03.820 | or they don't move.

00:17:05.580 | Now, they're constantly turning over in your gut,

00:17:08.060 | meaning they're being born, so to speak,

00:17:10.620 | and they're dying off.

00:17:12.640 | And some will stay there for very long periods of time

00:17:15.640 | within your gut and others will get excreted.

00:17:18.100 | About 60% of your stool,

00:17:20.920 | as unpleasant as that might be to think about,

00:17:23.480 | is made up of live and dead microbacteria.

00:17:27.700 | So you're constantly making

00:17:29.180 | and excreting these microbacteria.

00:17:32.220 | And which microbacteria you make

00:17:35.300 | and how many stay inside your gut and how many leave,

00:17:39.660 | meaning how many are excreted,

00:17:41.180 | depends a lot on the chemistry of your gut

00:17:45.300 | and depends very strongly on the foods that you eat

00:17:48.720 | and the foods that you do not eat.

00:17:50.900 | Now, just because what we eat

00:17:52.340 | strongly influences our microbiome,

00:17:55.020 | meaning our microbacteria,

00:17:56.940 | does not mean that there are not other influences

00:18:00.460 | on what constitutes our microbiome.

00:18:02.860 | Our microbiome is also made up by microbacteria

00:18:07.420 | that access our digestive tract through our mouth,

00:18:09.980 | through breathing, through kissing,

00:18:13.800 | and through skin contact.

00:18:16.080 | In fact, one of the major determinants of our microbiome

00:18:19.660 | is who we interact with

00:18:21.620 | and the environment that we happen to be in.

00:18:24.020 | And that actually includes

00:18:25.180 | whether or not we interact with animals.

00:18:27.800 | In a little bit, I'll talk about some data

00:18:30.140 | as to whether or not you grew up in a home that had animals,

00:18:33.300 | whether or not you grew up in the home,

00:18:34.480 | whether or not there was a lot of social contact,

00:18:36.360 | meaning skin contact,

00:18:38.040 | or whether or not you grew up

00:18:39.380 | in a more animal-sparse, contact-sparse environment

00:18:43.580 | and how that shapes your microbiome.

00:18:45.760 | But the simple point is

00:18:47.320 | that what you eat influences your microbiome,

00:18:49.660 | but also what you do, what you think, and what you feel,

00:18:52.360 | and many of the little microbacteria

00:18:55.100 | that get into your digestive tract

00:18:57.420 | do so by way of social interactions.

00:18:59.920 | In fact, if you ask a neurobiologist

00:19:02.520 | what the role of the microbiome is,

00:19:04.620 | they'll tell you almost certainly

00:19:06.940 | that it's there to impact brain function.

00:19:10.220 | But if you have friends that are microbiologists,

00:19:14.420 | such as I do, they'll tell you,

00:19:17.640 | well, maybe the brain and nervous system

00:19:19.460 | are there to support the microbiome.

00:19:21.000 | It's the other way around.

00:19:22.560 | You have all these little microorganisms

00:19:24.060 | that are taking residence in our body.

00:19:26.760 | They don't really know what they're doing as far as we know.

00:19:29.420 | We don't know that they have a consciousness or they don't.

00:19:31.420 | We can't rule that out, but it seems pretty unlikely.

00:19:33.800 | Nonetheless, they are taking advantage

00:19:36.320 | of the different environments all along your digestive tract.

00:19:39.760 | They are taking advantage

00:19:41.600 | of the sorts of social interactions.

00:19:43.780 | For instance, the people you talk to and that breathe on you,

00:19:46.220 | the people that you shake hands with,

00:19:47.980 | the people that you kiss or don't kiss,

00:19:50.120 | the people that you happen

00:19:50.960 | to be romantically involved with or not,

00:19:52.840 | your dog, your cat, your lizard, your rat,

00:19:54.880 | whatever pet you happen to own is impacting your microbiome.

00:19:59.080 | There's absolutely no question about that.

00:20:01.060 | So hopefully now you have some sense

00:20:02.560 | of the architecture of the digestive pathway

00:20:05.320 | and you have some sense of the trillions

00:20:08.220 | of little microbacteria that are living

00:20:10.440 | all along the different components of that digestive pathway.

00:20:14.320 | But what we haven't talked about yet

00:20:15.920 | and what I'd like to talk about now

00:20:17.600 | is what those little microbiota are actually doing

00:20:21.240 | in your digestive tract.

00:20:23.120 | In addition to just living there

00:20:24.300 | for their own intents and purposes,

00:20:26.320 | they are contributing, for instance, to your digestion.

00:20:29.480 | Many of the genes that those microbiota make

00:20:32.820 | are genes that are involved in fermentation

00:20:35.300 | and genes that are involved in digestion

00:20:37.560 | of particular types of nutrients.

00:20:40.000 | And in a little bit, we will talk about

00:20:41.920 | how what you eat can actually change the enzymes

00:20:46.120 | that those microbiome components make.

00:20:49.080 | Enzymes largely being things

00:20:50.720 | that are responsible for digestion.

00:20:52.720 | They catalyze other sorts of cellular events,

00:20:54.780 | but in the context of the digestive pathway,

00:20:56.880 | we're talking about enzymes that help digest your food.

00:20:59.280 | So those microbiota are indeed helping you in many ways.

00:21:02.760 | And if you lack certain microbiota that can help you digest,

00:21:06.100 | it stands to reason that you would have challenges

00:21:07.920 | digesting certain types of foods.

00:21:09.960 | The other amazing thing that these microbiota do

00:21:13.480 | is they change the way that your brain functions

00:21:16.680 | by way of metabolizing or facilitating the metabolism

00:21:20.840 | of particular neurotransmitters.

00:21:23.200 | So one of the ways that having certain microbiota

00:21:25.400 | present in your gut can improve your mood

00:21:28.200 | or degrade your mood, for instance,

00:21:31.080 | is by way of certain microbiota being converted into

00:21:36.080 | or facilitating the conversion of chemicals such as GABA.

00:21:40.980 | GABA is what we call an inhibitory neurotransmitter.

00:21:44.520 | It's involved in suppressing the action of other neurons.

00:21:48.860 | And that might sound like a bad thing,

00:21:50.780 | but all types of sedatives, for instance,

00:21:53.960 | alcohol and a lot of neurons that naturally make GABA

00:21:57.840 | can help quiet certain circuits in the brain.

00:21:59.740 | For instance, circuits responsible for anxiety.

00:22:03.240 | In people who have epilepsy,

00:22:05.240 | the GABAergic neurons, as they're called,

00:22:07.760 | can often be disrupted in their signaling,

00:22:10.520 | meaning they're not cranking out as much GABA,

00:22:12.600 | and therefore the excitatory neurons,

00:22:15.120 | which typically release other molecules like glutamate,

00:22:17.880 | can engage in what's called runaway excitation,

00:22:20.940 | and that can give rise to seizures.

00:22:22.960 | So the simple message here is that the microbiota,

00:22:26.420 | by way of making neurochemicals,

00:22:28.840 | can influence the way that your brain functions.

00:22:31.300 | So you want to support those microbiota,

00:22:33.000 | and we will give you tools to support those microbiota.

00:22:36.780 | But the takeaway at this point is that those microbiota

00:22:40.600 | are making things locally to help digest food.

00:22:43.440 | Other microbiota are helping to make

00:22:46.060 | certain neurotransmitters like GABA,

00:22:47.980 | and we'll also talk about dopamine and serotonin.

00:22:50.540 | And so the very specific microbiota that reside in your gut

00:22:54.800 | have a profound influence on many, many biological functions,

00:22:58.660 | especially immune system function,

00:23:01.060 | brain function, and digestion.

00:23:03.640 | So that should give you a fairly complete picture

00:23:05.860 | of your gut microbiome.

00:23:08.260 | Now I'd like to talk about how your microbiome

00:23:10.660 | and your brain communicate,

00:23:12.420 | or more accurately, how your microbiome

00:23:14.280 | and the rest of your nervous system communicate.

00:23:16.880 | Neurons, which simply means nerve cells,

00:23:19.600 | are the cells that do most of the heavy lifting

00:23:22.340 | in your nervous system.

00:23:23.280 | There are, of course, other cell types that are important.

00:23:25.380 | Glial cells, for instance, very, very important cell types.

00:23:28.340 | You have endothelial cells,

00:23:29.700 | which are responsible for blood flow,

00:23:31.380 | pericytes and other types of cells.

00:23:33.700 | But the neurons are really doing most of the heavy lifting

00:23:36.640 | for most of the things we think about

00:23:38.380 | in terms of nervous system function.

00:23:40.300 | You have neurons in your gut,

00:23:44.180 | and that should not surprise you.

00:23:46.080 | Neurons reside in your brain, your spinal cord, your eyes,

00:23:49.900 | in fact, all over your body,

00:23:51.720 | and you've got them in your heart,

00:23:54.020 | and you've got them in your lungs,

00:23:56.300 | and you've got them in your spleen,

00:23:58.220 | and they connect to all the different organs

00:24:00.620 | and tissues of your body.

00:24:02.780 | So that's not surprising that you have neurons in your gut.

00:24:05.500 | What is surprising, however,

00:24:07.180 | is the presence of particular types of neurons

00:24:09.940 | that reside near or in the mucosal lining

00:24:13.880 | just next to that lumen of the gut,

00:24:16.740 | and that are paying attention,

00:24:18.820 | and I'll explain what I mean by paying attention,

00:24:20.780 | to the components of the gut,

00:24:23.080 | both the nutrients and the microbiota,

00:24:26.700 | and thereby can send signals up to the brain

00:24:31.180 | by way of a long wire that we call an axon,

00:24:34.740 | and can communicate what the chemistry

00:24:39.680 | and what the nutritional quality

00:24:42.100 | and what the other aspects of the environment

00:24:44.040 | are at the gut at a given location up to the brain

00:24:47.620 | in ways that can influence the brain to, for instance,

00:24:49.920 | seek out more of a particular food.

00:24:52.600 | Let me give you a sort of action-based picture of this.

00:24:55.460 | Let's say, like most people, you enjoy sweet foods.

00:24:59.220 | I don't particularly enjoy sweet foods,

00:25:00.840 | but there are a few that I like.

00:25:01.900 | I'm a sucker for a really good dark chocolate,

00:25:05.460 | or really good ice cream,

00:25:07.300 | or I got this thing for donuts that seems to just not quit,

00:25:10.820 | although I don't tend to indulge it very often.

00:25:13.340 | I do like them.

00:25:14.180 | If I eat that particular food,

00:25:16.980 | obviously digestion starts in the mouth,

00:25:19.420 | there are enzymes there, it gets chewed up,

00:25:21.020 | the food goes down into the gut.

00:25:22.620 | These neurons are activated,

00:25:27.240 | meaning that causes the neurons to be electrically active

00:25:30.800 | when particular components,

00:25:32.440 | certain nutrients in those foods are present.

00:25:35.340 | And for the cell types,

00:25:37.100 | or I should say the neuron types that matter here,

00:25:40.540 | the nutrients that really trigger their activation

00:25:43.420 | are sugar, fatty acids, and amino acids.

00:25:48.380 | Now, these particular neurons

00:25:50.300 | have the name enteroendocrine cells,

00:25:53.160 | but more recently they've been defined as neuropod cells.

00:25:57.220 | Neuropod cells were discovered

00:25:58.580 | by Diego Bohorquez's lab at Duke University.

00:26:02.240 | This is a phenomenal set of discoveries

00:26:03.860 | made mostly in the last 10 years.

00:26:06.340 | These neuropod cells, as I mentioned,

00:26:08.740 | are activated by sugar, fatty acids, or amino acids,

00:26:12.540 | but have a particularly strong activation to sugars.

00:26:17.380 | They do seem to be part of the sweet sensing system.

00:26:20.380 | And even though I'm focusing on this particular example,

00:26:22.940 | they represent a really nice example

00:26:25.700 | of how a particular set of nerve cells in our gut

00:26:29.380 | is collecting information about what is there

00:26:31.860 | at a particular location in the gut

00:26:33.420 | and sending that information up to our brain.

00:26:36.020 | Now, they do that by way of a nerve pathway

00:26:39.220 | called the vagus nerve.

00:26:40.900 | The vagus nerve is part of the peripheral nervous system,

00:26:43.220 | and the vagus nerve is a little bit complex to describe

00:26:46.380 | if you're just listening to this.

00:26:48.220 | If you're watching this,

00:26:49.460 | I'll try and use my hands as a diagram,

00:26:51.580 | but really the best thing to do

00:26:53.300 | if you really want to learn neuroanatomy

00:26:55.620 | is to just imagine it in your mind as best you can,

00:26:58.040 | and if you can track down a picture of it, terrific.

00:26:59.840 | But here's how it works.

00:27:01.800 | Neurons have a cell body that we call a soma.

00:27:04.100 | That's where all the DNA are contained.

00:27:07.420 | That's where a lot of the operating machinery

00:27:09.740 | of the cells are contained,

00:27:11.300 | and a lot of the instructions for that cell

00:27:13.300 | of what to be and how to operate are contained.

00:27:16.320 | The cell bodies of these neurons or the relevant neurons

00:27:20.060 | are actually up near the neck.

00:27:22.060 | So you can think of them as kind of a clump of grapes

00:27:25.300 | 'cause cell bodies tend to be round or ovalish.

00:27:28.340 | And then they send a process that we call an axon

00:27:32.800 | in one direction out to the gut,

00:27:36.420 | and they'll send another process up into the brain.

00:27:40.500 | And that little cluster near the neck that's relevant here

00:27:43.780 | is called the nodos ganglion, N-O-D-O-S-E.

00:27:47.340 | The nodos ganglion is a little cluster of neurons

00:27:50.140 | on either side of the neck.

00:27:51.840 | It has a process that goes out to the gut

00:27:53.500 | and a process that goes up into the brain.

00:27:55.680 | And again, these are just one component

00:27:57.800 | of the so-called vagus nerve.

00:27:59.320 | The vagus nerve has many, many branches,

00:28:02.740 | not just to the gut.

00:28:03.820 | There are also branches to the liver,

00:28:06.360 | branches to the lungs, branches to the heart,

00:28:09.060 | branches to the larynx, and even to the spleen

00:28:11.960 | and other areas of the body that are important.

00:28:14.860 | But right now, we're just concentrating on the neurons

00:28:16.680 | that are in the gut that signal up to the brain.

00:28:19.200 | And what the Bohorkas lab has shown

00:28:22.540 | is that these neuropod cells are part of this network.

00:28:25.720 | They're sensing several different nutrients,

00:28:28.280 | but in particular, when they send sugar,

00:28:30.300 | they send signals in the form of electrical firing

00:28:34.160 | up to the brain in ways that trigger activation

00:28:37.100 | of other brain stations that cause you to seek out

00:28:40.500 | more of that particular food.

00:28:42.300 | Now, this brings us to some classic experiments

00:28:45.580 | that at least to me are incredible.

00:28:48.420 | And these are highly reproducible findings

00:28:50.740 | showing for instance, that even if you bypass taste

00:28:54.900 | by infusing sweet liquid or putting sweet foods into the gut

00:28:59.900 | and people can never taste them with their mouth,

00:29:04.460 | people will seek out more of that particular food.

00:29:07.780 | And if you give them the option to have a sweet food infused

00:29:12.780 | into their gut or a bitter food infused into their gut

00:29:16.840 | or a sweet versus sour or a more sweet

00:29:20.080 | versus less sweet food, people have a selective preference

00:29:24.140 | for sweet foods, even if they can't taste them.

