Dr. Justin Sonnenburg: How to Build, Maintain & Repair Gut Health

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

00:00:02.280 | where we discuss science and science-based tools

00:00:04.880 | for everyday life.

00:00:05.880 | I'm Andrew Huberman,

00:00:10.240 | and I'm a professor of neurobiology and ophthalmology

00:00:13.040 | at Stanford School of Medicine.

00:00:14.880 | Today, my guest is Dr. Justin Sonnenberg.

00:00:17.600 | Dr. Sonnenberg is a professor of microbiology and immunology

00:00:20.840 | at Stanford School of Medicine,

00:00:22.760 | and one of the world's leading experts

00:00:24.480 | on the gut microbiome.

00:00:26.400 | The gut microbiome is the existence

00:00:29.000 | of trillions of little microorganisms throughout your gut.

00:00:32.680 | And by your gut, I don't just mean your stomach,

00:00:35.200 | I mean your entire digestive tract.

00:00:37.560 | Turns out we also have a microbiome that exists in our nose,

00:00:42.000 | in any other location in which our body interfaces

00:00:45.040 | with the outside world.

00:00:46.680 | In fact, there's a microbiome on your skin.

00:00:49.400 | And while it might seem kind of intrusive

00:00:51.000 | or kind of disgusting to have all these little microorganisms

00:00:54.120 | they can be immensely beneficial for our health,

00:00:57.420 | meaning our hormonal health, our brain health,

00:01:00.080 | and our immune system function.

00:01:01.840 | Dr. Sonnenberg teaches us about the gut microbiome,

00:01:04.460 | how it's organized spatially,

00:01:05.960 | meaning which microbiota live where.

00:01:07.780 | He teaches us about these incredible things

00:01:09.780 | called crypts and niches,

00:01:11.360 | which are little caves within our digestive tract

00:01:14.200 | that certain microbiota take residence.

00:01:16.440 | And at that premier real estate,

00:01:18.400 | they're able to do incredible things to support our health.

00:01:21.000 | He also talks about the things that we can all do

00:01:23.020 | to support our microbiome in order for our microbiome

00:01:26.540 | to support our brain and body health.

00:01:29.360 | Dr. Sonnenberg co-runs his laboratory with his spouse,

00:01:32.800 | Dr. Erika Sonnenberg,

00:01:34.280 | and together they've also written a terrific

00:01:36.640 | and highly informative book called "The Good Gut,"

00:01:38.920 | taking control of your weight, your mood,

00:01:40.640 | and your long-term health.

00:01:42.160 | Even though that book was written a few years back,

00:01:44.160 | the information still holds up very nicely.

00:01:46.680 | And today he also builds on that information,

00:01:49.560 | informing us about recent studies that for instance,

00:01:52.360 | point to the important role of fermented foods

00:01:55.280 | and the role of fiber in supporting a healthy gut microbiome.

00:01:59.160 | So if you've heard about the gut microbiome,

00:02:01.260 | or even if you haven't,

00:02:02.340 | today you're going to hear about it

00:02:03.680 | from one of the world's leading experts.

00:02:06.140 | He makes it immensely clear as to what it is,

00:02:08.940 | how it functions, and how to support it

00:02:11.180 | for your brain and body health.

00:02:13.100 | During today's discussion,

00:02:14.280 | we don't just talk about nutrition.

00:02:16.100 | We also talk about the impact of behaviors and the microbiome,

00:02:20.520 | behaviors such as who you touch, who you kiss, who you hug,

00:02:23.960 | whether or not you interact with or avoid animals,

00:02:26.920 | whether or not those animals belong to you,

00:02:28.920 | or whether or not they belong to somebody else.

00:02:30.600 | If all that sounds a little bit bizarre,

00:02:32.560 | you'll soon understand that your microbiome

00:02:35.300 | is constantly being modified by the behavioral interactions,

00:02:38.880 | the nutritional interactions,

00:02:40.320 | and indeed your mood and internal reactions

00:02:43.840 | to the outside world.

00:02:45.660 | This is an incredible system.

00:02:47.520 | Everyone has one.

00:02:48.920 | Everyone should know how it works,

00:02:50.200 | and everyone should know how to optimize it.

00:02:52.100 | And today you're going to learn all of that

00:02:54.300 | from Dr. Sonnenberg.

00:02:55.720 | I'm pleased to announce that I'm hosting two live events

00:02:58.080 | in May, 2022.

00:03:00.000 | The first live event will take place

00:03:01.540 | in Seattle, Washington on May 17th.

00:03:04.360 | The second event will take place

00:03:05.680 | in Portland, Oregon on May 18th.

00:03:08.620 | Both are part of a series called the Brain-Body Contract.

00:03:11.840 | For this series, I will discuss science.

00:03:13.960 | So I will discuss the mechanistic science

00:03:15.640 | around things like sleep and focus and motivation,

00:03:18.360 | physical performance, mental health, physical health,

00:03:20.860 | a large number of topics

00:03:22.160 | that I believe many people are interested in

00:03:23.960 | and that certainly are important

00:03:25.520 | for our health and wellbeing and performance.

00:03:28.000 | In addition, I will, of course,

00:03:29.380 | describe tools and actionable items,

00:03:31.500 | most of which I have not discussed

00:03:33.580 | on the Huberman Lab podcast or anywhere else.

00:03:36.360 | Presale tickets for these two events go live Tuesday,

00:03:38.720 | March 8th at 10 a.m. Pacific time.

00:03:41.220 | We've made these tickets exclusively available

00:03:43.400 | to the listeners of the Huberman Lab podcast,

00:03:45.220 | so they are password protected.

00:03:47.120 | To find them, you can go to hubermanlab.com/tour

00:03:50.600 | and use the code Huberman.

00:03:52.380 | Before we begin, I'd like to emphasize

00:03:54.120 | that this podcast is separate from my teaching

00:03:56.100 | and research roles at Stanford.

00:03:57.800 | It is, however, part of my desire and effort

00:03:59.760 | to bring zero cost to consumer information

00:04:01.600 | about science and science-related tools

00:04:03.640 | to the general public.

00:04:05.040 | In keeping with that theme,

00:04:06.120 | I'd like to thank the sponsors of today's podcast.

00:04:08.920 | Our first sponsor is Athletic Greens, now called AG1.

00:04:13.060 | I've been taking AG1 since 2012,

00:04:15.440 | so I'm delighted that they're sponsoring the podcast.

00:04:17.880 | The reason I started taking AG1

00:04:19.200 | and the reason I still take AG1 once or twice a day

00:04:22.440 | is that it meets all my basic

00:04:24.280 | foundational supplementation needs.

00:04:26.400 | What I mean by that is it covers any vitamin

00:04:29.400 | and nutritional deficiencies that I might have,

00:04:32.240 | 'cause I'm trying to be good about my nutrition and diet,

00:04:34.560 | but I don't always manage to get everything that I need,

00:04:37.480 | and I'm sure that there are a lot of gaps in there.

00:04:39.760 | So it covers those gaps.

00:04:40.900 | It also has probiotics.

00:04:43.260 | And as you'll learn in today's episode,

00:04:45.080 | and I've talked about on previous episodes,

00:04:47.920 | the probiotics are essential for a healthy gut microbiome.

00:04:51.820 | We need probiotics in order for our microbiome to thrive,

00:04:55.420 | and our microbiome supports things like gut brain health,

00:04:57.900 | indeed, things like metabolism, mood, hunger.

00:05:00.720 | It also supports the immune system.

00:05:02.760 | So you'll learn today,

00:05:04.400 | your gut microbiome actually manufactures neurotransmitters,

00:05:07.600 | the very chemicals that impact mood and brain function.

00:05:10.400 | Athletic Greens primes your system

00:05:12.000 | for a healthy gut microbiome,

00:05:14.200 | something that can be achieved

00:05:15.420 | with food and lifestyle factors,

00:05:17.080 | but is often hard to achieve

00:05:18.680 | with just food and lifestyle factors.

00:05:20.700 | If you'd like to try Athletic Greens,

00:05:22.160 | you can go to athleticgreens.com/huberman

00:05:25.000 | to claim a special offer.

00:05:26.340 | They'll give you five free travel packs

00:05:27.760 | to make it very easy to mix up Athletic Greens

00:05:29.760 | while you're on the road,

00:05:31.180 | and a year's supply of vitamin D3K2.

00:05:33.720 | Vitamin D3 has many important biological functions

00:05:36.580 | that support your immediate and long-term health,

00:05:38.360 | and K2 as well is very important

00:05:40.440 | for things like cardiovascular health,

00:05:42.280 | calcium regulation, and so on.

00:05:44.000 | Again, if you go to athleticgreens.com/huberman,

00:05:46.800 | you can claim the special offer

00:05:48.000 | of the five free travel packs and the vitamin D3K2.

00:05:51.360 | Today's episode is also brought to us by Roka.

00:05:53.800 | Roka makes eyeglasses and sunglasses

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00:08:28.080 | And now for my discussion with Dr. Justin Sonnenberg.

00:08:31.660 | Justin, thanks so much for being here.

00:08:33.380 | - Great to be here.

00:08:34.220 | - Yeah.

00:08:35.160 | I am a true novice when it comes to the microbiome.

00:08:39.800 | So I'd like to start off with a really basic question,

00:08:43.360 | which is what is the microbiome?

00:08:45.960 | I imagine lots of little bugs running around in my gut,

00:08:50.200 | and I don't quite like the image of that,

00:08:52.960 | but I'm aware that our microbiome can be good for us,

00:08:57.000 | but we can also have an unhealthy microbiome.

00:08:59.800 | So if I were to look at the microbiome at the scale

00:09:03.320 | that I could see the meaningful things,

00:09:04.960 | what would it look like and what's going on in there?

00:09:08.060 | - Yeah, I mean, essentially you're correct.

00:09:11.700 | I mean, we have all of these little microorganisms

00:09:14.040 | running around in our gut.

00:09:15.120 | I think, you know, just to start off

00:09:16.800 | with clarifying terminology, microbiome and microbiota

00:09:21.800 | quite often are referred to,

00:09:23.960 | or used to refer to our microbial community interchangeably,

00:09:27.100 | and I'll probably switch between those two terms today.

00:09:29.880 | The other important thing to realize is that these microbes

00:09:32.320 | are not just in our gut, but they're all over our body.

00:09:36.360 | They're in our nose, they're in our mouths,

00:09:38.680 | they're on our skin.

00:09:40.000 | And so basically anywhere that the environment can get to

00:09:44.660 | in our body, which includes inside our digestive tract,

00:09:47.280 | of course, is, you know, colonized with microbes.

00:09:50.020 | And the vast majority of these are in our distal gut

00:09:55.020 | and in our colon, and so this is the gut microbiota

00:09:58.000 | or gut microbiome.

00:09:59.520 | And the density of this community is astounding.

00:10:04.320 | I mean, it really is.

00:10:05.660 | If you get down to the scale of, you know,

00:10:09.920 | being able to see individual microbes,

00:10:13.200 | you know, you start off with a zoomed out view

00:10:15.800 | and you see something that looks like, you know,

00:10:17.400 | fecal material that digest inside the gut,

00:10:21.400 | and you zoom in and you start to, you know,

00:10:23.560 | get to the microscopic level and see the microbes,

00:10:26.240 | they are just packed, you know, side to side, end to end.

00:10:29.340 | It's a super dense bacterial community,

00:10:32.120 | almost like a biofilm, you know,

00:10:34.620 | something that's just made up of microbes

00:10:36.660 | to the point where it's thought that, you know,

00:10:39.160 | around 30% of fecal matter is microbes, 30 to 50%.

00:10:43.880 | So, you know, it's an incredibly dense microbial community.

00:10:47.980 | We're talking of, you know, trillions of microbial cells

00:10:52.520 | and all those microbial cells,

00:10:54.600 | if you start to get to know them and see who they are,

00:10:58.920 | break out in the gut probably to hundreds

00:11:02.140 | to a thousand species,

00:11:03.880 | depending upon how you define a microbial species.

00:11:08.040 | And then most of these are bacteria,

00:11:11.640 | but there are a lot of other life forms there.

00:11:14.060 | There are archaea, which are little microbes

00:11:17.620 | that are bacteria-like, but they're different.

00:11:20.980 | There are eukaryotes.

00:11:23.260 | So, you know, we commonly think of eukaryotes in the gut

00:11:27.200 | as, you know, something like a parasite,

00:11:30.980 | but there are eukaryotes, there are fungi,

00:11:34.600 | there are also little viruses.

00:11:36.860 | There are these bacteriophages that infect bacterial cells.

00:11:41.060 | And so, and those actually outnumber the bacteria

00:11:44.840 | like 10 to one.

00:11:46.020 | So, they're just everywhere there.

00:11:48.080 | They kill bacteria.

00:11:50.360 | And so, there's these really interesting

00:11:52.160 | predator-prey interactions.

00:11:54.000 | But overall, it's just this really dense, complex,

00:11:57.880 | dynamic ecosystem.

00:11:59.900 | And so, you know, we're talking about the human

00:12:03.480 | as a single species, but we're also thinking of the human

00:12:06.580 | as this complex, integrated ecosystem

00:12:09.160 | of hundreds to thousands of species,

00:12:11.680 | interacting in concert to do all the fantastic things

00:12:15.040 | that we know happen in the human body.

00:12:17.120 | - Amazing.

00:12:17.960 | So, we've got a lot of cargo, or maybe we're the cargo.

00:12:20.920 | - Yeah, I mean, there have been people

00:12:23.640 | that have likened humans to just a really elaborate

00:12:27.080 | culturing flask for microbes, and that we've actually

00:12:30.520 | been designed over the course of evolution,

00:12:34.200 | designed to just efficiently propagate

00:12:38.640 | this microbial culture from person to person,

00:12:41.360 | from generation to generation.

00:12:43.040 | So, it's a different way of thinking of the human body.

00:12:45.160 | - Interesting.

00:12:46.000 | I believe that our pH, or the pH of our digestive system

00:12:53.580 | varies as you descend, as you go from mouth to, you know,

00:12:57.080 | to throat and stomach.

00:12:58.520 | And you said that most of the microbiota

00:13:00.920 | are in the distal colon.

00:13:02.780 | Are there distinct forms of microbiota

00:13:06.240 | all along the length of the digestive tract,

00:13:08.820 | and within these other interfaces with the outside world?

00:13:12.700 | - Totally, yeah.

00:13:13.540 | So, it starts like with our teeth, and in our mouth,

00:13:15.880 | and saliva, there's oral microbiota.

00:13:19.660 | These microbial species are very different

00:13:22.320 | than the ones that you find in the digestive tract.

00:13:24.700 | They're usually built to deal with oxygen very well.

00:13:29.700 | They're in an area that is exposed to a lot of oxygen.

00:13:33.700 | They, of course, see different nutrients

00:13:35.440 | than, for instance, the colonic bacteria would see.

00:13:38.160 | And they grow quite often in mats that live on teeth.

00:13:42.740 | So, they're very structured in terms of,

00:13:45.840 | and not moving around a lot.

00:13:49.900 | So, they're very fairly stationary.

00:13:52.260 | As you move down the digestive tract,

00:13:53.860 | there are microbes in our esophagus and our stomach,

00:13:56.260 | but those communities are not very dense,

00:13:59.660 | and actually not very well studied.

00:14:01.220 | We know of a very, you know,

00:14:03.500 | there's a very famous stomach bacteria

00:14:05.480 | known as Helicobacter pylori,

00:14:07.500 | which can cause stomach ulcers and cause gastric cancer

00:14:10.980 | in some, you know, less frequent situations.

00:14:15.460 | But, you know, this is a very different set of diseases

00:14:20.760 | and different set of microbes.

00:14:22.880 | They have to be adapted to a different environment

00:14:24.660 | in the stomach, especially incredibly acidic environment,

00:14:27.920 | but also very different in terms of their ability

00:14:30.440 | to interact with other microbes,

00:14:32.140 | just because the communities are less dense.

00:14:34.060 | They're less dynamic.

00:14:35.620 | There's less nutrients that stay there

00:14:37.860 | and passage through the community.

00:14:39.980 | So, a lot of times, those communities are reliant

00:14:43.020 | upon nutrients derived from the host

00:14:45.180 | as opposed to nutrients derived from our diet.

00:14:47.480 | As you move down out of the stomach into the small intestine,

00:14:50.180 | you start to see these communities,

00:14:52.180 | which are the ones that are becoming more well studied.

00:14:55.940 | Small intestine is still a bit of a black box

00:14:58.140 | just because it's hard to access,

00:14:59.740 | and so there's some really cool technologies out there

00:15:01.900 | for using, for instance, capsules to do sampling

00:15:06.260 | as the capsule passes through the digestive tract

00:15:09.020 | so that we have a better idea of what's going on

00:15:10.780 | in the small intestine.

00:15:12.060 | And then you get to the colon,

00:15:13.800 | and this is the community that's just so incredibly,

00:15:16.900 | you know, densely packed, doing a ton of,

00:15:20.020 | there's a ton of metabolic activity happening there

00:15:23.420 | and a bunch of interaction with the host,

00:15:26.340 | and that's the community that's really the best studied.

00:15:31.340 | Part of the reason for that is because stool

00:15:34.560 | is so easy to obtain compared to, for instance,

00:15:37.060 | something in the stomach or small intestine,

00:15:39.140 | and that stool is fairly representative.

00:15:42.120 | We know from studies that have been done

00:15:43.860 | using colonoscopies and so forth,

00:15:45.620 | stool is fairly representative

00:15:47.220 | of what's happening in the colon.

00:15:49.120 | So dense, super exciting community,

00:15:51.700 | but also the best studied just because it's the easiest

00:15:54.780 | to access in the lower digestive tract.

00:15:57.380 | - Very interesting.

00:15:58.380 | I imagine these microbiota have to get in there

00:16:02.300 | at some point.

00:16:03.780 | Are microbiota seen in newborns?

00:16:06.500 | In other words, where do they come from?

00:16:08.500 | And dare I ask, what direction do they enter the body?

00:16:12.580 | Or is it from multiple directions?

00:16:14.780 | - Yeah, yeah, great question.

00:16:16.280 | So, you know, one of the burning questions

00:16:18.100 | that we can come back to at the end of this

00:16:19.400 | is where does our microbiota come from?

00:16:21.120 | Because it is this kind of existential question

00:16:24.720 | in the field, like where is this community assembling from?

00:16:28.420 | And the reason that it's such an interesting question

00:16:30.980 | is that a fetus, when it's in the womb,

00:16:35.460 | that's actually a sterile environment.

00:16:37.840 | There have been some studies that have looked at

00:16:39.960 | whether there are microbes in the womb

00:16:41.920 | and microbes colonizing the fetus at that point.

00:16:45.620 | There's some debate about this,

00:16:46.680 | but overall it looks like that's not a big part

00:16:49.040 | of the equation of microbial colonization.

00:16:51.500 | And so each time an infant is born,

00:16:54.980 | it's this new ecosystem.

00:16:56.860 | It's like an island rising up out of the ocean

00:16:58.940 | that has no species on it.

00:17:00.320 | And suddenly there's this like land rush

00:17:02.160 | for this open territory.

00:17:04.960 | And so we know that infants go through

00:17:09.560 | this really complex process of microbiota assembly

00:17:13.420 | over the first days, weeks, months, years of life.

00:17:16.520 | And then you get into switching to solid food,

00:17:20.760 | two to three years of age.

00:17:22.880 | There are some changes in childhood,

00:17:25.400 | adolescents working into adulthood,

00:17:27.580 | but that first zero to one year

00:17:32.580 | is a super dynamic time with really kind of

00:17:36.520 | stereotypical developmental changes in the gut microbiota

00:17:39.460 | that appear to have the possibility of going wrong

00:17:44.020 | and causing problems for infants in some instances.

00:17:48.020 | But if you step away from that extreme side

00:17:51.700 | of things going wrong,

00:17:53.140 | there also are a lot of different trajectories

00:17:56.240 | that developmental process can take

00:17:57.860 | because our microbiota is so malleable and so plastic.

00:18:01.980 | And those trajectories can be affected

00:18:03.840 | by all sorts of factors in early life.

00:18:06.400 | So an example is whether an infant is born by C-section

00:18:10.240 | or born vaginally.

00:18:11.920 | We know from beautiful work that's been done in the field

00:18:15.040 | that infants that are born by C-section

00:18:18.240 | actually have a gut microbiota

00:18:21.940 | that looks more like human skin

00:18:24.560 | than it does like either the birth canal,

00:18:28.960 | the vagina microbiota or the mother's stool microbiota.

