back to indexDr. Justin Sonnenburg: How to Build, Maintain & Repair Gut Health | Huberman Lab Podcast #62
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Welcome to the Huberman Lab Podcast,
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where we discuss science and science-based tools
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for everyday life.
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I'm Andrew Huberman,
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and I'm a professor of neurobiology and ophthalmology
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at Stanford School of Medicine.
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Today, my guest is Dr. Justin Sonnenberg.
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Dr. Sonnenberg is a professor of microbiology and immunology
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at Stanford School of Medicine,
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and one of the world's leading experts
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on the gut microbiome.
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The gut microbiome is the existence
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of trillions of little microorganisms throughout your gut.
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And by your gut, I don't just mean your stomach,
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I mean your entire digestive tract.
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It turns out we also have a microbiome
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that exists in our nose, in any other location
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in which our body interfaces with the outside world.
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In fact, there's a microbiome on your skin.
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And while it might seem kind of intrusive
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or kind of disgusting to have
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all these little microorganisms,
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they can be immensely beneficial for our health,
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meaning our hormonal health, our brain health,
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and our immune system function.
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Dr. Sonnenberg teaches us about the gut microbiome,
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how it's organized spatially,
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meaning which microbiota live where.
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He teaches us about these incredible things
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called crypts and niches,
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which are little caves within our digestive tract
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that certain microbiota take residence.
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And at that premier real estate,
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they're able to do incredible things to support our health.
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He also talks about the things that we can all do
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to support our microbiome in order for our microbiome
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to support our brain and body health.
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Dr. Sonnenberg co-runs his laboratory
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with his spouse, Dr. Erika Sonnenberg,
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and together they've also written a terrific
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and highly informative book called
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''The Good Gut, Taking Control of Your Weight, Your Mood,
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and Your Long-Term Health.''
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Even though that book was written a few years back,
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the information still holds up very nicely.
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And today he also builds on that information,
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informing us about recent studies that for instance,
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point to the important role of fermented foods
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and the role of fiber in supporting a healthy gut microbiome.
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So if you've heard about the gut microbiome,
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or even if you haven't,
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today you're going to hear about it
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from one of the world's leading experts.
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He makes it immensely clear as to what it is,
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how it functions and how to support it
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for your brain and body health.
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During today's discussion,
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we don't just talk about nutrition.
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We also talk about the impact of behaviors
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and the microbiome.
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Behaviors such as who you touch, who you kiss, who you hug,
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whether or not you interact with or avoid animals,
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whether or not those animals belong to you,
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or whether or not they belong to somebody else.
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If all that sounds a little bit bizarre,
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you'll soon understand that your microbiome
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is constantly being modified by the behavioral interactions,
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the nutritional interactions, and indeed your mood
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and internal reactions to the outside world.
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This is an incredible system.
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Everyone should know how it works
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and everyone should know how to optimize it.
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And today you're going to learn all of that
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from Dr. Sonnenberg.
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I'm pleased to announce that I'm hosting two live events
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The first live event will take place
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in Seattle, Washington on May 17th.
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The second event will take place in Portland, Oregon
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Both are part of a series called the Brain Body Contract.
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For this series, I will discuss science.
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So I will discuss the mechanistic science
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around things like sleep and focus and motivation,
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physical performance, mental health, physical health,
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a large number of topics that I believe
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many people are interested in
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and that certainly are important
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for our health and wellbeing and performance.
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In addition, I will of course describe tools
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and actionable items,
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most of which I have not discussed
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on the Huberman Lab podcast or anywhere else.
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Presale tickets for these two events go live Tuesday,
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March 8th at 10 a.m. Pacific time.
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We've made these tickets exclusively available
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to the listeners of the Huberman Lab podcast.
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So they are password protected.
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To find them, you can go to hubermanlab.com slash tour
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and use the code Huberman.
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Before we begin, I'd like to emphasize that this podcast
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is separate from my teaching and research roles at Stanford.
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It is however, part of my desire and effort
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to bring zero cost to consumer information about science
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and science related tools to the general public.
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In keeping with that theme,
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I'd like to thank the sponsors of today's podcast.
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Our first sponsor is Athletic Greens, now called AG1.
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I've been taking AG1 since 2012.
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So I'm delighted that they're sponsoring the podcast.
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The reason I started taking AG1
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and the reason I still take AG1 once or twice a day
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is that it meets all my basic
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foundational supplementation needs.
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What I mean by that is it covers any vitamin
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and nutritional deficiencies that I might have,
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because I'm trying to be good about my nutrition and diet,
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but I don't always manage to get everything that I need.
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And I'm sure that there are a lot of gaps in there.
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So it covers those gaps.
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It also has probiotics.
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And as you'll learn in today's episode,
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and I've talked about on previous episodes,
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the probiotics are essential for a healthy gut microbiome.
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We need probiotics in order for our microbiome to thrive.
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And our microbiome supports things like gut brain health,
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indeed things like metabolism, mood, hunger.
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It also supports the immune system.
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So you'll learn today your gut microbiome
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actually manufactures neurotransmitters,
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the very chemicals that impact mood and brain function.
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Athletic Greens primes your system
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for a healthy gut microbiome,
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something that can be achieved
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with food and lifestyle factors,
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but is often hard to achieve
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with just food and lifestyle factors.
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If you'd like to try Athletic Greens,
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you can go to athleticgreens.com slash Huberman
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to claim a special offer.
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They'll give you five free travel packs
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to make it very easy to mix up Athletic Greens
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while you're on the road,
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and a year's supply of vitamin D3K2.
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Vitamin D3 has many important biological functions
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that support your immediate and long-term health,
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and K2 as well is very important
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for things like cardiovascular health,
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calcium regulation, and so on.
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Again, if you go to athleticgreens.com slash Huberman,
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you can claim the special offer
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of the five free travel packs and the vitamin D3K2.
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Today's episode is also brought to us by Roka.
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Roka makes eyeglasses and sunglasses
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that I believe are of the very highest quality.
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I've spent my lifetime working on the biology
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of the visual system,
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and I can tell you that the biology of the visual system
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has a lot of mechanisms in there,
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so that, for instance,
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if you move from a bright environment to a dim environment,
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your visual system needs to adapt.
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One issue with a lot of sunglasses and eyeglasses
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is you move from one environment to the next,
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and you have to take the sunglasses or eyeglasses off.
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You get a glare or you have to adjust
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because of the way that the lenses are designed.
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With Roka, they've taken the biology
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of the visual system into account,
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and so you never have to take them off and on
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in order to move from one environment to the next.
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They are also designed for movement and athletics,
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or you can wear them for just things like work
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and going out to dinner and so forth.
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They have a terrific aesthetic.
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They're extremely lightweight.
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In fact, I often forget that they're even on my face.
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I wear sunglasses when it's very bright
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and when I'm driving into sunlight,
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I wear readers at night.
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I hardly ever remember that they're on my face.
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They also won't slip off your face
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if you use them when running or cycling.
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The company was developed by two
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all-American swimmers from Stanford.
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So everything about these sunglasses and eyeglasses
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in a lot of different situations and scenarios.
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If you'd like to try Roka, you can go to roka.com,
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that's R-O-K-A.com, and enter the code Huberman
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to save 20% off your first order.
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Again, that's Roka, R-O-K-A.com,
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and enter the code Huberman at checkout.
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Today's episode is also brought to us by Helix Sleep.
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Helix makes mattresses and pillows
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that are designed for your particular sleep needs.
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What I mean by that is you can go to the Helix site,
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you can take a very brief two or three minute quiz,
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ask questions like, do you sleep on your side,
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your back, your stomach?
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Do you tend to run hot or cold through the night?
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Maybe you don't know the answers to those questions.
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And then they match you to a mattress
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that's designed for your particular sleep needs.
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I matched to the DUSK, D-U-S-K, mattress.
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I like a mattress that's not too firm, not too soft.
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I tend to sleep on my side,
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it's sort of in the like crawling soldier position.
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It seems to be the most common position I sleep in.
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And that really works terrifically well for me.
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But you need to take the quiz
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to see which mattress works best for you.
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So if you're interested in upgrading your mattress,
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go to helixsleep.com slash Huberman,
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take the two minute quiz,
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and they'll match you to a customized mattress.
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You can figure out how to get your optimal sleep,
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which I've talked about on this podcast
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so many times before.
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Sleep is the foundation of all mental and physical health
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and performance in any aspect of life.
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And the mattress you sleep on is key to the sleep you get.
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After matching you to a customized mattress,
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you can get up to $200 off any mattress order
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Again, if you're interested,
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you can go to helixsleep.com slash Huberman
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to get up to $200 off and two free pillows.
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And now for my discussion with Dr. Justin Sonnenberg.
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Justin, thanks so much for being here.
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I am a true novice when it comes to the microbiome.
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So I'd like to start off with a really basic question,
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which is what is the microbiome?
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I imagine lots of little bugs running around in my gut,
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and I don't quite like the image of that,
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but I'm aware that our microbiome can be good for us,
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but we can also have an unhealthy microbiome.
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So if I were to look at the microbiome at the scale
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that I could see the meaningful things,
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what would it look like and what's going on in there?
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Yeah, I mean, essentially you're correct.
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I mean, we have all of these little microorganisms
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running around in our gut.
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I think, you know,
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just to start off with clarifying terminology,
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microbiome and microbiota quite often are referred to,
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are used to refer to our microbial community interchangeably
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and I'll probably switch between those two terms today.
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The other important thing to realize
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is that these microbes are not just in our gut,
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but they're all over our body.
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They're in our nose, they're in our mouths,
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they're on our skin and so basically anywhere
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that the environment can get to in our body,
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which includes inside our digestive tract, of course,
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is, you know, colonized with microbes
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and the vast majority of these are in our distal gut
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and in our colon and so this is the gut microbiota
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or gut microbiome and the density
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of this community is astounding.
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I mean, it really is, if you get down to the scale
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of, you know, being able to see individual microbes,
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you know, you start off with a zoomed out view
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and you see something that looks like, you know,
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fecal material that I just inside the gut
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and you zoom in and you start to, you know,
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get to the microscopic level and see the microbes,
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they are just packed, you know, side to side, end to end.
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It's a super dense bacterial community,
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almost like a biofilm, you know,
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something that's just made up of microbes
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to the point where it's thought that, you know,
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around 30% of fecal matter is microbes, 30 to 50%.
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So, you know, it's an incredibly dense microbial community.
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We're talking of, you know, trillions of microbial cells
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and all those microbial cells,
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if you start to get to know them and see who they are,
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break out in the gut probably to hundreds
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to a thousand species,
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depending upon how you define a microbial species.