00:29:27.300 | Now, this is important to understand

00:29:28.860 | in the context of gut brain signaling,

00:29:30.420 | because we always think that we like sweet foods

00:29:33.040 | because of the way they taste.

00:29:34.740 | And indeed that's still true,

00:29:37.100 | but much of what we consider the great taste

00:29:40.660 | of a sweet food also has to do with a gut sensation

00:29:43.740 | that is below our conscious detection.

00:29:46.340 | How do we know that?

00:29:47.480 | Well, the Bohorquez lab has performed experiments

00:29:51.000 | using modern methods and their classic experiments

00:29:53.260 | showing that animals and humans will actively seek out

00:29:56.920 | more of a particular sweet food,

00:29:58.920 | even if it bypasses this taste system.

00:30:01.740 | And the reverse is also true.

00:30:04.020 | There have been experiments done in animals and in humans

00:30:07.240 | that have allowed animals or humans to select

00:30:10.820 | and eat sweet foods, and indeed that's what they do

00:30:12.940 | if they're given the option.

00:30:14.340 | And yet to somehow eliminate the activation of these neurons

00:30:20.680 | within the gut that can sense sweet foods.

00:30:23.660 | Now, there are a couple of different ways

00:30:24.700 | that those experiments have been done.

00:30:26.200 | In classic experiments that date back to the '80s,

00:30:29.420 | this was done by what's called subdiaphragmatic vagotomy.

00:30:32.460 | So this means cutting off the branch of the vagus

00:30:34.660 | that innervates the gut below the diaphragm

00:30:37.140 | so that the other organs can still function

00:30:38.920 | because the vagus is very important.

00:30:40.620 | But basically cutting off the sweet sensing in the gut,

00:30:43.420 | still giving people the opportunity

00:30:44.860 | to taste sweet foods with their mouth,

00:30:46.340 | and they don't actively seek out

00:30:48.460 | quite as much of the sweet food

00:30:50.500 | when they don't have this gut sensing mechanism

00:30:52.780 | that we now know to be dependent on these neuropod cells.

00:30:55.960 | More recent experiments involve selective silencing

00:30:59.540 | of these neuropod cells,

00:31:01.140 | and there've been a lot of different derivations

00:31:02.900 | of this sort of thing.

00:31:03.900 | But the takeaway from it is that our experience of,

00:31:07.000 | and our desire for particular foods

00:31:09.020 | has everything to do with how those foods taste.

00:31:11.480 | It also has to do, as you probably know, with their texture

00:31:15.460 | and the sensation of those foods in our mouth,

00:31:18.220 | and even indeed how they go down our throat

00:31:20.660 | sometimes can be very pleasing or very unpleasant.

00:31:23.160 | And it also has to do with the subconscious processing

00:31:28.180 | of taste that occurs in the gut itself.

00:31:31.860 | And again, when I say gut,

00:31:33.020 | I don't just mean in the stomach.

00:31:34.460 | There are actually neurons, neuropod cells

00:31:37.260 | further down your digestive tract,

00:31:39.020 | which are signaling to your brain

00:31:40.860 | about the presence of sweet foods,

00:31:42.420 | as well as foods such as amino acid rich foods

00:31:46.060 | or foods that are rich in particular types of fatty acids,

00:31:49.400 | signaling up to your brain

00:31:50.780 | and causing you to seek out more of those foods

00:31:54.820 | or to consume more of those foods.

00:31:57.180 | Now you're probably asking, what is the signal?

00:31:59.300 | How does it actually make me want more of those foods

00:32:01.900 | without me realizing it?

00:32:03.300 | Well, it does that by adjusting the release

00:32:05.340 | of particular neuromodulators.

00:32:07.780 | For those of you that are not familiar

00:32:09.420 | with neuromodulators, these are similar to neurotransmitters,

00:32:11.740 | but they tend to act more broadly.

00:32:13.760 | They tend to impact many more neurons all at once.

00:32:16.220 | And they go by names like dopamine, serotonin,

00:32:18.980 | acetylcholine, epinephrine, and so forth.

00:32:21.620 | Sometimes people refer to those as neurotransmitters.

00:32:24.020 | Technically they are neuromodulators.

00:32:25.860 | I'll refer to them almost always as neuromodulators.

00:32:28.820 | The neuropod cells signal by way

00:32:31.500 | of a particular branch of the vagus

00:32:33.860 | through the nodose ganglion that we talked about before,

00:32:36.940 | and through a number of different stations

00:32:39.740 | in the brainstem, eventually cause the release

00:32:43.420 | of the neuromodulator dopamine.

00:32:45.740 | Dopamine is often associated with a sense of pleasure

00:32:49.020 | and reward, but it is more appropriately thought of

00:32:52.260 | as a neuromodulator that impacts motivation,

00:32:54.740 | craving, and pursuit.

00:32:55.820 | It tends to put us into modes of action,

00:32:57.820 | not necessarily running and moving through space,

00:33:00.580 | although it can do that too.

00:33:01.980 | But in the context of feeding,

00:33:03.340 | it tends to make us look around more, chew more,

00:33:07.900 | reach for things more, and seek out more

00:33:09.940 | of whatever it is that's giving us that sensation

00:33:13.020 | of delight or satisfaction.

00:33:15.720 | And again, that sense of delight and satisfaction,

00:33:18.580 | you might experience only consciously

00:33:20.960 | as the way that something tastes on your mouth,

00:33:23.280 | but it actually is caused, again,

00:33:25.200 | by both the sensations in your mouth,

00:33:27.800 | but also by the activation of these neuropod cells.

00:33:31.080 | So this is an incredible system of gut-brain signaling,

00:33:34.120 | and it is but one system of gut-brain signaling.

00:33:36.700 | It turns out it's the system that we know the most about

00:33:39.740 | at this point in time.

00:33:41.120 | There are other components of gut-brain signaling

00:33:43.140 | that we'll talk about in a moment.

00:33:44.320 | For instance, the serotonin system.

00:33:46.860 | But in terms of examples of gut-brain signaling,

00:33:49.440 | for which we know a lot of the individual elements

00:33:51.800 | and how they work, I think this neuropod neuron sensing

00:33:55.960 | of sweet foods, fatty acids, and amino acids in the gut,

00:33:59.400 | and communicating that up to the brain by way of the vagus

00:34:03.320 | and causing us to seek out more of the foods

00:34:05.380 | that deliver those nutrients is an incredible pathway

00:34:08.840 | that really delineates the beauty

00:34:10.640 | and the power of this gut-brain axis.

00:34:13.260 | Let me talk about timescales.

00:34:14.560 | Here, I'm talking about a particular type of neuron

00:34:17.240 | that is signaling up to the brain using electrical signals

00:34:20.920 | to cause us to want to seek out

00:34:23.040 | a particular category of foods.

00:34:25.340 | That's happening relatively fast

00:34:28.760 | compared to the hormone pathways of the gut,

00:34:31.040 | which also involve neurons.

00:34:32.600 | So your gut is also communicating to your brain

00:34:35.080 | by way of neurons, nerve cells.

00:34:36.900 | But some of those nerve cells also release hormones,

00:34:41.920 | and those hormones go by names like CCK,

00:34:44.280 | glucagon-like peptide-1, PYY, et cetera.

00:34:49.060 | A good example of a hormone pathway,

00:34:51.680 | or what sometimes is called a hormone peptide pathway

00:34:54.420 | that is similar to the pathway I've talked about before,

00:34:58.180 | but a little bit slower is the ghrelin pathway.

00:35:01.740 | Ghrelin, G-H-R-E-L-I-N, increases with fasting.

00:35:06.740 | So the longer it's been since you've eaten,

00:35:10.100 | or if you're just eating very little food

00:35:12.200 | compared to your caloric needs,

00:35:14.020 | ghrelin levels are going to go up in your bloodstream,

00:35:16.360 | and they go up because of processes

00:35:18.720 | that include processes within the gut

00:35:21.140 | and include the nervous system.

00:35:22.900 | So it's a slow pathway driving you

00:35:24.820 | to seek out food generally.

00:35:27.060 | As far as we know, the ghrelin system is not partial

00:35:30.080 | to seeking out of sweet foods or fatty foods or so on.

00:35:33.220 | Ghrelin increases the longer it's been

00:35:38.520 | since you've eaten sufficient calories,

00:35:40.560 | and it stimulates a feeling of you wanting to seek out food.

00:35:44.140 | Well, how does it do that?

00:35:46.000 | It does that again by impacting neural circuits

00:35:48.280 | within the brain,

00:35:49.300 | neural circuits that include

00:35:50.700 | what we call the brainstem autonomic centers.

00:35:52.860 | So it tends to make you feel alert

00:35:54.860 | and quite, we say high levels of autonomic arousal.

00:35:58.480 | If you haven't eaten in a while,

00:35:59.940 | you might think that you just get really exhausted, right?

00:36:02.160 | Because we all hear that food is energy

00:36:03.860 | and caloric energy is what we need to burn,

00:36:05.940 | but you actually have a lot of energy stored in your body

00:36:08.360 | that you would be able to use if you really needed energy.

00:36:12.820 | But typically we haven't eaten in a while,

00:36:14.340 | we start to get agitated,

00:36:15.860 | and we get agitated by way of release of

00:36:18.300 | the neuromodulator epinephrine,

00:36:20.020 | which causes us to look around more,

00:36:22.140 | move around more and seek out food.

00:36:24.080 | That all occurs in brainstem autonomic centers

00:36:27.520 | and in the hypothalamus.

00:36:28.540 | We did an entire episode on feeding behavior

00:36:30.920 | and metabolism as well,

00:36:32.640 | and you can find those episodes at hubermanlab.com.

00:36:34.740 | So I don't want to go into a lot of detail

00:36:36.400 | about hypothalamic and brainstem centers,

00:36:38.660 | but there's a particular area of the brain

00:36:40.760 | called the nucleus of the solitary tract,

00:36:43.220 | the NST as it's called,

00:36:45.140 | that's very strongly impacted by these circulating hormones

00:36:48.220 | and tends to drive us toward feeding behavior.

00:36:50.700 | So the important point here is that we have a fast system

00:36:53.900 | that is paying attention to the nutrients in our gut

00:36:56.060 | or the absence of nutrients in our gut

00:36:57.700 | and stimulating us to seek out food

00:36:59.560 | or to stop eating certain foods.

00:37:01.300 | And we have a slower hormone related system

00:37:04.660 | that also originates in the gut and impacts the brain.

00:37:07.500 | But all of those converge on neural circuits for feeding.

00:37:12.320 | The neural circuits for feeding

00:37:13.480 | include things like the arcuate nucleus,

00:37:14.940 | the hypothalamus, they include

00:37:16.260 | a bunch of other neurochemicals.

00:37:18.020 | But the point is that you've got a fast route

00:37:20.380 | and a slow route to drive you to eat more or eat less,

00:37:25.020 | to seek out food and consume it,

00:37:26.820 | or to stop eating and to essentially kickstart

00:37:30.900 | the satiety mechanisms as they're called.

00:37:33.680 | And those are operating in parallel.

00:37:35.780 | It's not like one happens first, then stops, then the other.

00:37:38.020 | They're always operating in parallel.

00:37:39.620 | And I bring this up because there's a bigger theme here,

00:37:42.020 | which we see over and over again in biology,

00:37:44.260 | which is the concept of parallel pathways.

00:37:46.140 | You've always got multiple accelerators

00:37:48.340 | and multiple breaks on a system.

00:37:49.660 | It's very, very rare to have just one accelerator

00:37:52.180 | and one break on the system.

00:37:53.580 | And this will become important later

00:37:54.900 | when we talk about tools for optimizing your gut microbiome

00:37:58.260 | for healthy eating and for healthy digestion

00:38:00.500 | and for healthy brain function.

00:38:02.020 | I want to take a moment

00:38:02.860 | and talk about glucagon-like peptide one,

00:38:05.820 | which is also called GLP-1.

00:38:08.980 | GLP-1 is made by neurons in the gut

00:38:13.780 | and by neurons in the brain.

00:38:16.060 | This is a fairly recent discovery,

00:38:17.860 | but it's an important one.

00:38:20.260 | GLP-1 tends to inhibit feeding and tends to reduce appetite.

00:38:25.260 | There are a number of drugs released on the market now.

00:38:31.800 | One, for instance, goes by the name semaglutide,

00:38:34.760 | which is essentially an GLP-1 agonist.

00:38:38.220 | It causes the release of more GLP-1.

00:38:40.380 | It's being used to treat type two diabetes,

00:38:42.560 | which is insulin resistant diabetes.

00:38:44.380 | This is different than type one diabetes

00:38:46.320 | where people don't actually make insulin.

00:38:48.740 | It's also being used as a drug to reduce obesity.

00:38:53.740 | And it seems pretty effective,

00:38:55.580 | at least in certain populations.

00:38:57.900 | There are certain foods and substances that increase GLP-1.

00:39:01.180 | I've talked about a few of these on the podcast.

00:39:03.280 | One that I'm a particular fan of for entirely other reasons

00:39:06.000 | is yerba mate tea can stimulate the release of GLP-1.

00:39:10.580 | In South America, it's often used as an appetite suppressant,

00:39:13.240 | probably in large part

00:39:14.360 | because of its effects on GLP-1 release,

00:39:16.760 | but probably also because it does contain caffeine,

00:39:20.380 | which is a bit of a stimulant,

00:39:21.480 | which also can be involved in lipolysis,

00:39:23.300 | which is the utilization of fat stores for energy

00:39:25.400 | and so forth.

00:39:26.240 | A brief mention about yerba mate.

00:39:29.900 | There are some reports out there

00:39:31.860 | that yerba mate can increase certain types of cancers.

00:39:35.240 | The data that I've seen on this

00:39:37.960 | is that it tends to relate

00:39:39.160 | to whether or not those are smoked versions

00:39:41.580 | of the yerba mate tea,

00:39:43.020 | the amount of consumption and the debate is still out.

00:39:45.680 | So I invite you to look at those papers.

00:39:47.320 | You can search for those online.

00:39:49.020 | Nonetheless, yerba mate is one source of GLP-1 stimulation.

00:39:55.160 | Semaglutide is another source.

00:39:56.700 | It also can be stimulated by various foods,

00:39:58.740 | nuts, avocados, eggs, and so forth.

00:40:01.880 | Certain high fiber complex grains will also stimulate GLP-1.

00:40:06.680 | I raised this as not necessarily a route

00:40:09.920 | that you want to take in order to reduce food intake.

00:40:12.680 | I don't even know that that's your goal,

00:40:14.520 | but that GLP-1 is another one of these gut

00:40:19.100 | to brain signaling mechanisms that adjusts appetite

00:40:22.160 | that is dependent on diet,

00:40:24.520 | depends on what you eat or drink,

00:40:26.760 | and that the GLP-1 pathway does seem particularly sensitive

00:40:30.620 | to the constituents of diet.

00:40:32.640 | There's at least one quality study I was able to find

00:40:35.160 | showing that the ketogenic diet, for instance,

00:40:37.480 | which almost always involves ingestion

00:40:40.360 | of very low levels of carbohydrate, can increase GLP-1.

00:40:44.100 | Although, as I mentioned before,

00:40:45.220 | there are other foods that fall outside the range

00:40:48.000 | of what we would consider ketogenic

00:40:49.320 | that can also stimulate GLP-1.

00:40:50.880 | And as I mentioned, there are prescription drugs

00:40:52.480 | like semaglutide.

00:40:53.960 | There are other ones as well now that stimulate GLP-1.