00:18:33.960 | Babies that are born through the birth canal

00:18:37.220 | have initial colonization of vaginal microbes

00:18:40.980 | and of stool microbes from their mother.

00:18:43.220 | And so just these first days,

00:18:44.840 | whether you're born by C-section

00:18:46.200 | or through natural childbirth,

00:18:48.520 | your gut microbiota looks very different.

00:18:51.100 | And then compound on top of that,

00:18:53.100 | whether you're breastfed or formula fed,

00:18:55.480 | whether your family has a pet or doesn't have a pet,

00:18:58.480 | whether you're exposed to antibiotics,

00:19:01.060 | there are all these factors that really can change

00:19:04.360 | that developmental process

00:19:05.760 | and really change your microbial identity eventually in life.

00:19:09.360 | The reason that the field is paying really close attention

00:19:14.360 | to this and studying this right now

00:19:16.640 | is because we know from animal studies

00:19:20.780 | that depending upon the microbes that you get early in life,

00:19:25.660 | you can send the immune system or metabolism of an organism

00:19:30.660 | or other parts of their biology

00:19:33.140 | in totally different developmental trajectory.

00:19:35.500 | So what microbes you're colonized with early in life

00:19:39.100 | can really change your biology.

00:19:40.500 | And we can come back to that later.

00:19:41.780 | But getting back to that original question

00:19:45.260 | of where do your microbes come from,

00:19:47.420 | you'd think because you're born

00:19:49.300 | through your mother's birth canal

00:19:50.840 | or exposed to her skin microbes,

00:19:52.580 | that a lot of your microbes would come from your mother.

00:19:55.740 | But it actually turns out

00:19:57.100 | that we can certainly detect that signal.

00:19:59.460 | We certainly see maternal microbes in the infant,

00:20:02.700 | but there are a lot of microbes

00:20:04.220 | that are coming from other places, surfaces, other people,

00:20:08.640 | perhaps other caregivers, but perhaps strangers as well.

00:20:12.260 | So we acquire our microbes from a variety of sources.

00:20:16.620 | The first ones are from our mom

00:20:18.500 | or from our caregivers from the hospital,

00:20:20.640 | but then we add to that tremendously

00:20:22.780 | over the first year or so of life.

00:20:24.620 | - Incredible, you even said pets.

00:20:27.060 | So if a kid, if there's a dog in the home

00:20:30.940 | or a parakeet in the home,

00:20:32.660 | that clearly they have a microbiome also,

00:20:35.080 | then potentially the child is deriving microbiota species

00:20:38.780 | from those pets, correct?

00:20:40.660 | - Exactly, yeah.

00:20:41.500 | And so the best studies that have been done

00:20:46.140 | have just looked at pets in the household as a factor

00:20:48.880 | and whether that changes the group of infants

00:20:52.840 | that have a pet to look slightly different

00:20:54.980 | than the group of infants that don't have a pet.

00:20:57.500 | And then the question is,

00:20:58.340 | what is the pet doing to change those microbes?

00:21:01.280 | And some of it is probably actually contributing

00:21:03.940 | to direct members of the microbiota.

00:21:06.120 | Actually, I have a dog,

00:21:08.700 | that dog occasionally will lick my mouth

00:21:11.500 | without me like paying attention,

00:21:13.520 | and that's probably introducing microbes.

00:21:16.160 | We also know that pets are down in the dirt,

00:21:20.180 | they're outside, they're being exposed

00:21:23.760 | to a lot of environmental microbes.

00:21:25.720 | And so just pets serving as a conduit

00:21:30.100 | for a bunch of microbes that we wouldn't otherwise

00:21:33.180 | come in contact with is a possibility as well.

00:21:36.740 | - I'll show you what.

00:21:37.580 | We will return to pets and in particular, your dog,

00:21:40.140 | an amazing dog, by the way.

00:21:41.300 | I met your dog just the other day

00:21:43.260 | and I had to force myself.

00:21:44.460 | I had to pry myself away from, it's a Havanese, right?

00:21:47.180 | - Havanese.

00:21:48.020 | - Incredible, what is your dog's name?

00:21:48.860 | - Louis, Louis Pasteur.

00:21:50.640 | - Louis Pasteur, I don't know how appropriate.

00:21:53.380 | Amazing dog, what a personality on that dog.

00:21:55.920 | The issue that I think a lot of people

00:22:00.440 | are probably wondering is what is a healthy microbiome?

00:22:04.780 | And what is it supporting?

00:22:06.760 | We hear that you need a healthy microbiome

00:22:09.940 | to support the immune system or metabolism

00:22:11.880 | or even the gut brain access.

00:22:14.000 | How do we define a healthy versus a unhealthy microbiome?

00:22:17.720 | Some people might know the unhealthy microbiome

00:22:19.840 | as dysbiosis is the word that I encounter in the literature.

00:22:23.640 | But given that there are so many species of microbiota

00:22:26.540 | and given that I think we probably each have

00:22:28.640 | a signature pattern of microbiota,

00:22:31.220 | how do we define healthy versus unhealthy microbiota?

00:22:34.040 | Is there a test for this?

00:22:36.320 | Later we'll talk about technologies for testing microbiota.

00:22:39.360 | There are a lot of companies now,

00:22:41.040 | a lot of people sending stool samples in the mail.

00:22:44.380 | Never look at the postal service the same way again,

00:22:46.180 | but it's out there and it's getting analyzed.

00:22:49.380 | So how should I think about this?

00:22:50.820 | I can think about things like heart rate,

00:22:52.880 | heart rate variability, BMI, all sorts of metrics of health.

00:22:57.960 | How should I think about the microbiota?

00:22:59.740 | How do I know if my microbiome is healthy or unhealthy?

00:23:02.080 | - Yeah, it's a million dollar question right now

00:23:04.760 | in the field and there's a lot of different ways

00:23:06.440 | of thinking about that and I can talk about some of those.

00:23:08.340 | But I would say that there are sessions at conferences,

00:23:13.340 | there are review articles being commissioned.

00:23:15.280 | There are all sorts of kind of thought pieces

00:23:17.480 | about this right now, like what is a healthy microbiota?

00:23:19.980 | What are the features that define it?

00:23:22.260 | And I think before diving into this,

00:23:25.000 | the important thing to realize is it's a complex topic.

00:23:30.000 | Context matters a lot.

00:23:33.280 | What's healthy for one person or one population

00:23:35.460 | may not be healthy for another person or population.

00:23:38.760 | And the microbiota is malleable.

00:23:43.580 | It's plastic, it changes our human biology,

00:23:48.580 | which I think is how we think about health quite often,

00:23:52.720 | BMI and longevity, reproductive success,

00:23:56.360 | however you wanna define it.

00:23:57.720 | It certainly can accommodate a variety of configurations

00:24:04.360 | of gut microbiota and we don't have,

00:24:07.040 | it's really hard to untangle all of the different factors

00:24:11.960 | of what could be very healthy

00:24:14.000 | versus a little bit less healthy.

00:24:16.480 | So I will say that there's no single answer to this,

00:24:18.720 | but there's some really important considerations

00:24:20.880 | and perhaps the best way to start talking about this

00:24:23.800 | is to go back to the inception

00:24:27.200 | of the Human Microbiome Project,

00:24:28.680 | which was this program that NIH started.

00:24:31.400 | They invested a lot of money in 2008, 2009

00:24:35.000 | for really propelling the field of gut microbiome research.

00:24:40.000 | It was becoming evident at that point

00:24:43.800 | that this was not just a curiosity of human biology,

00:24:46.360 | that it was probably really important for our health.

00:24:48.600 | And they had all this wonderful sequencing technology

00:24:51.640 | from the Human Genome Sequencing Project.

00:24:54.340 | And with the human genome complete at that point,

00:24:56.640 | they started turning that technology

00:24:58.160 | to sequencing our gut microbes.

00:24:59.620 | And it's important to contextualize

00:25:01.880 | the amount of information that they're trying to document.

00:25:05.520 | The collective genome of our gut microbes

00:25:09.120 | is on the order of 100 to 500 times larger

00:25:13.460 | than our human genome.

00:25:15.040 | So it's just in terms of the number of genes.

00:25:17.440 | So it's just this vast number of genes.

00:25:20.040 | And then if you start getting

00:25:21.240 | into some of the fine variation,

00:25:22.720 | it's scales by 10 to 100 fold.

00:25:24.960 | So really a huge amount of information

00:25:27.240 | they're trying to document.

00:25:28.240 | And so it was a wonderful investment

00:25:31.960 | and it continues to pay dividends to this day.

00:25:34.920 | But one of their goals of that project

00:25:36.720 | was to try to define what a healthy microbiome is

00:25:39.680 | versus a diseased microbiome in different contexts.

00:25:42.220 | And so they started enrolling a bunch of healthy people

00:25:45.760 | and a bunch of people with, for instance,

00:25:47.120 | inflammatory bowel disease and other diseases.

00:25:49.480 | And the idea was let's document those microbiomes,

00:25:53.200 | what microbes are there, what genes are there.

00:25:55.400 | And then we can start to get a sense

00:25:56.860 | of what are the commonalities of the healthy people

00:26:00.000 | and how can that go wrong in these different disease states.

00:26:04.860 | And there were some answers from that,

00:26:09.860 | but through those studies,

00:26:13.440 | we really started to get the image

00:26:14.960 | that there is this tremendous individuality

00:26:17.600 | in the gut microbiome.

00:26:18.980 | And so it's really hard to start drawing conclusions

00:26:23.980 | after initial pass of that project

00:26:28.440 | of what is a healthy microbiome.

00:26:30.600 | But the other thing that we started to realize

00:26:32.700 | at the same time, there were studies going on

00:26:35.760 | documenting the gut microbiome of traditional populations

00:26:39.440 | of humans, hunter-gatherers,

00:26:41.640 | rural agricultural populations.

00:26:43.960 | And those studies were really mind blowing

00:26:46.880 | from the perspective of all these people are healthy,

00:26:49.920 | they're living very different lifestyles

00:26:52.460 | and their microbiome doesn't look anything

00:26:54.640 | like a healthy American microbiome.

00:26:57.560 | - So does that mean that the healthy American microbiome

00:27:00.800 | is healthy, but only in the context of living

00:27:05.560 | in the United States and consuming what's consumed here?

00:27:09.060 | Or is it that there is a superior microbiome signature

00:27:12.480 | somewhere in our history or currently in the world?

00:27:14.880 | - Yeah, I think that's kind of a big question right now.

00:27:19.520 | I think there's a great quote from Dabchansky

00:27:23.800 | that says, "Nothing in biology makes sense

00:27:25.560 | "except in the light of evolution."

00:27:27.520 | And these traditional populations are all modern people

00:27:32.440 | living on the planet now,

00:27:33.980 | but their lifestyle does represent the closest approximation

00:27:39.360 | to how our ancestors, early humans lived.

00:27:43.360 | And so those microbiomes,

00:27:46.080 | and now we know from sequencing of paleofeces,

00:27:48.920 | the microbiome of these traditional populations

00:27:51.140 | is more representative of the microbiome

00:27:55.200 | that we evolved with that potentially shaped

00:27:58.120 | our human genome.

00:27:59.440 | And so one possibility is that in the industrialized world,

00:28:04.440 | we have a different microbiome from traditional populations

00:28:08.640 | and that microbiome is well adapted

00:28:10.480 | to our current lifestyle and therefore healthy

00:28:13.040 | in the context of an industrialized society.

00:28:15.040 | And there probably are elements of that that are true.

00:28:18.060 | But another possibility is that this is a microbiome

00:28:20.740 | that's gone off the rails,

00:28:22.320 | that it is deteriorating in the face of antibiotic use

00:28:26.740 | and all the problems associated with industrialized diet,

00:28:31.740 | Western diet, and that even though the human microbiome

00:28:37.840 | project documented the microbiome of healthy people,

00:28:42.520 | healthy Americans,

00:28:43.800 | that what they really may have been documenting there

00:28:46.620 | is a perturbed microbiota that's really predisposing people

00:28:50.760 | to a variety of inflammatory and metabolic diseases.

00:28:54.860 | - It reminds me of the, as a neurobiologist,

00:28:57.520 | I was weaned in the landscape of so-called critical periods

00:29:01.400 | where early life environment very strongly shapes the brain

00:29:07.040 | and so many studies were done on animals

00:29:08.960 | raised in traditional cages with a water bottle

00:29:11.080 | and some food, maybe a few other animals of the same species

00:29:14.180 | and then people came along and said,

00:29:15.880 | "Wait, normally these species in the wild

00:29:17.760 | "would have things like things to climb over

00:29:19.760 | "and things to go through."

00:29:20.600 | And you provide those very basic elements

00:29:22.720 | and all of a sudden the architecture of neural circuits

00:29:25.080 | looks very different and you realize

00:29:26.300 | that you were studying a deprived condition.

00:29:29.120 | And earlier you actually referred to,

00:29:30.700 | if I understood correctly,

00:29:32.200 | to critical periods for gut microbiome development.

00:29:36.440 | Is it fair to say that there are critical periods?

00:29:39.680 | Meaning if my, let's say my, let's aim it at me,

00:29:42.120 | if my gut microbiome was dysbiotic,

00:29:46.440 | it was off early in life,

00:29:49.200 | can I rescue that through proper conditions and exercise?

00:29:52.600 | Or is there some sort of fixed pattern

00:29:55.340 | that's going to be hard for me to escape from?

00:29:57.200 | - Yeah, there's a big field that's emerging now

00:30:00.840 | that we refer to as kind of reprogramming the gut microbiome.

00:30:05.320 | And I think if we want to conceptualize humans

00:30:09.120 | as this aggregate human microbial biology,

00:30:12.580 | most people have heard of CRISPR

00:30:16.040 | and the ability to potentially change our human genome

00:30:19.120 | in ways that correct genetic problems.

00:30:21.980 | That's a wonderful technology

00:30:26.040 | and has kind of put on the table,

00:30:29.060 | genetic engineering for curing disease,

00:30:31.320 | but it's much easier to change gut microbes for a problem

00:30:35.000 | just because that community is malleable.

00:30:39.000 | The issue that I think we're seeing in the field

00:30:43.400 | is that microbiomes quite often,

00:30:47.120 | whether they're diseased or healthy,

00:30:49.280 | exist in stable states.

00:30:50.880 | They kind of tend towards this well

00:30:54.320 | that has gravity to it in a way, biological gravity,

00:30:58.040 | where it's really hard to dislodge that community

00:31:01.520 | from that state.

00:31:02.720 | So even individuals, for instance, that get antibiotics,

00:31:06.760 | you take oral antibiotics, the community takes this huge hit.

00:31:11.120 | We know that a bunch of microbes die,

00:31:13.380 | the composition changes,

00:31:15.400 | and that represents a period of vulnerability

00:31:18.280 | where pathogens can come in and take over and cause disease.

00:31:20.980 | But if that doesn't happen,

00:31:22.840 | the microbiota kind of works its way back

00:31:25.480 | to something that is not exactly like,

00:31:27.500 | but similar to the pre-antibiotic treatment.

00:31:31.140 | We know with dietary perturbations,

00:31:33.220 | quite often you'll see a really rapid change

00:31:37.020 | to the gut microbiome.

00:31:38.300 | And then it's almost like a memory where it snaps back

00:31:41.260 | to something that's very similar to the original state,

00:31:44.500 | even though the diet remains different.

00:31:46.900 | And so there's this incredible,

00:31:48.820 | what we refer to as resilience of the gut microbiome

00:31:51.740 | and resistance to change,

00:31:54.020 | or at least resistance to establishing a new stable state.

00:31:58.040 | So that doesn't mean it's hopeless to change

00:32:00.480 | an unhealthy microbiome to a healthy microbiome,

00:32:04.180 | but it does mean that we need to think carefully

00:32:06.380 | about restructuring these communities

00:32:10.180 | in ways where we can achieve a new stable state

00:32:13.340 | that will resist the microbial community

00:32:15.880 | getting pulled back to that original state.

00:32:18.200 | And one of the really kind of simplest and nicest examples

00:32:23.200 | of this is an experiment that we performed with mice,

00:32:29.620 | where we were feeding mice a normal mouse diet,

00:32:33.100 | a lot of nutrients there for the gut microbiota,

00:32:35.500 | things like dietary fiber.

00:32:37.220 | And we switched those mice,

00:32:39.940 | half the mice to a low fiber diet.

00:32:42.520 | And we were basically asking the question that,

00:32:45.220 | if you switch to kind of a Western like diet,

00:32:47.740 | a low fiber, higher fat diet,

00:32:49.940 | what happens to the gut microbiota?

00:32:51.740 | And we saw the microbiota change, it lost diversity.

00:32:54.940 | It was very similar to what we see

00:32:57.020 | in the difference between industrialized

00:32:59.780 | and traditional populations.

00:33:01.340 | But when we brought back a healthy diet,

00:33:03.980 | a lot of the microbes returned and it was fairly,

00:33:07.340 | you know, there was this kind of memory

00:33:09.340 | where it went back to very similar to its original state.

00:33:12.420 | The difference is that when we put the mice

00:33:14.940 | on a low fiber, high fat diet,

00:33:17.300 | and then kept them on that for multiple generations,

00:33:21.140 | we saw this progressive deterioration

00:33:23.540 | over the course of generations,

00:33:25.200 | where by the fourth generation,

00:33:27.060 | the gut microbiome was a, you know,

00:33:29.980 | a fraction of what it originally was.

00:33:31.720 | Let's say 30% of the species only remained,

00:33:35.060 | something like 70% of the species had gone extinct

00:33:38.200 | or appeared to have gone extinct.

00:33:40.420 | We then put those mice back onto a high fiber diet

00:33:43.540 | and we didn't see recovery.

00:33:45.360 | So in that case, it's a situation

00:33:48.020 | where a new stable state has been achieved.

00:33:50.580 | In that case, it's probably because those mice

00:33:52.440 | don't actually have access to the microbes they've lost.

00:33:56.300 | And we actually know that we did the control experiment

00:33:59.560 | of mice on a high fiber diet for four generations.

00:34:02.720 | They maintain all their microbes.

00:34:04.280 | If we take those fourth generation mice

00:34:06.740 | with all the diversity and do a fecal transplant

00:34:09.540 | into the mice that had lost their microbes,

00:34:11.980 | but had been returned to a high fiber diet,

00:34:14.340 | all of the diversity was reconstituted.

00:34:16.580 | So it was, you know, so your question of like,

00:34:19.520 | how do we establish new stable states?

00:34:21.600 | How do we get back to a healthy microbiota?

00:34:23.380 | If we have taken a lot of antibiotics

00:34:25.560 | or have a deteriorated microbiota,

00:34:27.460 | it's probably a combination of having access

00:34:29.960 | to the right microbes.

00:34:31.440 | And we can talk about what that access looks like.

00:34:33.880 | It may look like therapeutics in the future.

00:34:35.560 | There are a lot of companies working on creating cocktails

00:34:37.840 | of healthy microbes, but it will be a combination

00:34:40.200 | of access to the right microbes

00:34:42.540 | and nourishing those microbes with the proper diet.

00:34:46.940 | - Very interesting.

00:34:47.780 | This multi-generational study reminds me of something

00:34:49.640 | that I was told early in my training,

00:34:51.800 | which was that it takes a long time for a trait to evolve,

00:34:56.200 | but not a long time for traits to devolve.

00:34:59.400 | - Exactly.

00:35:00.240 | - Which generally is true of human behavior too,

00:35:04.360 | although it depends.

00:35:06.600 | We can all do better nonetheless.

00:35:07.920 | - Very interesting.

00:35:08.760 | - So I have a puzzle or a bit of a conundrum

00:35:13.400 | around this notion of species of microbiota.

00:35:17.520 | So if the pH, if the acidity differs

00:35:21.880 | along the digestive tract,

00:35:23.760 | but is more or less fixed for a given location, right?

00:35:26.120 | I mean, unless something is really off,

00:35:27.280 | the pH of the stomach is within a particular range

00:35:29.920 | and the intestine and so forth.

00:35:32.540 | And certain microbiota thrive at a given station,

00:35:36.980 | a given location along the digestive tract

00:35:39.520 | and the pH is sort of fixed more or less.

00:35:42.680 | I'm trying to figure out

00:35:44.420 | what is allowing certain microbiota

00:35:47.940 | to stay in a given location?

00:35:49.980 | Why don't they migrate up or down?

00:35:51.700 | So are they pH sensitive?

00:35:53.000 | And that's what they're selecting for along the tract.