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And then most of these are bacteria,
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but there are a lot of other life forms there.
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There are archaea, which are little microbes
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that are bacteria-like, but they're different.
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There are eukaryotes.
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So, you know, we commonly think of eukaryotes in the gut
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as, you know, something like a parasite,
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but there are eukaryotes, there are fungi,
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there are also little viruses.
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There are these bacteriophages that infect bacterial cells.
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And so, and those actually outnumber the bacteria
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So they're just everywhere there, they kill bacteria.
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And so there's these really interesting
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predator-prey interactions.
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But overall, it's just this really dense,
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complex, dynamic ecosystem.
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And so, you know, we're talking about the human
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as a single species, but we're also thinking of the human
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as this complex, integrated ecosystem
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of hundreds to thousands of species interacting in concert
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to do all the fantastic things that we know
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happen in the human body.
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So we've got a lot of cargo.
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Or maybe we're the cargo.
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Yeah, I mean, there have been people that have likened
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humans to just a really elaborate culturing flask
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for microbes and that we've actually been designed
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over the course of evolution, designed to just
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efficiently propagate this microbial culture
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from person to person, from generation to generation.
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So it's a different way of thinking of the human body.
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I believe that our pH, or the pH of our digestive system
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varies as you descend, as you go from mouth to, you know,
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to throat and stomach.
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And you said that most of the microbiota
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are in the distal colon.
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Are there distinct forms of microbiota all along
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the length of the digestive tract
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and within these other interfaces with the outside world?
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So it starts like with our teeth and in our mouth
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and saliva, there's oral microbiota.
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These microbial species are very different
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than the ones that you find in the digestive tract.
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They're usually built to deal with oxygen very well.
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They're in an area that is exposed to a lot of oxygen.
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They, of course, see different nutrients than,
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for instance, the colonic bacteria would see.
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And they grow quite often in mats that live on teeth.
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So they're very structured.
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And not moving around a lot.
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So they're very fairly stationary.
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As you move down the digestive tract,
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there are microbes in our esophagus and our stomach,
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but those communities are not very dense
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and actually not very well studied.
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We know of a very, you know,
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there's a very famous stomach bacteria
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known as Helicobacter pylori,
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which can cause stomach ulcers and cause gastric cancer
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in some, you know, less frequent situations.
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But, you know, this is a very different set of microbes.
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They have to be adapted to a different environment
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in the stomach, especially incredibly acidic environment,
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but also very different in terms of their ability
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to interact with other microbes,
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just because the communities are less dense,
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they're less dynamic, there's less nutrients that stay there
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and passage through the community.
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So a lot of times those communities are reliant
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upon nutrients derived from the host,
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as opposed to nutrients derived from our diet.
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As you move down out of the stomach into the small intestine,
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you start to see these communities,
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which are the ones that are becoming more well studied.
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Small intestine is still a bit of a black box
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just because it's hard to access.
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And so there's some really cool technologies out there
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for using, for instance, capsules to do sampling
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as the capsule passes through the digestive tract.
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So that we have a better idea of what's going on
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in the small intestine.
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And then you get to the colon and this is the community
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that's just so incredibly, you know, densely packed,
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doing a ton of, there's a ton of metabolic activity
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happening there and a bunch of interaction with the host.
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And that's the study, that's the community
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that's really the best studied.
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Part of the reason for that is because stool is so easy
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to obtain compared to, for instance,
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something in the stomach or small intestine.
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And that stool is fairly representative.
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We know from studies that have been done
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using colonoscopies and so forth,
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stool is fairly representative
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of what's happening in the colon.
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So dense, super exciting community,
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but also the best studied just because it's the easiest
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to access in the lower digestive tract.
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I imagine these microbiota have to get in there
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Are microbiota seen in newborns?
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In other words, where do they come from?
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And dare I ask, what direction do they enter the body?
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Or is it from multiple directions?
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Yeah, yeah, great question.
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So, you know, one of the burning questions
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that we can come back to at the end of this
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is where does our microbiota come from?
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Because it is this kind of, you know,
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existential question in the field,
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like where is this community assembling from?
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And the reason that it's such an interesting question
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is that, you know, a fetus when it's in the womb
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that's actually a sterile environment.
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There have been some studies that have looked at
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whether there are microbes in the womb
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and microbes colonizing the fetus at that point.
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There's some debate about this,
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but overall it looks like that's not a big part
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of the equation of microbial colonization.
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And so each time an infant is born,
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it's this new ecosystem.
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It's like an island rising up out of the ocean
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that has no species on it.
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And suddenly there's this like land rush
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for, you know, this open territory.
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And so the, you know, we know that infants
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go through this really complex process
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of microbiota assembly over the first days,
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weeks, months, years of life.
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And then, you know, you get into switching to solid food,
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two to three years of age.
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There are some changes in childhood,
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adolescents working into adulthood,
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but that first, you know, zero to one year
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is a super dynamic time with really kind of
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stereotypical developmental changes in the gut microbiota
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that appear to have the possibility of going wrong
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and causing problems for infants in some instances.
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But, you know, if you step away from that extreme side
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of things going wrong,
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there also are a lot of different trajectories
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that developmental process can take
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because our microbiota is so malleable and so plastic
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and those trajectories can be affected
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by all sorts of factors in early life.
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So an example is whether an infant is born by C-section
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or born vaginally.
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We know from beautiful work that's been done in the field
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that infants that are born by C-section
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actually have a gut microbiota
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that looks more like human skin
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than it does like either the birth canal,
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the vagina microbiota or the mother's stool microbiota.
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Babies that are born through the birth canal
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have initial colonization of vaginal microbes
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and of stool microbes from their mother.
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And so just these first days,
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whether you're born by C-section
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or through natural childbirth,
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your gut microbiota looks very different.
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And then compound on top of that,
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whether you're breastfed or formula fed,
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whether your family has a pet or doesn't have a pet,
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whether you're exposed to antibiotics,
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there are all these factors
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that really can change that developmental process
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and really change your microbial identity eventually in life.
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The reason that the field is paying really close attention
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to this and studying this right now
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is because we know from animal studies
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that depending upon the microbes that you get early in life,
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you can send the immune system
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or metabolism of an organism
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or other parts of their biology
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in totally different developmental trajectory.
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So what microbes you're colonized with early in life
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can really change your biology.
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And we can come back to that later.
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But getting back to that original question
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of where do your microbes come from,
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you'd think because you're born
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through your mother's birth canal
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or exposed to her skin microbes,
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that a lot of your microbes would come from your mother.
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But it actually turns out
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that we can certainly detect that signal.
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We certainly see maternal microbes in the infant,
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but there are a lot of microbes
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that are coming from other places,
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surfaces, other people, perhaps other caregivers,
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but perhaps strangers as well.
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So we acquire our microbes from a variety of sources.
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The first ones are from our mom
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or from our caregivers from the hospital,
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but then we add to that tremendously
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over the first year or so of life.
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Incredible, you even said pets.
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So if a kid, if there's a dog in the home
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or a parakeet in the home,
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that clearly they have a microbiome also,
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and potentially the child is deriving microbiota species
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from those pets, correct?
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And so the best studies that have been done
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have just looked at pets in the household as a factor
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and whether that changes the group of infants
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that have a pet to look slightly different
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than the group of infants that don't have a pet.
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And then the question is,
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what is the pet doing to change those microbes?
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And some of it is probably actually contributing
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direct members of the microbiota.
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Actually, I have a dog,
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that dog occasionally will lick my mouth
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without me like paying attention,
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and that's probably introducing microbes.
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We also know that pets are down in the dirt,
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they're outside, they're being exposed
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to a lot of environmental microbes.
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And so just pets serving as a conduit
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for a bunch of microbes
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that we wouldn't otherwise come in contact with
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is a possibility as well.
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I'll show you what, we will return to pets,
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and in particular, your dog, an amazing dog, by the way.
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I met your dog just the other day,
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and I had to force myself,
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I had to pry myself away from, it's a Havanese, right?
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Incredible, what is your dog's name?
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Louis, Louis Pasteur.
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Louis Pasteur, I don't know how appropriate.
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Amazing dog, what a personality on that dog.
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The issue that I think a lot of people
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are probably wondering is,
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what is a healthy microbiome?
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And what is it supporting?
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We hear that you need a healthy microbiome
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to support the immune system or metabolism,
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or even the gut brain axis.
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How do we define a healthy versus a unhealthy microbiome?
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Some people might know the unhealthy microbiome
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as dysbiosis is the word that I encounter in the literature.
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But given that there are so many species of microbiota,
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and given that I think we probably each have
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a signature pattern of microbiota,
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how do we define healthy versus unhealthy microbiota?
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Is there a test for this?
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Later, we'll talk about technologies for testing microbiota.
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There are a lot of companies now,
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a lot of people sending stool samples in the mail.
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Never look at the postal service the same way again,
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but it's out there and it's getting analyzed.
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So how should I think about this?
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I can think about things like heart rate,
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heart rate variability, BMI, all sorts of metrics of health.
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How should I think about the microbiota?
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How do I know if my microbiome is healthy or unhealthy?
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Yeah, it's a million dollar question right now in the field.
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And there's a lot of different ways of thinking about that.
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And I can talk about some of those,
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but I would say that there are sessions at conferences,
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there are review articles being commissioned.