00:40:57.480 | So how does GLP-1 reduce appetite?

00:40:59.440 | It does that in part by changing the activity of neurons

00:41:02.720 | in the hypothalamus, this cluster of neurons,

00:41:04.900 | just above the roof of our mouth,

00:41:06.880 | that themselves make GLP-1,

00:41:09.700 | and that cause the activation of motor circuits

00:41:12.880 | for reaching, chewing, all the things that we associate

00:41:16.560 | with feeding behavior.

00:41:18.040 | So I use GLP-1 as an example of a pathway

00:41:20.340 | that you might choose to tap into by ingestion

00:41:22.660 | of yerba mate or by ingestion of the foods I mentioned,

00:41:25.180 | or if it's something that interests you, ketogenic diet.

00:41:28.040 | But I also mention it simply

00:41:30.060 | because it's another beautiful example

00:41:32.620 | of how a hormone pathway can impact the activity

00:41:35.400 | of brain circuits that are directly involved

00:41:37.560 | in a particular behavior.

00:41:39.360 | So yet another example of how gut is communicating to brain

00:41:43.540 | in order to change what we think we want

00:41:46.400 | or to change what our actual behaviors are.

00:41:49.040 | So the next time you find yourself reaching for food

00:41:51.400 | or you find yourself wanting a particular sweet thing

00:41:55.400 | or fatty thing or something that contains

00:41:58.120 | a lot of amino acids, a protein-rich food,

00:42:01.620 | keep in mind that that's not just about

00:42:03.400 | the taste of the food.

00:42:04.600 | And it's not even necessarily about the nutrients

00:42:06.640 | that you need or don't need.

00:42:08.360 | It could be, but it's also about the subconscious signaling

00:42:11.480 | that's coming from your body all the time.

00:42:13.360 | Waves of hormones, waves of nerve cell signals,

00:42:17.480 | electrical signals that are changing

00:42:19.360 | the way that your brain works.

00:42:21.600 | And this raises for me a memory of the episode

00:42:25.080 | that I did with Dr. Robert Sapolsky,

00:42:27.800 | who's a world expert colleague of mine at Stanford,

00:42:30.500 | who is expert on things like hormones and behavior.

00:42:34.200 | But we got into the topic of free will,

00:42:36.320 | which is a bit of a barbed wire topic.

00:42:38.480 | As many of you know, it gets into the realm of philosophy,

00:42:40.680 | et cetera.

00:42:41.520 | And we were kind of batting back and forth the idea.

00:42:44.240 | I was saying, well, I think there's free will

00:42:46.920 | and can't there certainly be free will

00:42:48.720 | or certainly the idea that we can avoid certain choices.

00:42:52.960 | And Robert was saying, no.

00:42:55.900 | In fact, he said, nah.

00:42:57.920 | He doesn't believe that we have any free will.

00:42:59.800 | He thinks that events in our brain are determined

00:43:03.000 | by biological events that are below our conscious detection

00:43:06.780 | and that occur seconds to milliseconds

00:43:09.060 | before we make decisions or assessments.

00:43:11.240 | And therefore we just can't control what we do,

00:43:14.500 | what we think and what we feel.

00:43:16.340 | And at the time I sort of didn't buy it.

00:43:19.020 | I thought, I don't know.

00:43:20.460 | I just, I guess I really wanted to believe in free will.

00:43:23.240 | And to some extent I still do.

00:43:25.000 | But as we talk about how these neurons in our gut

00:43:27.580 | and these hormones in our gut are influencing our brain

00:43:30.600 | and the decisions that we are making

00:43:32.300 | at the level of circuits like the hypothalamus

00:43:34.660 | and the nucleus of the solitary tract,

00:43:36.540 | these are areas of the brain way below our frontal cortex

00:43:39.620 | and our conscious perception.

00:43:41.160 | I think these are examples that really fall in favor

00:43:44.700 | of what Dr. Sapolsky was arguing,

00:43:46.900 | which is that events that are happening within our body

00:43:49.620 | are actually changing the way our brain works.

00:43:51.140 | So we might think that we want the cupcake.

00:43:53.220 | We might think that we don't need to eat something

00:43:56.780 | or do need to eat something.

00:43:58.120 | And that is entirely on the basis of prior knowledge

00:44:01.660 | and decision-making that we're making with our head.

00:44:04.020 | But in fact, it's very clear to me based on the work

00:44:07.020 | from the Bohork's lab, classic work over the years

00:44:09.860 | dating back to the '80s and indeed back to the '50s

00:44:12.180 | that we'll talk about in a moment,

00:44:13.680 | that our body is shaping the decisions

00:44:16.380 | that our brain is making and we're not aware of it at all.

00:44:19.580 | Now, the good news is that whether or not

00:44:21.460 | you believe in free will or not,

00:44:23.180 | the simple knowledge that this whole process is happening

00:44:26.300 | can perhaps be a benefit to you.

00:44:27.880 | You can perhaps leverage it to get some insight

00:44:31.060 | and understanding and perhaps even a wedge

00:44:32.820 | into your own behavior.

00:44:33.660 | You might think, ah, I think I want that particular food

00:44:37.140 | or I think I want to avoid that particular food,

00:44:39.500 | but actually that's not a decision that I'm making

00:44:42.460 | on a purely rational basis.

00:44:44.160 | It has a lot to do with what my gut is telling my brain.

00:44:46.980 | So we've largely been talking about chemical communication

00:44:50.120 | between the gut and the brain.

00:44:51.740 | Chemical because even though these neuropod cells

00:44:55.580 | are communicating with the brain

00:44:57.000 | by way of electrical activity,

00:44:59.040 | what we call action potentials and in neural language,

00:45:02.300 | we call those spikes, spikes of action potentials.

00:45:04.960 | Spikes of action potentials, meaning those neural signals,

00:45:10.600 | cause the release of chemicals in the brain like dopamine.

00:45:14.160 | So it's chemical transmission.

00:45:16.960 | Similarly, hormones, even though they act more slowly,

00:45:21.380 | hormones like neuropeptide Y, like CCK, like ghrelin,

00:45:25.960 | they are signaling chemically.

00:45:28.020 | They're moving through the body.

00:45:30.100 | They're going in there affecting the chemical output

00:45:32.940 | of different cells.

00:45:34.140 | And they're changing the chemistry of those cells

00:45:36.140 | and the chemistry of the cells that those cells talk to.

00:45:38.620 | So that gives us one particular category of signaling

00:45:41.580 | from gut to brain, which is chemical signaling.

00:45:44.900 | But of course there are other forms of signals

00:45:47.520 | and those fall under the category of mechanical signaling.

00:45:51.500 | You're probably familiar with this.

00:45:52.840 | If you've ever eaten a very large meal

00:45:54.800 | or consumed a lot of fluid,

00:45:56.700 | you experience that as distension of the gut.

00:45:59.200 | And that doesn't just have to be distension of the stomach,

00:46:02.320 | but distension of your intestines as well.

00:46:06.080 | That distension is registered by neurons

00:46:08.260 | that reside in your gut.

00:46:09.880 | The signals go up to your brain

00:46:11.200 | and communicate with areas of the brain

00:46:12.780 | that are responsible for suppressing further consumption

00:46:15.780 | of food and or fluid.

00:46:17.700 | And under certain circumstances can also be associated

00:46:21.540 | with the activation of neural circuits

00:46:23.860 | that cause vomiting or the desire to vomit.

00:46:26.020 | So if ever you've eaten too much

00:46:28.040 | or you've eaten something that doesn't agree with you,

00:46:30.260 | that information is communicated by way of mechanosensors

00:46:33.940 | that sense the mechanics of your gut,

00:46:36.160 | possibly also the chemistry of your gut,

00:46:37.880 | but mostly the mechanics of your gut signal up to the brain

00:46:41.500 | and activate brain centers that are involved

00:46:43.600 | in stopping the eating behavior

00:46:46.640 | and activation of an area of the brainstem

00:46:50.440 | that is affectionately referred to as the vomit center

00:46:53.800 | among neuroanatomists.

00:46:55.060 | This is a area that more appropriately

00:46:57.800 | is called the chemoreceptor trigger zone, the CTZ,

00:47:00.800 | or area postrema.

00:47:02.000 | And neurons in this area actually will trigger

00:47:04.800 | the vomiting reflex.

00:47:06.780 | So the way that the gut and the brain communicate

00:47:10.100 | is both chemical and mechanical,

00:47:11.960 | and it can be both for sake of increasing

00:47:15.140 | certain types of behavior.

00:47:16.940 | Today, we're talking mainly about feeding behavior

00:47:18.760 | up until now anyway, but also ceasing to eat,

00:47:23.120 | closing your mouth, moving away from food,

00:47:25.160 | turning away from food,

00:47:26.820 | all behaviors that we're familiar with

00:47:28.260 | anytime we feel kind of sick on the basis of activation

00:47:31.240 | of this mechanosensor for gastric distress.

00:47:35.500 | So we've got chemical signaling and mechanical signaling.

00:47:38.340 | And I also want to emphasize

00:47:39.980 | that we have direct and indirect,

00:47:41.820 | signaling from the gut to the brain.

00:47:44.020 | Direct signaling is the kind of signaling

00:47:46.220 | of the sort I've been talking about mainly up until now,

00:47:48.720 | which is neurons in the gut,

00:47:51.360 | communicating with neurons in the brainstem

00:47:53.140 | that communicate with neurons in the hypothalamus.

00:47:55.360 | And of course, those are also going to interact

00:47:57.340 | with neurons of the prefrontal cortex,

00:47:59.460 | which is the area of your brain involved in decision-making.

00:48:01.540 | The, you know, I think it was the shrimp that made me sick.

00:48:05.220 | I'm going to, I just don't want any more of that.

00:48:07.320 | Or I'm never going back to that restaurant again

00:48:10.140 | because after I ate there about an hour later,

00:48:12.960 | I started feeling really not well.

00:48:14.580 | I felt, you know, kind of feverish,

00:48:15.940 | but my gut didn't feel well.

00:48:17.040 | My digestion was really off.

00:48:19.100 | All of that kind of information is handled

00:48:21.400 | in the prefrontal cortex at a conscious level,

00:48:23.720 | but the immediate decision to stop eating

00:48:25.980 | or to eat more of something,

00:48:27.420 | to move towards something or away from it,

00:48:28.780 | that's made by neural circuits that reside at the,

00:48:32.200 | we would say the subconscious level.

00:48:34.140 | But what we really mean is below the level of the neocortex.

00:48:36.820 | Below the cortex means essentially below our level

00:48:39.700 | of conscious awareness.

00:48:40.980 | So we talked about two types of information within the gut

00:48:43.660 | that are communicated to the brain, chemical information,

00:48:46.540 | meaning information about the nutrients

00:48:48.380 | that happen to be there and mechanical information,

00:48:50.420 | distention of the gut or lack of distention and so forth.

00:48:53.380 | And we talked about how these neuropod cells

00:48:55.560 | can signal the release of dopamine in circuits

00:48:57.420 | within the brain to cause you to seek out more of something.

00:49:00.580 | Now, in a very logically consistent way,

00:49:04.660 | dopamine is also involved in the whole business of vomiting.

00:49:08.780 | You might think, well, that doesn't make any sense.

00:49:10.360 | I thought dopamine was always a good thing.

00:49:12.100 | It's involved in moderation and reward, et cetera.

00:49:14.780 | But turns out the areopostrema, this vomit center

00:49:18.260 | and the brainstem is chock a block

00:49:20.420 | full of dopamine receptors.

00:49:22.060 | And if dopamine levels go too high,

00:49:24.700 | it can actually trigger vomiting.

00:49:26.380 | And this we see in the context of various drugs

00:49:29.500 | that are used to treat things like Parkinson's.

00:49:31.580 | Parkinson's is a deficiency in dopamine

00:49:34.300 | or a lack of dopamine neurons,

00:49:35.520 | typically that causes a resting tremor,

00:49:37.460 | difficulty in movement because dopamine is also associated

00:49:39.980 | with a lot of the neural circuits for movement.

00:49:43.140 | Many drugs that are used to treat Parkinson's like L-DOPA

00:49:47.380 | increase levels of dopamine so much,

00:49:49.880 | or at least activate dopamine receptors

00:49:52.820 | to such a great degree in certain areas of the brain

00:49:55.920 | that they can cause activation of things

00:49:58.360 | like the trigger to vomit.

00:50:01.700 | Now, this should also make sense in the natural context

00:50:04.180 | of if you gorge yourself with food, gorge yourself with food

00:50:07.000 | gorge yourself with food, the neurons in your gut

00:50:09.860 | that respond to that are simply detecting

00:50:12.300 | the presence of nutrients,

00:50:13.500 | but they don't really make decisions themselves.

00:50:16.340 | They don't know to stop eating.

00:50:18.100 | Your brain knows to stop eating or to eject that food.

00:50:21.220 | And so it's a wonderful thing that those neurons

00:50:23.560 | are communicating with areas of the brain,

00:50:25.580 | not just that stimulate consuming more food,

00:50:27.880 | but that are communicating with areas of the brain,

00:50:31.080 | for instance, areopostrema,

00:50:32.740 | that when dopamine levels get too high

00:50:35.940 | cause us to either stop eating that food

00:50:38.800 | or in the case of vomiting to eject that food.

00:50:41.900 | So I raise this and not to give you a kind of a disgusting

00:50:45.840 | counter example to what we call a pettative behaviors,

00:50:49.000 | the things that we like to do more of,

00:50:51.080 | but simply to give you a sense of just how strongly

00:50:54.440 | even these reflexes that we think of

00:50:56.340 | as feeling sick and vomiting,

00:50:58.220 | or the desire to seek out more food

00:51:00.220 | are really being controlled by a kind of push-pull system,

00:51:03.180 | by parallel pathways that are arriving from our gut.

00:51:05.440 | And the same neurochemicals, in this case, dopamine,

00:51:08.140 | are being used to create two opposite type behaviors,

00:51:12.140 | one behavior to consume more,

00:51:13.700 | one behavior to get rid of everything

00:51:15.180 | you've already consumed.

00:51:16.460 | So our brain is actually sensitive

00:51:18.600 | to the amount of signaling coming from our gut,

00:51:21.400 | not just the path by which that signal arrives.

00:51:24.980 | Our brain is very carefully paying attention

00:51:28.820 | to whether or not the levels of dopamine

00:51:30.420 | that are being triggered are within a normal range

00:51:32.860 | for typical eating behavior,

00:51:34.220 | or whether or not we've gorged ourselves

00:51:35.700 | to the point where enough already.

00:51:37.640 | Now, of course, mechanical signals will also play

00:51:41.060 | into areopostrema and into the vomiting reflex.

00:51:44.960 | If we have a very distended gut, we feel lousy,

00:51:47.260 | it actually can hurt very badly,

00:51:49.480 | and we will have the desire to vomit,

00:51:51.520 | or we will just simply vomit.

00:51:53.080 | Mechanical and chemical signals

00:51:56.540 | are always arriving in parallel.

00:51:58.340 | They never work in unison.

00:52:00.940 | And so now we have chemical signals, mechanical signals,

00:52:04.660 | and now I'd like to talk about direct and indirect signals,

00:52:07.580 | because almost everything I've talked about

00:52:09.380 | up until now are direct signals,

00:52:11.580 | a neural pathway that converges in the brain

00:52:13.400 | to create a particular feeling, thought, or behavior,

00:52:15.920 | but there are also indirect pathways,

00:52:18.280 | and that's what takes us back to the gut microbiome

00:52:21.220 | and to these little microbiota.