00:35:56.300 | And I'm also trying to figure out how these changes in food

00:36:01.100 | so robustly change the microbiome.

00:36:03.440 | The way you describe it almost makes it sound like food

00:36:05.620 | is the variable that's going to dictate

00:36:07.840 | the quality of the microbiome.

00:36:09.780 | Although I'm sure there are other factors as well.

00:36:11.900 | And then in the back of my mind,

00:36:13.460 | I don't know that I want to ask this question,

00:36:15.220 | but I really want to ask this question,

00:36:16.660 | which is where are they in there exactly?

00:36:19.720 | And why don't they all get flushed out, right?

00:36:22.580 | If 30% of fecal matter is microbiota,

00:36:26.580 | then where are they living?

00:36:29.340 | Are they along the lining

00:36:32.560 | and the little microvilli of the intestine?

00:36:34.980 | And what are they attaching to and interacting with?

00:36:38.140 | We know there are neurons in there,

00:36:40.660 | especially within the stomach.

00:36:41.900 | There's a lot of work now being done on the gut neurons

00:36:45.300 | and how they signal to the brain and so forth.

00:36:47.380 | But who are they talking to in terms of the host cells?

00:36:51.700 | And because if it's just from food,

00:36:54.100 | I imagine that they're in there

00:36:55.140 | having their good time or not.

00:36:57.380 | And then some are getting flushed out or not.

00:36:59.980 | But how do they actually stay in there?

00:37:01.980 | Who are they attaching to?

00:37:03.420 | What are they talking about?

00:37:04.580 | What are they doing for fun and so forth?

00:37:06.540 | - Yeah, yeah, super interesting.

00:37:08.340 | So I'll come back to the attachment question

00:37:11.800 | and kind of like why they don't get washed out

00:37:13.760 | 'cause this is a super fascinating question.

00:37:15.820 | And I think your initial point

00:37:19.140 | of like the kind of regional differences

00:37:22.460 | in what's happening in terms of physiology,

00:37:24.660 | biochemistry along the length of the gut

00:37:26.800 | is really interesting.

00:37:27.640 | There certainly is a pH gradient

00:37:29.320 | along the length of the gut.

00:37:30.580 | There is actually bicarbonate that's secreted

00:37:33.680 | into the small intestine to try to neutralize stomach acid.

00:37:37.380 | There also is bile that's secreted.

00:37:39.940 | That creates a different chemical environment

00:37:42.500 | and there are bile loving bacteria

00:37:44.640 | that kind of live in that region of the gut.

00:37:47.040 | And then there is a nutrient gradient

00:37:51.180 | just because as food leaves the stomach,

00:37:54.040 | a lot of the simple nutrients are absorbed.

00:37:58.380 | And so you might see microbes in the small intestine,

00:38:01.860 | for instance, that are better at consuming simple sugars,

00:38:04.720 | but you won't find many microbes in the colon like that

00:38:07.220 | because all the simple sugars

00:38:08.420 | have been depleted at that point.

00:38:10.660 | And then the immune system is a big factor as well.

00:38:13.820 | And the immune system is incredibly active

00:38:16.400 | in the small intestine.

00:38:18.300 | The small intestine is this really interesting challenge

00:38:20.580 | for the host because it's a tissue that's been,

00:38:22.860 | its purpose is mainly absorptive.

00:38:25.100 | And so there has to be flow of a lot of things,

00:38:30.100 | a lot of nutrients from the luminal contents

00:38:35.100 | into host cells.

00:38:36.700 | And so that means the barrier can't be as fortified.

00:38:40.700 | And so the immune system is incredibly active

00:38:44.340 | in the small intestine to make sure

00:38:46.260 | that microbes aren't getting so close.

00:38:48.420 | And if they are getting close,

00:38:49.900 | there's a response to them to put them back

00:38:51.860 | in their right location.

00:38:53.680 | So there's, and then along this whole kind of architecture

00:38:58.680 | of the gut, there's the longitudinal gradients,

00:39:04.000 | things like pH and so forth.

00:39:06.100 | And I should say that pH starts to drop again in the colon

00:39:09.500 | because a lot of those microbes are fermenting things

00:39:12.220 | and producing acids.

00:39:13.840 | And so you actually end up with the pH starting to drop,

00:39:17.940 | not as low as the stomach, but starting to drop again

00:39:20.300 | if there's a lot of fermentation happening in the colon.

00:39:23.840 | In addition, you also have a gradient

00:39:25.740 | from the host surface epithelium

00:39:28.740 | out to the middle of the gut.

00:39:31.660 | And that is likely the key for what is retained in the gut

00:39:36.660 | and how the community isn't washed out.

00:39:41.160 | So lining the gut, we have epithelial cells

00:39:44.620 | in the small intestine, they're largely absorptive.

00:39:47.320 | In the colon, there's a lot of mucus production.

00:39:50.780 | And we also see this in the small intestine.

00:39:53.620 | And this mucus lining is this substance that we secrete,

00:39:58.460 | largely made of carbohydrate actually.

00:40:01.020 | And the purpose of that is to keep microbes

00:40:04.940 | in the right spot and to allow nutrients and water

00:40:09.500 | to be absorbed in the small intestine and large intestine.

00:40:12.700 | And so it's this mesh work that is supposed

00:40:15.260 | to keep out large things like bacteria

00:40:17.180 | and let in small things like nutrients.

00:40:19.720 | That mucus layer, it turns over more slowly

00:40:25.840 | than the luminal contents passing by.

00:40:29.460 | And so if a microbe learns to hold on to that mucus layer,

00:40:34.120 | it can actually resist the flow of the contents of the gut.

00:40:39.120 | And so there's many microbes in the gut

00:40:42.340 | that are not just good at attaching to mucus,

00:40:44.580 | but also good at nibbling on it, at eating it.

00:40:48.360 | And there are these bacteria like Acromancea muciniphila,

00:40:51.940 | mucus-loving, one of its main things it does

00:40:54.860 | is actually eat mucus in the gut, that's its lifestyle.

00:40:58.580 | And so there's an incredible gradient of activity

00:41:03.580 | from the host tissue working your way

00:41:05.780 | out to the middle of the gut.

00:41:07.260 | What's amazing is some microbes actually do penetrate

00:41:10.140 | past the mucus and there are these invaginations

00:41:12.980 | in the intestine known as crypts,

00:41:15.200 | actually where the stem cells live,

00:41:17.520 | that produce the epithelium.

00:41:18.980 | And there are microbial communities

00:41:20.780 | that can form in those crypts.

00:41:22.740 | And we don't know completely what their function is,

00:41:25.300 | but we've done some studies that appear to indicate

00:41:27.860 | that if you can localize to a crypt,

00:41:30.620 | you've hit the jackpot as a microbe

00:41:33.400 | for being able to maintain dominance in the gut.

00:41:36.460 | So if you sit in the crypt and something similar to you,

00:41:40.380 | another microbe that's similar to you comes into the gut,

00:41:42.920 | you can actually exclude that microbe.

00:41:45.400 | And the thinking is that it can't find a spot

00:41:49.380 | to resist being washed out of the gut.

00:41:52.080 | So there probably are these little niches

00:41:54.080 | close to host tissue in the mucus

00:41:55.940 | that are absolutely essential for resisting

00:41:59.380 | getting washed out with the flow of all the contents.

00:42:02.860 | - Incredible.

00:42:04.480 | That raises a question about two things

00:42:06.600 | that are reasonably popular.

00:42:08.940 | One is this notion of cleanses from either direction.

00:42:13.060 | People will consume things by mouth

00:42:14.660 | to try and cleanse their digestive tract.

00:42:17.340 | There's a long history of this.

00:42:19.060 | I'm not recommending this.

00:42:20.260 | There's differing opinions on whether or not

00:42:21.860 | this is good or bad.

00:42:23.020 | And the other is fasting or time-restricted feeding.

00:42:26.900 | The reason I ask about time-restricted feeding

00:42:29.780 | is my understanding is that

00:42:31.260 | after a prolonged period of fasting,

00:42:33.980 | there's some auto absorption or digestion

00:42:38.300 | of one's own digestive tract that then gets renewed.

00:42:41.860 | In other words, your intestine and stomach

00:42:43.780 | start eating its own lining to some extent

00:42:45.720 | in the absence of food.

00:42:47.100 | So what do we know about cleanses?

00:42:49.220 | Oh, and then I suppose there's cleanses

00:42:50.460 | from the other direction too, right?

00:42:51.860 | Which are less popular,

00:42:53.300 | but I've never run the statistics,

00:42:55.820 | but certainly exist out there.

00:42:59.180 | What's the idea about cleanses and fasting

00:43:03.760 | as it relates to the health

00:43:05.060 | or the dysbiosis of the microbiota?

00:43:07.540 | - Yeah, there hasn't been a lot of high quality science

00:43:10.760 | in this area.

00:43:11.600 | And so it's really hard to conclude

00:43:12.900 | whether these are good for health or bad for health.

00:43:15.820 | I think the fasting,

00:43:17.540 | we're in a really interesting situation

00:43:21.500 | in the industrialized world

00:43:23.100 | because we have so many problems

00:43:24.740 | associated with our digestive tract.

00:43:26.520 | And that probably has to do with our highly processed diet

00:43:30.140 | and perhaps having a microbiota

00:43:31.860 | that's fairly perturbed as well.

00:43:34.020 | And so whether doing things like this are good or bad,

00:43:39.020 | it's really hard to define

00:43:46.980 | because we may be starting off in a fairly bad state anyway.

00:43:50.420 | There are so many diseases

00:43:52.380 | that we're dealing with, metabolic syndrome,

00:43:54.380 | inflammatory bowel disease,

00:43:56.140 | that just put a massive portion of the population

00:44:00.420 | in a very different category

00:44:02.640 | than people that are thinking about how do I maintain health?

00:44:05.520 | How do I live a long life from starting off

00:44:09.000 | in what we consider a fairly healthy state?

00:44:11.540 | And so things like fasting and a lot of other therapies

00:44:16.540 | that have been developed in the field,

00:44:18.700 | I think ketogenic diet

00:44:21.060 | may be kind of in this category as well.

00:44:23.700 | There can be tremendous benefits

00:44:25.960 | in terms of their impact

00:44:28.580 | in the context of metabolic syndrome

00:44:30.860 | and for people that are battling

00:44:32.660 | eating a continual bad diet or something like that.

00:44:37.260 | - And adherence.

00:44:38.700 | I think one of the reasons for the popularity

00:44:41.100 | of intermittent fasting, time-restricted feeding,

00:44:45.540 | and sort of what do they call them now?

00:44:48.400 | Exclusion diets where you entirely exclude meat

00:44:51.360 | or you entirely exclude plants or whatever it is,

00:44:54.100 | that adherence is sometimes easier in the all or none.

00:44:56.900 | As neurobiologists, we think of it as a go-no-go circuitry.

00:45:00.940 | It's harder to make decisions,

00:45:04.540 | nuanced decisions often about food

00:45:06.320 | than it is to just eliminate entire categories of food.

00:45:09.440 | Not eating for many people

00:45:11.460 | is easier than eating smaller portions.

00:45:16.400 | So some of it I think is neurobiological and psychological.

00:45:19.180 | - Absolutely, and we've had gastroenterology fellows

00:45:22.060 | in our lab that come in and we kind of,

00:45:24.500 | I think that to kind of slice through the nuance

00:45:28.060 | of all this, there's a very simple recipe

00:45:30.100 | and a really well-accepted kind of broad definition

00:45:33.060 | of what a healthy diet is.

00:45:34.500 | Kind of the Mediterranean diet, plant-based diet is,

00:45:38.980 | there's just a ton of data that,

00:45:40.700 | particularly people of European ancestry,

00:45:43.020 | but there's a pretty broad acceptance

00:45:46.300 | that if you eat mostly plants,

00:45:48.560 | for most people that's gonna be very healthy

00:45:50.900 | to the point where a wonderful colleague of ours,

00:45:54.660 | Christopher Gardner, who's studied diet his whole life,

00:45:58.940 | trying to establish what a healthy diet is

00:46:00.920 | and people was giving advice.

00:46:02.240 | I saw him giving advice to a dietician

00:46:05.280 | who was trying to get all the rules

00:46:07.120 | of what she should be recommending

00:46:09.520 | to people that she deals with

00:46:11.160 | that are interested in a healthy diet.

00:46:12.860 | And she said, so the number one,

00:46:14.420 | I'm gonna say plant-based fiber is probably super important

00:46:18.100 | and that should be very high on the list.

00:46:20.080 | And she goes on to number two and he said, stop.

00:46:23.420 | He said, if people do number one well,

00:46:26.580 | you don't need to know any other rules.

00:46:28.540 | I mean, it's basically like

00:46:29.540 | if you can have a high fiber plant-based diet,

00:46:33.480 | for most people, at least talking about the bucket

00:46:35.980 | of people that are already in a healthy state,

00:46:38.200 | you don't really need to think about other things

00:46:39.860 | because you can't eat too much meat,

00:46:41.340 | you can't eat too many sweets,

00:46:42.580 | you've already eaten a huge amount of plant-based fiber.

00:46:45.780 | Your gut is full, you're not gonna be hungry

00:46:49.460 | and it kind of takes care of worrying

00:46:52.020 | about what should I eat or what shouldn't I eat.

00:46:54.300 | Just eat a ton of whole grains, legumes, vegetables,

00:46:59.300 | fruit that's high fiber-based, not high sugar.

00:47:02.740 | - It doesn't completely exclude meat and fish and dairy.

00:47:05.660 | - And he was saying people can add their own spins on this,

00:47:08.980 | but I think that the main rule

00:47:11.300 | is just start off with,

00:47:13.060 | and it kind of gets back to Michael Pollan's mantra,

00:47:15.860 | eat food, not too much, mostly plants.

00:47:20.020 | I think if you stick with kind of these simple rules

00:47:22.940 | and don't overthink like, should I have this,

00:47:25.360 | can I eat eggs, can I eat,

00:47:27.100 | just kind of stick to these simple rules,

00:47:28.760 | it makes it very approachable.

00:47:30.440 | But I agree, so these gastroenterology fellows

00:47:32.660 | that we've had in our lab say that it's really hard,

00:47:35.580 | we kind of say to them,

00:47:36.640 | why won't you give this dietary advice?

00:47:38.560 | It's really well known.

00:47:39.780 | And they just said, well, it's really hard

00:47:41.700 | to get people to change their diet

00:47:43.600 | unless you're doing either a go, no-go sort of thing,

00:47:47.200 | or eliminating something.

00:47:49.060 | So if carrots are giving you problems, don't eat carrots.

00:47:52.000 | And that's a very simple, easy instruction to follow,

00:47:55.540 | but doesn't really deal with the root problem

00:47:58.940 | of why can't you eat carrots?

00:48:00.900 | Because you should be able to eat carrots.

00:48:02.760 | Most people can eat carrots.

00:48:04.160 | And so I think that we,

00:48:08.660 | yeah, when we're thinking about things like fasting

00:48:13.660 | and all these different dietary regimes

00:48:18.140 | and cleanses that people do,

00:48:20.480 | we have to step back for a moment and say,

00:48:22.420 | okay, well, what are really the big high-level rules

00:48:26.300 | that we should take home?

00:48:27.640 | And then if you are experiencing problems

00:48:29.840 | and you want to think about how to deal with them,

00:48:31.600 | it's good to go to an evidence-based method

00:48:33.880 | where there's actually data to back it up.

00:48:35.900 | The data in the field really shows that with fasting,

00:48:40.900 | particularly if you go to animals that hibernate

00:48:43.520 | or things like that, where there's really extended fast,

00:48:45.700 | you actually have a microbiota come up

00:48:48.900 | that blooms in the absence of food coming in through diet.

00:48:53.900 | That's really good at eating mucus.

00:48:57.260 | So you have bacteria that specialize

00:49:01.140 | in eating nutrients derived from the host

00:49:03.240 | because there's no other nutrients to live on.

00:49:05.560 | Now, whether this is good or bad, we don't know,

00:49:08.420 | but it seems like the consumption of mucus in excess

00:49:13.420 | is a problem from the standpoint of microbes

00:49:18.980 | getting too close to host tissue and inciting inflammation,

00:49:21.680 | which is what we see in animal models

00:49:23.260 | when we deprive of dietary fiber.

00:49:25.760 | We see these mucus utilizers become abundant

00:49:28.460 | and inflammatory markers start to come on.

00:49:30.460 | So fasting short-term might be fine.

00:49:33.540 | Probably there's definitely benefits

00:49:36.220 | that are seen metabolically.

00:49:37.940 | In terms of what it means for long-term health

00:49:40.520 | from the standpoint of the gut microbiota,

00:49:42.320 | I would say we don't have the answer to that yet.

00:49:44.720 | In terms of the cleanses and the flushes and all this,

00:49:48.840 | personally, I think it's a terrible idea.

00:49:51.280 | We know that in studies that are being done now

00:49:55.480 | to reprogram the gut microbiota

00:49:57.460 | to install a completely new microbial community,

00:50:00.360 | the first step is to wash away the resident microbial

00:50:03.620 | community that's there.

00:50:04.900 | So if you're in the process of acquiring

00:50:07.060 | a really good microbiota and you know how to do that,

00:50:09.760 | then the flushing everything out is great.

00:50:12.700 | Otherwise, what is happening is you're kind of leaving

00:50:16.100 | rebuilding of the community to chance, like what is it?

00:50:19.600 | And so what microbes are gonna colonize?

00:50:23.240 | Who's gonna take up space after you do this flush or cleanse?

00:50:26.620 | And I think it's a little bit like playing Russian roulette.

00:50:31.200 | You may end up with a good microbial community

00:50:34.060 | in there afterwards, you may not.

00:50:36.060 | You certainly want to pay close attention

00:50:37.700 | to what you're eating while you're doing

00:50:39.900 | the reconstitution of the community

00:50:41.380 | after you do something like that.

00:50:43.060 | - Yeah, thank you for that.

00:50:45.180 | I know a lot of people are interested

00:50:46.560 | in these kinds of elimination diets

00:50:48.460 | and intermittent fasting/time-restricted feeding

00:50:52.060 | seems to be getting some traction in part

00:50:53.700 | because at some level, we are all doing this

00:50:56.540 | when we sleep.

00:50:57.780 | Most of us aren't eating while we sleep anyway.

00:50:59.720 | And adjusting the numbers seems more accessible

00:51:03.780 | for a lot of people.

00:51:04.620 | We have a lot of colleagues at Stanford

00:51:05.700 | who I know happen to follow that regimen

00:51:08.920 | or a time-restricted feeding regimen,

00:51:10.740 | but also some who follow the more traditional meal spacing

00:51:15.380 | as well, of course.

00:51:16.640 | One of the things that I wonder about as we talk about

00:51:21.300 | primarily plant-based with some,

00:51:23.740 | what did you say the pollen thing was?

00:51:25.040 | It was eat mostly plants and then maybe some meat,

00:51:28.820 | but not too much or not too much.

00:51:30.500 | - Eat food, mostly plants, not too much.

00:51:32.460 | - Got it. - Or sorry,

00:51:33.440 | eat food, not too much, mostly plants.

00:51:35.060 | - Got it.

00:51:35.900 | I hear this again and again.

00:51:40.420 | I know there are a number of people

00:51:42.060 | who do seem to do well on a lower carbohydrate.

00:51:45.940 | Even some people who report feeling much better

00:51:49.120 | on a really strictly almost meat organ only diet.

00:51:53.500 | And the only reason I raised this is not,

00:51:55.500 | I don't participate in it.

00:51:56.900 | I'm one of those omnivores out there.

00:52:01.060 | I do eat some meat and I do eat plants as well.

00:52:04.540 | But the reason I raised this is that earlier

00:52:06.720 | you were talking about communities

00:52:09.040 | that may have microbiota that are healthier than ours

00:52:13.360 | or at least different than ours.

00:52:14.980 | And there are communities in the world

00:52:16.400 | that subsist largely on animal products

00:52:20.580 | or for which unprocessed animal products

00:52:23.460 | are considered the richest nutrient foods

00:52:25.900 | in those communities.

00:52:27.100 | Protein is very scarce and ancestrally protein

00:52:30.860 | was more scarce.

00:52:31.900 | So eggs and meat and things of that sort.

00:52:33.700 | So could there be a genetic component?