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There are all sorts of kind of thought pieces
link |
about this right now, like what is a healthy microbiota?
link |
What are the features that define it?
link |
And I think before diving into this,
link |
the important thing to realize is it's a complex topic.
link |
Context matters a lot.
link |
What's healthy for one person or one population
link |
may not be healthy for another person or population.
link |
And the microbiota is malleable.
link |
It's plastic, it changes our human biology,
link |
which I think is how we think about health quite often,
link |
BMI and longevity, reproductive success,
link |
however you wanna define it.
link |
It certainly can accommodate a variety of configurations
link |
of gut microbiota.
link |
And we don't have, you know,
link |
it's really hard to untangle all of the different factors
link |
of what could be very healthy
link |
versus a little bit less healthy.
link |
So I will say that there's no single answer to this,
link |
but there's some really important considerations.
link |
And perhaps the best way to start talking about this
link |
is to go back to the inception
link |
of the Human Microbiome Project,
link |
which was this program that NIH started.
link |
They invested a lot of money in 2008, 2009
link |
for really propelling the field of gut microbiome research.
link |
It was becoming evident at that point
link |
that this was not just a curiosity of human biology,
link |
that it was probably really important for our health.
link |
And they had all this wonderful sequencing technology
link |
from the Human Genome Sequencing Project.
link |
And with the human genome complete at that point,
link |
they started turning that technology
link |
to sequencing our gut microbes.
link |
And, you know, it's important to contextualize
link |
the amount of information that they're trying to document.
link |
The, you know, collective genome of our gut microbes
link |
is on the order of 100 to 500 times larger
link |
than our human genome.
link |
So it's just in terms of the number of genes.
link |
So it's just this vast number of genes.
link |
And then if you start getting
link |
into some of the fine variation,
link |
it's, you know, scales by 10 to 100 fold.
link |
So really a huge amount of information
link |
they're trying to document.
link |
And so it was a wonderful investment
link |
and it continues to pay dividends to this day.
link |
But one of their goals of that project
link |
was to try to define what a healthy microbiome is
link |
versus a diseased microbiome in different contexts.
link |
And so they started enrolling a bunch of healthy people
link |
and a bunch of people with, for instance,
link |
inflammatory bowel disease and other diseases.
link |
And the idea was let's document those microbiomes,
link |
what microbes are there, what genes are there.
link |
And then we can start to get a sense of
link |
what are the commonalities of the healthy people
link |
and how can that go wrong in these different disease states.
link |
And, you know, there were some answers from that,
link |
but through those studies,
link |
we really started to get the image
link |
that there is this tremendous individuality
link |
in the gut microbiome.
link |
And so it's really hard to start drawing, you know,
link |
conclusions after initial pass of that project
link |
of what is a healthy microbiome.
link |
But the other thing that we started to realize
link |
at the same time, there were studies going on
link |
documenting the gut microbiome of traditional populations
link |
of humans, hunter-gatherers,
link |
rural agricultural populations.
link |
And those studies were really mind blowing
link |
from the perspective of, you know,
link |
all these people are healthy,
link |
they're living very different lifestyles
link |
and their microbiome doesn't look anything
link |
like a healthy American microbiome.
link |
So does that mean that the healthy American microbiome
link |
is healthy, but only in the context of living
link |
in the United States and consuming what's consumed here?
link |
Or is it that there is a superior microbiome signature
link |
somewhere in our history or currently in the world?
link |
Yeah, you know, I think that's kind of
link |
a big question right now.
link |
I think, you know, there's a great quote from Dabchansky
link |
that says, nothing in biology makes sense
link |
except in the light of evolution.
link |
And, you know, these traditional populations
link |
are all modern people living on the planet now,
link |
but their lifestyle does represent, you know,
link |
the closest approximation to how our ancestors,
link |
early humans lived.
link |
And so those microbiomes, and now we know from sequencing
link |
of paleo feces, the microbiome of these traditional
link |
populations is representative, more representative
link |
of the microbiome that we evolved with,
link |
that potentially shaped our human genome.
link |
And so one possibility is that in the industrialized world,
link |
we have a different microbiome from traditional populations
link |
and that microbiome is well adapted
link |
to our current lifestyle and therefore healthy
link |
in the context of an industrialized society.
link |
And there probably are elements of that that are true.
link |
But another possibility is that this is a microbiome
link |
that's gone off the rails, that it is, you know,
link |
deteriorating in the face of antibiotic use
link |
and all the problems associated with industrialized diet,
link |
Western diet, and that even though the human microbiome
link |
project documented the microbiome of healthy people,
link |
healthy Americans, that what they really may have been
link |
documenting there is a perturbed microbiota
link |
that's really predisposing people to a variety
link |
of inflammatory and metabolic diseases.
link |
It reminds me of the, as a neurobiologist,
link |
was weaned in the landscape of so-called critical periods
link |
where early life environment very strongly shapes the brain.
link |
And so many studies were done on animals raised
link |
in traditional cages with a water bottle and some food,
link |
maybe a few other animals of the same species.
link |
And then people came along and said,
link |
wait, normally these species in the wild would have things
link |
like things to climb over and things to go through
link |
and you provide those very basic elements
link |
and all of a sudden the architecture of neural circuits
link |
looks very different and you realize
link |
that you were studying a deprived condition.
link |
And earlier you actually referred to,
link |
if I understood correctly, to critical periods
link |
for gut microbiome development.
link |
Is it fair to say that there are critical periods?
link |
Meaning if my, let's say my, let's aim it at me,
link |
if my gut microbiome was dysbiotic,
link |
it was off early in life,
link |
can I rescue that through proper conditions and exercise?
link |
Or is there some sort of fixed pattern
link |
that's going to be hard for me to escape from?
link |
Yeah, there's a big field that's emerging now
link |
that we refer to as kind of reprogramming the gut microbiome.
link |
And I think if we want to conceptualize humans
link |
as this aggregate human microbial biology,
link |
most people have heard of CRISPR
link |
and the ability to potentially change our human genome
link |
in ways that correct genetic problems.
link |
That's a wonderful technology
link |
and has kind of put on the table,
link |
genetic engineering for curing disease,
link |
but it's much easier to change gut microbes for a problem
link |
just because that community is malleable.
link |
The issue that I think we're seeing in the field
link |
is that microbiomes quite often,
link |
whether they're diseased or healthy, exist in stable states.
link |
They kind of tend towards this well that has gravity to it,
link |
in a way, biological gravity,
link |
where it's really hard to dislodge that community
link |
So even individuals, for instance, that get antibiotics,
link |
you take oral antibiotics,
link |
the community takes this huge hit.
link |
We know that a bunch of microbes die,
link |
the composition changes,
link |
and that represents a period of vulnerability
link |
where pathogens can come in and take over
link |
and cause disease.
link |
But if that doesn't happen,
link |
the microbiota kind of works its way back
link |
to something that is not exactly like,
link |
but similar to the pre-antibiotic treatment.
link |
We know with dietary perturbations,
link |
quite often you'll see a really rapid change
link |
to the gut microbiome.
link |
And then it's almost like a memory
link |
where it snaps back to something that's very similar
link |
to the original state,
link |
even though the diet remains different.
link |
And so there's this incredible,
link |
what we refer to as resilience of the gut microbiome
link |
and resistance to change,
link |
or at least resistance to establishing a new stable state.
link |
So that doesn't mean it's hopeless
link |
to change an unhealthy microbiome to a healthy microbiome,
link |
but it does mean that we need to think carefully
link |
about restructuring these communities
link |
in ways where we can achieve a new stable state
link |
that will resist the microbial community
link |
getting pulled back to that original state.
link |
And one of the really kind of simplest
link |
and nicest examples of this is an experiment
link |
that we performed with mice
link |
where we were feeding mice a normal mouse diet,
link |
a lot of nutrients there for the gut microbiota,
link |
things like dietary fiber,
link |
and we switched those mice,
link |
half the mice, to a low fiber diet.
link |
And we were basically asking the question that
link |
if you switch to kind of a Western-like diet,
link |
a low fiber, higher fat diet,
link |
what happens to the gut microbiota?
link |
And we saw the microbiota change, it lost diversity.
link |
It was very similar to what we see
link |
in the difference between industrialized
link |
and traditional populations.
link |
But when we brought back a healthy diet,
link |
a lot of the microbes returned.
link |
You know, it was fairly,
link |
you know, there was this kind of memory
link |
where it went back to very similar to its original state.
link |
The difference is that when we put the mice
link |
on a low fiber, high fat diet,
link |
and then kept them on that for multiple generations,
link |
we saw this progressive deterioration
link |
over the course of generations
link |
where by the fourth generation,
link |
the gut microbiome was a fraction
link |
of what it originally was.
link |
Let's say 30% of the species only remained,
link |
something like 70% of the species had gone extinct
link |
or appeared to have gone extinct.
link |
We then put those mice back onto a high fiber diet
link |
and we didn't see recovery.
link |
So in that case, it's a situation
link |
where a new stable state has been achieved.
link |
In that case, it's probably because those mice
link |
don't actually have access to the microbes they've lost.
link |
And we actually know that we did the control experiment
link |
of mice on a high fiber diet for four generations.
link |
They maintain all their microbes.
link |
If we take those fourth generation mice
link |
with all the diversity and do a fecal transplant
link |
into the mice that had lost their microbes,
link |
but had been returned to a high fiber diet,
link |
all of the diversity was reconstituted.
link |
So it was, you know, so your question of like,
link |
how do we establish new stable states?
link |
How do we get back to a healthy microbiota?
link |
If we have taken a lot of antibiotics
link |
or have a deteriorated microbiota,
link |
it's probably a combination of having access
link |
to the right microbes.
link |
And we can talk about what that access looks like.
link |
It may look like therapeutics in the future.
link |
There are a lot of companies working on creating cocktails
link |
of healthy microbes, but it'll be a combination
link |
of access to the right microbes
link |
and nourishing those microbes with the proper diet.
link |
This multi-generational study reminds me of something
link |
that I was told early in my training,
link |
which was that it takes a long time for a trait to evolve,
link |
but not a long time for traits to devolve.
link |
Which generally is true of human behavior too,
link |
although it depends.
link |
We can all do better nonetheless.
link |
So I have a puzzle or a bit of a conundrum
link |
around this notion of species of microbiota.
link |
So if the pH, if the acidity differs
link |
along the digestive tract,
link |
but is more or less fixed for a given location, right?
link |
I mean, unless something is really off,
link |
the pH of the stomach is within a particular range
link |
and the intestine and so forth.
link |
And certain microbiota thrive at a given station,
link |
a given location along the digestive tract.
link |
And the pH is sort of fixed more or less.
link |
I'm trying to figure out
link |
what is allowing certain microbiota
link |
to stay in a given location?
link |
Why don't they migrate up or down?
link |
So are they pH sensitive?
link |
And that's what they're selecting for along the tract.
link |
And I'm also trying to figure out how these changes in food
link |
so robustly change the microbiome.
link |
The way you describe it almost makes it sound like food
link |
is the variable that's going to dictate
link |
the quality of the microbiome.
link |
Although I'm sure there are other factors as well.
link |
And then in the back of my mind,
link |
I don't know that I want to ask this question,
link |
but I really want to ask this question,
link |
which is where are they in there exactly?
link |
And why don't they all get flushed out, right?
link |
If 30% of fecal matter is microbiota,
link |
then where are they living?
link |
Are they along the lining
link |
and the little microvilli of the intestine?
link |
And what are they attaching to and interacting with?
link |
We know there are neurons in there,
link |
especially within the stomach.
link |
There's a lot of work now being done on the gut neurons
link |
and how they signal to the brain and so forth.
link |
But who are they talking to in terms of the host cells?
link |
And because if it's just from food,
link |
I imagine that they're in there
link |
having their good time or not.
link |
And then some are getting flushed out or not,
link |
but how do they actually stay in there?
link |
Who are they attaching to?
link |
What are they talking about?
link |
What are they doing for fun and so forth?