00:52:22.860 | And to just give you the takeaway message at the front here,

00:52:26.180 | and then I'll give you a little more detail

00:52:28.380 | as to how it comes about,

00:52:30.740 | you have neurotransmitters in your brain

00:52:33.820 | and in your spinal cord and in your eyes

00:52:35.540 | and in your peripheral nervous system,

00:52:37.220 | they cause the activation or the suppression

00:52:39.820 | of nerve activity,

00:52:41.100 | meaning they either electrically activate other nerve cells

00:52:44.060 | or they cause other nerve cells

00:52:45.260 | to be less electrically active,

00:52:46.940 | and they do that by way of neurotransmitters.

00:52:49.180 | But as it turns out, the gut microbiota

00:52:53.240 | are capable of influencing metabolic events,

00:52:55.740 | and in some cases are capable

00:52:57.340 | of synthesizing neurotransmitters themselves.

00:53:00.180 | So what that means is that these little bugs,

00:53:02.500 | these little microbiota that are cargo in your gut,

00:53:05.120 | the six pounds of cargo,

00:53:06.740 | they actually can make neurochemicals

00:53:08.540 | that can pass into the bloodstream and into your brain

00:53:11.440 | and actually impact the other cells

00:53:13.220 | of your body and brain indirectly.

00:53:15.540 | So without involving these very intricate nerve pathways

00:53:18.080 | that we've been talking about.

00:53:19.700 | In other words, the foods you eat,

00:53:22.460 | the environment of your gut microbiome

00:53:25.740 | can actually create the chemical substrates

00:53:27.920 | that allow your brain to feel one way or the other,

00:53:30.320 | to feel great or to feel lousy,

00:53:32.160 | to seek out more of a particular type of behavior

00:53:34.900 | or to avoid that behavior.

00:53:36.320 | And that would constitute indirect signaling.

00:53:38.760 | So I've been talking a lot about the structure and function

00:53:41.320 | of the gut to brain pathway,

00:53:42.980 | focusing mainly on feeding behaviors,

00:53:45.840 | and in some cases, avoiding feeding

00:53:47.900 | or even ejecting food from the digestive tract.

00:53:51.020 | I'd like to drill a little bit deeper

00:53:52.760 | into this indirect signaling pathway

00:53:55.100 | from the gut to the brain,

00:53:56.320 | because it bridges us nicely

00:53:58.300 | from neuronal signals in the gut to the brain,

00:54:01.460 | hormonal signals from the gut to the brain,

00:54:04.020 | to what also includes the microbiome,

00:54:06.540 | which is what we started talking about

00:54:08.020 | at the beginning of the episode.

00:54:09.620 | As I mentioned a couple of minutes ago,

00:54:12.660 | certain gut microbiota can actually synthesize

00:54:16.980 | certain neurotransmitters that can go impact the brain.

00:54:19.700 | And we actually have some knowledge

00:54:21.020 | about which microbiota can synthesize

00:54:23.740 | particular neurotransmitters.

00:54:25.220 | For instance, the neuromodulator dopamine

00:54:28.200 | can be synthesized by or from bacillus and serratia.

00:54:33.200 | Now, these are just names of microbiota.

00:54:36.260 | I don't expect that any of you

00:54:37.720 | would necessarily recognize them.

00:54:39.060 | These aren't the sorts of things

00:54:39.960 | that you necessarily would have run out and buy

00:54:41.500 | to get more dopamine.

00:54:43.140 | But the point is that particular gut microbiota

00:54:47.200 | can create dopamine in our gut

00:54:49.740 | that can get into our bloodstream

00:54:51.300 | and can generally change our baseline levels of dopamine,

00:54:55.100 | within the brain and other areas of the body.

00:54:57.300 | I mentioned baseline levels of dopamine

00:55:00.020 | because as I talked about on an episode all about dopamine,

00:55:03.500 | but I'll just repeat the basics here now,

00:55:07.140 | we have baseline levels of neurotransmitters

00:55:09.860 | or neuromodulators that act as sort of

00:55:11.740 | the level of the tide, the overall level.

00:55:14.900 | And then we can have peaks of dopamine

00:55:16.860 | that are created by behaviors or by ingestion

00:55:19.100 | of particular foods or drugs, et cetera.

00:55:21.660 | So bacillus and serratia tend to increase

00:55:25.380 | our baseline levels of dopamine.

00:55:28.100 | So if it turns out that we are creating

00:55:30.860 | the right gut microbiome environment

00:55:33.760 | that these particular gut microbiota can thrive in,

00:55:37.980 | well then our baseline levels of dopamine will be elevated.

00:55:41.340 | And in general, that leads to enhancement of mood.

00:55:43.840 | Similarly, there are other gut microbiota,

00:55:48.600 | for instance, candida, streptococcus, various enterococcus.

00:55:53.240 | These always have these kind of strange

00:55:54.940 | and not so attractive names,

00:55:56.540 | at least to me as a neurobiologist.

00:55:58.420 | Nonetheless, those particular microbiota

00:56:01.820 | support the production of,

00:56:04.120 | or can even be metabolized into serotonin,

00:56:07.640 | which is a neuromodulator associated with mood,

00:56:10.760 | with social interactions,

00:56:11.980 | with a huge number of different types

00:56:13.960 | of events and behaviors.

00:56:15.780 | Again, these gut microbiota, when present

00:56:20.200 | and allowed to thrive in our gut,

00:56:21.980 | will increase our overall levels of serotonin.

00:56:25.640 | And riding on top of that level of serotonin

00:56:28.980 | will be the serotonin that's specifically released

00:56:31.700 | in response to certain behaviors.

00:56:33.640 | And I really want to drive home this point

00:56:35.940 | of baselines and peaks.

00:56:37.700 | The baseline level of serotonin might set our overall mood,

00:56:40.740 | whether or not we wake up feeling pretty good

00:56:43.260 | or really lousy if our serotonin levels

00:56:45.760 | happen to be very, very low.

00:56:47.380 | Whether or not we tend to be in a kind of a calm space

00:56:50.100 | or whether or not we tend to be somewhat irritable.

00:56:52.500 | But then of course, individual events,

00:56:54.900 | as we go about our day,

00:56:56.060 | maybe a compliment that we get,

00:56:57.440 | or maybe somebody says something irritating to us,

00:56:59.880 | whatever it may be,

00:57:00.900 | will also influence levels of serotonin.

00:57:02.880 | But those serotonin events are going to be related to events

00:57:06.460 | at particular neural circuits in the brain.

00:57:08.860 | And this is an important topic

00:57:10.480 | because I think that a lot of people here

00:57:13.180 | quite accurately, oh, 90 to 95% of our serotonin

00:57:16.960 | is manufactured in the gut.

00:57:18.420 | And indeed that's true.

00:57:19.280 | It's manufactured from the sorts of microbiota

00:57:21.760 | that I just described.

00:57:23.680 | And there are many, many experiments now,

00:57:25.140 | mostly in animal models,

00:57:26.280 | but also some in humans that show

00:57:28.760 | that if the gut microbiome is deficient in some way

00:57:31.740 | to these particular bacteria,

00:57:34.880 | that serotonin levels drop and people's mood suffers,

00:57:37.420 | maybe even their immune system functions,

00:57:39.460 | maybe even exacerbates certain psychiatric illnesses.

00:57:43.020 | However, a lot of people take that to mean

00:57:45.620 | that the serotonin of the brain all comes from the gut

00:57:50.100 | or mostly comes from the gut.

00:57:51.560 | That's not the case.

00:57:52.400 | It's still the case that you have neurons in the brain

00:57:54.820 | that are responsible for releasing their serotonin

00:57:57.220 | directly in response to certain things like social touch

00:58:00.160 | or through other types of positive social experiences.

00:58:04.100 | So we've got gut microbiota

00:58:07.540 | that can literally be turned into dopamine

00:58:10.060 | and raise our baseline levels of dopamine.

00:58:11.800 | We've got gut microbiota

00:58:12.980 | that can literally raise our baseline levels of serotonin.

00:58:16.360 | And indeed, there are other gut microbiota

00:58:18.380 | like lactobacillus or bifidobacterium,

00:58:23.380 | hard complex names to pronounce,

00:58:26.020 | bifidobacterium that can give rise

00:58:29.020 | to increases in GABA levels,

00:58:30.880 | this inhibitory neurotransmitter

00:58:32.380 | that can act as a little bit of a mild sedative,

00:58:34.740 | can reduce irritability, et cetera.

00:58:37.260 | But that's just the baseline,

00:58:38.920 | the kind of tide of those neuromodulators.

00:58:41.280 | Again, I want to emphasize

00:58:42.300 | that we still have neural circuits within the brain and body

00:58:44.660 | that are specifically releasing in a very potent way,

00:58:47.860 | dopamine, serotonin, and GABA.

00:58:50.100 | So the two things act in concert.

00:58:52.260 | Even though the gut and the brain

00:58:53.780 | are acting both in parallel

00:58:56.420 | and directly influencing one another,

00:58:59.100 | it is a powerful synergistic effect.

00:59:01.820 | And there are now hundreds of studies,

00:59:04.220 | maybe even thousands by this point,

00:59:06.820 | mostly performed in animal models, typically mice,

00:59:10.340 | but also some studies in humans

00:59:12.260 | that show that creating the correct environment

00:59:15.560 | for these gut microbiota to thrive

00:59:17.320 | really does enhance mood and wellbeing.

00:59:20.560 | And that when our gut microbiome is not healthy,

00:59:25.200 | that it really can deplete our mood and sense of wellbeing.

00:59:28.780 | Now, there are two major phases

00:59:31.500 | to creating a healthy gut microbiome.

00:59:33.920 | One you can control,

00:59:35.580 | and the other one is less under your control.

00:59:38.620 | I get into this in a lot of detail

00:59:40.860 | in the episode with Dr. Sonnenberg,

00:59:42.780 | which is coming out immediately after this one,

00:59:46.540 | the following Monday, that is.

00:59:48.500 | But for now, I want to just capture a few of the main points

00:59:52.420 | about the early establishment of the gut microbiome.

00:59:55.440 | It turns out that the environment that we are exposed to,

01:00:01.060 | the things that come into contact

01:00:02.180 | with our skin and digestive tract

01:00:03.960 | and any other mucosal lining,

01:00:05.440 | even the urethra, the nasal passages,

01:00:08.380 | any opening to the outside world

01:00:10.140 | that brings in certain, excuse me,

01:00:13.600 | certain microbiota in the first three years of life

01:00:17.820 | is going to have a profound impact

01:00:20.100 | on the overall menu of microbiota

01:00:22.920 | that we will be able to carry within our body.

01:00:27.300 | And it really does seem that getting exposure to

01:00:30.340 | and building a diverse microbiome

01:00:32.300 | in those first three years is critical.

01:00:34.900 | There's a lot of speculation and some data

01:00:37.580 | as to cesarean-delivered babies

01:00:40.520 | having less diverse microbiomes

01:00:43.140 | compared to vaginally-delivered babies.

01:00:44.760 | There have been attempts,

01:00:45.940 | although not conclusive attempts,

01:00:47.980 | to link that to the presence of autism spectrum disorders,

01:00:51.600 | which at least by some statistics

01:00:53.580 | seem to be of higher probability in cesarean deliveries,

01:00:57.740 | although there are other studies that refute that,

01:01:00.420 | and I want to make that clear.

01:01:01.860 | However, it's clear that babies do not get much,

01:01:06.220 | if any, exposure to microbiota inside of the womb,

01:01:10.460 | maybe a little bit, but not much.

01:01:11.900 | But it is during the birth process

01:01:13.660 | and in the days and weeks immediately after

01:01:16.460 | they arrive in the world

01:01:18.740 | that their gut microbiome is established,

01:01:20.860 | that those gut microbiota take residence within the gut.

01:01:24.380 | So it will depend on whether or not

01:01:25.860 | they were breastfed or bottle fed.

01:01:27.360 | It will depend on whether or not

01:01:28.540 | they were exposed to a household pet or not,

01:01:30.780 | whether or not they were held by multiple caregivers

01:01:33.360 | or just by one, whether or not they were a preemie baby

01:01:36.180 | and were contained in a particularly restrictive environment

01:01:39.680 | in order to encourage their further development

01:01:41.520 | before they could be brought home or not.

01:01:43.700 | I don't want to give the picture that if you were isolated

01:01:46.700 | or you were delivered by C-section

01:01:48.740 | that you're somehow doomed to have a poor microbiome.

01:01:50.780 | That's simply not the case.

01:01:52.540 | However, it is the case that the more diversity

01:01:55.540 | of microbiota that one can create early in life

01:02:00.060 | is really helpful for long-term outcomes

01:02:03.380 | in terms of brain to gut signaling, gut to brain signaling,

01:02:07.840 | and for sake of the immune system.

01:02:10.940 | There are some decent studies showing that

01:02:14.940 | if children are exposed to a lot of antibiotic treatment

01:02:18.340 | early in life, that can be very detrimental

01:02:21.040 | to establishment of a healthy gut microbiome.

01:02:23.760 | And fortunately, that reestablishing

01:02:26.060 | a healthy gut microbiome can help rescue

01:02:28.260 | some of those deficits.

01:02:29.660 | So doctors nowadays are much more cautious

01:02:32.520 | about the prescription of antibiotic drugs

01:02:35.180 | to children in their early years,

01:02:37.140 | not just up to three years,

01:02:38.220 | but extending out to five and seven and 10 years.

01:02:40.960 | And even in adults, they're very, very careful about that,

01:02:44.580 | or they ought to be.

01:02:46.120 | One reason is the existence or I would say the proliferation

01:02:50.260 | of antibiotic resistant bacteria

01:02:52.940 | that are becoming more common in hospitals and elsewhere,

01:02:55.760 | and that can cause serious problems.

01:02:57.500 | But in addition to that, because of this understanding

01:02:59.720 | that the gut microbiome is influencing and actually creating

01:03:03.240 | neurotransmitters that can impact mood and mental health,

01:03:05.980 | impact immune health, and so on.

01:03:08.140 | As I mentioned earlier, there are hundreds,

01:03:09.760 | if not thousands of studies emphasizing the key role

01:03:12.900 | of the microbiome on brain health,

01:03:15.500 | psychiatric health, et cetera.

01:03:18.060 | I want to just highlight a few of those studies,

01:03:20.580 | and in particular, some recent studies that come from labs

01:03:23.880 | that have been working on this sort of thing

01:03:25.060 | for a very long time.

01:03:26.600 | One of the more exciting studies comes from the work

01:03:28.860 | of Mauro Costa-Matioli's lab,

01:03:31.080 | which is at Baylor College of Medicine.

01:03:33.180 | Mauro's lab has been working on mouse models

01:03:36.160 | of autism spectrum disorder for a long time,

01:03:39.140 | and looking at social behavior using a mouse model

01:03:42.420 | for a long time.

01:03:43.520 | And they've been able to identify particular types

01:03:47.300 | of microbiota that when they take resonance in the gut

01:03:52.300 | can help offset some of the symptoms of autism,

01:03:56.480 | at least the symptoms of autism that exist

01:03:58.300 | in these mouse models, okay?

01:03:59.500 | So again, this is not human work.