00:52:35.380 | In other words, if we fast forward 10 years

00:52:37.600 | and we actually can make sense

00:52:38.840 | of all this human genome stuff,

00:52:40.260 | are we going to find that someone who has Scandinavian roots

00:52:45.260 | or somebody who has South American roots

00:52:47.180 | or somebody had descended from a different tribe

00:52:49.700 | will do better on one particular diet versus another

00:52:52.540 | and thereby, or I should say, and in parallel with that,

00:52:56.320 | that their gut microbiome will have different signatures

00:52:58.600 | that are, so your microbiome might thrive on plants

00:53:02.060 | and mine might thrive on organ meats.

00:53:04.180 | And as I say this, I'm not a big consumer of organ meats.

00:53:06.900 | I'm just laying this out for sake of example.

00:53:09.300 | - Yeah, yeah, great.

00:53:11.800 | So a few notes.

00:53:16.300 | The first one has to do with the carbohydrates

00:53:18.900 | and restriction of carbohydrates

00:53:20.300 | and some people feeling healthier

00:53:21.740 | when they cut carbohydrates out.

00:53:23.740 | My guess is, this is my theory to be tested,

00:53:28.740 | that people feel better cutting carbohydrates out

00:53:33.300 | because the diet that we eat in the United States

00:53:37.460 | and in industrialized countries,

00:53:39.400 | the carbohydrates are largely crap.

00:53:42.240 | - Processed. - They're processed.

00:53:43.780 | It's like starch, simple sugar.

00:53:46.360 | It's things that contribute to glycemic index.

00:53:49.100 | It's these sugars that we eat.

00:53:52.220 | They make it to our small intestine.

00:53:54.260 | They get chopped up into simple sugars,

00:53:56.780 | absorbed into our bloodstream

00:53:58.180 | and we have a ton of glucose then coursing through our veins

00:54:00.860 | which we know is bad and can lead to things like diabetes.

00:54:04.580 | If the carbohydrates that were in our diet

00:54:08.940 | were complex carbohydrates, dietary fiber,

00:54:12.820 | and we like to refer to the subset of dietary fiber

00:54:15.660 | that the microbiota can actually access as microbiota

00:54:19.500 | accessible carbohydrates.

00:54:21.540 | And the reason that we like that term

00:54:22.960 | is it has the word carbohydrate in it.

00:54:24.840 | And it's to point out that not all carbs are bad.

00:54:28.280 | It's just there are bad carbs or carbs that are bad

00:54:31.300 | if you consume them in too high a quantity,

00:54:33.140 | things like table sugar and simple starches,

00:54:36.820 | but there are good carbs as well.

00:54:38.500 | And these microbiota accessible carbohydrates

00:54:40.940 | are the complex ones that we can't digest

00:54:43.420 | and fuel our gut microbiota.

00:54:46.220 | Our gut microbiota can ferment them.

00:54:48.060 | And so I think we probably all would be better off

00:54:53.060 | with less of the carbs that were typically served,

00:54:59.020 | but most of us and probably the vast majority of us

00:55:03.420 | would be better off by consuming a lot more carbs

00:55:06.820 | that were complex, that were microbiota accessible.

00:55:09.700 | And I'll come back to why that's important

00:55:11.600 | in terms of our biology.

00:55:12.680 | There are some mechanisms that are known

00:55:14.340 | as to why those complex carbohydrates are so important

00:55:17.460 | for our health for most of us.

00:55:19.560 | I think this aspect of human genetic adaptation to diet

00:55:23.860 | is super interesting.

00:55:25.440 | And then layer on top of that,

00:55:27.140 | gut microbiota adaptation to diet,

00:55:29.960 | which is another layer of this that is also fascinating.

00:55:33.180 | It's very clear that over very short periods of time,

00:55:35.940 | humans can adapt to differences in their diet.

00:55:38.600 | Lactase persistence is kind of the classic example of this.

00:55:41.820 | Just over the past 10,000 years,

00:55:44.680 | humans, certain groups of humans have adapted

00:55:49.020 | to being able to consume dairy by taking this enzyme lactase

00:55:54.020 | that normally is just expressed

00:55:55.700 | in most of the world's population early in life

00:55:58.200 | to be able to metabolize lactose in breast milk.

00:56:02.980 | By extending the expression of that throughout life,

00:56:05.860 | now you can consume milk for your whole life.

00:56:09.100 | And so that is an example of specific populations

00:56:12.500 | of human genome genetically adapting to diet

00:56:16.660 | in a very short period of time.

00:56:17.960 | And there are other examples of this,

00:56:19.740 | and undoubtedly this has happened throughout the world

00:56:22.500 | to various aspects of diets.

00:56:23.780 | So certainly it's important to remember

00:56:26.120 | that there will be different diets that are better

00:56:30.860 | for different groups based on what genes you harbor

00:56:35.200 | and have in your human genome.

00:56:37.500 | The other aspect on top of that

00:56:39.300 | is that there are good examples of the gut microbiome

00:56:44.300 | adapting to cultural differences in diet.

00:56:49.120 | And the classic example of this

00:56:51.100 | is the degradation of seaweed.

00:56:54.060 | So we know that most Americans,

00:56:56.220 | if you eat sushi and there's nori there

00:56:59.440 | and you eat some of this seaweed,

00:57:03.460 | it has a dietary fiber in it known as porphyrin.

00:57:06.900 | That porphyrin will shoot through most of us untransformed.

00:57:10.180 | Inert substance, it'll do other things like retain water

00:57:13.620 | and serve as kind of something like cellulose,

00:57:15.700 | not be fermented at a high level.

00:57:18.820 | If somebody from Southeast Asia

00:57:20.300 | that's always consumed seaweed

00:57:23.180 | and is part of a culture that consumes seaweed, eat seaweed,

00:57:26.780 | they have a gut microbe that can now metabolize porphyrin.

00:57:31.220 | And so there are these very specific gene transfer events

00:57:34.560 | where the genes for breaking down porphyrin

00:57:37.480 | have been imported into the microbiome

00:57:41.200 | of many people in Southeast Asia to,

00:57:44.440 | we can think of it as helping digest porphyrin,

00:57:47.520 | but it's really just a microbe that's found a niche,

00:57:50.140 | found a way to make a living in the gut

00:57:52.440 | by consuming something that's common in the diet there.

00:57:55.480 | So there are these different layers.

00:57:56.740 | There are human genetic adaptations

00:57:58.240 | and there are microbiome adaptations that are cultural

00:58:00.840 | and based on people's geographic location.

00:58:04.540 | But there's no escaping the fact

00:58:07.340 | that for much of human evolution,

00:58:09.660 | the vast majority of people that are on this planet

00:58:13.780 | had ancestors that were hunter-gatherers foraging,

00:58:18.660 | consuming huge quantities of plant material,

00:58:22.120 | just because that's what was there.

00:58:24.360 | And so one of the groups that we study,

00:58:26.240 | the Hadza hunter-gatherers in Africa,

00:58:29.220 | and I should take a moment just to say that our research

00:58:34.080 | and research of many people in our field and other fields

00:58:36.800 | rely on study of indigenous communities.

00:58:39.960 | And it's really important to think of these communities

00:58:43.680 | as our equals, they're modern people on the planet.

00:58:48.520 | They have interesting lifestyles that are informative

00:58:50.900 | with regard to certain aspects of human biology.

00:58:54.540 | But in many cases, they also are

00:58:56.640 | leading vulnerable existence.

00:58:59.920 | And so we really take great care in our research program

00:59:02.640 | and it's important for people to realize

00:59:04.220 | that these populations take partner research

00:59:07.360 | because they're wonderful research partners.

00:59:09.660 | And we need to be mindful of kind of thinking about how,

00:59:14.120 | yeah, both we talk about them and use our data

00:59:17.000 | that has been gained through their generous contribution

00:59:21.080 | to our research program.

00:59:22.720 | The Hadza hunter-gatherers, it's estimated,

00:59:24.680 | consume on the order of 100 to 150 grams

00:59:27.680 | of dietary fiber per day.

00:59:29.660 | And that's in stark contrast to the typical American

00:59:32.900 | that consumes about 15 grams.

00:59:35.500 | So somewhere seven to 10 fold decrease in the main nutrient

00:59:40.180 | that feeds our gut microbiome in the American diet.

00:59:43.720 | The Hadza are, you know, one example,

00:59:48.000 | there are many different foraging populations,

00:59:50.740 | but the vast majority of these populations

00:59:54.020 | consume huge amounts of dietary fiber

00:59:56.700 | because plants are the reliable, consistent source that,

01:00:00.240 | you know, if you, as a hunter-gatherer, go on a hunt,

01:00:03.900 | usually that hunt is unsuccessful.

01:00:06.200 | You know, I think the data that, you know,

01:00:08.280 | one out of 20 to 30 hunts are successful

01:00:10.960 | in landing actually big game for the Hadza.

01:00:13.740 | They have, you know, birds that they shoot

01:00:16.420 | and small animals, but quite often day after day,

01:00:19.840 | they're relying upon berries, tubers, baobab fruit.

01:00:24.900 | You know, they're relying on the plants in their environment.

01:00:27.600 | And actually, if you go to the data

01:00:30.360 | and look at what their food preferences are,

01:00:33.380 | their food preferences are actually meat and honey.

01:00:35.920 | So they don't eat a high fiber diet because they love fiber.

01:00:39.380 | They eat a high fiber diet because that's what's available

01:00:42.400 | and consistent for them to survive.

01:00:45.840 | But, you know, our brains are wired for caloric density.

01:00:49.020 | And so if you took a Hadza and put them in a restaurant

01:00:51.680 | in the United States, they would make

01:00:53.360 | the same crappy decisions that we make

01:00:55.240 | because we, you know, all want sugar and fat and calories.

01:00:59.500 | It's how our brain is wired.

01:01:01.440 | - And protein and fat are essential for brain development

01:01:03.760 | as far as we know, right?

01:01:04.760 | So it sounds like the Hadza,

01:01:06.760 | I hope I'm pronouncing that correctly.

01:01:08.500 | Oh, you said would prefer to eat meat and honey,

01:01:12.060 | but they do, they happen to consume a lot of plant fiber

01:01:15.560 | as a consequence of what's available.

01:01:17.560 | The, one of the questions I have as it relates

01:01:22.360 | to all of this is it sounds to me like there is no question

01:01:27.360 | from the pure vegan all the way to the extreme opposite,

01:01:34.000 | which would be pure meat diet that avoiding processed foods

01:01:39.520 | is a good idea or heavily processed foods in general.

01:01:42.840 | And I mean, not that, you know,

01:01:44.420 | the occasional consumption is necessarily bad,

01:01:47.860 | but whether or not one is thinking

01:01:50.360 | about one macronutrient profile or another,

01:01:52.440 | it sounds like consuming processed foods

01:01:54.780 | is just bad for the microbiome.

01:01:56.720 | Can we say that categorically?

01:01:58.480 | - For sure.

01:01:59.320 | - Okay. - Yeah, absolutely.

01:02:00.140 | - Whether, you know, so you're low carb person,

01:02:01.620 | you're zero carb person, you're extreme vegan, no meat,

01:02:04.520 | whether or not you're all meat, organ meat,

01:02:06.520 | it sounds to me as if the number one thing,

01:02:10.120 | maybe even dare I say above Chris's point about plants,

01:02:14.760 | so that I'm not going to challenge Chris Gardner

01:02:16.100 | on nutrition, I would be way outside the lane lines

01:02:19.400 | to do that, but is it to avoiding processed foods is paramount.

01:02:23.920 | - Yeah, and I think that's completely compatible

01:02:26.040 | with what Christopher was saying.

01:02:27.000 | He was saying, if you prioritize getting a huge amount

01:02:30.520 | of whole plant-based food with a lot of fiber first,

01:02:34.980 | you're not going to have room

01:02:36.000 | for eating a lot of processed food.

01:02:37.420 | So it's kind of the same as avoiding processed food.

01:02:40.080 | So I think that those are exactly the same rule.

01:02:42.320 | And I think that you're exactly right.

01:02:44.680 | And we can break down, you know, there's a lot of data

01:02:47.400 | of why different components of processed food are so bad

01:02:49.720 | for us and so bad for our microbiome.

01:02:51.520 | And I can talk about a few examples of that.

01:02:53.720 | But the flip side of this is this mechanism of, you know,

01:02:58.040 | and again, thinking about the spectrum of a plant-based diet

01:03:01.080 | versus a meat-based diet, you know, there's a lot of data

01:03:06.080 | to tell us that a meat or ketogenic or high fat diet

01:03:11.160 | may have big benefits in terms of short-term metabolic

01:03:14.360 | health, that's typically how people think about that diet.

01:03:17.220 | There's also a lot of heart disease

01:03:18.740 | that's linked with that as well.

01:03:20.040 | There's good literature for that,

01:03:21.240 | which is something for people to look at and be aware of.

01:03:25.120 | The plant-based diet, if you're eating a bunch of complex,

01:03:29.140 | you know, fibers that feed your gut microbiota,

01:03:31.960 | your gut microbiota produces these substances

01:03:34.760 | called short-chain fatty acids, things like butyrate.

01:03:37.560 | And it's known that these short-chain fatty acids

01:03:40.260 | play really essential components,

01:03:42.000 | both in terms of fueling colonocytes,

01:03:44.340 | enforcing the barrier, keeping inflammation low,

01:03:46.960 | regulating the immune system, regulating metabolism.

01:03:49.840 | And so, you know, a lot of people think of dietary fiber

01:03:53.480 | as this inert substance that passes through,

01:03:55.540 | makes us feel full maybe for a little bit,

01:03:57.400 | but we get hungry afterwards right away.

01:03:59.160 | If you're eating a lot of fiber

01:04:00.440 | that's feeding your gut microbiota,

01:04:02.160 | your gut microbiota is just producing this vast array

01:04:06.260 | of fermentation and products that then get absorbed

01:04:09.780 | into our bloodstream and have all of these tremendous

01:04:12.560 | cascading effects that appear to be largely beneficial

01:04:15.920 | in our biology.

01:04:17.120 | And so to think about that paradigm of simple carbs

01:04:19.880 | versus complex carbs, in the case of simple carbs,

01:04:22.600 | you end up with high blood sugar, you know,

01:04:24.560 | something that will spike your insulin and, you know,

01:04:27.140 | have all kinds of weird metabolic effects.

01:04:29.400 | In the case of complex carbohydrates,

01:04:31.620 | you'll end up with very low blood sugar

01:04:34.060 | because most of those have low glycemic index

01:04:36.600 | and a bunch of short-chain fatty acids

01:04:38.400 | that are having regulatory rules.

01:04:39.840 | So just to round out that topic,

01:04:42.860 | I think there is a reason to think that, you know,

01:04:45.500 | maybe not appropriate for absolutely everyone out there,

01:04:48.440 | but I think the vast majority of people,

01:04:51.160 | particularly given the statistics of what we know people eat

01:04:54.060 | in the United States and in industrialized countries,

01:04:56.880 | most people would reap tremendous health benefits

01:04:59.720 | from eating more whole plant-based dietary fiber.

01:05:03.620 | Now, processed foods, I think, is this other dimension

01:05:06.340 | where you have all of these weird chemicals,

01:05:08.160 | artificial sweeteners, weird fats, you know,

01:05:12.060 | a lot of refined simple nutrients.

01:05:14.600 | The simple nutrients we've talked about,

01:05:16.080 | but we know that, for instance, artificial sweeteners

01:05:18.540 | can have a massive negative impact on the gut microbiome

01:05:21.540 | and can lead us towards metabolic syndrome, actually.

01:05:23.960 | There's been beautiful work

01:05:25.400 | out of the Weizmann Institute on this.

01:05:27.200 | And then emulsifiers, these compounds

01:05:29.400 | that are put in processed foods

01:05:31.180 | to help them maintain shelf stability

01:05:34.180 | so things don't separate.

01:05:35.560 | And so, you know, all the moisture content

01:05:39.220 | is retained appropriately.

01:05:41.560 | Many of these are known to disrupt the mucus layer.

01:05:45.040 | And as soon as you start disrupting that barrier,

01:05:47.260 | that can lead you in the direction of inflammation.

01:05:49.800 | And in animal models, we know that can lead

01:05:51.760 | towards metabolic syndrome as well.

01:05:53.400 | So there's components of processed food

01:05:56.920 | that are, when studied in isolation,

01:05:58.700 | known to have a direct negative impact

01:06:00.520 | on gut biology and the microbiota.

01:06:02.760 | - Yeah, the mention of artificial sweeteners is interesting.

01:06:05.600 | I confess, it's a third rail on social,

01:06:09.080 | talking about artificial sweeteners.

01:06:10.280 | There are two camps, it seems, or at least two camps.

01:06:13.720 | One that say artificial sweeteners

01:06:15.660 | are not detrimental at all.

01:06:17.200 | Another that says they're very detrimental,

01:06:18.680 | mainly based on the mouse studies.

01:06:20.000 | And then there are people in the middle

01:06:21.160 | that are, I put myself in that category.

01:06:23.160 | I drink the occasional diet soda.

01:06:25.000 | I don't consume them in large volume,

01:06:26.500 | but I'm sort of in the middle there.

01:06:28.060 | However, and so I just throw that out there

01:06:30.900 | because I know immediately people are jumping on that.

01:06:33.840 | But I will just mention there's some recent data

01:06:36.320 | out of Diego Borges' lab at Duke University

01:06:38.760 | that the neurons that live in the gut mucus

01:06:40.440 | of these neuropod cells can actually distinguish

01:06:43.120 | between artificial and true sweet,

01:06:46.700 | sugar versus artificial sweeteners.

01:06:50.240 | They send different patterns of neural signals

01:06:52.200 | up to the brain and the brain circuitry

01:06:54.400 | seems strongly impacted.

01:06:55.760 | So I think that as the data emerge,

01:06:57.620 | we're hearing more and more of these artificial sweeteners

01:07:00.360 | either are problematic or at least are signaling

01:07:02.960 | different events in the gut.

01:07:05.880 | I do want to make sure that we distinguish

01:07:08.920 | artificial sweeteners from non-caloric plant-based sweeteners.

01:07:13.300 | And this is based on a mistake that I've made

01:07:15.240 | over and over again on the podcast,

01:07:16.940 | where I'll just kind of lump artificial sweeteners

01:07:20.040 | into one big category and then I'll mention stevia.

01:07:23.160 | So what about plant-based sweeteners

01:07:24.940 | that are not artificial?

01:07:26.560 | They weren't manufactured in a laboratory

01:07:28.120 | like saccharin or sucralose or aspartame.

01:07:31.120 | Do we know anything about plant-based non-caloric sweeteners

01:07:34.880 | or low-caloric sweeteners?

01:07:36.960 | - Very little.

01:07:38.020 | A lot of those have a lot more bang for the buck.

01:07:41.200 | They're incredibly sweet so it takes a really small amount

01:07:44.120 | for them to trigger a huge amount of sweetness.

01:07:46.320 | And so it's depending upon the mechanism of action

01:07:51.200 | by which these sweeteners that are not sugar

01:07:54.640 | are impacting our biology.

01:07:57.400 | It may be that those are actually less negative

01:08:02.280 | or more healthy than the ones that are artificial

01:08:05.800 | just because it requires less of them in the food

01:08:08.500 | for us to perceive that sweet taste.

01:08:10.320 | It may also be that because they're,

01:08:12.480 | I don't think that everything that's natural

01:08:14.560 | is better necessarily than things that are artificial,

01:08:17.380 | but it may be that because of kind of evolutionary exposure

01:08:21.360 | to these compounds in our diet,

01:08:23.680 | historically there are, I think, traditional populations

01:08:26.320 | that use these, for instance, to sweeten different foods

01:08:31.460 | that our bodies just kind of know how to deal

01:08:34.000 | with those compounds better than the ones that are synthetic.

01:08:37.140 | But I think the studies still need to be done.

01:08:39.980 | - Do you actively avoid artificial sweeteners,

01:08:42.480 | sucralose, aspartame, saccharin, you personally?

01:08:45.720 | - Yeah, you know, so I do.

01:08:48.520 | I avoid them, but I'm not, you know,

01:08:50.980 | so I work closely with my wife, Erica, as you know.

01:08:55.960 | We were in the lab together and we wrote this book,

01:09:00.480 | "The Good Gut," where we kind of document our journey

01:09:03.520 | in changing our lifestyle, dietary habits,

01:09:06.640 | choices we make based on the research

01:09:08.400 | as we've gotten to know it in the gut microbiota

01:09:10.280 | over the past 15 years.

01:09:11.860 | And, you know, I think that one of the lessons

01:09:16.860 | that we've learned is that just doing things in moderation

01:09:21.560 | makes it a lot easier and doing things slowly

01:09:25.240 | makes it a lot easier.