link |
Yeah, yeah, super interesting.
link |
So I'll come back to the attachment question
link |
and kind of like why they don't get washed out
link |
because this is a super fascinating question.
link |
And I think your initial point
link |
of like the kind of regional differences
link |
in what's happening in terms of physiology,
link |
biochemistry along the length of the gut
link |
is really interesting.
link |
There certainly is a pH gradient
link |
along the length of the gut.
link |
There is actually bicarbonate that's secreted
link |
into the small intestine to try to neutralize stomach acid.
link |
There also is bile that's secreted.
link |
That creates a different chemical environment
link |
and there are bile-loving bacteria
link |
that kind of live in that region of the gut.
link |
And then there is a nutrient gradient
link |
just because as food leaves the stomach,
link |
a lot of the simple nutrients are absorbed.
link |
And so you might see microbes in the small intestine,
link |
for instance, that are better at consuming simple sugars,
link |
but you won't find many microbes in the colon like that
link |
because all the simple sugars
link |
have been depleted at that point.
link |
And then the immune system is a big factor as well.
link |
And the immune system is incredibly active
link |
in the small intestine.
link |
The small intestine is this really interesting challenge
link |
for the host because it's a tissue that's been,
link |
its purpose is mainly absorptive.
link |
And so there has to be flow of a lot of things,
link |
a lot of nutrients from the luminal contents
link |
And so that means the barrier can't be as fortified.
link |
And so the immune system is incredibly active
link |
in the small intestine to make sure
link |
that microbes aren't getting so close.
link |
And if they are getting close,
link |
there's a response to them to put them back
link |
in their right location.
link |
So there's, and then along this whole kind of architecture
link |
of the gut, there's the longitudinal gradients,
link |
things like pH and so forth.
link |
And I should say that pH starts to drop again in the colon
link |
because a lot of those microbes are fermenting things
link |
and producing acids.
link |
And so you actually end up with the pH starting to drop,
link |
not as low as the stomach, but starting to drop again
link |
if there's a lot of fermentation happening in the colon.
link |
In addition, you also have a gradient
link |
from the host surface epithelium
link |
out to the middle of the gut.
link |
And that is likely the key for what is retained in the gut
link |
and how the community isn't washed out.
link |
So lining the gut, we have epithelial cells
link |
in the small intestine, they're largely absorptive.
link |
In the colon, there's a lot of mucus production.
link |
And we also see this in the small intestine.
link |
And this mucus lining is this substance that we secrete,
link |
largely made of carbohydrate actually.
link |
And the purpose of that is to keep microbes
link |
in the right spot and to allow nutrients and water
link |
to be absorbed in the small intestine and large intestine.
link |
And so it's this mesh work
link |
that is supposed to keep out large things like bacteria
link |
and lead in small things like nutrients.
link |
That mucus layer, it turns over more slowly
link |
than the luminal contents passing by.
link |
And so if a microbe learns to hold on to that mucus layer,
link |
it can actually resist the flow of the contents of the gut.
link |
And so there's many microbes in the gut
link |
that are not just good at attaching to mucus,
link |
but also good at nibbling on it, at eating it.
link |
And there are these bacteria like acromancea,
link |
muciniphila, mucus-loving, one of its main things it does
link |
is actually eat mucus in the gut, that's its lifestyle.
link |
And so there's an incredible gradient of activity
link |
from the host tissue working your way
link |
out to the middle of the gut.
link |
What's amazing is some microbes
link |
actually do penetrate past the mucus
link |
and there are these invaginations
link |
in the intestine known as crypts,
link |
actually where the stem cells live,
link |
that produce the epithelium.
link |
And there are microbial communities
link |
that can form in those crypts.
link |
And we don't know completely what their function is,
link |
but we've done some studies that appear to indicate
link |
that if you can localize to a crypt,
link |
you've hit the jackpot as a microbe
link |
for being able to maintain dominance in the gut.
link |
So if you sit in the crypt and something similar to you,
link |
another microbe that's similar to you comes into the gut,
link |
you can actually exclude that microbe.
link |
And the thinking is that it can't find a spot
link |
to resist being washed out of the gut.
link |
So there probably are these little niches
link |
close to host tissue in the mucus
link |
that are absolutely essential for resisting
link |
getting washed out with the flow of all the contents.
link |
That raises a question about two things
link |
that are reasonably popular.
link |
One is this notion of cleanses from either direction.
link |
People will consume things by mouth
link |
to try and cleanse their digestive tract.
link |
There's a long history of this.
link |
I'm not recommending this.
link |
There are differing opinions
link |
on whether or not this is good or bad.
link |
And the other is fasting or time restricted feeding.
link |
The reason I ask about time restricted feeding
link |
is my understanding is that
link |
after a prolonged period of fasting,
link |
there's some auto absorption or digestion
link |
of one's own digestive tract that then gets renewed.
link |
your intestine and stomach start eating its own lining
link |
to some extent in the absence of food.
link |
So what do we know about cleanses?
link |
Oh, and then I suppose there's cleanses
link |
from the other direction too, right?
link |
Which are less popular,
link |
but I've never run the statistics,
link |
but certainly exist out there.
link |
What's the idea about cleanses and fasting
link |
as it relates to the health
link |
or the dysbiosis of the microbiota?
link |
Yeah, you know, there hasn't been
link |
a lot of high quality science in this area.
link |
And so it's really hard to conclude
link |
whether these are good for health or bad for health.
link |
I think the fasting,
link |
we're in a really interesting situation
link |
in the industrialized world
link |
because we have so many problems
link |
associated with our digestive tract.
link |
And that probably has to do with our highly processed diet
link |
and perhaps having a microbiota
link |
that's fairly perturbed as well.
link |
whether doing things like this are good or bad,
link |
it's really hard to define
link |
because we may be starting off in a fairly bad state anyway.
link |
There are so many diseases
link |
that we're dealing with,
link |
metabolic syndrome, inflammatory bowel disease,
link |
that just put a massive portion of the population
link |
in a very different category
link |
than people that are thinking about
link |
how do I maintain health?
link |
How do I live a long life
link |
from starting off in what we consider
link |
a fairly healthy state?
link |
And so things like fasting
link |
and a lot of other therapies
link |
that have been developed in the field,
link |
I think ketogenic diet
link |
may be kind of in this category as well.
link |
There can be tremendous benefits
link |
in terms of their impact
link |
in the context of metabolic syndrome
link |
and for people that are battling,
link |
you know, eating a continual bad diet
link |
or something like that.
link |
I think one of the reasons for the popularity
link |
of intermittent fasting, time-restricted feeding,
link |
and sort of, what do they call them now?
link |
Exclusion diets where you entirely exclude meat
link |
or you entirely exclude plants or whatever it is.
link |
That adherence is sometimes easier in the all or none.
link |
As neurobiologists, we think of it as a go-no-go circuitry.
link |
It's harder to make decisions,
link |
nuanced decisions often about food
link |
than it is to just eliminate entire categories of food.
link |
Not eating for many people
link |
is easier than eating smaller portions.
link |
So some of it I think is neurobiological and psychological.
link |
And we've had gastroenterology fellows in our lab
link |
that come in and we kind of,
link |
you know, I think that to kind of slice through
link |
the nuance of all this,
link |
there's a very simple recipe
link |
and a really well-accepted kind of broad definition
link |
of what a healthy diet is.
link |
You know, kind of the Mediterranean diet, plant-based diet
link |
is, you know, there's just a ton of data
link |
that particularly people of European ancestry,
link |
but there's a pretty broad acceptance
link |
that if you eat mostly plants,
link |
for most people that's gonna be very healthy
link |
to the point where, you know,
link |
a wonderful colleague of ours, Christopher Gardner,
link |
who's studied diet his whole life,
link |
trying to establish what a healthy diet is
link |
and people was giving advice.
link |
I saw him giving advice to a dietician
link |
who was trying to get all the rules
link |
of like what she should be recommending
link |
to people that she deals with
link |
that are interested in a healthy diet.
link |
And she said, so the number one,
link |
I'm gonna say plant-based fiber is probably super important
link |
and that should be, you know, very high on the list.
link |
And she goes on to number two and he said, stop.
link |
He said, if people do number one well,
link |
you don't need to know any other rules.
link |
I mean, it's basically like,
link |
if you can have a high fiber plant-based diet,
link |
for most people, at least, you know,
link |
talking about the bucket of people
link |
that are already in a healthy state,
link |
you don't really need to think about other things
link |
because you can't eat too much meat,
link |
you can't eat too many sweets,
link |
you've already eaten a huge amount of plant-based fiber.
link |
Your gut is full, you're not gonna be hungry
link |
and it kind of takes care of worrying
link |
about what should I eat or what shouldn't I eat.
link |
Just eat a ton of whole plant, you know,
link |
whole grains, legumes, vegetables,
link |
fruit that's high fiber-based, not high sugar.
link |
Doesn't completely exclude meat and fish and dairy.
link |
And he was saying like, you know,
link |
people can add their own spins on this,
link |
but I think that the main rule is just
link |
start off with, you know,
link |
and it kind of gets back to Michael Pollan's mantra,
link |
you know, eat food, not too much, mostly plants.
link |
You know, I think if you stick
link |
with kind of these simple rules
link |
and don't overthink like, should I have this,
link |
you know, can I eat eggs, can I eat,
link |
you know, just kind of stick to these simple rules,
link |
it makes it very approachable.
link |
But I agree, like, so these gastroenterology fellows
link |
that we've had in our lab say that they,
link |
it's really hard, we kind of say to them,
link |
why won't you give this dietary advice?
link |
It's really well known.
link |
And they just said, well, it's really hard to get people
link |
to change their diet unless you're doing
link |
either a go, no go sort of thing,
link |
like, or eliminating something.
link |
So, you know, if carrots are giving you problems,
link |
don't eat carrots.
link |
And that's a very simple, easy instruction to follow,
link |
but doesn't really deal with the root problem
link |
of why can't you eat carrots?
link |
Because you should be able to eat carrots.
link |
Most people can eat carrots.
link |
And so I think that, you know, there, we, yeah, we, we,
link |
when we're thinking about things like fasting
link |
and, you know, all these different dietary regimes
link |
and cleanses that people do,
link |
we have to step back for a moment and say,
link |
okay, well, what are really the big high level rules
link |
that we should take home?
link |
And then if you are experiencing problems
link |
and you wanna think about how to deal with them,
link |
it's good to go to an evidence-based method
link |
where there's actually data to back it up.
link |
The, you know, the data in the field really shows
link |
that with like fasting, particularly if you go
link |
to like animals that hibernate or things like that
link |
where there's really extended fast,
link |
you actually have a microbiota come up that's,
link |
that blooms in the absence of food coming in through diet.