01:04:01.400 | This is work being done on mouse models

01:04:03.000 | for the simple reason

01:04:04.020 | that you can do these kinds of manipulations,

01:04:06.020 | where basically they took mice

01:04:07.880 | that were in germ-free environments

01:04:09.300 | or non-germ-free environments,

01:04:11.580 | or they exposed mice to particular microbiota

01:04:13.980 | and not other microbiota,

01:04:15.380 | and they discovered that a particular microbiota

01:04:18.700 | called L-reuteri, it's L period, R-E-U-T-E-R-I,

01:04:24.060 | treatment with L-reuteri corrects the social deficits

01:04:28.380 | present in these autism models.

01:04:30.180 | And it does so by way of activating our old friend,

01:04:32.940 | the vagus nerve,

01:04:34.300 | but not simply because the vagus nerve triggers

01:04:36.940 | the release of dopamine,

01:04:38.220 | but it turns out that this particular gut microbiota,

01:04:41.120 | L-reuteri, can correct the social deficits

01:04:43.620 | in this autism spectrum disorder model.

01:04:45.980 | It does that by way of a vagal nerve pathway

01:04:48.220 | that stimulates both dopamine release

01:04:49.940 | and oxytocin release.

01:04:50.980 | And they established this really mechanistically

01:04:52.980 | by showing, for instance, if you get rid

01:04:54.540 | of the oxytocin receptor, you don't see this rescue.

01:04:57.480 | Now, those are mouse models.

01:04:58.620 | So we have to take those with the appropriate grain of salt,

01:05:01.700 | but they're really exciting.

01:05:02.780 | And they come to us in parallel with other studies

01:05:06.820 | that are being done taking the microbiomes

01:05:09.180 | of people who have one condition or lack of condition

01:05:13.780 | and putting it into people who have one condition

01:05:16.460 | or another condition.

01:05:17.420 | Let me explain what I mean by that.

01:05:19.180 | The early discovery of the gut microbiome

01:05:22.320 | and its potential to impact health was not in the context

01:05:26.300 | of the gut to brain pathway,

01:05:28.480 | but rather it was in the context of colitis.

01:05:30.800 | This dates back to studies in the '50s,

01:05:33.320 | whereby people with very severe intractable colitis

01:05:36.900 | for which no other treatment was going to work

01:05:39.120 | received fecal transplants.

01:05:40.840 | So yes, that's exactly as it sounds,

01:05:42.700 | taking the stool of healthy people who do not have colitis,

01:05:46.120 | transplanting those stools into the lower digestive tract

01:05:49.580 | of people who do have colitis.

01:05:51.340 | And they saw significant improvement,

01:05:53.880 | if not rescue of the colitis.

01:05:55.940 | That was one of the first indications

01:05:57.420 | that something within stool of all things

01:06:00.800 | could actually rescue another individual from disease,

01:06:04.720 | which sounds kind of wild and crazy

01:06:07.040 | and may even sound disgusting to some of you.

01:06:09.380 | But as I mentioned at the beginning of the episode,

01:06:12.940 | almost 60% of stool is live or dead bacteria, microbiota.

01:06:18.960 | And it really opened up this entire field

01:06:21.740 | of exploring how different microbiota

01:06:24.180 | might have therapeutic effects.

01:06:26.360 | And indeed, that has been shown to be the case

01:06:28.900 | also in fecal transplants for certain psychiatric illnesses.

01:06:32.900 | These are still ongoing studies.

01:06:35.280 | They vary in quality.

01:06:36.720 | These are hard studies to do for all sorts of reasons,

01:06:40.380 | getting the appropriate patient populations,

01:06:42.120 | getting agreement, et cetera,

01:06:43.560 | making sure that everything's handled properly.

01:06:46.800 | But what this involves is fecal transplants

01:06:49.340 | from individuals that lack a particular

01:06:52.100 | psychiatric condition or metabolic condition

01:06:54.440 | into people who have a particular metabolic condition.

01:06:57.980 | And there has been tremendous success in some cases.

01:07:00.680 | One of the more powerful and salient examples

01:07:03.600 | is for obesity.

01:07:04.960 | There are some people for which,

01:07:06.060 | even if they ingest very low numbers of calories,

01:07:09.420 | even if they go on a liquid protein diet,

01:07:11.440 | simply can't lose weight.

01:07:13.560 | These are somewhat rare disorders,

01:07:14.920 | but these are people that would either

01:07:16.960 | get gastric bypass surgery.

01:07:18.320 | Some people are now getting these fecal transplants

01:07:20.380 | from people that have healthy weight

01:07:25.380 | and they take the stool from them,

01:07:28.480 | they put it into lower digestive tract,

01:07:30.400 | and they can see substantial improvement in weight loss

01:07:34.360 | in people that were otherwise unable to do that.

01:07:36.720 | In some cases, actually,

01:07:37.960 | they can start eating relatively normal levels of food

01:07:40.340 | and still lose weight.

01:07:41.240 | So pretty remarkable.

01:07:42.260 | And that tells us there's something in these microbiota

01:07:44.480 | that's really powerful.

01:07:45.860 | Now, how those effects are generated isn't clear.

01:07:49.120 | One idea is that it's impacting

01:07:51.480 | the metabolome components of the metabolism.

01:07:54.600 | Almost certainly that's going to be the case.

01:07:56.580 | Another idea is that it's impacting neurotransmitters,

01:07:59.380 | which change behavior and food choices within the brain.

01:08:02.440 | Although, as I mentioned,

01:08:03.280 | some of these people are already eating

01:08:04.920 | very little food to begin with.

01:08:06.700 | So that's a little bit harder of an argument to create.

01:08:10.720 | There are also some somewhat famous examples now

01:08:13.180 | of how fecal transplants can lead to negative outcomes.

01:08:16.780 | But those negative outcomes further underscore

01:08:19.400 | the power of the microbiome in impacting bodily health.

01:08:23.280 | One key example of this, for instance,

01:08:26.720 | is transfer of fecal matter into another person

01:08:31.040 | in order to treat something like colitis.

01:08:33.200 | And it effectively does that.

01:08:35.840 | But if the donor of the stool of the fecal matter

01:08:40.640 | happened to be obese or have some other metabolic syndrome,

01:08:43.680 | it's been observed that the recipient

01:08:45.440 | can also develop that metabolic syndrome

01:08:47.900 | simply by way of receiving

01:08:50.340 | that donor's particular microbiota.

01:08:53.260 | So these microbiota can create positive outcomes

01:08:55.820 | or they can create negative outcomes.

01:08:57.960 | Now, most of us, of course, are not interested in

01:09:00.280 | or pursuing fecal transplants.

01:09:01.720 | Most people are interested in just creating

01:09:03.540 | a healthy gut microbiome environment

01:09:05.720 | for sake of immune system and brain function.

01:09:07.560 | And we will talk about how to do that in just a few minutes.

01:09:10.620 | But I just want to further underscore

01:09:13.440 | the power of the microbiota in shaping brain chemistry

01:09:17.940 | and in shaping things like mood

01:09:20.140 | or other aspects of mental health

01:09:21.500 | that typically we don't associate with our gut.

01:09:24.440 | There are several studies published in recent years.

01:09:26.760 | One that I'll just highlight now,

01:09:28.200 | first author, it's Tanya Nguyen, N-G-U-Y-E-N.

01:09:32.480 | The title of the paper is Association of Loneliness

01:09:35.160 | and Wisdom with Gut Microbial Diversity and Composition,

01:09:38.840 | an exploratory study.

01:09:40.280 | It's an interesting study,

01:09:41.540 | looked at 184 community dwelling adults, excuse me,

01:09:45.960 | ranging from 28 to 97 years old.

01:09:49.200 | They explored whether or not

01:09:52.100 | having enhanced microbial diversity

01:09:54.580 | somehow related to these variables

01:09:56.760 | that they refer to as loneliness and wisdom.

01:09:58.600 | They used a number of different tests to evaluate those.

01:10:02.140 | Those are common tests in the psychology literature,

01:10:04.600 | not so much in the biology literature,

01:10:06.380 | but nonetheless, there are ways of measuring things

01:10:08.900 | like loneliness and wisdom.

01:10:10.800 | Wisdom in this case being the opposite of loneliness,

01:10:16.500 | at least in the context of this study.

01:10:18.040 | And what they found was the more microbial diversity,

01:10:20.660 | the more diverse one's microbiome was,

01:10:22.920 | the lower incidence of loneliness.

01:10:25.840 | And they did this by taking fecal samples,

01:10:28.120 | profiling them for RNA.

01:10:29.520 | So essentially doing gene sequencing of the stool,

01:10:31.640 | of these individuals,

01:10:32.760 | getting ratings of how lonely or not lonely they felt

01:10:35.720 | and correlating those.

01:10:37.000 | And that's just but one study.

01:10:38.720 | I pointed out because it's particularly recent

01:10:41.180 | and it looked like it was particularly well done.

01:10:43.600 | There is another study that I'll just refer you to.

01:10:45.560 | This was a study published in 2020 in Scientific Reports.

01:10:49.240 | The title of the study is emotional wellbeing

01:10:51.080 | and gut microbiome profiles by enterotype.

01:10:54.240 | What I particularly like about this study

01:10:55.740 | is that they were able to correlate

01:10:57.120 | the presence of certain microbiota

01:10:59.900 | with feelings of subjective wellbeing

01:11:02.620 | and lack of or presence of depressive symptoms.

01:11:06.540 | They did high throughput gene sequencing

01:11:08.780 | of the microbiomes of individuals.

01:11:10.520 | So that meant measuring the microbiota,

01:11:13.440 | figuring out which microbiota were present,

01:11:15.660 | how diverse their microbiome was.

01:11:17.220 | In general, gut microbiome diversity is a good thing.

01:11:20.780 | And then to correlate that

01:11:22.340 | with what's called the PANAS score.

01:11:26.220 | PANAS stands for positive affect, negative affect schedule.

01:11:29.880 | This is a test that my lab has used extensively

01:11:31.900 | that other labs use to evaluate mood and wellbeing.

01:11:34.820 | And they defined what were called three enterotypes,

01:11:38.620 | three different categories of people

01:11:40.100 | that ate very different diets

01:11:42.140 | that tended to fall into categories

01:11:44.040 | of having more or fewer emotional symptoms that were negative

01:11:48.840 | or more or fewer emotional symptoms that were positive,

01:11:52.040 | and whether or not they tend to be more depressed, anxious,

01:11:55.260 | or have more stress-related behaviors, et cetera.

01:11:57.760 | And what they were able to derive from this study

01:12:00.980 | was some strong indications about what types of things

01:12:04.120 | we should ingest in our diet,

01:12:05.940 | maybe even certain things that we should avoid,

01:12:07.700 | but certainly the types of things that we should ingest

01:12:10.100 | that can enhance mood and wellbeing

01:12:12.400 | and can tend to shift people away from more depressive-like

01:12:16.240 | anxiety and stress-related symptoms.

01:12:18.240 | Before we get into what the particular food items were

01:12:20.920 | that lend themselves to a healthy microbiome,

01:12:23.740 | I want to raise a bigger and perhaps more important issue,

01:12:25.740 | which is what is a healthy microbiome?

01:12:28.480 | I think if you asked any number of world experts,

01:12:32.060 | and I certainly asked this of Dr. Sonnenberg,

01:12:33.880 | what is a healthy microbiome?

01:12:35.460 | They're all going to tell you it's a microbiome

01:12:37.200 | that has a lot of diversity,

01:12:38.940 | that includes a lot of different types of bacteria.

01:12:42.140 | And that makes sense because it logically would include

01:12:45.020 | the bacteria that produce GABA and dopamine and serotonin,

01:12:48.860 | and that support the immune system

01:12:50.420 | and do a number of different things.

01:12:51.900 | But is it simply the case that adding microbiota diversity

01:12:56.380 | is always a good thing?

01:12:58.420 | Well, that doesn't seem to be the case.

01:13:02.180 | Probiotics and prebiotics,

01:13:04.020 | both of which can enhance microbiota diversity,

01:13:06.980 | can improve mood digestion, immune system, and so on.

01:13:10.660 | That's been established,

01:13:11.760 | but it's mainly been established in the context

01:13:13.580 | of post antibiotic treatment

01:13:15.880 | or people that are recovering from illness

01:13:17.720 | or people that have been very stressed

01:13:20.900 | or have been dealing with all sorts of challenges,

01:13:24.020 | mental or physical,

01:13:25.260 | and they are an attempt to replenish the gut microbiome.

01:13:28.900 | However, it's also clear that excessive microbiota

01:13:33.900 | brought about by excessive intake of probiotics

01:13:38.700 | can lead to things like brain fog.

01:13:40.240 | There's actually some good studies that point to the fact

01:13:42.800 | that certain metabolites of the microbiome,

01:13:46.380 | certain chemicals produced in the gut and in the body

01:13:49.480 | can actually lead to brain fog states.

01:13:51.840 | This is thought to come about

01:13:52.840 | through the lactate pathways of the gut

01:13:55.860 | that can then impact the brain.

01:13:57.960 | If you want to look more into this issue

01:14:00.080 | of whether or not probiotics taken in excess, perhaps,

01:14:04.340 | can lead to brain fog,

01:14:06.500 | I'd encourage you to look at a particular paper.

01:14:08.340 | This is a paper published in

01:14:09.780 | Clinical and Translational Gastroenterology,

01:14:12.780 | and the title of the paper is

01:14:13.620 | "Brain Fogginess, Gas, and Bloating,

01:14:15.580 | A Link Between SIBO, Probiotics, and Metabolic Acidosis."

01:14:19.580 | It was published in 2018.

01:14:20.780 | We can provide a link to this study.

01:14:22.420 | And there are several other studies in the references

01:14:25.560 | that point to the fact that in some cases,

01:14:29.900 | excessive intake of probiotics

01:14:31.540 | and excessive proliferation of gut microbiota

01:14:33.740 | can actually be problematic.

01:14:35.180 | I mentioned this not to confuse you,

01:14:37.740 | but because it is confusing out there.

01:14:41.100 | We all would think that just increasing microbiota diversity

01:14:44.420 | is always a good thing,

01:14:45.760 | but there are thresholds beyond which

01:14:49.140 | excessive microbiota diversity might be problematic.

01:14:52.020 | I think everyone agrees that having too few

01:14:55.840 | microbial species living in us is not a good idea.

01:14:59.440 | Now, none of that answers the questions

01:15:01.040 | that I think everyone really wants answers to,

01:15:03.920 | which are what should we do?

01:15:06.420 | What should we not do to improve our gut microbiome?

01:15:09.280 | I mean, clearly we can't time travel back

01:15:11.760 | to when we were zero to three years old

01:15:13.960 | and get a dog if we didn't have a dog,

01:15:16.740 | get breastfed if we weren't breastfed,

01:15:18.880 | be delivered vaginally as opposed to by C-section

01:15:21.560 | if we didn't have that opportunity,

01:15:23.240 | we just can't time travel and do that.

01:15:25.260 | All of us, however,

01:15:26.100 | should be seeking to improve the conditions

01:15:28.360 | of our gut microbiome because of the critical ways

01:15:30.580 | in which it impacts the rest of our brain

01:15:33.120 | and bodily health.

01:15:34.660 | So what should we do?

01:15:35.500 | What shouldn't we do?

01:15:36.480 | Clearly we know that stress can negatively impact

01:15:39.020 | the gut microbiome.

01:15:40.080 | However, some forms of stress that can quote unquote

01:15:44.000 | negatively impact the microbiome include fasting,

01:15:47.200 | long periods of fast, which makes sense

01:15:49.240 | because a lot of microbiota need food in order to thrive.

01:15:52.860 | In fact, many, if not all of them do at some point.

01:15:55.820 | There are other questions such as,

01:15:59.460 | should we eat particular foods

01:16:00.960 | and how often should we eat those foods?