01:09:26.200 | And so there are very few rules that I have

01:09:29.640 | that are hard and fast.

01:09:30.720 | I'm a pretty flexible eater.

01:09:32.600 | I don't believe that having an artificial, you know,

01:09:34.560 | having a diet Coke will, you know,

01:09:36.920 | somehow cascade into some terrible disease

01:09:39.280 | or something like that.

01:09:40.840 | I try to avoid them.

01:09:42.140 | I don't really like the flavor of them.

01:09:43.520 | I'm super sensitive to the nuances of the flavor,

01:09:47.120 | even with the, you know, stevia and magra sites

01:09:49.500 | from monk fruit and stuff like that.

01:09:50.680 | I just really, the off flavors are really hard

01:09:52.660 | for me to deal with.

01:09:53.720 | But I also, in this journey of changing our diet,

01:09:58.840 | like when we started off in microbiome research,

01:10:01.560 | I was in the habit of, you know, in the afternoons,

01:10:03.500 | having a sweet, a muffin or a cookie or something like that.

01:10:06.400 | And when we started to realize that, you know,

01:10:09.080 | we should be eating less sweets

01:10:10.480 | and eating more dietary fiber,

01:10:12.560 | this was an incredibly difficult change for me to make.

01:10:14.960 | I was just wired to kind of crave, you know, this.

01:10:18.280 | - Classic scientist.

01:10:19.920 | Scientists love the pastry in the afternoon and the coffee.

01:10:23.040 | - Yeah, yeah.

01:10:23.880 | - And in the old days, it used to be a cigarette too.

01:10:25.720 | - Right, right, exactly.

01:10:26.560 | - When I started my training, a lot of people still smoke.

01:10:29.080 | - Yeah, right.

01:10:29.920 | - And it was only during my postdoctoral training

01:10:32.160 | that they eliminated smoking on campuses.

01:10:33.940 | And productivity took a trough for a while.

01:10:37.240 | And until these people developed other tools

01:10:39.280 | to focus their attention.

01:10:41.080 | - Exactly, exactly.

01:10:42.240 | So there is this kind of like need.

01:10:44.180 | And then once you have an ingrained behavior

01:10:46.040 | and maybe things that are addictive,

01:10:47.340 | it becomes incredibly difficult to break that habit.

01:10:50.800 | And so I would say, you know, gradually over the course

01:10:55.120 | of like, you know, five or more years,

01:10:58.160 | we have, you know, migrated our diet away from sweet foods

01:11:02.040 | to things that are less sweet.

01:11:05.800 | And it's, you know, it's been a journey.

01:11:07.920 | It's been a slow process.

01:11:09.720 | But we've gotten to the point now

01:11:10.920 | where we've just retrained our palates.

01:11:12.760 | And it's amazing how this happens now

01:11:14.960 | where I'll have something that, you know,

01:11:17.680 | is something that I would have used to have like daily.

01:11:20.720 | And it's unpalatable.

01:11:22.440 | I like, I just can't deal with the sweetness of it.

01:11:24.900 | And so I avoid, I certainly avoid artificial sweeteners,

01:11:28.940 | but I also avoid just sweet things in general

01:11:31.440 | that have sugar in them just because they now they,

01:11:34.680 | you know, as originally I was trying to be disciplined

01:11:38.520 | and trying to change my diet,

01:11:39.540 | but now they just don't taste good to me.

01:11:41.280 | - Yeah, likewise.

01:11:42.120 | I completely lost my appetite for sugar

01:11:44.760 | at the turn of the last year.

01:11:45.960 | And I don't know how to explain it, but the way I,

01:11:49.220 | even though I don't have a mechanistic explanation,

01:11:51.260 | I just, I say, I like sweet people.

01:11:52.820 | I don't like sweet food anymore.

01:11:54.440 | I just don't.

01:11:55.340 | I have not lost my appetite for fatty foods.

01:11:58.300 | I love cheese and certain meats for me.

01:12:02.560 | I blame my Argentine lineage as I gravitate towards them.

01:12:07.200 | But in any case, avoiding processed foods,

01:12:10.480 | probably avoiding sugars, emulsifiers,

01:12:12.920 | these kinds of things.

01:12:13.760 | And for people listening or watching,

01:12:15.800 | we're not setting up strict guidelines.

01:12:17.760 | We're just bouncing around the carnival

01:12:21.640 | that is the microbiome and nutrition,

01:12:24.120 | because I think that these, we hear this everywhere,

01:12:27.440 | eat this, don't eat that,

01:12:28.460 | or this is best for microbiome or worst for microbiome,

01:12:30.720 | but I'm hearing fiber again and again.

01:12:32.600 | So we're going to come back to fiber,

01:12:34.040 | but I want to make sure that we close the hatch

01:12:36.720 | on this issue of fasting and cleansing.

01:12:39.180 | Based on your answer earlier,

01:12:40.720 | it sounds to me like it is not necessary to do a cleanse

01:12:44.440 | or fast prior to an attempt to repopulate the microbiome.

01:12:48.620 | In other words, if I want to make my microbiome healthier,

01:12:51.240 | it sounds like I don't have to try

01:12:52.720 | and flush all the current microbiota out of there first.

01:12:56.280 | Is that correct?

01:12:57.120 | - Yeah, it's a very good question.

01:12:59.200 | And I don't mean to suggest that those things

01:13:00.920 | are known to be terrible,

01:13:03.800 | or I would just say the studies haven't been done.

01:13:06.780 | And to me, wiping out this microbial community,

01:13:10.760 | unless it's done with some sort of,

01:13:13.440 | unless it's done in an informed way,

01:13:15.260 | and we don't really have the information

01:13:16.740 | for how that would be done,

01:13:18.080 | it just seems like playing the lottery a little bit.

01:13:21.960 | And so I think, I don't want to say that those are,

01:13:25.000 | it may be that when the study is done,

01:13:26.840 | those are shown to be amazing,

01:13:28.520 | but I just don't think we have the data to know that yet.

01:13:30.640 | So it's somewhat of an arbitrary thing.

01:13:33.340 | If somebody out there feels way better when they do this

01:13:36.960 | and are not experiencing problems with it,

01:13:39.360 | then maybe it's the right thing for them.

01:13:40.960 | But I certainly can't say that it's something great to do.

01:13:44.120 | I can't imagine a future where as the microbiome

01:13:48.720 | gets incorporated into this emerging paradigm of precision

01:13:52.040 | health, you go into a clinic,

01:13:54.160 | somebody types your microbiome and says,

01:13:56.120 | oh, there's this huge, massive misconfiguration.

01:13:59.360 | You have all these engrafted bacteria that live

01:14:02.080 | that are residents in your gut microbiome

01:14:04.040 | that are sending out molecules

01:14:06.080 | that are not good for your health.

01:14:07.720 | It would be good if we do a mass reprogramming of it.

01:14:10.620 | The way that we do that is we flush your gut

01:14:13.640 | and we actually give a light antibiotic treatment

01:14:16.080 | to try to kill everything that's there.

01:14:18.080 | And then we repopulate with this other consortium

01:14:21.480 | of microbes that we've studied and know are healthy,

01:14:24.160 | know are compatible with your human genome

01:14:26.480 | and can be reinforced with a diet

01:14:28.440 | that we know is good for you.

01:14:30.040 | We'll install those microbes.

01:14:31.720 | We'll help you along in the diet

01:14:33.960 | so you know how to nourish those microbes.

01:14:36.400 | And that will be the way that we'll reconfigure

01:14:38.460 | your gut microbiome.

01:14:39.400 | So I can't imagine a future where that sort of flushing

01:14:42.880 | or cleansing is part of something for repopulating the gut.

01:14:46.700 | But right now it seems a little half baked to me, yeah.

01:14:50.400 | - Great.

01:14:51.920 | I'd love to talk about fiber and fermented foods

01:14:54.920 | because you and Chris had a really,

01:14:58.460 | what I think is a really interesting and exciting paper

01:15:01.620 | at the end of last year about comparing the inflammatome,

01:15:06.620 | so inflammatory markers of people

01:15:08.740 | who ate a certain amount of fiber

01:15:11.260 | or a certain amount of these fermented foods.

01:15:13.600 | This study is amazing for several reasons,

01:15:16.680 | but almost as amazing is how diverse the interpretation

01:15:21.680 | of this study was in the media.

01:15:24.660 | If ever there was a study that was kind of hijacked

01:15:28.820 | by different priority schemes out there, it's this study.

01:15:33.520 | So you performed the study with Chris

01:15:36.460 | and your postdocs and graduate students and staff.

01:15:39.300 | What are the major conclusions and what sorts of directives,

01:15:42.640 | if any, emerge from this study?

01:15:44.540 | - And I'll just preface this again by saying,

01:15:46.780 | if I wasn't clear, some news reports said,

01:15:50.300 | ah, this means fiber is not important.

01:15:53.140 | And then others said, this means fermented foods

01:15:55.980 | and fiber are important.

01:15:57.460 | And others said, fermented foods are the thing

01:16:00.100 | and the only thing, it was all over the place.

01:16:03.360 | And one of the reasons for doing this podcast at all

01:16:06.940 | is so that we can go straight to the people

01:16:09.640 | who perform the work.

01:16:10.900 | And even though I'm certainly not an expert in microbiome,

01:16:13.880 | give you the opportunity to share with me and me

01:16:16.260 | to ask the kinds of questions that have zero agenda.

01:16:18.980 | I do like sauerkraut.

01:16:20.820 | I do drink the occasional kombucha.

01:16:25.220 | I do like low sugar, not so sweet forms of fermented foods.

01:16:29.180 | So I would be delighted if fermented foods are good for me,

01:16:31.540 | but I have no steak in the fermented food industry.

01:16:34.540 | - Yeah, absolutely. - Yeah.

01:16:35.860 | - Yeah, great.

01:16:36.700 | Yeah, wonderful.

01:16:38.500 | And an important note there is the one you pointed out

01:16:41.480 | that this is an incredible collaboration

01:16:43.020 | with Christopher Gardner's lab and a bunch of people.

01:16:46.800 | Erica Sonnenberg helped lead this study

01:16:48.560 | and then tons of, like you were saying, post-doc staff

01:16:51.460 | and other people at Stanford

01:16:53.800 | and then wonderful participants

01:16:55.160 | that were part of this study.

01:16:57.320 | So a huge team effort.

01:16:59.000 | Before I dive into that study, let me take a step back

01:17:02.580 | because I think the reason that we did this study

01:17:04.880 | and kind of Christopher's group and our group

01:17:07.880 | has started to pursue this line

01:17:10.960 | of looking at dietary interventions

01:17:13.460 | and how they impact our microbiome,

01:17:14.920 | how they impact human biology,

01:17:17.580 | goes back to this kind of epiphany

01:17:20.820 | that we had while studying the gut microbiome

01:17:23.580 | because I think when we started studying it at Stanford,

01:17:26.540 | we were thinking about it

01:17:27.540 | as this kind of newly appreciated aspect of our biology,

01:17:30.900 | almost like finding an organ that we didn't know was there

01:17:35.360 | and starting to think about all the drug targets

01:17:37.880 | that were there.

01:17:38.720 | Can we go in with small molecule drugs

01:17:40.360 | and think of ways to manipulate this community

01:17:42.600 | to ameliorate disease?

01:17:44.260 | And this is largely the mindset of Western medicine

01:17:47.360 | and largely born out of the era of infectious disease.

01:17:50.300 | You wait for an infection to start a bacterial infection,

01:17:53.560 | you treat with antibiotics

01:17:54.820 | and that's the way medicine is practiced

01:17:56.840 | and that's become less successful over time

01:17:59.760 | as we've moved into this era

01:18:02.000 | of inflammatory Western diseases

01:18:04.800 | and with the exception of the current pandemic

01:18:09.080 | that's sweeping the world,

01:18:10.960 | largely moved out of the era of infectious diseases,

01:18:15.040 | at least infectious bacterial diseases,

01:18:17.260 | that this paradigm of waiting for diseases to appear

01:18:21.200 | and come into the clinic is not really very effective

01:18:25.000 | in the context of inflammatory Western diseases,

01:18:27.800 | autoimmune diseases, metabolic syndrome,

01:18:30.220 | heart diseases and inflammatory disease.

01:18:32.280 | The list goes on and on.

01:18:33.880 | And so we started to think a lot about

01:18:37.920 | how can we get out in front of this?

01:18:39.360 | How can we think about preventative ways

01:18:42.240 | of dealing with this crisis

01:18:44.480 | of metabolic and inflammatory diseases?

01:18:47.160 | And this tremendous beautiful body of literature

01:18:50.120 | started to come forward in the field about 10 years ago

01:18:53.920 | that showed that the gut microbiome is absolutely critical

01:18:57.880 | to modulating our immune status.

01:18:59.720 | So if you change the microbiome,

01:19:01.720 | you can fundamentally change how the immune system operates.

01:19:05.420 | And we know that the immune system is at the basis

01:19:09.420 | of a lot of these diseases, inflammatory, chronic diseases.

01:19:13.460 | And so it brought up this possibility

01:19:15.580 | that maybe the fact that we're not nourishing

01:19:18.580 | this community well enough,

01:19:19.760 | maybe the fact that it's deteriorated over time

01:19:23.740 | due to all of the things that go along

01:19:25.520 | with an industrialized lifestyle,

01:19:27.500 | antibiotics and so forth,

01:19:29.760 | maybe we have a microbiome right now

01:19:32.660 | in the industrialized world

01:19:34.140 | that is setting our immune system at a set point,

01:19:36.780 | simmering inflammation that's driving us

01:19:39.460 | towards these inflammatory diseases.

01:19:41.480 | And wouldn't it be wonderful if we could figure out

01:19:43.640 | how to use diet specifically,

01:19:48.640 | but just kind of learn the rules of how to reconfigure

01:19:51.980 | both the composition and function of our gut microbiome

01:19:54.840 | so that inflammation was different in our bodies

01:19:58.360 | so that each one of us was less likely to go on

01:20:01.540 | and to develop an inflammatory disease,

01:20:03.320 | leading to better longevity and health

01:20:07.080 | over the course of our life.

01:20:08.400 | And so we were studying this actually in mouse models

01:20:13.400 | and realizing that we really needed

01:20:17.540 | to start doing human studies.

01:20:19.040 | We needed to start studying microbiome in humans.

01:20:23.300 | And because we were studying diet,

01:20:25.600 | we knew that this was something

01:20:26.820 | we could go in and do right away.

01:20:28.080 | We didn't have to apply for FDA approval for a drug

01:20:30.880 | before we could do a human study.

01:20:32.480 | We could just start doing human dietary interventions,

01:20:35.280 | longitudinally monitoring the immune system

01:20:38.560 | and the microbiome and starting to put the pieces together

01:20:42.000 | of what is it in diet that can change our microbiome

01:20:44.500 | in a healthy way, help us define what a healthy microbiome is

01:20:48.240 | and monitor the immune system in great detail.

01:20:51.360 | And so there were really two critical components of this

01:20:53.820 | in addition to our microbiome expertise.

01:20:56.120 | One was Christopher Gardner's group.

01:20:58.560 | We wanted to do these human studies,

01:21:00.520 | but we're absolutely terrified of humans.

01:21:03.040 | We work with mice, humans are terrifying in many ways.

01:21:06.640 | - But they house themselves.

01:21:07.760 | You don't have to pay for their housing.

01:21:10.040 | - That's true, yeah.

01:21:10.880 | - For those that can afford housing, of course, yeah.

01:21:13.880 | - Yeah, sadly, just for that portion of the population.

01:21:16.600 | So Christopher's group,

01:21:19.240 | they are masters at working with human populations.

01:21:21.940 | And then the other wonderful thing that we have at Stanford

01:21:24.440 | is this Human Immune Monitoring Center

01:21:26.720 | run by Mark Davis and Holden Maker.

01:21:28.640 | They started this beautiful center

01:21:30.840 | for allowing people to do immunology in humans.

01:21:35.320 | Critical element because a lot of the mouse studies

01:21:37.740 | don't translate well to humans.

01:21:39.140 | So if you can do the studies in humans,

01:21:41.040 | similar to how we were thinking about the microbiome,

01:21:43.600 | you learn something that you know is relevant to humans.

01:21:45.920 | And so having that immune profiling capability

01:21:49.000 | where we can monitor hundreds to thousands

01:21:52.240 | of different parameters in the immune system,

01:21:54.360 | longitudinally in people from a blood draw,

01:21:57.040 | and not just know if CRP goes up

01:21:59.440 | or if interleukin-6 goes up or down,

01:22:01.500 | but to be able to see all these facets

01:22:03.400 | of the immune system change in concert

01:22:05.280 | as we're changing the microbiome with diet

01:22:07.480 | was really a key component of this.

01:22:09.400 | And so our flagship study supported by wonderful donors,

01:22:14.040 | so this actually isn't funded by typical foundations

01:22:17.320 | and national institutes of health,

01:22:18.560 | it was funded by philanthropy.

01:22:21.440 | We wanted to understand

01:22:23.120 | if we put people on a high fiber diet,

01:22:26.000 | how would that affect their microbiome and immune system?

01:22:28.240 | And if we put them on a high fermented food diet,

01:22:30.720 | a diet rich in live microbes and all the metabolites

01:22:33.600 | that are present from fermentation and foods,

01:22:36.320 | how would that change microbiome and immune system?

01:22:38.520 | - Could you give us some examples

01:22:39.600 | of what those diets look like?

01:22:40.720 | And were you changing their basal diet

01:22:43.000 | or were you just adding things on top

01:22:44.480 | of what they were already eating?

01:22:46.520 | - So-

01:22:47.560 | - 'Cause it's hard to change people's diets.

01:22:49.360 | - It's very hard.

01:22:50.200 | - And you have to trust that they actually do it

01:22:51.680 | and they're not sneaking and-

01:22:54.000 | - Totally, yeah.

01:22:54.960 | And so we, and we've started

01:22:57.840 | the Center for Human Microbiome Studies at Stanford

01:23:00.000 | for doing a lot of these studies.

01:23:01.600 | And a portion of the studies we do focus on supplements,

01:23:04.760 | probiotics, microbes delivered in pill form,

01:23:07.940 | prebiotics, which are purified forms of fiber.

01:23:11.880 | And in those cases, we actually can have placebo groups

01:23:16.600 | because it's more like a drug study

01:23:19.340 | and we don't change people's diets,

01:23:22.120 | so we can just administer this on top of what they're doing.

01:23:24.880 | So in a way they're a lot more controlled,

01:23:26.800 | but it's not food.

01:23:28.320 | When you start doing food studies,

01:23:30.040 | you can't do a placebo group

01:23:31.520 | 'cause people know what they're eating.

01:23:33.040 | And the other problem is that it's really hard

01:23:37.960 | to just change one thing

01:23:39.440 | because as soon as you start adding something,

01:23:41.720 | people usually eliminate something else.

01:23:43.560 | So the idea was to basically give these people

01:23:46.880 | simple instructions for, in the case of the high fiber diet,

01:23:50.680 | just increasing plant-based fiber.

01:23:53.400 | So can you eat more whole grains,

01:23:55.000 | more legumes, more vegetables, nuts,

01:23:57.600 | get the fiber up in the range of from 15 to 20 grams per day

01:24:02.460 | up to over 40 grams per day.

01:24:04.380 | So can you kind of double or more the amount of fiber

01:24:07.580 | that you eat per day,

01:24:09.160 | knowing that that would have a tremendous impact

01:24:12.280 | on a lot of other facets of their diet.

01:24:15.080 | They eat less meat, animal-based protein,

01:24:20.620 | less animal-based fats as a product of this.

01:24:23.860 | I will say that getting back to Christopher's rule

01:24:27.580 | for a healthy diet,

01:24:29.320 | a lot of the macronutrient changes that we saw in their diet

01:24:33.900 | were consistent with healthy changes in diet,

01:24:38.000 | less saturated fat, less animal-based protein,

01:24:41.160 | more plant-based protein.

01:24:42.600 | So a lot of changes that are known to be beneficial

01:24:46.720 | kind of came in concert with just telling people

01:24:48.660 | eat a high fiber diet, high plant-based fiber diet.

01:24:52.520 | The people that were eating the high fermented food diet,

01:24:57.340 | they were instructed to basically eat

01:25:00.880 | foods that you could buy at a grocery store

01:25:04.720 | that were naturally fermented and contain live microbes.

01:25:07.920 | And so this largely consisted of yogurt,

01:25:11.760 | kefir, sauerkraut, kimchi, some fermented vegetables,

01:25:18.460 | kind of brined fermented vegetables, pickles,

01:25:21.140 | things like that.