link |
That's really good at eating mucus.
link |
So you have, you know, bacteria that specialize
link |
in eating nutrients derived from the host
link |
because there's no other nutrients to live on.
link |
Now, whether this is good or bad, we don't know,
link |
but it seems like the, you know, consumption of mucus
link |
in excess is a problem from the standpoint
link |
of microbes getting too close to host tissue
link |
and inciting inflammation,
link |
which is what we see in animal models
link |
when we deprive of dietary fiber.
link |
We see these mucus utilizers become abundant
link |
and inflammatory markers start to come on.
link |
So fasting short-term might be fine.
link |
Probably, you know, there's definitely benefits
link |
that are seen metabolically.
link |
In terms of what it means for long-term health
link |
from the standpoint of the gut microbiota,
link |
I would say we don't have the answer to that yet.
link |
In terms of the, you know, the cleanses and the flushes
link |
and all this, personally, I think it's a terrible idea.
link |
I mean, we know that like if, you know,
link |
in studies that are being done now
link |
to reprogram the gut microbiota
link |
to install a completely new microbial community,
link |
the first step is to wash away
link |
the resident microbial community that's there.
link |
So if you're in the process
link |
of acquiring a really good microbiota
link |
and you know how to do that,
link |
then the flushing everything out is great.
link |
Otherwise, what is happening is you're kind of leaving
link |
rebuilding of the community to chance, like, what is it?
link |
And so, you know, what microbes are gonna colonize,
link |
who's gonna take up space after you do this flush or cleanse
link |
and, you know, that I think it's a little bit
link |
like playing Russian roulette.
link |
You may end up with a good microbial community
link |
in there afterwards.
link |
You certainly want to pay close attention
link |
to what you're eating
link |
while you're doing the reconstitution of the community
link |
after you do something like that.
link |
Thank you for that.
link |
I know a lot of people are interested
link |
in these kinds of elimination diets
link |
and intermittent fasting slash time restricted feeding
link |
seems to be getting some traction in part
link |
because at some level, we are all doing this when we sleep.
link |
Most of us aren't eating while we sleep anyway.
link |
And adjusting the numbers seems more accessible
link |
for a lot of people.
link |
We have a lot of colleagues at Stanford
link |
who I know happen to follow that regimen
link |
or a time restricted feeding regimen,
link |
but also some who follow
link |
the more traditional meal spacing as well, of course.
link |
One of the things that I wonder about as we talk about
link |
primarily plant-based with some, you know,
link |
what did you say the pollen thing was?
link |
It was eat mostly plants and then maybe some meat,
link |
but not too much or not too much.
link |
Eat food, mostly plants, not too much.
link |
Or sorry, eat food, not too much, mostly plants.
link |
You know, and just, I hear this again and again.
link |
I know there are a number of people
link |
who do seem to do well on a lower carbohydrate,
link |
you know, even some people who report feeling much better
link |
on a like really strictly almost meat organ only diet.
link |
And the only reason I raise this is not,
link |
I don't participate in any other,
link |
I'm one of those omnivores out there.
link |
I do eat some meat and I do eat plants as well.
link |
But the reason I raise this is that earlier
link |
you were talking about communities
link |
that may have microbiota that are healthier than ours
link |
or at least different than ours.
link |
And there are communities in the world
link |
that subsist largely on animal products
link |
or for which unprocessed animal products
link |
are considered the richest nutrient foods
link |
in those communities.
link |
Protein is very scarce and ancestrally protein
link |
So eggs and meat and things of that sort.
link |
So could there be a genetic component?
link |
In other words, if we fast forward 10 years
link |
and we actually can make sense
link |
of all this human genome stuff,
link |
are we going to find that someone
link |
who has Scandinavian roots
link |
or somebody who has South American roots
link |
or somebody had descended from a different tribe
link |
will do better on one particular diet versus another
link |
and thereby, or I should say, and in parallel with that,
link |
that their gut microbiome will have different signatures
link |
that are, so your microbiome might thrive on plants
link |
and mine might thrive on organ meats.
link |
And as I say this, I'm not a big consumer of organ meats.
link |
I'm just laying this out for sake of example.
link |
Yeah, yeah, great.
link |
The first one has to do with the carbohydrates
link |
and restriction of carbohydrates
link |
and some people feeling healthier
link |
when they cut carbohydrates out.
link |
My guess is, this is my theory to be tested,
link |
that people feel better cutting carbohydrates out
link |
because the diet that we eat in the United States
link |
and in industrialized countries,
link |
the carbohydrates are largely crap.
link |
They're processed.
link |
It's like starch, simple sugar.
link |
It's things that contribute to glycemic index.
link |
It's these sugars that we eat.
link |
They make it to our small intestine.
link |
They get chopped up into simple sugars
link |
absorbed into our bloodstream
link |
and we have a ton of glucose then coursing through our veins
link |
which we know is bad and can lead to things like diabetes.
link |
If the carbohydrates that were in our diet
link |
were complex carbohydrates, dietary fiber,
link |
and we like to refer to the subset of dietary fiber
link |
that the microbiota can actually access
link |
as microbiota accessible carbohydrates
link |
and the reason that we like that term
link |
is it has the word carbohydrate in it
link |
and it's to point out that not all carbs are bad.
link |
It's just there are bad carbs or carbs that are bad
link |
if you consume them in too high a quantity,
link |
things like table sugar and simple starches
link |
but there are good carbs as well
link |
and these microbiota accessible carbohydrates
link |
are the complex ones that we can't digest
link |
and fuel our gut microbiota,
link |
our gut microbiota can ferment them
link |
and so I think we probably all would be better off
link |
with less of the carbs that were typically served
link |
but most of us and probably the vast majority of us
link |
would be better off by consuming a lot more carbs
link |
that were complex, that were microbiota accessible
link |
and I'll come back to why that's important
link |
in terms of our biology.
link |
There are some mechanisms that are known
link |
as to why those complex carbohydrates
link |
are so important for our health for most of us.
link |
I think this aspect of human genetic adaptation to diet
link |
is super interesting and then layer on top of that
link |
gut microbiota adaptation to diet
link |
which is another layer of this that is also fascinating.
link |
It's very clear that over very short periods of time,
link |
humans can adapt to differences in their diet.
link |
Lactase persistence is kind of the classic example of this.
link |
Just over the past 10,000 years,
link |
humans, certain groups of humans have adapted
link |
to being able to consume dairy by taking this enzyme,
link |
lactase, that normally is just expressed
link |
in most of the world's population early in life
link |
to be able to metabolize lactose in breast milk.
link |
By extending the expression of that throughout life,
link |
now you can consume milk for your whole life
link |
and so that is an example of specific populations
link |
of human genome genetically adapting to diet
link |
in a very short period of time.
link |
And there are other examples of this
link |
and undoubtedly this has happened throughout the world
link |
to various aspects of diet.
link |
So certainly it's important to remember
link |
that there will be different diets
link |
that are better for different groups
link |
based on what genes you harbor
link |
and have in your human genome.
link |
The other aspect on top of that is that
link |
there are good examples of the gut microbiome
link |
adapting to cultural differences in diet.
link |
And the classic example of this
link |
is the degradation of seaweed.
link |
So we know that most Americans,
link |
if you eat sushi and there's nori there
link |
and you eat some of this seaweed,
link |
it has a dietary fiber in it known as porphyrin.
link |
That porphyrin will shoot through most of us untransformed.
link |
Inert substance, it'll do other things like retain water
link |
and serve as kind of something like cellulose,
link |
not be fermented at a high level.
link |
If somebody from Southeast Asia
link |
that's always consumed seaweed
link |
and is part of a culture that consumes seaweed,
link |
eats seaweed, they have a gut microbe
link |
that can now metabolize porphyrin.
link |
And so there are these very specific gene transfer events
link |
where the genes for breaking down porphyrin
link |
have been imported into the microbiome
link |
of many people in Southeast Asia to...
link |
We can think of it as helping digest porphyrin,
link |
but it's really just a microbe that's found a niche,
link |
found a way to make a living in the gut
link |
by consuming something that's common in the diet there.
link |
So there are these different layers.
link |
There are human genetic adaptations
link |
and there are microbiome adaptations that are cultural
link |
and based on people's geographic location.
link |
But there's no escaping the fact
link |
that for much of human evolution,
link |
the vast majority of people that are on this planet
link |
had ancestors that were hunter-gatherers,
link |
foraging, consuming huge quantities of plant material,
link |
just because that's what was there.
link |
And so one of the groups that we study,
link |
the Hadza hunter-gatherers in Africa,
link |
and I should take a moment just to say that
link |
our research and research of many people in our field
link |
and other fields rely on study of indigenous communities.
link |
And it's really important to think of these communities
link |
They're modern people on the planet.
link |
They have interesting lifestyles that are informative
link |
with regard to certain aspects of human biology.
link |
But in many cases, they also are leading vulnerable existence.
link |
And so we really take great care in our research program.
link |
And it's important for people to realize
link |
that these populations take partner research
link |
because they're wonderful research partners.
link |
And we need to be mindful of kind of thinking about how,
link |
yeah, both we talk about them and use our data
link |
that has been gained through their generous contribution
link |
to our research program.
link |
The Hadza hunter-gatherers, it's estimated,
link |
consume on the order of 100 to 150 grams
link |
of dietary fiber per day.
link |
And that's in stark contrast to the typical American
link |
that consumes about 15 grams.
link |
So somewhere seven to tenfold decrease in the main nutrient
link |
that feeds our gut microbiome in the American diet.
link |
The Hadza are, you know, one example.
link |
There are many different foraging populations,
link |
but the vast majority of these populations
link |
consume huge amounts of dietary fiber
link |
because plants are the reliable, consistent source.
link |
You know, if you, as a hunter-gatherer, go on a hunt,
link |
usually that hunt is unsuccessful.
link |
You know, I think the data that, you know,
link |
one out of 20 to 30 hunts are successful
link |
in landing actually big game for the Hadza.
link |
They have, you know, birds that they shoot and small animals.
link |
But quite often, day after day,
link |
they're relying upon berries, tubers, baobab fruit.
link |
You know, they're relying on the plants in their environment.
link |
And actually, if you go to the data
link |
and look at what their food preferences are,
link |
their food preferences are actually meat and honey.
link |
So they don't eat a high-fiber diet because they love fiber.
link |
They eat a high-fiber diet because that's what's available
link |
and consistent for them to survive.
link |
But, you know, our brains are wired for caloric density.