01:16:02.960 | We've all been told that fiber is incredibly important

01:16:05.920 | because of the presence of prebiotic fiber,

01:16:08.680 | which can essentially feed the microbiome,

01:16:11.640 | but is fiber really necessary

01:16:15.000 | and how necessary is it to encourage a healthy microbiome?

01:16:17.940 | Clearly there are a number of people following

01:16:20.100 | relatively low fiber diets such as ketogenic diets,

01:16:22.880 | and those can have in some cases anti-inflammatory effects

01:16:26.680 | and can sometimes also improve certain microbiota species.

01:16:31.040 | So it can all be rather confusing.

01:16:32.440 | And for that matter, I asked our resident expert,

01:16:35.860 | Dr. Justin Sonnenberg at Stanford, all of these questions.

01:16:39.780 | And he answers them very systematically in the episode

01:16:43.000 | that comes out after this one.

01:16:45.000 | But I don't want to withhold anything from you.

01:16:46.620 | So I'll just give a very top contour version

01:16:49.280 | of those answers, and then you'll get more in-depth answers

01:16:52.520 | during that episode.

01:16:54.120 | I asked about fasting.

01:16:55.400 | And the reason I asked about fasting is that years ago,

01:16:57.820 | I was at a meeting as part

01:16:59.280 | of the Pew Biomedical Scholars meeting.

01:17:02.120 | And one of the other Pew Biomedical Scholars

01:17:05.560 | was an expert in gut microbiome.

01:17:07.160 | And I said, "Hey, are probiotics good for the microbiome?

01:17:11.480 | "And if so, which one should I take?"

01:17:14.200 | And his answer was very interesting.

01:17:15.480 | He said, "In certain cases, they can be,

01:17:18.400 | "especially if you're traveling or you're stressed.

01:17:21.200 | "But it turns out that the particular bacteria

01:17:24.720 | "that they put in most probiotics

01:17:26.640 | "don't actually replenish the microbiota that you need most."

01:17:30.720 | And I thought, "Oh, well, why don't they make ones

01:17:32.860 | "that replenish the microbiota that you need most?"

01:17:35.640 | And his answer was, "Well, they don't replenish those,

01:17:39.160 | "but they replenish other ones that then in turn encourage

01:17:43.320 | "the development of the microbiota that you do want

01:17:46.020 | "once you start eating the appropriate foods."

01:17:47.920 | So they changed the environment,

01:17:49.280 | which makes the environment better,

01:17:50.480 | which indirectly supports the proliferation

01:17:53.320 | of quote unquote good microbiota.

01:17:55.580 | Okay, so that was a somewhat convoluted answer,

01:17:57.480 | but I did appreciate his answer.

01:17:58.980 | Then I asked him about fasting.

01:18:00.700 | I said, "Well, a lot of people are getting interested

01:18:02.740 | "in intermittent fasting now.

01:18:04.680 | "People are spending a significant portion

01:18:06.820 | "of each 24 hour cycle avoiding food

01:18:08.820 | "for sake of time restricted feeding.

01:18:10.260 | "What does that do to the gut microbiome?

01:18:11.700 | "Does it make it healthier?

01:18:13.040 | "Or does it make it unhealthier?"

01:18:14.480 | Well, my colleague from Yale and Dr. Sonnenberg

01:18:17.920 | both confirmed that during periods of fasting,

01:18:20.440 | especially prolonged periods of fasting,

01:18:22.400 | we actually start to digest away much

01:18:24.200 | of our digestive tract.

01:18:26.040 | Now, the whole thing doesn't start to disappear,

01:18:28.000 | but there's thinning of the mucosal lining,

01:18:29.880 | or at least disruption of the mucosal lining.

01:18:31.820 | A lot of the microbiota species can start to die off.

01:18:35.360 | And so it was surprising to me, but nonetheless interesting,

01:18:38.920 | that fasting may actually cause a disruption

01:18:42.080 | to certain healthy elements of the gut microbiome.

01:18:45.260 | But again, there's a caveat.

01:18:47.400 | The caveat is that when people eat after a period of fast,

01:18:52.060 | there may be a compensatory proliferation,

01:18:55.080 | meaning an increase in healthy gut microbiota.

01:18:58.240 | So you start to get the picture

01:18:59.400 | that fasting is neither good nor bad.

01:19:02.040 | You start to get the picture that particular diets,

01:19:04.800 | meaning certain restriction diets

01:19:07.700 | or macronutrient rich diets may not be good

01:19:10.120 | or bad for the microbiome.

01:19:11.880 | And yet there are some answers that arrive to us

01:19:15.480 | from Dr. Sonnenberg, but from other experts in the field,

01:19:18.440 | that there are certain foods

01:19:20.920 | and certain things that we can ingest,

01:19:22.560 | which definitely enhance the microbiome

01:19:25.480 | and make it healthier than it would be

01:19:27.600 | were we to not ingest those foods.

01:19:30.080 | So next, I'd like to talk about what I think

01:19:32.220 | is a really pioneering and important study in this area.

01:19:35.160 | This is a study that was carried out by the Sonnenberg Lab

01:19:38.640 | in collaboration with Chris Gardner's lab, also at Stanford,

01:19:42.280 | where they compared two general types of diets in humans,

01:19:47.120 | diets that were fiber rich,

01:19:49.200 | which has been proposed time and time again

01:19:51.460 | to enhance microbiota diversity

01:19:54.280 | and to enhance gut brain signaling even,

01:19:56.440 | and to enhance the immune system, perhaps,

01:19:59.220 | and diets that were enriched

01:20:01.200 | in so-called low sugar fermented foods.

01:20:04.040 | Before I dive into that study and what the conclusions were,

01:20:06.840 | because they are very interesting and very actionable

01:20:08.960 | for all of us, I do want to touch on probiotics

01:20:12.320 | because I want to avoid confusion.

01:20:14.680 | It is not the case that ingestion of probiotics

01:20:18.480 | will always lead to brain fog.

01:20:20.160 | I want to make that clear.

01:20:21.920 | It is the case that ingestion of probiotics,

01:20:24.720 | even if those probiotics don't directly contain

01:20:28.320 | the microbiota species that one is trying to proliferate,

01:20:31.600 | can be useful for improving microbiota diversity.

01:20:35.840 | In general, it seems that maintaining a healthy gut microbiome

01:20:40.660 | involves ingesting certain types of foods,

01:20:42.960 | and we'll talk about those in a moment,

01:20:45.520 | but perhaps also augmenting the microbiota system

01:20:50.040 | through prebiotics or probiotics

01:20:52.520 | at a fairly low level on a consistent basis.

01:20:54.800 | So these are not high dose probiotics,

01:20:56.500 | except under conditions of dysbiosis,

01:21:00.280 | where, for instance,

01:21:01.260 | if somebody has done a round of antibiotics

01:21:04.340 | and they need to replenish their gut microbiome,

01:21:07.040 | there are foods and there are pill form

01:21:09.380 | and powder form prebiotics and probiotics

01:21:11.940 | that can be very useful.

01:21:13.140 | Or in cases where people have been very stressed

01:21:17.000 | or are undergoing excessive travel

01:21:19.500 | or have shifted their diet radically,

01:21:22.540 | maybe that's due to travel, maybe that's due to illness,

01:21:24.560 | maybe that's due to stress.

01:21:26.020 | But when there are a number of different converging events

01:21:28.580 | that are stressing or depleting microbiota diversity,

01:21:33.580 | that's when, at least I believe,

01:21:35.340 | it can be useful to support the gut microbiome

01:21:37.900 | through the ingestion of quality probiotics or prebiotics.

01:21:41.980 | So it would be under conditions where people are stressed

01:21:45.360 | or their system is generally stressed

01:21:47.740 | for environmental or illness-related reasons,

01:21:50.680 | that it might be useful to lean towards higher doses

01:21:54.040 | of prebiotics or probiotics than one might normally use,

01:21:57.780 | but that under normal conditions,

01:21:59.680 | that one would focus on quality nutrients

01:22:03.200 | through diet and focus on ingestion of probiotics

01:22:08.200 | at a fairly low to moderate level

01:22:11.260 | and/or prebiotics at a fairly low to moderate level.

01:22:15.020 | That just seems like the logical approach

01:22:16.720 | based on the experts that I've spoken to,

01:22:18.960 | but certainly if your doctor prescribes

01:22:22.140 | or suggests that you take high levels of probiotics

01:22:24.580 | for any reason,

01:22:25.580 | you should definitely pay attention to your physician

01:22:27.180 | and you should obviously pay attention to your physician.

01:22:29.220 | In any case, you should never add or remove anything

01:22:32.360 | from your nutritional plan or supplementation plan

01:22:34.980 | without consulting a physician.

01:22:37.100 | So what should we do in order to maximize the health

01:22:39.500 | of our gut brain axis, as it's called?

01:22:42.100 | How should we support the diversity of the good microbiota

01:22:45.880 | that help us create all these neurotransmitters

01:22:47.820 | that we want, improve our immune system function,

01:22:52.020 | and so on and so forth?

01:22:53.860 | Well, some of that is going to be through the basics.

01:22:57.700 | When I say the basics, I mean the foundational things

01:22:59.720 | that really set us up for overall health.

01:23:02.220 | So this is going to be getting deep sleep

01:23:05.260 | of sufficient duration, 80 plus percent of the time.

01:23:09.600 | I mean, if you could get 100% of the time, that'd be great,

01:23:11.360 | but very few people accomplish that.

01:23:12.960 | It's going to be proper hydration.

01:23:14.220 | It's going to be proper social interactions.

01:23:16.100 | It's going to be proper nutrition,

01:23:17.680 | and we'll talk more about nutrition in a moment.

01:23:19.220 | It's going to be limiting excessive prolonged stressors

01:23:23.000 | or stress, and indeed we've done episodes

01:23:25.920 | about just about all of those things,

01:23:27.560 | but certainly about stress.

01:23:29.000 | We have an episode of the Huberman Lab podcast

01:23:30.960 | that you can find at HubermanLab.com

01:23:32.520 | all about mastering stress,

01:23:33.820 | how to avoid long periods of intense stress,

01:23:37.180 | what to do to offset those.

01:23:38.640 | Given that stress can disrupt the microbiome,

01:23:43.400 | whether or not you're fasting or not,

01:23:45.920 | those tools ought to be useful.

01:23:48.440 | Now, in what I consider to be a landmark study

01:23:51.320 | exploring the relationship between the gut microbiome,

01:23:54.200 | food intake, and overall health is this paper

01:23:58.020 | from Justin Sonnenberg's lab and Chris Gardner's lab,

01:24:01.560 | both of which are at Stanford,

01:24:03.620 | and the paper entitled "Gut Microbiota Targeted Diets

01:24:06.500 | Modulate Human Immune Status"

01:24:08.080 | was published in the journal Cell,

01:24:09.540 | which is among the three top journals,

01:24:11.760 | perhaps in the world, Nature, Science, and Cell

01:24:13.840 | really being the apex journals for overall science,

01:24:17.500 | and especially for biomedical sciences.

01:24:21.120 | Now, this is a very interesting study.

01:24:23.420 | It was done on humans.

01:24:24.700 | There were two major groups.

01:24:25.960 | One group of humans was instructed

01:24:28.140 | to increase the amount of fiber in their diet,

01:24:30.820 | and in fact, ate a high fiber diet.

01:24:33.360 | The other group was instructed

01:24:35.120 | to eat a high fermented food diet.

01:24:38.640 | Now, both groups started off

01:24:41.160 | not having eaten a lot of fiber or a lot of fermented foods,

01:24:45.100 | and were told to increase the amount of either fiber

01:24:47.800 | or fermented foods that they were ingesting

01:24:49.700 | over a four-week ramp-up period,

01:24:51.600 | and that was to avoid any major gastric distress.

01:24:54.600 | It turns out that if you're not already accustomed

01:24:56.720 | to eating a lot of fiber,

01:24:57.760 | increasing your amount of fiber dramatically

01:25:00.140 | can cause some gastric distress,

01:25:02.000 | but if you ease into it over time,

01:25:03.560 | as we'll see, there's a mechanism behind this,

01:25:05.860 | which was unveiled in this study,

01:25:08.020 | but if you ease into it over time,

01:25:09.620 | then the system can tolerate it.

01:25:11.560 | Likewise, high fermented foods can be readily tolerated

01:25:16.140 | if there's a ramp-up phase of ingesting

01:25:18.640 | maybe one serving a day, then maybe two servings,

01:25:20.780 | and ramping up, in this case,

01:25:23.180 | as high as six servings per day.

01:25:25.180 | However, after this ramp-up period,

01:25:29.920 | the group assigned to the high fiber condition

01:25:32.040 | maintained high fiber intake for six weeks,

01:25:34.900 | and the high fermented food group

01:25:36.600 | maintained high fermented food intake for six weeks,

01:25:40.360 | after which they went off either the high fiber

01:25:44.200 | or the high fermented food diet,

01:25:45.580 | and there was a four-week follow-up period

01:25:47.660 | during which they gradually returned to baseline.

01:25:50.440 | Throughout the study,

01:25:51.280 | their gut microbiome was evaluated

01:25:53.600 | for the diversity of gut microbiota,

01:25:56.200 | and there were also a number of measures

01:25:58.140 | of immune system function,

01:25:59.820 | in particular, measures of the so-called inflammatome.

01:26:03.200 | The immune system has a lot of different molecules involved.

01:26:05.520 | I did a whole episode about the immune system.

01:26:07.200 | If you're interested in learning

01:26:08.220 | what some of those molecules are,

01:26:09.840 | various cytokines and signaling molecules

01:26:11.960 | that reflect either high inflammation states

01:26:14.800 | or reduced inflammation states in the brain and body,

01:26:17.400 | you're welcome to check out that episode.

01:26:19.080 | It's also at hubermanlab.com.

01:26:21.600 | Regardless, in this study,

01:26:24.000 | they explored the sorts of immune markers

01:26:27.400 | that were expressed in either of the two groups

01:26:29.600 | and compared those.

01:26:30.860 | The basic takeaway of this paper

01:26:32.800 | was that contrary to what they predicted,

01:26:36.240 | the high fiber diet did not lead

01:26:39.120 | to increased microbiota diversity,

01:26:41.440 | at least not in all cases,

01:26:43.020 | and that was somewhat surprising.

01:26:45.520 | You know, the idea is that prebiotic fiber

01:26:48.160 | and a lot of the material in fruits and vegetables

01:26:50.720 | and grains and so forth

01:26:51.940 | are supposed to support microbiota diversity

01:26:56.380 | and the proliferation of existing microbiota,

01:26:59.320 | and that is not what they observed,

01:27:01.640 | although I want to be very clear in pointing out

01:27:03.580 | that the results did not indicate

01:27:06.040 | that fiber is not useful for health overall,

01:27:10.040 | but it does point to the fact

01:27:11.280 | that increasing fiber intake

01:27:13.040 | did not increase microbiota diversity,

01:27:15.120 | which in general, as I mentioned before,

01:27:17.560 | is associated with improvements

01:27:19.760 | in microbiota function, health, and overall wellbeing.

01:27:24.760 | Now, the high fermented food diet condition

01:27:26.960 | was very interesting.

01:27:28.440 | It resulted in increased microbiome diversity

01:27:31.540 | and decreased inflammatory signals and activity.

01:27:35.000 | So there was a twofer,

01:27:36.560 | basically by ingesting high fermented foods

01:27:39.200 | in fair abundance, right?