01:25:22.140 | But one of the things that I think is a pitfall

01:25:25.620 | in choosing fermented foods is you can go down

01:25:28.640 | the canned food aisle and there's this huge section

01:25:31.760 | of pickles and jars that are canned.

01:25:34.420 | Those are not fermented foods.

01:25:36.280 | Those are cucumbers that they've put in,

01:25:38.480 | acetic acid and vinegar to reconstitute

01:25:41.560 | that fermented flavor,

01:25:43.040 | but there's no live microbes involved in that.

01:25:45.640 | And even sauerkrauts in the canned food aisle,

01:25:47.920 | even if they were naturally fermented,

01:25:49.740 | quite often they're not.

01:25:50.580 | Quite often, they're just brined in vinegar.

01:25:54.120 | But even if they are naturally fermented,

01:25:56.000 | all of the microbes are killed prior to canning

01:25:58.800 | or during the process of canning.

01:26:00.400 | And so if you want to, so what we use for this study,

01:26:02.780 | and if you want to have live fermented foods

01:26:04.680 | that contain live microbes,

01:26:05.900 | you need to buy those out of the refrigerated section,

01:26:10.060 | essentially.

01:26:10.900 | - And I'm really glad you pointed this out

01:26:13.240 | because you can find sauerkraut

01:26:15.240 | on the non-refrigerated shelf that is indeed non-fermented.

01:26:20.120 | A lot of fermented foods that are available in the US

01:26:23.800 | can be high in sugar.

01:26:26.720 | So was there any instruction as to getting people

01:26:29.960 | to make sure that they were consuming yogurts

01:26:32.320 | that weren't loaded with sugar,

01:26:34.720 | or did you let them just select

01:26:36.320 | for the stuff in the cold section that is fermented?

01:26:40.840 | - No, it's a super important point.

01:26:42.480 | We instructed people to eat non-sweetened yogurts.

01:26:46.120 | I think a huge pitfall in this area

01:26:50.280 | is you can have a yogurt loaded with bacteria,

01:26:52.640 | kind of the base of what's healthy,

01:26:54.640 | and then a ton of artificial flavoring and sugar

01:26:58.040 | loaded on top of that.

01:26:59.020 | Manufacturers put a ton of sugar in after the fact

01:27:01.940 | to kind of mask the sour taste of fermented foods,

01:27:04.480 | which is hard for some people to become accustomed to.

01:27:07.400 | When we were switching to more fermented foods,

01:27:09.900 | our daughters were young at that point,

01:27:11.680 | we would take plain yogurt,

01:27:13.600 | which they didn't like, just kind of neat.

01:27:17.080 | We would mix in a little maple syrup or honey,

01:27:20.120 | just a little bit,

01:27:20.960 | and gradually we reduced that over time

01:27:23.160 | to the point where they're palate adjusted

01:27:25.640 | and now they just really like plain yogurt.

01:27:28.620 | But I think getting used to that sour flavor is difficult,

01:27:33.240 | but people really should try to stay away

01:27:35.100 | from those fermented foods that are loaded with sugar,

01:27:37.800 | and that's what we instructed people in the study.

01:27:40.160 | - And beer was not included, right?

01:27:42.040 | There were a number of people that asked

01:27:43.520 | when I did a brief thing on social media about this study,

01:27:46.840 | and hopefully I got it right, I think I did,

01:27:49.680 | but people just ask about beer.

01:27:51.200 | I'm not a drinker, so for me, beer has no appeal anyway,

01:27:56.060 | but beer is fermented, correct?

01:28:00.080 | But were they instructed to avoid beer or to drink beer?

01:28:03.200 | - Just to go with their normal dietary habits,

01:28:05.320 | but that did not count as a fermented food.

01:28:07.840 | - And kombucha was, as I recall.

01:28:09.200 | - Kombucha was, and kombucha can have small amounts

01:28:11.320 | of alcohol in it, but kombucha actually was one

01:28:16.320 | of the major things that people consumed

01:28:20.760 | during the fermented food phase.

01:28:22.400 | And the deal with beer is that there may be

01:28:27.400 | beneficial properties of the microbial communities

01:28:31.920 | in naturally fermented beer,

01:28:33.160 | but most of the beer that we buy, again,

01:28:34.720 | is canned and filtered and there's no live microbes there.

01:28:38.120 | So very different than if you siphon it off of your home brew

01:28:41.640 | and drink it probably than if you buy it in a store.

01:28:44.520 | - I will get to the results of the study in just one moment,

01:28:47.360 | but I want to say a lot of people shy away

01:28:49.640 | from the high quality fermented foods

01:28:51.980 | because they can be quite costly.

01:28:54.520 | I'll just refer people to a resource in Tim Ferriss' book,

01:28:57.700 | "The 4-Hour Chef."

01:28:58.760 | He actually gives an excellent recipe

01:29:00.400 | for making your own sauerkraut,

01:29:01.640 | which basically involves cabbage and water and salt,

01:29:06.560 | but you have to do it properly

01:29:08.040 | because you can grow some, not necessarily lethal,

01:29:11.680 | but some somewhat dangerous bacteria

01:29:13.920 | if you don't scrape off the top layer properly.

01:29:16.080 | But he gives beautiful instructions

01:29:17.480 | for how to do this in vats.

01:29:18.880 | We've started doing this at home now, actually,

01:29:21.800 | which is a ceramic vat.

01:29:22.760 | And so you can make large amounts

01:29:24.240 | of truly fermented sauerkraut just from cabbage,

01:29:27.800 | water, and salt, if you're willing to follow the protocol.

01:29:30.920 | And if you're interested in science,

01:29:32.060 | that protocol looks a lot like what you'll do

01:29:34.020 | for most of your graduate career,

01:29:35.880 | except maybe some sequencing too.

01:29:37.840 | So anyway, just to refer people to a source

01:29:39.680 | that's very low cost compared to buying

01:29:42.520 | the high quality fermented foods.

01:29:43.700 | Even kombucha's, for some people,

01:29:45.640 | it's like $5 a bottle, only this much.

01:29:48.600 | And if you consume liquids the way I consume them,

01:29:50.680 | that's just the start.

01:29:53.580 | - But if you can get your hands on a scoby,

01:29:56.920 | kombucha's another one that's super simple.

01:29:58.760 | - You can grow your own.

01:29:59.800 | - You can just make your own and it's super easy to do.

01:30:03.040 | I constantly have a batch of kombucha going at home

01:30:06.080 | and it's just a scoby, a symbiotic community

01:30:09.520 | of bacteria and yeast that you brew tea,

01:30:13.320 | you add sugar to it, and you put the scoby in

01:30:15.600 | and you wait a week or two, depending upon the temperature.

01:30:18.240 | And then you just move the scoby over to a new batch

01:30:22.880 | and what the scoby was in is kombucha and it's wonderful.

01:30:26.560 | - I love it.

01:30:27.400 | I would love it if members of this audience

01:30:28.680 | would start to make their own kombucha and sauerkraut.

01:30:31.800 | I've been having so much fun.

01:30:33.080 | Well, I don't do it, but it's done in our home.

01:30:37.320 | I don't go anywhere near the food production

01:30:39.520 | and it's for everyone's benefit.

01:30:41.160 | So how much fermented food and then were they consuming?

01:30:46.680 | 'Cause you mentioned the number of grams approximately

01:30:48.880 | of fiber, but was it in servings, ounces,

01:30:53.880 | how many times a day, early day, late day?

01:30:56.480 | - Right, yeah, so we had a wonderful dietician

01:31:00.800 | instructing people for this and her name's Dahlia Perlman

01:31:03.680 | and she really was the key and is the key

01:31:05.480 | for many of our studies for getting people

01:31:06.880 | to eat differently.

01:31:08.200 | And the general instructions were for people

01:31:11.840 | to eat as much fermented foods as possible, more is better.

01:31:14.800 | And the reason is that with this initial study,

01:31:18.080 | we really wanted to maximize our chance of seeing a signal

01:31:21.260 | if there was something biological going on

01:31:23.880 | with the idea that if the dose was excessive

01:31:27.640 | and not easily achievable by a lot of people in the end,

01:31:30.280 | we can go back and say, okay, this is the point

01:31:33.080 | at which we lose the biological signal.

01:31:35.280 | But people during the height of the intervention phase,

01:31:38.680 | the intervention phase was six weeks.

01:31:40.840 | During the height of that, we're up over six servings

01:31:44.200 | on average per day of fermented foods,

01:31:46.280 | so kind of two servings at each meal.

01:31:48.640 | And the ounces or weight or size,

01:31:52.600 | it really depended on what the fermented food was

01:31:55.280 | and we just told them to stick to what was a recommended dose

01:31:58.400 | on the package that they were buying.

01:32:01.940 | For kombucha, it'd be like a six to eight ounce glass,

01:32:05.360 | sauerkraut, like a half cup or something like that

01:32:07.560 | and the same with yogurt.

01:32:08.720 | - Great, so what were the results?

01:32:12.560 | - Yeah, so the results astounded us in a way,

01:32:17.160 | but then thinking more deeply and it'll be evident

01:32:21.160 | even after I explain it in the context of this conversation,

01:32:24.680 | likely why we saw the results we saw.

01:32:27.720 | The results were astounding

01:32:28.840 | because our hypothesis going into this

01:32:32.040 | was that the high fiber diet

01:32:33.940 | was going to give the massive signal.

01:32:35.600 | We know that this is the big deficiency

01:32:37.160 | in the Western diet.

01:32:38.240 | All the mouse studies have told us that high fiber

01:32:42.480 | really leads to a much healthier microbiota,

01:32:44.320 | can lead to positive changes in the immune system.

01:32:47.080 | And in fact, even when we had a limited,

01:32:49.200 | we had wonderful donor support,

01:32:50.480 | but still a limited amount of money

01:32:51.760 | when we started this study,

01:32:53.760 | my lab was really very eager to do the high fiber

01:32:58.160 | part of this really well.

01:33:00.280 | And Christopher kind of had to twist our arms

01:33:02.560 | to do the fermented food side of it.

01:33:04.640 | And we thought it was kind of quirky and neat,

01:33:07.360 | like live microbes should be exciting, like let's try it.

01:33:10.880 | So we put that in and it turns out

01:33:12.920 | that we were very thankful that he twisted our arms

01:33:15.560 | because it was that high fermented food arm

01:33:18.440 | that really gave us the big signal,

01:33:20.120 | even though our hypothesis was that the high fiber

01:33:22.900 | was gonna lead to more short chain fatty acids

01:33:25.120 | produced in the gut, more diverse microbiota,

01:33:29.180 | less inflammation in the immune system.

01:33:31.420 | We didn't see that across the cohort.

01:33:33.500 | We actually saw very individualized responses

01:33:37.040 | to the dietary fiber.

01:33:38.520 | And I'll come back to what those responses were.

01:33:40.760 | The big signal really was in the fermented food group.

01:33:44.200 | We saw all the things that you would hope to see

01:33:46.880 | in a Western microbiota and Western human.

01:33:49.800 | We saw this increase in microbiota diversity

01:33:52.400 | over the course of the six weeks

01:33:53.700 | while they were consuming the fermented foods.

01:33:56.300 | And we can't always say that higher diversity is better

01:34:01.300 | when it comes to our microbial communities.

01:34:03.320 | We know there are cases, for instance, bacterial vaginosis,

01:34:06.240 | where higher diversity is actually indicative

01:34:08.340 | of a disease state.

01:34:10.320 | But we know in the context of the gut

01:34:13.620 | and for people living in the industrialized world,

01:34:16.880 | higher diversity is generally better.

01:34:19.680 | We know that there's a spectrum of diversity.

01:34:21.420 | People with higher diversity generally are healthier.

01:34:24.520 | If you can push your diversity higher,

01:34:26.180 | you're in better shape.

01:34:27.320 | And so we saw that increase in diversity.

01:34:29.640 | And then the major question is what happened

01:34:31.400 | to the immune system as these people

01:34:33.340 | were increasing their gut microbiota diversity

01:34:35.640 | through the fermented foods.

01:34:37.100 | So we did this massive immune profiling

01:34:41.520 | and we see a couple dozen immune markers,

01:34:45.040 | inflammatory markers decrease over the course of the study.

01:34:48.960 | So we measure these at multiple time points

01:34:51.960 | throughout the course of the study.

01:34:52.960 | And there's kind of this stepwise reduction

01:34:55.800 | in things like interleukin-6 and interleukin-12,

01:35:00.200 | a variety of kind of famous inflammatory mediators.

01:35:03.800 | And then even if you go into the immune cells

01:35:06.260 | and you start looking at their signaling cascades,

01:35:08.780 | we see that those signaling cascades are less activated

01:35:12.120 | at the end of the study compared to the beginning

01:35:13.980 | of the study indicating an attenuation of inflammation.

01:35:17.000 | So kind of exactly what we would hypothesize

01:35:20.680 | would lead to less propensity

01:35:22.460 | for inflammatory disease over time.

01:35:24.780 | That's a huge extension of a very short study.

01:35:28.160 | - How long was the study again?

01:35:29.460 | - So the complete protocol I think was 14 to 17 weeks

01:35:33.960 | or something like that.

01:35:35.080 | The actual intervention phase consisted of a four-week ramp

01:35:38.880 | and then a six-week maintenance period.

01:35:41.320 | So the intervention itself was 10 weeks,

01:35:43.240 | but there were six weeks of really kind of hardcore

01:35:45.760 | high levels of fiber or fermented foods.

01:35:48.800 | - Yeah, and I'm glad you've mentioned the ramp

01:35:51.220 | 'cause my experience with fermented foods

01:35:53.840 | is that it can be beneficial to give the system

01:35:56.600 | an opportunity to acclimate.

01:35:57.780 | I mean, if you consume a giant bowl of sauerkraut,

01:36:01.100 | it's not gonna be the worst day and night of your life,

01:36:03.100 | but you'll know you did.

01:36:05.560 | We'll just leave it at that.

01:36:06.520 | And so you want to kind of acclimate to it.

01:36:09.400 | I'm at the point now where some people

01:36:11.360 | might think this is gross,

01:36:12.240 | but after I exercised, I've been sweating a lot,

01:36:15.160 | I like the saltiness of the...

01:36:16.680 | I actually drink the liquid

01:36:18.760 | that the sauerkraut has been stewing in.

01:36:21.960 | And I like to think that I consume

01:36:24.360 | some fermentation that way.

01:36:26.760 | It's salty, it acts as kind of a post-training replenishment.

01:36:30.860 | But if I had done that six months ago straight off,

01:36:34.440 | I think it would have been pretty rough on my system.

01:36:36.320 | I started taking little bits of it

01:36:37.920 | and then adding it each day.

01:36:39.080 | - Totally.

01:36:39.920 | And so both with the fermented foods and the fiber,

01:36:41.560 | it's well known that this kind of gradual ramping

01:36:44.400 | is a really important way of mitigating bloating

01:36:48.080 | and other kind of digestive discomfort

01:36:50.360 | that can happen when your microbiome reconfigures

01:36:52.680 | and starts fermenting more and changing community members.

01:36:55.560 | So you should take that ramp at your own pace.

01:36:58.640 | If something seems to be going wrong,

01:37:00.200 | just kind of level off, stay there.

01:37:01.640 | You know, we did this in a very delicate way

01:37:03.500 | to get people up to the high dose.

01:37:05.120 | The brine question, just a tangent here for a second.

01:37:10.120 | That was actually one of the products

01:37:12.580 | that we had people use in the fermented food phase.

01:37:16.780 | There's actually a product called Gut Shots,

01:37:18.580 | which is just the brine that they've marketed.

01:37:21.960 | We actually are now studying it in the lab.

01:37:24.440 | I just actually, before this came from a lab meeting

01:37:27.280 | where a GI fellow in my lab is actually putting Gut Shots,

01:37:31.280 | sterilized gut microbes or the fermentation microbes

01:37:35.280 | removed or present into mice

01:37:40.920 | and looking at changes in their mucosal immune system.

01:37:44.300 | So we're studying this in detail now

01:37:46.100 | because it's a rich source of lactate

01:37:48.820 | and a bunch of other interesting metabolites.

01:37:51.100 | - I love that my weird behavior

01:37:52.460 | is inadvertently being studied at Stanford Medicine.

01:37:56.500 | I want to just mention something about the Gut Shots.

01:37:59.400 | Those are sold as a drink.

01:38:02.120 | Those also, just for certain listeners in different budgets,

01:38:04.540 | they can be very expensive if you really think about,

01:38:06.740 | some of them are exceedingly expensive,

01:38:08.760 | but what I described before with making your own kombucha,

01:38:13.400 | it's not quite brining, but the homemade sauerkraut,

01:38:16.800 | that protocol is out there, as I mentioned,

01:38:18.500 | in Tim's book, "The 4-Hour Chef,"

01:38:20.880 | and you get a lot of the brining

01:38:22.740 | from that, an almost endless amount.

01:38:24.820 | A cautionary note, I once went into the refrigerator

01:38:28.480 | and saw something similar to Gut Shot, it wasn't Gut Shot,

01:38:31.320 | and I drank the whole 12-ounce bottle

01:38:33.860 | and realized that it was 24 servings.

01:38:36.180 | And that's where I got my initial experience

01:38:39.340 | with what it is to not do a ramp-up phase.

01:38:41.300 | I do not recommend doing that.

01:38:43.140 | Some of these, it's very potent, it seems,

01:38:45.360 | and you can consume even a half an ounce or an ounce.

01:38:47.940 | - Yeah, I mean, very potent

01:38:49.760 | from the standpoint of fermentation, but also very salty.

01:38:52.100 | So there's a lot of effects that can, yeah.

01:38:55.060 | - Don't do what I do, at least not at the outset.

01:38:58.300 | But so that is an experienced warning.

01:39:02.940 | So they did this, as I recall, there was a swap condition

01:39:05.700 | or there was a halt condition, so you did controls, right?

01:39:08.740 | It wasn't just comparing groups.

01:39:10.100 | You had individuals who were initially in one group

01:39:13.060 | or the other move to a different group.

01:39:16.180 | - Well, so we- - Or stop and then return.

01:39:18.700 | - Yeah, we actually just did a stop

01:39:20.620 | and followed them during a washout phase.

01:39:22.300 | And the ideal situation for dietary interventions like this

01:39:26.940 | are to do crossover studies, as you're suggesting.

01:39:30.140 | We've recently completed

01:39:31.940 | a ketogenic versus Mediterranean diet intervention-

01:39:34.420 | - So are those data published yet?

01:39:35.900 | - Not yet, but Christopher's been tweeting

01:39:37.380 | a lot of these data,

01:39:38.260 | and there's a paper in revision right now.

01:39:39.780 | So if you go to Christopher Gardner's Twitter feed,

01:39:43.220 | you'll be able to find him reporting

01:39:45.780 | some of the early results of this study.

01:39:48.460 | - Can you give us a snippet of, was there a superior,

01:39:50.600 | just give us, you don't have to tell us which one,

01:39:52.680 | but was there a superior condition

01:39:55.800 | of either Mediterranean versus ketogenic?

01:39:57.780 | - So the metabolic effects of these, it's a beautiful study.

01:40:02.500 | I should let his group comment on that.

01:40:04.420 | The microbiota data, we actually are just generating now.

01:40:07.280 | So the study that his group has put together from this

01:40:10.940 | is largely independent of the microbiota data,

01:40:14.300 | and now we're doing a more in-depth analysis,

01:40:16.140 | and I'll have more to say about that in the future.

01:40:17.980 | - We'll return to that, yeah.

01:40:19.420 | - But it's a super exciting study

01:40:20.700 | because it is one of these where people eat a certain way.

01:40:24.480 | And what's really beautiful about this

01:40:26.340 | is we even got food delivered for part of the intervention.

01:40:29.660 | So we had complete control over what they at least

01:40:32.900 | had available to eat.

01:40:34.420 | And then the second phase, they make the food on their own,

01:40:39.420 | and then we cross over and do the same thing.

01:40:43.580 | And so that's really like the,

01:40:45.540 | if you have a good enough budget,

01:40:47.100 | the right way to do a study like this.

01:40:48.260 | For this, we didn't have the time or money

01:40:51.720 | to do a crossover, but we did do a washout phase

01:40:54.460 | where people, we didn't make them stop eating whatever,

01:40:57.580 | if they were enjoying it, but we monitored,

01:40:59.340 | and there was some recidivism where there was a decrease

01:41:01.620 | in fiber fermented food.