link |
And so if you took a Hadza and put them in a restaurant
link |
in the United States, they would make the same crappy decisions
link |
that we make because we, you know,
link |
all want sugar and fat and calories.
link |
It's how our brain is wired.
link |
And protein and fat are essential for brain development
link |
as far as we know, right?
link |
So it sounds like the Hadza,
link |
I hope I'm pronouncing that correctly.
link |
Oh, you said would prefer to eat meat and honey,
link |
but they happen to consume a lot of plant fiber
link |
as a consequence of what's available.
link |
One of the questions I have as it relates to all of this,
link |
is it sounds to me like there is no question
link |
from the pure vegan all the way to the extreme opposite,
link |
which would be pure meat diet,
link |
that avoiding processed foods is a good idea
link |
or heavily processed foods in general.
link |
And I mean, not that, you know,
link |
the occasional consumption is necessarily bad,
link |
but whether or not one is thinking
link |
about one macronutrient profile or another,
link |
it sounds like consuming processed foods
link |
is just bad for the microbiome.
link |
Can we say that categorically?
link |
Whether, you know, so you're low carb person,
link |
you're zero carb person, you're extreme vegan, no meat,
link |
whether or not you're all meat, organ meat,
link |
sounds to me as if the number one thing,
link |
maybe even dare I say above Chris's point about plants,
link |
although I'm not going to challenge Chris Gardner
link |
on nutrition, I would be way outside the lane lines
link |
But is it to avoiding processed foods is paramount?
link |
Yeah, and I think that's completely compatible
link |
with what Christopher was saying.
link |
He was saying, if you prioritize getting a huge amount
link |
of whole plant-based food with a lot of fiber first,
link |
you're not going to have room
link |
for eating a lot of processed food.
link |
So it's kind of the same as avoiding processed food.
link |
So I think that those are exactly the same rule.
link |
And I think that you're exactly right.
link |
And we can break down, you know,
link |
there's a lot of data of why different components
link |
of processed food are so bad for us
link |
and so bad for our microbiome.
link |
And I can talk about a few examples of that.
link |
But the flip side of this is this mechanism of,
link |
you know, and again, thinking about the spectrum
link |
of a plant-based diet versus a meat-based diet,
link |
you know, there's a lot of data to tell us that meat
link |
or ketogenic or high-fat diet may have big benefits
link |
in terms of short-term metabolic health.
link |
That's typically how people think about that diet.
link |
There's also a lot of heart disease
link |
that's linked with that as well.
link |
There's good literature for that,
link |
which is something for people to look at and be aware of.
link |
The plant-based diet, if you're eating a bunch
link |
of complex, you know, fibers that feed your gut microbiota,
link |
your gut microbiota produces these substances
link |
called short-chain fatty acids, things like butyrate.
link |
And it's known that these short-chain fatty acids
link |
play really essential components,
link |
both in terms of fueling colonocytes,
link |
enforcing the barrier, keeping inflammation low,
link |
regulating the immune system, regulating metabolism.
link |
And so, you know, a lot of people think of dietary fiber
link |
as this inert substance that passes through,
link |
makes us feel full maybe for a little bit,
link |
but we get hungry afterwards right away.
link |
If you're eating a lot of fiber
link |
that's feeding your gut microbiota,
link |
your gut microbiota is just producing this vast array
link |
of fermentation and products that then get absorbed
link |
into our bloodstream and have all of these tremendous
link |
cascading effects that appear to be largely beneficial
link |
And so to think about that paradigm of simple carbs
link |
versus complex carbs, in the case of simple carbs,
link |
you end up with high blood sugar, you know,
link |
something that will spike your insulin and, you know,
link |
have all kinds of weird metabolic effects.
link |
In the case of complex carbohydrates,
link |
you'll end up with very low blood sugar
link |
because most of those have low glycemic index
link |
and a bunch of short-chain fatty acids
link |
that are having regulatory rules.
link |
So just to round out that topic,
link |
I think there is a reason to think that, you know,
link |
maybe not appropriate for absolutely everyone out there,
link |
but I think the vast majority of people,
link |
particularly given the statistics of what we know
link |
people eat in the United States
link |
and in industrialized countries,
link |
most people would reap tremendous health benefits
link |
from eating more whole plant-based dietary fiber.
link |
Now, processed foods, I think, is this other dimension
link |
where you have all of these weird chemicals,
link |
artificial sweeteners, weird fats, you know,
link |
a lot of refined simple nutrients.
link |
The simple nutrients we've talked about,
link |
but we know that, for instance, artificial sweeteners
link |
can have a massive negative impact on the gut microbiome
link |
and can lead us towards metabolic syndrome, actually.
link |
There's been beautiful work
link |
out of the Weizmann Institute on this.
link |
And then emulsifiers, these compounds
link |
that are put in processed foods
link |
to help them maintain shelf stability
link |
so things don't separate and so, you know,
link |
all the moisture content is retained appropriately.
link |
Many of these are known to disrupt the mucus layer,
link |
and as soon as you start disrupting that barrier,
link |
that can lead you in the direction of inflammation
link |
and in animal models, we know that can lead
link |
towards metabolic syndrome as well.
link |
So there's components of processed food
link |
that are, when studied in isolation,
link |
known to have a direct negative impact
link |
on gut biology and the microbiota.
link |
The mention of artificial sweeteners is interesting.
link |
I confess, it's a third rail on social,
link |
talking about artificial sweeteners,
link |
there are two camps, it seems, or at least two camps,
link |
one that say artificial sweeteners
link |
are not detrimental at all,
link |
another that says they're very detrimental,
link |
mainly based on the mouse studies,
link |
and then there are people in the middle
link |
that are, I put myself in that category,
link |
I drink the occasional diet soda,
link |
I don't consume them in large volume,
link |
but I'm sort of in the middle there.
link |
However, and so I just throw that out there
link |
because I know immediately people are jumping on that,
link |
but I will just mention there's some recent data
link |
out of Diego Borges' lab at Duke University
link |
that the neurons that live in the gut mucosa,
link |
these neuropod cells can actually distinguish
link |
between artificial and true sweet,
link |
sugar versus artificial sweeteners.
link |
They send different patterns of neural signals
link |
up to the brain and the brain circuitry
link |
seems strongly impacted.
link |
So I think that as the data emerge,
link |
we're hearing more and more of these artificial sweeteners
link |
either are problematic or at least are signaling
link |
different events in the gut.
link |
I do want to make sure that we distinguish
link |
artificial sweeteners from non-caloric plant-based sweeteners
link |
and this is based on a mistake that I've made
link |
over and over again on the podcast
link |
where I'll just kind of lump artificial sweeteners
link |
into one big category and then I'll mention stevia.
link |
So what about plant-based sweeteners
link |
that are not artificial?
link |
They weren't manufactured in a laboratory
link |
like saccharin or sucralose or aspartame.
link |
Do we know anything about plant-based non-caloric sweeteners
link |
or low-caloric sweeteners?
link |
A lot of those have a lot more bang for the buck.
link |
They're incredibly sweet so it takes a really small amount
link |
for them to trigger a huge amount of sweetness.
link |
And so it's depending upon the mechanism of action
link |
by which these sweeteners that are not sugar
link |
are impacting our biology.
link |
It may be that those are actually less negative
link |
or more healthy than the ones that are artificial
link |
just because it requires less of them in the food
link |
for us to perceive that sweet taste.
link |
It may also be that because they're,
link |
I don't think that everything that's natural
link |
is better necessarily than things that are artificial
link |
but it may be that because of kind of evolutionary exposure
link |
to these compounds in our diet,
link |
historically there are I think traditional populations
link |
that use these for instance to sweeten different foods
link |
that our bodies just kind of know how to deal
link |
with those compounds better than the ones
link |
that are synthetic.
link |
But I think the studies still need to be done.
link |
Do you actively avoid artificial sweeteners,
link |
sucralose, aspartame, saccharin, you personally?
link |
I avoid them but I'm not,
link |
so I work closely with my wife Erica as you know.
link |
We were in the lab together and we wrote this book,
link |
The Good Gut, where we kind of document our journey
link |
in changing our lifestyle, dietary habits,
link |
choices we make based on the research
link |
as we've gotten to know it in the gut microbiota
link |
over the past 15 years.
link |
And I think that one of the lessons that we've learned
link |
is that just doing things in moderation
link |
makes it a lot easier
link |
and doing things slowly makes it a lot easier.
link |
And so there are very few rules that I have
link |
that are hard and fast.
link |
I'm a pretty flexible eater.
link |
I don't believe that having an artificial,
link |
having a diet Coke will somehow cascade
link |
into some terrible disease or something like that.
link |
I try to avoid them.
link |
I don't really like the flavor of them.
link |
I'm super sensitive to the nuances of the flavor
link |
even with the stevia and magra sites from monk fruit
link |
and stuff like that.
link |
The off flavors are really hard for me to deal with.
link |
But I also in this journey of changing our diet,
link |
when we started off in microbiome research,
link |
I was in the habit of, in the afternoons,
link |
having a sweet, a muffin or a cookie or something like that.
link |
And when we started to realize
link |
that we should be eating less sweets
link |
and eating more dietary fiber,
link |
this was an incredibly difficult change for me to make.
link |
I was just wired to kind of crave this.
link |
Classic scientist.
link |
Scientists love the pastry in the afternoon and the coffee.
link |
And in the old days, it used to be a cigarette too.
link |
When I started my training,
link |
a lot of people still smoked.
link |
And it was only during my postdoctoral training
link |
that they eliminated smoking on campuses.
link |
And productivity took a trough for a while.
link |
And until these people developed other tools
link |
to focus their attention.
link |
So there is this kind of like need.
link |
And then once you have an ingrained behavior
link |
and maybe things that are addictive,
link |
it becomes incredibly difficult to break that habit.
link |
And so I would say gradually over the course of like,
link |
you know, five or more years,
link |
we have, you know, migrated our diet away from sweet foods
link |
to things that are less sweet.
link |
And it's, you know, it's been a journey.
link |
It's been a slow process.
link |
But we've gotten to the point now
link |
where we've just retrained our palates.
link |
And it's amazing how this happens now
link |
where I'll have something that, you know,
link |
is something that I would have used to have like daily.
link |
And it's unpalatable.
link |
I like, I just can't deal with the sweetness of it.
link |
And so I avoid, I certainly avoid artificial sweeteners,
link |
but I also avoid just sweet things in general
link |
that have sugar in them,
link |
just because they now, they, you know,
link |
as originally I was trying to be disciplined
link |
and trying to change my diet,
link |
but now they just don't taste good to me.
link |
I completely lost my appetite for sugar
link |
at the turn of the last year.