01:27:41.600 | You know, four to six servings or more per day

01:27:43.800 | is a lot of fermented food intake.

01:27:46.100 | We'll talk about what some of those foods were,

01:27:48.120 | but the outcome was very positive.

01:27:50.360 | There was a clear increase in microbiome diversity

01:27:53.540 | and decreased inflammatory signals.

01:27:56.040 | So things like interleukin-6,

01:27:58.320 | a number of other interleukins and cytokines

01:28:00.700 | that are associated with increased inflammation

01:28:03.520 | in the brain and body were reduced significantly.

01:28:06.400 | Now, let's talk a little bit about this notion

01:28:08.880 | of number of servings, et cetera.

01:28:11.060 | One somewhat minor point of the study,

01:28:13.960 | but I think is useful in terms of taking

01:28:16.100 | an actionable stance with this,

01:28:18.000 | is that the number of servings of fermented foods

01:28:21.220 | was not as strong a predictor of improvements

01:28:25.400 | in the inflammatome, meaning reduced inflammation,

01:28:28.280 | and improvements in microbiota diversity,

01:28:30.960 | as was the duration of time

01:28:33.240 | that the individuals were ingesting fermented foods.

01:28:36.580 | In other words, the longer that one is consistently

01:28:38.780 | ingesting fermented foods on a daily basis,

01:28:41.220 | the better the outcomes in terms of the gut microbiome

01:28:44.160 | and for reducing inflammation.

01:28:46.320 | So I think that's an important point.

01:28:48.340 | And I make that point, especially because

01:28:50.780 | for a lot of people, even if you do this ramp up phase,

01:28:53.340 | six servings per day of fermented foods

01:28:55.660 | can seem like quite a lot.

01:28:57.340 | So what are these fermented foods, right?

01:28:59.900 | I think many of us are familiar with certain cheeses

01:29:03.440 | and being fermented and beer being fermented

01:29:05.780 | and kombucha is fermented.

01:29:07.580 | In this study, they focus specifically

01:29:09.280 | on low sugar fermented foods.

01:29:11.540 | So this would be plain yogurt,

01:29:13.240 | in some cases, kimchi or sauerkraut.

01:29:17.840 | An important consideration, however,

01:29:19.520 | is that it needs to contain

01:29:21.360 | what are called live active cultures,

01:29:23.140 | which means there actually have to be microbiota

01:29:26.460 | that are alive inside the sauerkraut.

01:29:28.480 | One way you know whether or not that's happening

01:29:30.240 | is if you purchase sauerkraut or pickles or kimchi

01:29:34.440 | from a jar or a container that's on the non-refrigerated

01:29:38.340 | shelf or the non-refrigerated section of your grocery store,

01:29:41.560 | it is not going to contain

01:29:43.380 | live active cultures of microbiota.

01:29:46.460 | And likewise, if you consume yogurt that has a lot of sugar

01:29:50.420 | or other components added to it,

01:29:53.080 | it's not going to have the same positive effect

01:29:55.380 | on the microbiome, at least that's the prediction,

01:29:57.940 | given some of the relationship between

01:29:59.940 | the sorts of microbiota that live in sugar

01:30:01.940 | versus plain type yogurts.

01:30:04.180 | They gave people the option of consuming

01:30:05.980 | any number of different low sugar fermented foods.

01:30:08.780 | So again, that could be sauerkraut, kimchi,

01:30:10.920 | things like kefir, natto.

01:30:13.920 | In Japan, they consume natto, which is a fermented food.

01:30:17.780 | Beer was not one of the fermented foods

01:30:20.400 | that was included in the fermented food list.

01:30:22.860 | And when we say six servings per day,

01:30:25.100 | that is indeed six ounce servings

01:30:29.060 | or four to six ounce servings.

01:30:31.580 | It was not six servings of what's listed on the package.

01:30:34.820 | So again, that turns out to be

01:30:36.740 | a fair amount of fermented foods.

01:30:38.300 | How should you gauge whether or not

01:30:39.340 | you're getting enough of this?

01:30:40.180 | Well, if you decide to take on this protocol

01:30:43.380 | of ingesting more fermented foods,

01:30:44.860 | which at least by my read of this study

01:30:47.140 | and some of the follow-up work that's being done,

01:30:49.180 | sounds like a terrific idea.

01:30:50.900 | If you want to improve your gut microbiome

01:30:52.780 | for all the great reasons that one would want to,

01:30:55.540 | brain, body, health, reduced inflammation, and on and on,

01:30:59.500 | well then you definitely want to focus on fermented foods

01:31:03.000 | that you enjoy consuming.

01:31:04.420 | So for you, if that's kefir, or for you that's plain yogurt,

01:31:07.780 | or for you that's sauerkraut,

01:31:09.180 | which happens to be my personal favorite,

01:31:12.040 | then you want to make sure that it's going to be something

01:31:14.660 | that you are going to enjoy ingesting quite a lot of,

01:31:17.780 | and that you're going to be okay with ingesting

01:31:20.380 | probably throughout the day.

01:31:21.860 | Now, people follow different meal schedules, of course,

01:31:23.960 | but this does require not just eating

01:31:26.100 | all the fermented foods just before bedtime or one meal.

01:31:29.980 | I suppose you could do that.

01:31:31.540 | But in general, it's going to work best

01:31:33.340 | in terms of limiting gastric distress

01:31:35.320 | by spreading it out throughout the day.

01:31:37.500 | I also want to mention brine.

01:31:39.020 | Brine is the liquid that surrounds sauerkraut.

01:31:43.600 | It's that very salty fluid,

01:31:46.980 | and that contains a lot of active live cultures.

01:31:49.700 | And they did include,

01:31:52.140 | or they allowed people to include brine in this study.

01:31:55.740 | And in discussions with Dr. Sonnenberg,

01:31:57.860 | which we'll go into in more detail on the episode

01:32:00.980 | that comes out next week,

01:32:02.180 | we talk a lot about the particular value

01:32:04.140 | that brine might hold

01:32:05.360 | in terms of bringing about microbiota diversity

01:32:08.540 | because of the richness of live cultures that it contains.

01:32:12.020 | I do want to focus for a moment on the high fiber condition

01:32:14.500 | because there were some interesting observations

01:32:16.180 | about the people that were placed into that condition.

01:32:18.780 | First of all, increasing the amount of fiber

01:32:23.140 | definitely increased the number of enzymes

01:32:26.960 | that can be used to digest fiber.

01:32:29.820 | This is in keeping with this idea of this ramp up phase

01:32:32.860 | where accumulation of more fiber intake

01:32:35.100 | can over time lead to less gastric distress,

01:32:37.660 | but also to more utilization of fiber,

01:32:39.560 | which overall should be a good thing.

01:32:41.300 | So while they didn't observe an increase

01:32:43.780 | in immune system function

01:32:45.520 | or an increase in microbiota diversity,

01:32:47.660 | there was an increase in these fiber digesting enzymes.

01:32:51.580 | They also observed

01:32:52.420 | what they called personalized immune responses.

01:32:55.180 | There were some subgroups within the high fiber group

01:32:57.980 | that had interesting changes in terms of their reactions to,

01:33:02.700 | or I should say their inflammatome,

01:33:05.060 | meaning the inflammatory markers they expressed

01:33:06.860 | as well as their microbiota diversity.

01:33:09.660 | So there were essentially three groups.

01:33:11.060 | One group actually showed an increase in inflammatory markers

01:33:14.580 | so that was quite surprising

01:33:15.820 | and probably not wonderful for the message

01:33:19.580 | that fiber is always good for us,

01:33:21.140 | but that was a small cohort within the fiber intake group.

01:33:25.820 | Another group, and still another group,

01:33:28.660 | both showed reductions in baseline microbiota diversity,

01:33:31.860 | although to varying degrees.

01:33:34.300 | So I don't want to paint the picture that fiber is bad,

01:33:36.660 | but fiber certainly did not have the positive effects

01:33:39.060 | on microbiota diversity

01:33:40.780 | that the high fermented food diet did.

01:33:43.180 | So my read of this study,

01:33:44.340 | and I think the stance that many others have taken

01:33:46.980 | as a consequence of these data,

01:33:48.620 | is that we should be increasing our fermented food intake,

01:33:52.540 | that that's simply a good thing to do

01:33:54.640 | in order to support our gut microbiome

01:33:56.500 | and to reduce inflammatory signals in our brain and body.

01:34:00.540 | And there are a number of different ways to do that.

01:34:02.500 | I mentioned some of the particular foods.

01:34:04.220 | However, anytime you're talking about

01:34:05.580 | ingesting fermented foods,

01:34:07.420 | especially the high quality ones

01:34:09.340 | that come from the refrigerated section of the grocery store

01:34:12.240 | or that end that have low sugar content, et cetera,

01:34:16.440 | we do have to be considerate of cost

01:34:18.340 | because certain things like kombuchas, for instance,

01:34:20.400 | can be quite costly.

01:34:22.480 | I should also mention some kombuchas

01:34:23.820 | actually contain alcohol, some do not,

01:34:26.700 | or contain very little amounts of alcohol.

01:34:28.860 | One way to avoid the high cost of fermented foods

01:34:32.800 | while still being able to accumulate

01:34:34.540 | a lot of fermented food intake

01:34:35.920 | is to simply make those fermented foods yourself.

01:34:38.260 | This is something that we've started exploring

01:34:40.520 | and experimenting with in our home.

01:34:42.820 | One simple way to do this

01:34:43.940 | is to just make your own sauerkraut.

01:34:45.600 | It involves very few ingredients.

01:34:46.980 | It basically involves cabbage, water, and salt,

01:34:50.000 | but there's a specific process that you need to follow

01:34:52.100 | in order to create these large volumes of sauerkraut at home

01:34:56.180 | using that low cost method.

01:34:58.340 | The best resource that I know of

01:35:00.580 | in order to follow a great recipe to make homemade sauerkraut

01:35:04.540 | would be the recipe for homemade sauerkraut

01:35:07.100 | that's contained in Tim Ferriss' book, "The 4-Hour Chef."

01:35:09.820 | There's an excellent protocol there.

01:35:11.520 | It involves chopping up the cabbage,

01:35:13.100 | putting into a bowl, mashing it up with your hands,

01:35:16.500 | which can be fun, putting water in there,

01:35:18.900 | some salt, covering it,

01:35:19.940 | and then keeping it in a particular environment,

01:35:21.960 | and then routinely scraping off

01:35:23.820 | some of the material from the surface.

01:35:25.500 | You have to do that in order to make sure

01:35:27.780 | that you're not getting microbes and things growing in it

01:35:32.200 | that are bad for you.

01:35:33.120 | So you definitely want to pay careful attention

01:35:34.780 | to the protocol, but that's a very, very low cost way

01:35:37.580 | of generating lots and lots of fermented food

01:35:40.000 | so you don't go broke trying to improve your microbiome.

01:35:43.100 | The other thing that you can do

01:35:44.060 | if you're really obsessed with kombucha

01:35:46.500 | or something like that to avoid the high cost of kombucha

01:35:48.820 | is there are ways that you can get the SCOBY,

01:35:51.060 | which basically allows you to make your own kombucha at home.

01:35:53.340 | I've never tried this, but when I was a postdoc,

01:35:55.800 | there was an undergraduate in the lab, I think,

01:35:58.860 | well, I won't out him, but he's now gone on

01:36:00.760 | to medical school, and I think he's passed his residency

01:36:04.600 | and is a practicing doctor.

01:36:06.320 | But nonetheless, he was always making kombucha at home.

01:36:08.760 | He told me it was exceedingly easy, but then again,

01:36:10.860 | he had a number of other skills and attributes

01:36:12.620 | that made me think that he could do

01:36:14.520 | pretty much anything with ease,

01:36:15.860 | whereas I tend to struggle with even basic cooking.

01:36:18.420 | So maybe if you're feeling a little more adventurous,

01:36:20.740 | you could explore making your own kombucha.

01:36:23.320 | But there are a number of different protocols

01:36:24.740 | and recipes out there

01:36:25.680 | for making your own low sugar fermented foods.

01:36:28.380 | So you needn't run out

01:36:30.100 | and buy fresh sauerkraut all the time.

01:36:32.260 | I should also mention for those of you

01:36:33.500 | that are interested in getting your fermented intake

01:36:37.500 | from pickles, jarred pickles rarely, if ever,

01:36:41.460 | contain ferment.

01:36:42.660 | Mostly they're just soaked in vinegar water

01:36:45.180 | and with some spices,

01:36:46.060 | but there are some that contain ferment.

01:36:48.140 | You actually have to look for that on the container.

01:36:50.700 | And I don't know, maybe someone out there

01:36:51.900 | knows how to make natto and knows how to make kimchi well

01:36:54.660 | and things of that sort.

01:36:56.180 | It certainly is the case based on the data from the study

01:36:59.120 | that ingesting more servings of fermented food per day

01:37:02.180 | ought to be beneficial for our gut microbiome.

01:37:04.260 | And since this is an episode,

01:37:05.420 | not just about gut microbiome, but gut brain health,

01:37:08.480 | I should mention that one form of signaling

01:37:11.000 | between the gut microbiome and the brain,

01:37:12.700 | which we did not discuss, and I'll just touch on briefly,

01:37:15.980 | is that when the inflammatome

01:37:19.300 | or the genes and markers of inflammation

01:37:22.200 | are kept in a healthy range,

01:37:25.220 | there's an active signaling

01:37:27.100 | of that immune system status to the brain.

01:37:29.400 | There's an intermediate cell type

01:37:31.520 | that communicates immune status to the brain.

01:37:34.300 | And that cell type is the microglial cell.

01:37:36.220 | It's a type of glia, as the name suggests.

01:37:38.700 | When there's a lot of inflammation in the body,

01:37:41.500 | these microglia actually get activated

01:37:43.780 | and can start eating away at various components

01:37:47.180 | of the brain and nervous system.

01:37:48.420 | And I don't mean massive eating away.

01:37:49.760 | They're not going to digest the whole brain,

01:37:51.240 | but these microglia are sort of the resident macrophages

01:37:55.220 | of the brain.

01:37:56.060 | Macrophages are in the periphery

01:37:57.420 | and they gobble up debris and things of that sort.

01:37:59.800 | The microglia on a regular basis are eating up debris

01:38:03.380 | that accumulates across waking cycles

01:38:05.840 | and in response to micro-damage of the brain

01:38:08.140 | that occurs on a daily basis.

01:38:09.440 | So they have a lot of important basic everyday

01:38:11.820 | what we call housekeeping functions.

01:38:13.720 | But when there's a lot of inflammation in the body,

01:38:15.920 | when there's a massive immune response,

01:38:18.680 | the microglia can be hyperactivated

01:38:20.800 | and that's thought to lead to any number

01:38:22.440 | of different cognitive defects or challenges thinking,

01:38:25.700 | or maybe even some forms of neurodegeneration over time.

01:38:29.200 | Although that last point is more of a hypothesis

01:38:31.440 | than a well tamped down fact at this point.

01:38:34.080 | There's still a lot of investigation to be done in humans.

01:38:36.680 | The animal data, however, are very, very strong

01:38:39.560 | that when the immune system is activated

01:38:41.480 | or chronically activated or hyperactivated,

01:38:44.140 | that neural tissue, meaning brain tissue

01:38:45.820 | and other central nervous system tissue can suffer.

01:38:47.980 | So there are a lot of reasons

01:38:49.700 | to want to not just improve microbiome diversity,

01:38:53.200 | but to also improve immune system function

01:38:56.160 | and to limit the number of inflammatory markers

01:38:58.800 | that are present in the body

01:39:00.120 | because of the way those inflammatory markers

01:39:02.320 | can signal deleterious events in the brain.