01:41:03.100 | And we could see, for instance,

01:41:04.820 | diversity start to plateau and reverse

01:41:06.860 | in many of these people.

01:41:08.100 | So there does appear to be like a need for maintenance

01:41:11.420 | of the intervention to maintain the perceived health benefits

01:41:15.980 | that we were measuring.

01:41:17.220 | - Great, we will provide a link to the study in the caption.

01:41:20.240 | And thank you for that very clear and thorough description

01:41:23.860 | from one of the investigators involved in the study.

01:41:27.620 | It's great to go direct to the source.

01:41:29.500 | Anecdotally, were there improvements in mood,

01:41:34.780 | in resistance to colds and infection

01:41:38.420 | during the course of the study?

01:41:39.820 | And this is kind of a prelude to where I'm headed next,

01:41:43.140 | which is there is a tremendous amount of interest

01:41:45.280 | in the so-called gut brain access,

01:41:46.620 | but also I want to make sure that we talk about

01:41:49.220 | how these microbes and the conditions they're establishing

01:41:52.260 | in the gut are creating positive or negative health effects.

01:41:55.880 | I mean, basically how signals get out of the gut.

01:41:58.260 | - Totally, yeah.

01:41:59.100 | - I certainly noticed that when I'm eating

01:42:01.580 | more fermented foods or there's probiotics

01:42:03.660 | in drinks I consume and so forth that I feel,

01:42:06.860 | quote unquote, air quotes, completely subjective,

01:42:08.760 | I feel better.

01:42:09.840 | I wish there was an objective measure of feeling better,

01:42:14.780 | but I seem to think more clearly,

01:42:18.300 | sleep better, mood, et cetera.

01:42:19.720 | And I know I'm not alone in that.

01:42:21.480 | And people, and anytime I've taken harsh antibiotics,

01:42:25.240 | I feel worse, but then again, I'm usually taking them

01:42:27.060 | because I'm feeling bad about something else, right?

01:42:29.060 | I don't take them just because.

01:42:30.700 | So did people say they were feeling better in any way?

01:42:33.540 | And if so, what did you observe?

01:42:34.940 | And again, we're highlighting these as antic data.

01:42:38.060 | - Yeah, totally.

01:42:39.060 | You know, we, as part of this effort

01:42:43.080 | to look at how dietary interventions affect our health

01:42:48.140 | and wellbeing and so forth and microbiome and immune system,

01:42:51.540 | we interact with a lot of people who have like read our book

01:42:55.840 | or kind of have become microbiome enthusiasts

01:42:59.620 | and have implemented a lot of these changes

01:43:01.880 | in their personal life.

01:43:02.720 | And I hear the same thing that you're saying, Andrew,

01:43:04.880 | that tons of people say they have more energy,

01:43:07.660 | they think more clearly, they sleep better,

01:43:09.760 | their family is nicer to each other,

01:43:11.840 | like the number of crazy things.

01:43:13.640 | And it's really hard to uncouple like,

01:43:15.560 | is this because these people have taken charge now

01:43:18.580 | of what they're eating and just feel better in general

01:43:20.440 | for being in control of kind of what they're doing?

01:43:23.240 | Or is there this cascading set of effects

01:43:26.700 | that are actually impacting or kind of emanating

01:43:31.040 | from the gut brain axis?

01:43:32.400 | And so we actually implemented a bunch of questionnaires

01:43:36.780 | and even a cognitive test to try to get at some of this.

01:43:40.560 | And I should say, the list of this goes on and on.

01:43:44.020 | There are people who claim that their complexion improves

01:43:46.300 | and that their allergies,

01:43:48.100 | and there's probably all sorts of ripple effects.

01:43:50.280 | If you can affect your inflammation,

01:43:52.880 | we know that you can affect your cognition.

01:43:54.720 | We know that you can affect your skin

01:43:57.960 | and inflammation that's occurring on your skin.

01:43:59.960 | So I really think that there is a basis

01:44:02.800 | for a lot of those anecdotes.

01:44:04.640 | It may just be hard to see in a short study

01:44:07.780 | and in a small cohort of people

01:44:11.840 | over a short period of time.

01:44:13.120 | But we didn't really see significant things

01:44:17.400 | associated with cognition and moods and all of the things

01:44:21.720 | that we were testing for, which yeah,

01:44:25.360 | there could be a variety of explanations for that.

01:44:28.000 | We also have a standardized stool measure that people use,

01:44:33.000 | and there was kind of less constipation,

01:44:38.160 | better bowel movements over the course

01:44:40.160 | of both of these interventions.

01:44:41.320 | So it did seem like bowel habits improved,

01:44:44.220 | which a lot of times can lead to better moods,

01:44:46.760 | but that we weren't able to measure that.

01:44:49.120 | - The classic psychoanalyst would have a field day with that.

01:44:53.240 | What sorts of interesting things did you observe

01:44:55.800 | in the fiber group?

01:44:56.620 | Because it's clear that that group yielded

01:44:59.040 | some unexpected findings in both directions.

01:45:02.520 | Things you expected to see, you didn't see

01:45:04.360 | as to the same amplitude as you did

01:45:06.160 | in the fermented food group,

01:45:07.280 | but I'm guessing you also saw some very interesting things

01:45:09.800 | in the fiber group.

01:45:11.240 | - Totally, yeah.

01:45:12.080 | So we started looking at the data in more detail

01:45:14.840 | when we didn't see the cohort-wide response.

01:45:17.840 | And one of the things we observed is that

01:45:20.200 | in measuring all these immune parameters,

01:45:22.040 | there appeared to be three different groups

01:45:24.640 | of kind of immune responses that we were seeing.

01:45:28.200 | One group that got overall less inflammatory,

01:45:31.280 | and then two other groups that kind of had a mixed result,

01:45:34.640 | partly more inflammatory, partly less inflammatory

01:45:37.120 | in all these markers that we were looking at.

01:45:39.140 | And when we started digging into like what aspect

01:45:43.360 | of the biology of those people dictated or predicted

01:45:48.360 | which group they fell into, the really interesting part

01:45:52.040 | is the people with the highest diversity gut microbiomes

01:45:55.280 | to start the study were the ones that were most likely

01:45:59.240 | to have the decreases in inflammation.

01:46:03.520 | And so the data seemed to be telling us

01:46:07.800 | that if you start off with a diverse microbiota,

01:46:10.480 | maybe one that's better equipped to degrade

01:46:13.760 | a wide variety of dietary fiber,

01:46:16.680 | you're more likely to respond positively to it.

01:46:18.960 | If you have a very depleted gut microbiome,

01:46:21.440 | you're not as likely to be able to respond to it.

01:46:23.440 | And thinking back to that experiment

01:46:24.960 | that we talked about before with the multi-generational

01:46:27.520 | loss of fiber-fermenting microbes in mice

01:46:31.120 | that were fed a Western diet,

01:46:34.320 | it may be that many of us in the industrialized world

01:46:38.400 | have a microbiome that's so depleted now

01:46:41.000 | that even if we consume a high fiber diet,

01:46:43.960 | at least for a short period of time,

01:46:45.600 | we don't have the right microbes in our gut

01:46:47.600 | to degrade that fiber.

01:46:48.860 | And this has actually been observed by other groups,

01:46:50.760 | beautiful study out of University of Minnesota

01:46:53.080 | looking at immigrants coming to the United States.

01:46:55.880 | And within nine months, but certainly over the course

01:46:59.080 | of years, immigrants that come here lose a lot

01:47:03.840 | of the diversity in their gut microbiome,

01:47:05.640 | but a lot of the fiber degrading capacity in their gut

01:47:08.480 | microbiome too.

01:47:09.300 | So it could be that over time,

01:47:11.040 | this becomes a one-way street and it's hard for us

01:47:13.760 | to recover the microbes that actually can degrade the fiber.

01:47:18.000 | And I think that this probably intersects with sanitation

01:47:21.020 | in our environment and the fact that we don't have access

01:47:23.780 | to new microbes that might help us degrade the fiber,

01:47:27.180 | that we actually have lost these microbes

01:47:30.420 | and they're in some ways, irrecoverable

01:47:32.760 | without deliberate reintroduction

01:47:34.440 | of fiber degrading microbes.

01:47:35.840 | - I can recall from childhood,

01:47:36.940 | there were kids that would eat dirt and snails

01:47:40.540 | and stuff that just sounds totally disgusting,

01:47:42.560 | but kids covered with mud and that maybe not so much anymore.

01:47:47.560 | And certainly during the pandemic,

01:47:49.260 | there's been a lot more use of these hand sanitizers

01:47:52.120 | that prior to that, people seemed pretty spooked about,

01:47:54.360 | but then obviously they prioritize them.

01:47:57.500 | So do you, while you have children,

01:48:00.400 | did you encourage them to,

01:48:02.880 | when they were young, did you encourage them to interact

01:48:05.760 | with pets and dirt and stuff in the environment,

01:48:09.960 | provided that stuff wasn't immediately toxic?

01:48:12.080 | - Exactly.

01:48:12.900 | So this is really, it's a continual cost benefit analysis.

01:48:17.400 | I think I will say that with the pandemic now

01:48:22.240 | and certainly just with infectious diseases in general,

01:48:25.720 | it's really important to be aware of the possibility

01:48:30.640 | for compromising your health through the spread of germs.

01:48:33.280 | And so that is just, hand-washing is important

01:48:36.040 | and we have to be careful with the spread of germs.

01:48:40.260 | But I do think that the sanitization of our environment

01:48:45.260 | has gone overboard with various things being impregnated

01:48:52.380 | with antibiotics, shopping carts and things like that

01:48:55.740 | and toothbrushes and it's like antibiotics

01:48:59.240 | and things for killing microbes are everywhere.

01:49:03.960 | And when we were raising, when our daughters were young

01:49:08.100 | and we were making these decisions,

01:49:10.280 | the calculations that we would make were really one,

01:49:14.100 | how likely are they to encounter a disease-causing microbe?

01:49:19.080 | If we've been out on a hike or in our garden,

01:49:22.640 | just kind of working in the dirt or whatever,

01:49:24.840 | maybe it's not as important to wash your hands

01:49:26.880 | before you have lunch,

01:49:27.800 | even if there's a little bit of dirt on them.

01:49:29.880 | If they've been in a public playground

01:49:31.480 | where maybe there's other kids with germs

01:49:34.700 | or maybe even chemicals like pesticides

01:49:37.220 | and herbicides that are being used,

01:49:39.360 | maybe it's more important than to wash your hands.

01:49:42.840 | Certainly if you've been in the grocery store

01:49:44.680 | or on the subway, probably a good idea to wash your hands.

01:49:47.840 | So I think you really need to think

01:49:49.160 | about kind of the context of it.

01:49:51.120 | Exposure to microbes from the environment

01:49:56.200 | is likely an important part of educating our immune system

01:50:00.120 | and keeping the proper balance in our immune system.

01:50:02.140 | And it's just a matter of figuring out

01:50:03.920 | the right way to do that safely.

01:50:05.620 | And it may be that the fermented food result that we saw

01:50:08.180 | is a way of tapping into those same pathways,

01:50:10.420 | kind of an environmental exposure to microbes that's safe.

01:50:13.400 | - Interesting.

01:50:14.740 | I'd like to touch on how signals get from the gut

01:50:17.920 | to the rest of the body.

01:50:19.020 | And we probably don't have time to go into all the systems

01:50:22.700 | that benefit from having a diverse microbiome

01:50:24.960 | or a healthy microbiome,

01:50:26.320 | but we talked about the immune system.

01:50:28.900 | There's active signaling and transport from the gut

01:50:32.960 | all along its length, as far as I know,

01:50:34.620 | into the bloodstream and to other organs and tissues.

01:50:37.040 | So for the immune system, it seems straightforward.

01:50:41.600 | You can reduce the amount or number of inflammatory cytokines

01:50:45.200 | like IL-6 and so forth,

01:50:46.520 | maybe increase the anti-inflammatory cytokines

01:50:49.080 | like IL-10 and others.

01:50:51.640 | But we know there's a gut brain access in neurons

01:50:54.080 | that literally talk in both directions

01:50:55.860 | between brain and gut.

01:50:57.160 | But let's say I'm eating my fermented foods,

01:50:59.840 | I'm doing all the right things and my gut is diverse

01:51:03.340 | and I have all the goodies at all the right places.

01:51:06.420 | How is it that the fact that those microbiota are thriving

01:51:11.420 | is conveyed to the rest of the body?

01:51:14.840 | Because they're in there doing their thing

01:51:16.240 | and I don't know that they have a mind,

01:51:17.980 | but they're probably not thinking of taking care of me,

01:51:19.940 | Andrew, but I get feel better

01:51:22.480 | or I might get sick less often

01:51:25.080 | or combat any illness more quickly.

01:51:27.920 | How is that actually happening?

01:51:29.740 | I mean, is it that the microbiota

01:51:31.480 | stay restricted to the gut,

01:51:33.740 | but the signaling molecules are all in a downstream way

01:51:38.440 | are making good or bad things happen?

01:51:40.600 | Or is there some sort of direct recognition

01:51:43.440 | at the body level or are there cells in the body

01:51:45.840 | that are responding to, ah, the gut microbiome is healthy

01:51:48.640 | and therefore I can make more of the good stuff

01:51:51.520 | and less of the bad stuff, so to speak?

01:51:53.280 | - Yeah, great.

01:51:54.600 | You're right, it's super complex.

01:51:57.480 | There's a huge array of ways

01:51:59.480 | that our body perceives both the microbes

01:52:03.440 | and the molecules that they produce in our gut

01:52:05.940 | and the molecules they produce are of course a product

01:52:08.320 | of what microbes are there

01:52:09.420 | and then what they receive as kind of metabolic inputs,

01:52:12.360 | what we're eating and what other microbes

01:52:14.360 | are present in the environment providing molecules to them.

01:52:17.600 | So, it's this complex matrix,

01:52:19.520 | but probably the simplest place to start

01:52:24.040 | is just the immune system.

01:52:25.280 | We have an immune system that the vast majority

01:52:29.400 | of immune cells in our body are located in our gut

01:52:31.760 | just because there's such a dense population of microbes

01:52:35.760 | there that have, we consider them beneficial microbes,

01:52:40.760 | but they're only beneficial

01:52:42.560 | if they're in the right spot in the gut.

01:52:44.080 | As soon as they mislocalize,

01:52:45.800 | we know that they can become opportunistic pathogens.

01:52:48.760 | And so, the immune system really playing an important role

01:52:51.880 | to keep them in place is essential for the system

01:52:56.300 | not moving into a disease space.

01:52:58.960 | The immune system has a variety of ways

01:53:01.160 | of monitoring what microbes are there.

01:53:03.160 | There are actually specialized structures in the gut

01:53:06.160 | known as Peyer's patches that actually take up microbes.

01:53:10.860 | They actually allow microbes to transit

01:53:14.360 | into this population of immune cells in a very controlled way

01:53:19.360 | so that that set of immune cells becomes educated

01:53:23.720 | as to what microbes are just on the other side

01:53:26.040 | of the barrier.

01:53:26.880 | - Wow, it's kind of like a border patrol.

01:53:28.880 | - Exactly, yeah.

01:53:29.880 | So, they bring them in, they fingerprint them,

01:53:33.420 | and then have kind of this set of responses

01:53:38.420 | ready to go if needed.

01:53:41.360 | - Amazing.

01:53:42.360 | - There are other cells known as dendritic cells,

01:53:44.960 | special types that actually send long arms,

01:53:48.760 | these processes out into the lumen of the gut

01:53:51.640 | and do the same thing, take up microbes,

01:53:53.960 | bring them back in and sample them.

01:53:56.120 | In addition to these direct sampling mechanisms,

01:53:59.160 | the cells that line the gut have a huge array of receptors,

01:54:03.040 | specialized proteins that perceive patterns

01:54:06.760 | that the molecular patterns that the microbes make.

01:54:10.120 | So, things like endotoxin, lipopolysaccharide,

01:54:13.600 | just the cell wall of the bacteria.

01:54:16.720 | We have specialized receptors that recognize those.

01:54:19.580 | If those signals become too profound

01:54:21.760 | or if they're perceived in the wrong place,

01:54:24.660 | that can stimulate an inflammatory response.

01:54:26.760 | So, there's all these ways of kind of monitoring

01:54:29.000 | the membership and where it is and how close it is,

01:54:32.080 | but then there's this whole other set of ways

01:54:35.760 | of perceiving metabolic activity

01:54:37.920 | and what's happening in the gut.

01:54:38.760 | And you mentioned before these cell types

01:54:42.760 | that express taste receptors in the gut

01:54:46.200 | and have ways of sampling dietary components.

01:54:48.980 | They're those same types of analogous cells in our gut

01:54:53.980 | that are perceiving metabolites produced by the microbiota

01:54:58.600 | so that our bodies can perceive

01:55:00.600 | what sort of metabolic activity is going on.

01:55:03.360 | And then, in addition to that,

01:55:05.780 | there's this tremendously important enteric nervous system

01:55:10.600 | that's sending signals back to the brain,

01:55:13.220 | dictating things like motility.

01:55:15.660 | Do I get rid of what's in here?

01:55:17.120 | Do I move it along quickly?

01:55:18.480 | What actually is happening?

01:55:20.680 | Do I need to interact with immune cells?

01:55:23.200 | So, there's this really complex array of interactions

01:55:27.100 | between the different cell types.

01:55:28.460 | And then, a lot of the cells that are in the gut

01:55:31.780 | perceiving all of these signals,

01:55:33.320 | a lot of the immune cells can actually get up and leave.

01:55:37.120 | They can get into the blood, cycle through,

01:55:39.560 | and then home to other regions of the mucosal surfaces

01:55:44.360 | so that mucosal surfaces are educated broadly

01:55:48.460 | against what's passing through our gut.

01:55:51.280 | So, there's a variety of ways of cells communicating.

01:55:55.860 | And then, a lot of the molecules that the microbiota makes

01:56:00.600 | can actually make their way into the bloodstream directly.

01:56:04.100 | And so, the array of molecules is still being defined.

01:56:08.600 | We're trying to figure out what all these chemicals are.

01:56:11.520 | We've mentioned the short chain fatty acids,

01:56:13.280 | but those are just the tip of the iceberg.

01:56:15.360 | They're really interesting compounds

01:56:17.220 | like indole derivatives and phenols

01:56:21.760 | and derived from amino acids metabolized by gut microbes

01:56:26.480 | taken up into the bloodstream.

01:56:28.200 | And then, we further metabolize these.

01:56:30.440 | They become kind of co-microbe host metabolites.

01:56:33.920 | And then, they can go on and bind to different receptors

01:56:37.180 | throughout our body, anywhere our bloodstream has access to

01:56:40.360 | and start to trigger signaling cascades.

01:56:43.360 | - Is it known whether or not any of those molecules

01:56:45.400 | are small enough to cross the blood-brain barrier?

01:56:47.960 | Because the hypothesis and the current thinking

01:56:51.720 | is that neurotransmitters manufactured in the gut

01:56:55.560 | and signaling along the gut-brain axis,

01:56:57.720 | literally neurons talking back and forth electrically

01:57:00.560 | from brain to gut and gut to brain

01:57:02.440 | is what regulates things like mood

01:57:04.160 | or at least in animal models.

01:57:05.360 | And there are some emerging human studies improvement

01:57:07.900 | of symptoms in autism spectrum disorders,

01:57:11.400 | maybe even in ADHD.

01:57:12.840 | What I'm basically saying here is there is some evidence

01:57:15.920 | emerging that improving the gut microbiome

01:57:18.160 | can improve outcomes in psychiatric

01:57:20.600 | and developmental disorders.

01:57:22.320 | But what you're telling me is that the microbiota themselves

01:57:26.140 | are manufacturing chemicals that can make it

01:57:27.920 | into the bloodstream.

01:57:28.760 | And therefore, I'm asking if those chemicals

01:57:30.760 | can move from the bloodstream into the brain directly,

01:57:33.400 | it may not be a gut-brain access via neurons.

01:57:37.360 | It actually could just be seepage of serotonin

01:57:39.760 | into the brain or acetylcholine into the brain

01:57:42.800 | for that matter.

01:57:43.680 | - Totally, yeah.

01:57:44.520 | And the biology of most of these molecules

01:57:48.520 | is not well understood,

01:57:52.080 | but certainly in like cerebrospinal fluid

01:57:54.420 | that's been analyzed, you can perceive

01:57:58.160 | these microbial metabolites.

01:57:59.540 | So they are there.

01:58:00.380 | - That's the answer.

01:58:01.200 | Some of them are getting across the barrier.