link |
And I don't know how to explain it,
link |
but the way I, even though
link |
I don't have a mechanistic explanation,
link |
I just, I say, I like sweet people.
link |
I don't like sweet food anymore.
link |
I have not lost my appetite for fatty foods.
link |
I love cheese and certain meats for me.
link |
I blame my Argentine lineage as I gravitate towards them.
link |
But in any case, avoiding processed foods,
link |
probably avoiding sugars, emulsifiers,
link |
these kinds of things.
link |
And for people listening or watching,
link |
we're not setting up strict guidelines.
link |
We're just bouncing around the carnival
link |
that is the microbiome and nutrition,
link |
because I think that these,
link |
we hear this everywhere, eat this, don't eat that,
link |
or this is best for microbiome or worse for microbiome,
link |
but I'm hearing fiber again and again.
link |
So we're going to come back to fiber,
link |
but I want to make sure that we close the hatch
link |
on this issue of fasting and cleansing.
link |
Based on your answer earlier,
link |
it sounds to me like it is not necessary
link |
to do a cleanse or fast prior to an attempt
link |
to repopulate the microbiome.
link |
In other words, if I want to make my microbiome healthier,
link |
it sounds like I don't have to try
link |
and flush all the current microbiota out of there first.
link |
Yeah, it's a very good question.
link |
And I don't mean to suggest that those things
link |
are known to be terrible,
link |
or I would just say the studies haven't been done.
link |
And to me, wiping out this microbial community,
link |
unless it's done with some sort of,
link |
unless it's done in an informed way,
link |
and we don't really have the information
link |
for how that would be done,
link |
it just seems like playing the lottery a little bit.
link |
And so I think, I don't want to say that those,
link |
it may be that when the study is done,
link |
those are shown to be amazing,
link |
but I just don't think we have the data to know that yet.
link |
So it's somewhat of an arbitrary thing.
link |
If somebody out there feels way better when they do this
link |
and are not experiencing problems with it,
link |
then maybe it's the right thing for them.
link |
But I certainly can't say that it's something great to do.
link |
I can't imagine a future where as the microbiome
link |
gets incorporated into this emerging paradigm
link |
of precision health, you go into a clinic,
link |
somebody types your microbiome and says,
link |
oh, there's this huge, massive misconfiguration.
link |
You have all these engrafted bacteria that live
link |
that are residents in your gut microbiome
link |
that are sending out molecules
link |
that are not good for your health.
link |
It would be good if we do a mass reprogramming of it.
link |
The way that we do that is we flush your gut
link |
and we actually give a light antibiotic treatment
link |
to try to kill everything that's there.
link |
And then we repopulate with this other consortium
link |
of microbes that we've studied and know are healthy,
link |
know are compatible with your human genome
link |
and can be reinforced with a diet
link |
that we know is good for you.
link |
We'll install those microbes.
link |
We'll help you along in the diet
link |
so you know how to nourish those microbes.
link |
And that will be the way that we'll reconfigure
link |
your gut microbiome.
link |
So I can't imagine a future where that sort of flushing
link |
or cleansing is part of something for repopulating the gut.
link |
But right now it seems a little half-baked to me, yeah.
link |
I'd love to talk about fiber and fermented foods
link |
because you and Chris had a really,
link |
what I think is a really interesting and exciting paper
link |
at the end of last year about comparing the inflammatome,
link |
so inflammatory markers of people
link |
who ate a certain amount of fiber
link |
or a certain amount of these fermented foods.
link |
This study is amazing for several reasons,
link |
but almost as amazing is how diverse the interpretation
link |
of this study was in the media.
link |
If ever there was a study that was kind of hijacked
link |
by different priority schemes out there, it's this study.
link |
So you performed the study with Chris
link |
and your postdocs and graduate students and staff.
link |
What are the major conclusions
link |
and what sorts of directives, if any,
link |
emerge from this study?
link |
And I'll just preface this again by saying,
link |
if I wasn't clear, some news reports said,
link |
ah, this means fiber is not important.
link |
And then others said, this means fermented foods
link |
and fiber are important.
link |
And others said, fermented foods are the thing
link |
and the only thing, it was all over the place.
link |
And one of the reasons for doing this podcast at all
link |
is so that we can go straight to the people
link |
who perform the work.
link |
And even though I'm certainly not an expert in microbiome,
link |
give you the opportunity to share with me
link |
and me to ask the kinds of questions
link |
that I have zero agenda.
link |
I do like sauerkraut.
link |
I do drink the occasional kombucha.
link |
I do like low sugar, not so sweet forms of fermented foods.
link |
So I would be delighted if fermented foods are good for me,
link |
but I have no steak in the fermented food industry.
link |
And an important note there is the one you pointed out
link |
that this is an incredible collaboration
link |
with Christopher Gardner's lab and a bunch of people.
link |
Erika Sonnenberg helped lead this study
link |
and then tons of, like you were saying, postdoc staff
link |
and other people at Stanford
link |
and then wonderful participants
link |
that were part of this study.
link |
So a huge team effort.
link |
Before I dive into that study, let me take a step back
link |
because I think the reason that we did this study
link |
and kind of Christopher's group and our group
link |
has started to pursue this line
link |
of looking at dietary interventions
link |
and how they impact our microbiome,
link |
how they impact human biology
link |
goes back to this kind of epiphany that we had
link |
while studying the gut microbiome
link |
because I think when we started studying it at Stanford,
link |
we were thinking about it
link |
as this kind of newly appreciated aspect of our biology,
link |
almost like finding an organ that we didn't know was there
link |
and starting to think about all the drug targets
link |
Can we go in with small molecule drugs
link |
and think of ways to manipulate this community
link |
to ameliorate disease?
link |
And this is largely the mindset of Western medicine
link |
and largely born out of the era of infectious disease.
link |
You wait for an infection to start a bacterial infection,
link |
you treat with antibiotics
link |
and that's the way medicine is practiced
link |
and that's become less successful over time
link |
as we've moved into this era
link |
of inflammatory Western diseases
link |
and with the exception of the current pandemic
link |
that's sweeping the world,
link |
largely moved out of the era of infectious diseases,
link |
at least infectious bacterial diseases,
link |
that this paradigm of waiting for diseases to appear
link |
and come into the clinic is not really very effective
link |
in the context of inflammatory Western diseases,
link |
autoimmune diseases, metabolic syndrome,
link |
heart diseases and inflammatory disease,
link |
the list goes on and on.
link |
And so we started to think a lot about
link |
how can we get out in front of this?
link |
How can we think about like preventative ways
link |
of dealing with this crisis
link |
of metabolic and inflammatory diseases
link |
and this tremendous beautiful body of literature
link |
started to come forward in the field about 10 years ago
link |
that showed that the gut microbiome is absolutely critical
link |
to modulating our immune status.
link |
So if you change the microbiome,
link |
you can fundamentally change how the immune system operates.
link |
And we know that the immune system is at the basis
link |
of a lot of these diseases, inflammatory, chronic diseases.
link |
And so it brought up this possibility
link |
that maybe the fact that we're not nourishing
link |
this community well enough,
link |
maybe the fact that it's deteriorated over time
link |
due to all of the things that go along
link |
with an industrialized lifestyle, antibiotics and so forth,
link |
maybe we have a microbiome right now
link |
in the industrialized world
link |
that is setting our immune system at a set point,
link |
simmering inflammation that's driving us
link |
towards these inflammatory diseases.
link |
And wouldn't it be wonderful if we could figure out
link |
how to use diet specifically,
link |
but just kind of learn the rules of how to reconfigure
link |
both the composition and function of our gut microbiome
link |
so that inflammation was different in our bodies
link |
so that each one of us was less likely to go on
link |
and to develop an inflammatory disease
link |
leading to better longevity and health
link |
over the course of our life.
link |
And so we were studying this actually in mouse models
link |
and realizing that we really needed
link |
to start doing human studies.
link |
We needed to start studying microbiome in humans.
link |
And because we were studying diet,
link |
we knew that this was something
link |
we could go in and do right away.
link |
We didn't have to apply for FDA approval for a drug
link |
before we could do a human study.
link |
We could just start doing human dietary interventions,
link |
longitudinally monitoring the immune system
link |
and the microbiome and starting to put the pieces together
link |
of what is it in diet that can change our microbiome
link |
in a healthy way, help us define what a healthy microbiome is
link |
and monitor the immune system in great detail.
link |
And so there were really two critical components of this
link |
in addition to our microbiome expertise.
link |
One was Christopher Gardner's group.
link |
We wanted to do these human studies,
link |
but we're absolutely terrified of humans.
link |
We work with mice, humans are terrifying in many ways.
link |
But they house themselves.
link |
You don't have to pay for their housing.
link |
That's true, yeah.
link |
For those that can afford housing, of course, yeah.
link |
Yeah, sadly, just for that portion of the population.
link |
So Christopher's group,
link |
they are masters at working with human populations.
link |
And then the other wonderful thing that we have at Stanford
link |
is this Human Immune Monitoring Center
link |
run by Mark Davis and Holden Maker.
link |
They started this beautiful center
link |
for allowing people to do immunology in humans.
link |
Critical element because a lot of the mouse studies
link |
don't translate well to humans.
link |
So if you can do the studies in humans,
link |
similar to how we're thinking about the microbiome,
link |
you learn something that you know is relevant to humans.
link |
And so having that immune profiling capability
link |
where we can monitor hundreds to thousands
link |
of different parameters in the immune system longitudinally
link |
in people from a blood draw,
link |
and not just know if CRP goes up
link |
or if interleukin-6 goes up or down,
link |
but to be able to see all these facets
link |
of the immune system change in concert
link |
as we're changing the microbiome with diet
link |
was really a key component of this.
link |
And so our flagship study supported by wonderful donors,
link |
so this actually isn't funded by typical foundations
link |
and National Institutes of Health.
link |
It was funded by philanthropy.
link |
We wanted to understand
link |
if we put people on a high fiber diet,
link |
how would that affect their microbiome and immune system?
link |
And if we put them on a high fermented food diet,
link |
a diet rich in live microbes and all the metabolites
link |
that are present from fermentation and foods,
link |
how would that change microbiome and immune system?
link |
Could you give us some examples
link |
of what those diets look like?
link |
And were you changing their basal diet
link |
or were you just adding things on top
link |
of what they were already eating?
link |
Because it's hard to change people's diets.
link |
And you have to trust that they actually do it
link |
and they're not sneaking and-
link |
And so we've started
link |
the Center for Human Microbiome Studies at Stanford
link |
for doing a lot of these studies.
link |
And a portion of the studies we do focus on supplements,
link |
probiotics, microbes delivered in pill form,
link |
prebiotics, which are purified forms of fiber.