01:39:05.340 | And while eating fermented foods

01:39:07.840 | and making your own fermented foods

01:39:09.840 | and buying high quality fermented foods

01:39:11.880 | might seem like an inconvenience,

01:39:13.760 | I would say that from the perspective of cost benefit

01:39:17.500 | or effort benefit, it's actually quite a good situation

01:39:21.020 | where if you can just ramp up the number of fermented foods

01:39:24.180 | or servings of fermented foods that you're eating per day

01:39:26.380 | over a period of a few weeks

01:39:27.700 | so that you're tolerating that well,

01:39:30.220 | that ought to have a very positive effect

01:39:32.240 | on your microbiome diversity

01:39:34.180 | and indeed on gut brain function.

01:39:36.720 | And I'll be the last to suggest

01:39:38.100 | that people completely forgo on fiber.

01:39:40.500 | I think there's some debate out there

01:39:41.860 | as to how much fiber we need

01:39:43.400 | and whether or not certain forms of fiber

01:39:46.100 | are better than others.

01:39:47.260 | I'm not going to get into that debate.

01:39:48.620 | It's barbed wire enough

01:39:49.760 | without me injecting my own views into that debate.

01:39:52.740 | But I think there's ample evidence to support the fact

01:39:55.060 | that for most people,

01:39:57.020 | ingesting a fair amount of fiber is going to be a good idea.

01:40:00.360 | I would just say that make sure

01:40:01.340 | that you're also ingesting a fair amount of fermented foods.

01:40:04.160 | And along the lines of fiber,

01:40:06.100 | in an accompanying article published in Cell,

01:40:08.660 | which was sort of a, what we call a news and views piece

01:40:11.660 | about the Sonnenberg and Gardner paper,

01:40:15.320 | they make a quite good point,

01:40:16.880 | which is that the increase in fiber intake

01:40:19.600 | that led to this increase in carbohydrate active enzymes,

01:40:23.120 | these CAZ-zymes as they're called,

01:40:25.520 | these are enzymes that help digest fiber,

01:40:28.280 | quote, "Indicating an enhanced capacity for the microbiome

01:40:31.820 | to degrade complex carbohydrates present in fibrous foods."

01:40:35.400 | So in other words, eating more fiber and fibrous foods

01:40:40.880 | allowed for an increase in these enzymes

01:40:42.520 | that allow you to eat still more fibrous foods

01:40:44.840 | or to better digest fibrous foods

01:40:47.020 | that are coming in through other sources.

01:40:48.760 | So there is at least one utility for increasing fiber,

01:40:52.560 | even though it's separate from the gut microbiota diversity

01:40:55.560 | and reducing inflammation.

01:40:57.400 | And I'd be remiss if I didn't touch on some of the data

01:40:59.840 | and controversy about artificial sweeteners

01:41:02.460 | and the gut microbiome.

01:41:04.440 | I want to be very clear that what I'm about to tell you

01:41:06.800 | has only been established in animal models,

01:41:09.280 | in a mouse model, at least to my knowledge.

01:41:11.780 | What the studies have shown, and there were several,

01:41:14.560 | but one published in the journal "Nature" a few years back

01:41:16.720 | is the one that got the most amount of attention,

01:41:18.680 | is that animals that consume large amounts

01:41:20.760 | of artificial sweeteners,

01:41:22.200 | in particular things like saccharin or sucralose,

01:41:25.020 | show disruptions in their gut microbiome.

01:41:27.620 | I'm not aware of any studies in humans

01:41:29.360 | that show the equivalent effect,

01:41:30.680 | and I'm not aware of any studies in humans

01:41:32.840 | that show the equivalent effect

01:41:34.720 | for things like plant-based low-calorie sweeteners,

01:41:37.840 | things like stevia, monk fruit, and things of that sort.

01:41:41.040 | And at least by my exploration,

01:41:43.380 | I couldn't find any data specifically related

01:41:45.440 | to the sweetener aspartame.

01:41:47.760 | So right now it's somewhat controversial,

01:41:50.320 | and actually this is kind of a third rail topic out there

01:41:52.840 | when one group will come out saying

01:41:54.780 | that artificial sweeteners are bad

01:41:56.060 | because they disrupt the gut microbiome.

01:41:58.080 | The response generally from a number of people as well,

01:42:01.360 | that's only been shown in animal models,

01:42:02.860 | and indeed that's true.

01:42:04.280 | So right now I don't think that there's a strong case

01:42:06.800 | one way or the other.

01:42:08.080 | I think that people should basically ask themselves

01:42:10.220 | whether or not they like artificial sweeteners or not,

01:42:13.080 | whether or not they're willing to risk it or not,

01:42:15.560 | and obviously that's an individual choice.

01:42:18.080 | I also want to point out a recent study

01:42:20.640 | from Diego Bohorquez's lab,

01:42:23.000 | which actually shows, however, that neurons in the gut,

01:42:26.840 | those neuropod cells, are actually capable

01:42:29.680 | of distinguishing between real sugars

01:42:32.080 | and artificial sweeteners.

01:42:33.780 | This is a really interesting body of work.

01:42:36.240 | It was published just recently, I should say, February, 2022.

01:42:40.600 | The title of the paper is

01:42:41.720 | "The preference for sugar over sweetener

01:42:43.520 | depends on a gut sensor cell."

01:42:45.640 | And to make a long story short,

01:42:47.160 | what they showed was there's a category of neuropod cells

01:42:50.320 | that recognize sugar in the gut

01:42:52.960 | and signal that information

01:42:55.040 | about the presence of sugar in the gut

01:42:57.320 | to the brain via the pathways we talked about before,

01:42:59.840 | the nodose ganglia, the vagus, dopamine, et cetera, et cetera.

01:43:03.560 | Interestingly, the very same category of neurons

01:43:06.760 | can respond to artificial sweeteners

01:43:10.240 | and signal that information to the brain,

01:43:12.120 | but the pattern of signaling,

01:43:14.720 | and indeed the signature pattern

01:43:17.620 | that is conveyed to the brain and received by the brain,

01:43:20.660 | is actually quite a bit different

01:43:22.720 | when these same neurons are responding

01:43:25.800 | to artificial sweeteners versus actual sugar.

01:43:29.700 | This is very interesting because what it means is,

01:43:32.020 | first of all, that neurons have incredible specificity

01:43:36.140 | in terms of what they are signaling

01:43:37.660 | from the gut to the brain.

01:43:39.440 | And it also means that there may be a particular signal

01:43:42.880 | that the brain receives that says,

01:43:44.480 | I'm receiving some intake of food or drink that tastes sweet,

01:43:49.480 | but doesn't actually offer much nutrients

01:43:52.800 | in the direction of sweetness,

01:43:53.960 | meaning that it doesn't have calories despite being sweet.

01:43:56.700 | Now, again, this is all subconscious processing.

01:43:59.040 | And like with the previous studies,

01:44:00.860 | we were just discussing about artificial sweeteners

01:44:03.440 | generally and the gut microbiome generally,

01:44:05.600 | it's unclear how this relates to humans

01:44:08.920 | at this point in time.

01:44:10.200 | But given the similarity of cellular processes

01:44:12.660 | and molecular processes at the level of gut brain in mice,

01:44:15.860 | I think it stands to reason that these neuropod cells

01:44:18.400 | very likely are capable of signaling presence

01:44:21.880 | of real sweetener versus artificial sweetener

01:44:23.720 | in humans as well,

01:44:24.920 | although that still remains to be determined empirically.

01:44:27.620 | So I'd like to just briefly recap what I've covered today.

01:44:30.640 | I started off by talking about the structure and function

01:44:33.360 | of the gut brain axis.

01:44:35.080 | I described the basic structure and function

01:44:37.540 | of the digestive pathway

01:44:39.520 | and how that digestive pathway harbors microbiota species,

01:44:42.820 | meaning many, many little bacteria

01:44:45.240 | that can signal all sorts of things

01:44:47.700 | to the rest of the brain and body.

01:44:49.860 | And indeed, we talked about the various ways

01:44:51.460 | that they do that.

01:44:52.480 | We talked about direct pathways,

01:44:54.460 | literally nerve networks that extend from the gut

01:44:57.400 | up to the brain and from the brain back to the gut.

01:45:00.400 | And we talked about indirect pathways,

01:45:02.880 | how some of the gut microbiota

01:45:04.820 | can actually synthesize neurotransmitters

01:45:06.980 | that get out into the bloodstream,

01:45:08.480 | can impact the body, can impact the immune system

01:45:11.440 | and can get into the brain

01:45:13.120 | and act as neurotransmitters in the brain,

01:45:15.280 | just as would neurotransmitters

01:45:17.440 | that originate from within the brain.

01:45:19.500 | We also talked about what constitutes

01:45:22.720 | a healthy versus unhealthy microbiome.

01:45:25.360 | And it's very clear that having a diverse microbiome

01:45:28.400 | is healthier than having a non-diverse microbiome.

01:45:32.800 | But as I pointed out, there's still a lot of questions

01:45:35.700 | as to exactly what microbiota species you want to enhance

01:45:38.860 | and which ones you want to suppress in the gut

01:45:41.300 | in order to achieve the best gut brain access function.

01:45:44.460 | We talked about how things like fasting

01:45:47.080 | might impact the microbiome

01:45:48.720 | and how some of that might be a little bit counterintuitive

01:45:51.160 | based on some of the other positive effects of fasting,

01:45:54.040 | or if we're not just discussing fasting,

01:45:56.160 | some other types of somewhat restrictive diets,

01:45:58.840 | either restrictive in time

01:46:00.100 | or restrictive in terms of macronutrient intake,

01:46:02.920 | how those may or may not improve

01:46:05.120 | the health of the gut microbiome.

01:46:06.600 | And the basic takeaway was that

01:46:08.400 | because we don't know exactly how specific diets

01:46:11.420 | impact the gut microbiome,

01:46:13.040 | and we don't know how fasting

01:46:15.040 | either promotes or degrades the microbiome,

01:46:17.820 | we really can't say whether or not they are improving

01:46:20.460 | or degrading the microbiome at this time.

01:46:22.920 | However, it is clear that stress,

01:46:25.880 | in particular chronic stress,

01:46:27.100 | can disrupt the gut microbiome.

01:46:28.800 | It's also clear, of course,

01:46:29.760 | that antibiotics can disrupt the gut microbiome.

01:46:32.440 | And that brings us to the topic of prebiotics and probiotics.

01:46:35.780 | And I emphasize the fact that for most people,

01:46:38.400 | ingesting high quality non-processed foods

01:46:42.000 | that includes some prebiotic fiber,

01:46:44.680 | but also that includes some probiotics

01:46:47.360 | will probably be healthy,

01:46:48.560 | but not excessive levels of probiotics.

01:46:50.840 | High levels of supplemented probiotics

01:46:52.820 | of the sort that would come in a probiotic pill

01:46:54.540 | or even prescription probiotics

01:46:56.480 | would probably lend themselves best

01:46:58.400 | to when people were under severe chronic stress

01:47:01.020 | or had just come off a serious round

01:47:03.260 | or an ongoing or repeated rounds of antibiotics.

01:47:06.740 | That does not mean that ingesting probiotics

01:47:09.400 | in any form or any kind is not good.

01:47:11.520 | It just means that the very high dose probiotics,

01:47:14.960 | again, typically found in prescription form

01:47:16.960 | or capsule pill form,

01:47:18.900 | probably are best reserved to cases where,

01:47:21.020 | of course, your doctor prescribes them.

01:47:22.820 | You should always follow your doctor's advice.

01:47:24.720 | But in cases where perhaps you are jet lagged,

01:47:27.280 | you're traveling excessively for any reason

01:47:29.760 | or working excessively, you're not getting enough sleep

01:47:32.240 | or your diet is radically changed from normal.

01:47:35.200 | And we talked about how increasing the amount of fiber

01:47:38.220 | in your diet might be useful

01:47:39.880 | for increasing fiber digesting enzymes

01:47:43.080 | and the assimilation of fibrous foods,

01:47:45.240 | but that it's really the ingestion of fermented foods.

01:47:48.000 | And in fact, getting anywhere from four

01:47:50.040 | or even up to six servings a day of fermented foods

01:47:52.400 | can be immensely beneficial

01:47:53.980 | for reducing inflammatory markers in the body

01:47:56.860 | and for improving microbiota diversity all along the gut

01:48:01.160 | and thereby improving signaling

01:48:03.700 | and outcomes along the gut brain axis.

01:48:07.620 | So we went all the way from structure to function

01:48:11.020 | to the four kinds of signaling, mechanical, chemical,

01:48:13.660 | indirect, direct, probiotics, fiber, and fermented foods.

01:48:17.680 | And I tossed in a little bit at the end there

01:48:19.820 | also about ways that you can make your own fermented foods

01:48:23.400 | at home in order to try and offset some of the costs.

01:48:25.680 | Also, it's just kind of fun to do.

01:48:27.300 | And some of those actually taste quite good.

01:48:29.560 | I've actually found that the fermented sauerkraut

01:48:32.540 | that we're making at home actually rivals the sauerkraut

01:48:35.440 | that you can buy out of the refrigerated section

01:48:37.560 | at the grocery store.

01:48:39.280 | And I am by no means a skilled cook or chef

01:48:42.960 | and basically have no culinary skill whatsoever.

01:48:45.600 | So if I can do it, you can do it.

01:48:47.120 | I hope you found this information useful

01:48:49.040 | and perhaps also actionable.

01:48:51.760 | One of my motivations for doing this episode was again,

01:48:55.240 | as a primer for the episode with Dr. Justin Sonnenberg,

01:48:58.520 | where we go really deep into the gut microbiome,

01:49:00.760 | less so into the gut brain axis,

01:49:02.560 | but really deep into the gut microbiome,

01:49:04.480 | what it is, what it does, what it doesn't do,

01:49:06.560 | and some of the emerging findings from his lab

01:49:08.560 | that are yet to be published.

01:49:10.240 | And I also was excited to do this episode

01:49:12.400 | because I think many of us have heard

01:49:14.400 | about the gut microbiome.

01:49:15.640 | We hear about these bacteria that live in our gut.

01:49:17.880 | We hear about the gut brain axis

01:49:19.560 | or that 90% or more of the serotonin

01:49:22.280 | that we make is made in our gut.

01:49:23.760 | We hear about the gut as a second brain and so forth.

01:49:26.440 | But I think for many people,

01:49:28.840 | they don't really have a clear picture

01:49:30.660 | of what the gut microbiome is

01:49:32.400 | and the pathways and mechanisms

01:49:33.960 | by which it can signal to the brain

01:49:36.060 | and to the other parts of the body.

01:49:37.880 | So I hope that today's information

01:49:39.400 | at least improved the clarity around that topic

01:49:42.560 | and leaves you with a more vivid picture

01:49:44.600 | of this incredible system that is our gut brain axis.

01:49:48.180 | If you're enjoying and or learning from this podcast,

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01:50:28.420 | On many previous episodes of the Huberman Lab Podcast,

01:50:30.780 | we talk about supplements.

01:50:32.080 | While supplements aren't necessary for everybody,

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01:50:36.720 | One of the key issues with supplements, however,

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01:50:41.920 | And oftentimes that relates to the precision,

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01:52:10.160 | (upbeat music)

01:52:12.740 | you

How to Enhance Your Gut Microbiome for Brain & Overall Health | Huberman Lab Podcast #61

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