01:58:03.400 | - But so really interesting thing is I think a lot

01:58:05.960 | of these molecules are, if they're experienced

01:58:10.280 | at high enough doses are toxic or have toxic properties.

01:58:14.360 | We know that a lot of these metabolites,

01:58:17.620 | when they make their way into the bloodstream,

01:58:19.380 | eventually are excreted through the kidneys and urine.

01:58:21.760 | So actually we can monitor the metabolism

01:58:23.840 | that's going on in your gut by actually looking

01:58:26.260 | at the metabolites that are present in your urine

01:58:28.220 | because many of those originated in your gut

01:58:31.700 | from your gut microbes.

01:58:33.060 | But people with kidney disease,

01:58:35.360 | whose kidneys filtering processes not functioning properly,

01:58:39.240 | actually build up high levels of many of these metabolites

01:58:43.960 | into the bloodstream.

01:58:46.040 | And that can lead to more of these molecules

01:58:50.420 | making it across the blood-brain barrier.

01:58:52.760 | And in fact, some of the transporters in the kidney

01:58:56.060 | that are responsible for shuttling these molecules

01:58:58.420 | out into urine are also found at the blood-brain barrier

01:59:01.820 | for shuttling the molecules back into the bloodstream

01:59:04.560 | if they do get across.

01:59:06.220 | And we know that like mental fog is a big,

01:59:09.080 | one of the big symptoms of kidney disease potentially

01:59:12.960 | because a lot of these metabolites accumulate in blood

01:59:16.260 | and then make their way across the blood-brain barrier

01:59:19.140 | into the central nervous system.

01:59:21.380 | - Amazing.

01:59:22.220 | You mentioned mental fog.

01:59:23.140 | A few years back, there were some reports,

01:59:25.880 | some scientific reports and as a consequence in the media

01:59:30.060 | that excessive intake of pill-form probiotics

01:59:33.820 | could create mental fog.

01:59:35.540 | I don't know if that ever took hold.

01:59:37.940 | And it raises a general question about pill-form probiotics.

01:59:42.020 | I took them for a few years just thinking

01:59:43.860 | that would be good for my gut microbiome.

01:59:45.480 | And then I switched to the fermented food thing largely

01:59:48.260 | as a consequence of the work that you and Chris published.

01:59:52.580 | But what's the thought about probiotics

01:59:55.260 | for the typical person that's not recovering

01:59:57.220 | from a round of antibiotics

01:59:58.900 | or that has been prescribed them?

02:00:01.100 | I've heard that the species of microbiota

02:00:06.380 | that they proliferate might not be the species

02:00:10.000 | that we want to proliferate,

02:00:11.340 | but I've also heard that maybe that doesn't matter.

02:00:13.380 | So what's your general stance?

02:00:14.500 | They can be quite expensive also.

02:00:16.820 | I know I've been talking about expense law today,

02:00:18.360 | but I always want to take into account

02:00:19.580 | that people are showing up to the table

02:00:22.340 | with a variety of budgets.

02:00:23.940 | And probiotics are one of the more expensive supplements

02:00:26.880 | out there.

02:00:27.720 | You can quickly get into the several hundreds of dollars

02:00:29.420 | per month if you're getting the quote unquote,

02:00:32.520 | best quality ones.

02:00:33.860 | And if they're actually causing brain fog,

02:00:35.780 | then I'm not sure I'd want to use them.

02:00:37.820 | - No, completely.

02:00:38.660 | And there's a ton of snake oil out there.

02:00:39.940 | I mean, there's just, people know that they,

02:00:41.980 | I think that many of these companies are aware

02:00:45.800 | that they can pray off of people's fears

02:00:47.460 | and get a lot of money from them with absolutely no data

02:00:50.140 | to back up that their probiotic is doing anything.

02:00:52.580 | So I think the first thing to say is buyer beware

02:00:56.660 | because it's a supplement market, it's largely unregulated.

02:00:59.980 | And that means that there are a lot of bad products

02:01:02.460 | out there and a lot of products that,

02:01:05.740 | even though they're not intended to be bad,

02:01:07.580 | just don't have great quality control.

02:01:09.380 | There have been several studies that have taken off the,

02:01:13.020 | over the counter, just kind of off the shelf probiotics,

02:01:15.680 | surveyed what's in there based on sequencing

02:01:18.940 | and shown that what is in there

02:01:22.540 | does not match what's on the label.

02:01:24.300 | - And that's true of many supplements

02:01:26.180 | and unfortunately supplement companies.

02:01:27.700 | This is something we get into on the podcast a lot.

02:01:29.500 | There are reputable brands

02:01:31.180 | and they go through a lot of work to get things right.

02:01:34.340 | And there are many that just, for whatever reason,

02:01:37.820 | it just doesn't match what's listed.

02:01:39.200 | - Exactly.

02:01:40.040 | And so there are places that probiotic companies

02:01:44.760 | can send their product to have it independently validated.

02:01:48.260 | So you wanna look for that sort of validation on a product.

02:01:52.500 | There also are names that are just very well-known

02:01:55.460 | and it's,

02:01:57.660 | their reputations are on the line.

02:02:02.220 | So they probably invest a little bit more

02:02:04.140 | in quality control than maybe some of the

02:02:06.420 | other lesser known names.

02:02:08.520 | But there's a huge range of data on probiotics

02:02:14.220 | and I think the thing that we kind of recommend is

02:02:18.460 | try to find good products and then experiment for yourself

02:02:22.920 | and see if you can find something that works for you.

02:02:24.780 | I know people who have experienced constipation

02:02:28.060 | and don't wanna change their diet

02:02:31.040 | and have found a probiotic that helps them with that.

02:02:33.820 | If you can find that right mix, great, that's wonderful.

02:02:38.440 | I would say that the data right now

02:02:40.800 | is not overwhelmingly positive for what probiotics

02:02:45.800 | do to the gut microbiota.

02:02:48.560 | So there have been some nice studies

02:02:49.820 | looking at the impact of probiotics on recovery

02:02:52.960 | after antibiotic treatment and it appears to slow down

02:02:56.240 | the recovery of the mucosal microbiota.

02:02:59.180 | And some other studies that have,

02:03:03.280 | where the big signal isn't seen, as you might hope,

02:03:07.440 | with a probiotic that's supposed to treat

02:03:09.340 | a different disease.

02:03:10.360 | There have been meta-analysis that do suggest

02:03:12.880 | in certain instances recovery from antibiotics

02:03:17.040 | that there, even though it may cause your microbiota

02:03:19.680 | to recover more slowly, that it may actually prevent

02:03:23.040 | diarrheal disease, recovery from viral diarrhea,

02:03:26.360 | probiotics may help, but because there's such a huge range

02:03:29.400 | of products and because each person is their own

02:03:32.360 | little caper when it comes to the microbiome,

02:03:34.680 | it's really hard to know whether there are great products

02:03:39.520 | for a given indication.

02:03:41.080 | The really good advice that I've heard

02:03:43.000 | is try to find a study that supports

02:03:48.000 | in a really well-designed study,

02:03:50.240 | and this is very hard for people who aren't scientists

02:03:52.400 | to evaluate, so if you're experiencing a medical problem

02:03:56.160 | or wanna consult a doctor, that might be helpful,

02:04:00.520 | but finding a study where a specific probiotic

02:04:03.280 | has successfully done whatever it is you're looking for

02:04:07.080 | and then sticking with that probiotic is really

02:04:09.960 | the best recipe as a place to start in this space, I think.

02:04:13.320 | - And what about prebiotics?

02:04:14.520 | Is there a number of reasons why I can imagine

02:04:17.520 | that prebiotics would be beneficial?

02:04:20.240 | Which essentially, you're pushing the fiber system,

02:04:23.840 | which we talked a lot about today.

02:04:25.080 | - Yeah, yeah, absolutely.

02:04:27.000 | You know, the studies that have been done on prebiotics,

02:04:32.000 | it's really kind of a mixed bag of results.

02:04:36.480 | There have been studies done with purified fibers

02:04:41.120 | where you actually see microbiota diversity plummet

02:04:43.720 | over the course of the study because you get

02:04:46.480 | a very specific bloom in a small number of bacteria

02:04:49.240 | that are good at using that one type of fiber,

02:04:52.120 | and that's at the expense of all the other microbes

02:04:54.300 | that are in the gut.

02:04:55.280 | And so it's really hard to replicate with purified fiber

02:04:59.720 | what you'd get, for instance, at a salad bar

02:05:01.720 | in terms of the array of complex carbohydrates

02:05:04.720 | that you would be exposing your microbiota to.

02:05:06.840 | And I think the kind of broad view of this in the field

02:05:11.840 | is that consuming a broad variety of plants

02:05:17.640 | and all the diverse fiber that comes with that

02:05:21.560 | is probably better in fostering diversity

02:05:23.640 | in your microbiota than purified fibers.

02:05:26.200 | Now, there are, again, a lot of people

02:05:28.920 | who benefit from purified fibers,

02:05:30.760 | either for GI motility or for other aspects

02:05:34.560 | of GI health problems that they've been experiencing.

02:05:37.480 | Again, I think it's the type of thing

02:05:38.760 | where you have to try to find the thing

02:05:41.000 | that that's right for you.

02:05:42.520 | But there also are studies that suggest

02:05:46.400 | that if you layer rapidly fermentable fibers

02:05:50.920 | on top of a Western diet, you actually can result

02:05:55.480 | in weird metabolism happening in your liver

02:05:58.720 | because you have this incredibly rapid fermentation of fiber

02:06:01.720 | along with a lot of fat coming into the system.

02:06:04.760 | At least that's the theory.

02:06:06.760 | And in a mouse study that was published a few years ago,

02:06:09.840 | they actually see that a subset of the mice

02:06:11.880 | develop hepatocellular carcinoma

02:06:14.160 | when they're fed a high dose prebiotic liver cancer

02:06:18.320 | on top of a Western diet.

02:06:21.240 | So whether that's representative of human biology,

02:06:23.960 | we don't know, but purified fibers

02:06:27.160 | are definitely very different

02:06:29.200 | both in terms of the diversity of structures

02:06:30.960 | but also in terms of how rapidly

02:06:33.560 | they're fermented in the gut.

02:06:34.760 | Because if you are eating plants,

02:06:38.520 | the complex structures there really slow the microbes down

02:06:41.680 | in terms of fermentation and you end up

02:06:43.320 | with a slow rate of fermentation

02:06:45.400 | over the length of your colon

02:06:46.880 | as opposed to this big burst of fermentation

02:06:49.440 | that can happen if you eat something that is highly soluble

02:06:52.920 | and easily accessed by the microbes.

02:06:56.000 | - Interesting.

02:06:56.840 | So I guess, is it fair to come back to this idea,

02:06:59.360 | try and avoid processed foods,

02:07:01.280 | the highly palatable foods,

02:07:03.280 | they're all sometimes super highly palatable foods

02:07:05.440 | they're now called that are packed

02:07:07.080 | with hidden sugars, emulsifiers.

02:07:08.480 | So it sounds like some fiber is good.

02:07:12.160 | And despite the outcome of the study,

02:07:14.000 | you identified that if you have the appropriate microbiota,

02:07:16.520 | then you will background,

02:07:18.480 | then one will respond even better to the fiber,

02:07:21.760 | maybe a longer ramp up phase for those folks.

02:07:24.600 | And then the fermented foods,

02:07:26.520 | 'cause there's no reason why you can't do both.

02:07:28.080 | And as we've talked about before,

02:07:29.720 | a lot of fermented foods have fiber.

02:07:31.840 | So you can kill two birds with one stone.

02:07:33.760 | - Totally, and it could be that the diversity increase

02:07:36.200 | that we saw in the high fermented food group

02:07:38.760 | could be something that would aid the high fiber group.

02:07:41.840 | And so now we're planning another study coming up

02:07:44.320 | where we're doing high fiber, high fermented food,

02:07:46.880 | and then fiber plus fermented food

02:07:48.520 | just to see if there's a synergistic effect there.

02:07:50.360 | - Great, I wanna enroll.

02:07:51.960 | Seriously, although I guess I'm biased

02:07:54.200 | 'cause I sort of know where you're trying to,

02:07:56.520 | well, is it blood draws that you use

02:07:58.640 | to measure the inflammatome?

02:08:00.240 | - Exactly, so we do blood draws like two weeks.

02:08:02.880 | - So that's good.

02:08:04.080 | So you've covered a tremendous amount of information

02:08:06.880 | and I'm incredibly grateful.

02:08:08.160 | This was a area of biology

02:08:09.880 | that despite having learned a lot about through papers

02:08:12.260 | and going to talks and reading articles in the media

02:08:16.240 | has remained somewhat mysterious to me until today.

02:08:19.120 | You've given us a very vivid picture

02:08:20.760 | of how this system works.

02:08:23.480 | Where can people find out more

02:08:24.780 | about the work that you're doing?

02:08:26.320 | We can certainly provide links.

02:08:27.520 | And you and your wife who co-run your lab,

02:08:31.580 | you have a book on this topic.

02:08:32.980 | So could you tell us about the book

02:08:34.060 | where we can learn more about the Sonnenberg Lab

02:08:36.280 | and the work that you're doing?

02:08:37.840 | Maybe people will even try and enroll

02:08:39.400 | in some of these studies.

02:08:40.320 | - Yeah, fantastic.

02:08:41.160 | Yeah, it'd be great if we could get people to enroll.

02:08:43.120 | We're always looking for willing participants.

02:08:47.080 | Yeah, so Erica, my wife and I wrote a book

02:08:49.800 | called "The Good Gut."

02:08:51.000 | And that really was a response

02:08:54.600 | to how we were changing our lives

02:08:57.100 | in response to being in the field,

02:08:58.720 | being very familiar with the research,

02:09:00.700 | seeing that a lot of our friends

02:09:01.840 | that weren't studying the gut microbiome,

02:09:03.360 | but were very well-informed, many of them scientists,

02:09:06.080 | were not doing the same things we were doing.

02:09:08.660 | And it was very clear that it was just the lack

02:09:11.840 | of information funneling out of the field to other people.

02:09:16.180 | And so we wanted to make that accessible

02:09:19.160 | to people who are not microbiome scientists.

02:09:21.600 | There's also a really interesting story.

02:09:23.280 | We were at a conference site

02:09:24.840 | that just has scientific conferences all summer long,

02:09:27.580 | week after week after week, different fields.

02:09:30.040 | And so it's people that work there

02:09:31.680 | that are just dealing with these new groups

02:09:33.340 | coming in week after week.

02:09:34.800 | And the week we were there for a microbiome conference,

02:09:38.300 | people that work in the dining commons came up to us

02:09:43.160 | and they said, "What group is this?

02:09:44.520 | This is weird."

02:09:45.360 | And we're like, "What's weird?"

02:09:46.360 | And they said, "We can't keep the salad bar stocked."

02:09:48.920 | And it was just, it was very clear

02:09:50.360 | that nobody was doing what we were doing

02:09:52.120 | until we'd go to a microbiome conference

02:09:54.020 | and then everybody was doing the same stuff

02:09:55.920 | that we were doing.

02:09:56.920 | And so anyway, we wrote this book

02:09:59.120 | to talk about our personal journey

02:10:00.400 | and kind of the science in the field.

02:10:02.300 | And yeah, just to lay a foundation for people

02:10:05.920 | if they wanna start thinking about these changes.

02:10:07.960 | And then in terms of kind of connecting with our research,

02:10:11.720 | certainly there's the Center for Human Microbiome Studies

02:10:14.620 | at Stanford, which is kind of our home base

02:10:16.660 | for doing a lot of these dietary interventions.

02:10:18.640 | We list the studies there,

02:10:20.400 | give more information on what we're doing.

02:10:22.440 | And then we have a lab website too

02:10:24.240 | that people can go to and read more about our research.

02:10:27.380 | Yeah, and we're always looking

02:10:29.560 | for participants for our studies.

02:10:31.140 | - Great, well, we will provide links

02:10:32.760 | to all of those sources.

02:10:34.280 | And I just wanna say thank you so much

02:10:36.520 | for sharing with us your knowledge

02:10:38.540 | for the incredible work that you and Erica,

02:10:41.200 | your wife and Chris do and are continuing to do.

02:10:45.760 | I think this is an area that when I started my training,

02:10:48.860 | I heard a little bit about microbiota

02:10:51.800 | and I always just thought those are people

02:10:52.840 | that work on infectious disease and like all the bad stuff.

02:10:55.380 | So it's interesting and really important

02:10:59.400 | that people realize that we're carrying all this vital cargo

02:11:02.300 | and we need to take care of the cargo

02:11:03.900 | so it can take care of us.

02:11:05.600 | So thank you so much for your time and for the work you do.

02:11:08.620 | And I hope we can do it again.

02:11:10.000 | - Thanks, Andrew.

02:11:10.840 | This was a great conversation.

02:11:12.360 | - Terrific.

02:11:13.200 | Thank you for joining me today

02:11:14.040 | for my discussion with Dr. Justin Sonnenberg,

02:11:16.220 | all about the gut microbiome

02:11:17.840 | and how to optimize your gut microbiome for health.

02:11:21.100 | Please check out the Sonnenberg Lab webpage.

02:11:23.480 | That's Sonnenberg spelled S-O-N-N-E-N-B-U-R-G-L-A-B

02:11:28.480 | dot Stanford dot E-D-U.

02:11:30.940 | That's Sonnenberg lab dot Stanford dot E-D-U.

02:11:34.260 | They often recruit for studies

02:11:36.220 | exploring how different aspects of nutrition

02:11:38.460 | impact the gut microbiome,

02:11:39.920 | much as we discussed during today's episode.

02:11:42.520 | Please also check out the book that he and his wife,

02:11:44.960 | Dr. Erica Sonnenberg wrote called "The Good Gut."

02:11:47.560 | It's readily available on all the usual sites,

02:11:49.740 | such as Amazon and so forth.

02:11:51.380 | If you're learning from and are enjoying this podcast,

02:11:53.660 | please subscribe to our YouTube channel.

02:11:55.340 | That's a terrific zero cost way to support us.

02:11:58.100 | In addition, please subscribe to the podcast

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02:12:20.980 | that you've heard or watched on this podcast.

02:12:23.840 | Please also check out the sponsors

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02:12:27.340 | That's the best way to support this podcast.

02:12:30.040 | We also have a Patreon.

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02:12:37.280 | On many episodes of the Huberman Lab Podcast,

02:12:39.100 | including today, we discuss supplements.

02:12:41.460 | While supplements are certainly not necessary for everybody,

02:12:44.120 | many people derive tremendous benefit from them

02:12:46.420 | for things like sleep and focus,

02:12:48.240 | and indeed got microbiome support.

02:12:51.160 | The one issue with supplements, however,

02:12:52.760 | is that many of the supplement companies out there

02:12:55.200 | do not independently test their supplements.

02:12:57.520 | So there isn't tremendous confidence in all supplements

02:13:01.400 | that they contain the amounts of the ingredients

02:13:03.580 | that are listed on the bottle

02:13:04.840 | and that the quality of the ingredients is where it should be.

02:13:07.560 | For that reason, we've partnered with Thorne,

02:13:09.300 | that's Thorne, T-H-O-R-N-E,

02:13:11.260 | because Thorne supplements are known to have

02:13:13.300 | the very highest levels of stringency

02:13:15.080 | with respect to the quality of the supplements

02:13:18.120 | and the amounts of the supplements listed on their bottles

02:13:21.160 | lists what's actually in the containers, which is essential.

02:13:24.900 | If you'd like to see the Thorne supplements that I take,

02:13:26.800 | you can go to Thorne, thorne.com/u/huberman,

02:13:31.800 | and you can get 20% off any of the Thorne supplements

02:13:34.360 | that are listed there.

02:13:35.400 | Also, if you navigate deeper into the Thorne site

02:13:37.680 | through that portal, thorne.com/u/huberman,

02:13:40.620 | you can also get 20% off any of the other supplements

02:13:43.360 | that Thorne makes.

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02:13:49.140 | There I cover topics about science and science-based tools,

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02:13:58.360 | We also have a newsletter.

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02:14:01.540 | Once a month, we put out short summaries

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02:14:25.680 | So thank you once again for joining me

02:14:27.220 | for today's discussion about the gut microbiome.

02:14:29.480 | And last, but certainly not least,

02:14:31.840 | thank you for your interest in science.

02:14:33.540 | [upbeat music]

02:14:36.120 | (upbeat music)

Dr. Justin Sonnenburg: How to Build, Maintain & Repair Gut Health | Huberman Lab Podcast #62

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