link |
And in those cases, we actually can have placebo groups
link |
because it's more like a drug study
link |
and we don't change people's diets.
link |
So we can just administer this on top of what they're doing.
link |
So in a way, they're a lot more controlled,
link |
but it's not food.
link |
When you start doing food studies,
link |
you can't do a placebo group
link |
because people know what they're eating.
link |
And the other problem is that
link |
it's really hard to just change one thing
link |
because as soon as you start adding something,
link |
people usually eliminate something else.
link |
So the idea was to basically give these people
link |
simple instructions for, in the case of the high fiber diet,
link |
just increasing plant-based fiber.
link |
So can you eat more whole grains,
link |
more legumes, more vegetables, nuts,
link |
get the fiber up in the range of,
link |
from 15 to 20 grams per day, up to over 40 grams per day.
link |
So can you kind of double or more
link |
the amount of fiber that you eat per day,
link |
knowing that that would have a tremendous impact
link |
on a lot of other facets of their diet.
link |
They eat less meat, animal-based protein,
link |
less animal-based fats as a product of this.
link |
I will say that getting back to Christopher's rule
link |
for a healthy diet, a lot of the macronutrient changes
link |
that we saw in their diet were consistent
link |
with healthy changes in diet, less saturated fat,
link |
less animal-based protein, more plant-based protein.
link |
So a lot of changes that are known to be beneficial
link |
kind of came in concert with just telling people
link |
to eat a high fiber diet, high plant-based fiber diet.
link |
The people that were eating the high fermented food diet,
link |
they were instructed to basically eat
link |
foods that you could buy at a grocery store
link |
that were naturally fermented and contain live microbes.
link |
And so this largely consisted of yogurt,
link |
kefir, sauerkraut, kimchi, some fermented vegetables,
link |
kind of brined fermented vegetables, pickles,
link |
things like that, but one of the things
link |
that I think is a pitfall in choosing fermented foods
link |
is you can go down the canned food aisle
link |
and there's this huge section of pickles
link |
and jars that are canned.
link |
Those are not fermented foods.
link |
Those are cucumbers that they've put in,
link |
acetic acid and vinegar to reconstitute
link |
that fermented flavor, but there's no live microbes
link |
And even sauerkrauts in the canned food aisle,
link |
even if they were naturally fermented,
link |
quite often they're not.
link |
Quite often they're just brined in vinegar,
link |
but even if they are naturally fermented,
link |
all of the microbes are killed prior to canning
link |
or during the process of canning.
link |
And so what we use for this study,
link |
and if you want to have live fermented foods
link |
that contain live microbes, you need to buy those
link |
out of the refrigerated section, essentially.
link |
And I'm really glad you pointed this out
link |
because you can find sauerkraut on the non-refrigerated shelf
link |
that is indeed non-fermented.
link |
A lot of fermented foods that are available in the US
link |
can be high in sugar.
link |
So was there any instruction as to getting people
link |
to make sure that they were consuming yogurts
link |
that weren't loaded with sugar,
link |
or did you let them just select for the stuff in the cold,
link |
the cold section that is fermented?
link |
No, it's a super important point, we instructed people
link |
to eat non-sweetened yogurts.
link |
I think a huge pitfall in this area
link |
is you can have a yogurt loaded with bacteria,
link |
kind of the base of what's healthy,
link |
and then a ton of artificial flavoring
link |
and sugar loaded on top of that.
link |
Manufacturers put a ton of sugar in after the fact
link |
to kind of mask the sour taste of fermented foods,
link |
which is hard for some people to become accustomed to.
link |
When we were switching to more fermented foods,
link |
our daughters were young at that point,
link |
we would take plain yogurt, which they didn't like,
link |
just kind of neat.
link |
We would mix in a little maple syrup or honey,
link |
just a little bit, and gradually we reduced that over time
link |
to the point where they're palate adjusted
link |
and now they just really like plain yogurt.
link |
But I think getting used to that sour flavor is difficult,
link |
but people really should try to stay away
link |
from those fermented foods that are loaded with sugar,
link |
and that's what we instructed people in the study.
link |
And beer was not included, right?
link |
There were a number of people that asked
link |
when I did a brief thing on social media about this study
link |
and hopefully I got it right, I think I did,
link |
but people just ask about beer.
link |
I'm not a drinker, so for me, beer has no appeal anyway,
link |
but beer is fermented, correct?
link |
But were they instructed to avoid beer or to drink beer?
link |
Just to go with their normal dietary habits,
link |
but that did not count as a fermented food.
link |
And kombucha was, as I recall.
link |
Kombucha was, and kombucha can have
link |
small amounts of alcohol in it.
link |
But kombucha actually was one of the major things
link |
that people consumed during the fermented food phase.
link |
And the deal with beer is that there may be
link |
beneficial properties of the microbial communities
link |
in naturally fermented beer, but most of the beer
link |
that we buy, again, is canned and filtered
link |
and there's no live microbes there.
link |
So very different than if you siphon it off of your homebrew
link |
and drink it, probably, than if you buy it in a store.
link |
I will get to the results of the study in just one moment,
link |
but I want to say a lot of people shy away
link |
from the high quality fermented foods
link |
because they can be quite costly.
link |
I'll just refer people to a resource
link |
in Tim Ferriss' book, The 4-Hour Chef.
link |
He actually gives an excellent recipe
link |
for making your own sauerkraut,
link |
which basically involves cabbage and water and salt,
link |
but you have to do it properly because you can grow some,
link |
not necessarily lethal, but some somewhat dangerous bacteria
link |
if you don't scrape off the top layer properly.
link |
But he gives beautiful instructions
link |
for how to do this in vats.
link |
We've started doing this at home now, actually,
link |
which is a ceramic vat.
link |
And so you can make large amounts
link |
of truly fermented sauerkraut
link |
just from cabbage, water, and salt
link |
if you're willing to follow the protocol.
link |
And if you're interested in science,
link |
that protocol looks a lot like what you'll do
link |
for most of your graduate career,
link |
except maybe some sequencing too.
link |
So anyway, just to refer people to a source
link |
that's very low cost compared to buying
link |
the high quality fermented foods.
link |
Even kombuchas, for some people,
link |
it's like $5 a bottle, only this much.
link |
And if you consume liquids the way I consume them,
link |
that's just the start.
link |
But if you can get your hands on a scoby,
link |
kombucha is another one that's super simple.
link |
You can grow your own.
link |
You can just make your own and it's super easy to do.
link |
I make it, I constantly have a batch
link |
of kombucha going at home.
link |
And it's just, you know, it's a scoby,
link |
a symbiotic community of bacteria and yeast
link |
that you brew tea, you add sugar to it,
link |
and you put the scoby in and you wait a week or two,
link |
depending upon the temperature.
link |
And then you just move the scoby over to a new batch
link |
What the scoby was in is kombucha and it's wonderful.
link |
I would love it if members of this audience
link |
would start to make their own kombucha and sauerkraut.
link |
I've been having so much fun.
link |
I don't do it, but you know, it's done in our home.
link |
I don't go anywhere near the food production
link |
and it's for everyone's benefit.
link |
So how much fermented food and then were they consuming?
link |
And, cause you mentioned the number of grams,
link |
approximately, of fiber,
link |
but was it in servings, ounces,
link |
how many times a day, early day, late day?
link |
Right, yeah, so we had a wonderful dietician
link |
instructing people for this and her name's Dahlia Perlman
link |
and she really was the key and is the key
link |
for many of our studies for getting people
link |
to eat differently.
link |
And the general instructions were for people
link |
to eat as much fermented foods as possible, more is better.
link |
And the reason is that with this initial study,
link |
we really wanted to maximize our chance of seeing a signal
link |
if there was something biological going on,
link |
with the idea that if the dose was excessive
link |
and not easily achievable by a lot of people in the end,
link |
we can go back and say, okay, this is the point
link |
at which we lose the biological signal.
link |
But people during the height of the intervention phase,
link |
the intervention phase was six weeks,
link |
during the height of that, we're up over six servings
link |
on average per day of fermented foods.
link |
So kind of two servings at each meal
link |
and the ounces or weight or size,
link |
it really depended on what the fermented food was.
link |
And we just told them to stick
link |
to what was a recommended dose on the package
link |
that they were buying.
link |
You know, for kombucha, it'd be like a six
link |
to eight ounce glass sauerkraut, like a half cup
link |
or something like that and the same with yogurt.
link |
Great, so what were the results?
link |
Yeah, so the results astounded us in a way,
link |
but then thinking more deeply and it'll be evident
link |
even after I explain it in the context of this conversation,
link |
likely why we saw the results we saw.
link |
The results were astounding because our hypothesis
link |
going into this was that the high fiber diet
link |
was going to give the massive signal.
link |
We know that this is the big deficiency
link |
in the Western diet.
link |
All the mouse studies have told us
link |
that high fiber really leads to a much healthier microbiota,
link |
can lead to positive changes in the immune system.
link |
And in fact, even when we had a limited,
link |
we had wonderful donor support,
link |
but still a limited amount of money
link |
when we started this study.
link |
My lab was really very eager to do the high fiber
link |
part of this really well.
link |
And Christopher kind of had to twist our arms
link |
to do the fermented food side of it.
link |
And we thought it was kind of quirky and neat,
link |
like live microbes should be exciting, like let's try it.
link |
So we put that in and it turns out
link |
that we were very thankful that he twisted our arms
link |
because it was that high fermented food arm
link |
that really gave us the big signal.
link |
Even though our hypothesis was that the high fiber
link |
was gonna lead to more short chain fatty acids
link |
produced in the gut, more diverse microbiota,
link |
less inflammation in the immune system,
link |
we didn't see that across the cohort.
link |
We actually saw very individualized responses
link |
to the dietary fiber.
link |
And I'll come back to what those responses were.
link |
The big signal really was in the fermented food group.
link |
We saw all the things that you would hope to see
link |
in a Western microbiota and Western human.
link |
We saw this increase in microbiota diversity
link |
over the course of the six weeks
link |
while they were consuming the fermented foods.
link |
And we can't always say that higher diversity is better
link |
when it comes to our microbial communities.
link |
We know there are cases, for instance,
link |
bacterial vaginosis where higher diversity
link |
is actually indicative of a disease state.
link |
But we know in the context of the gut
link |
and for people living in the industrialized world,
link |
higher diversity is generally better.
link |
We know that there's a spectrum of diversity.
link |
People with higher diversity generally are healthier.
link |
If you can push your diversity higher,
link |
you're in better shape.
link |
And so we saw that increase in diversity.
link |
And then the major question is what happened
link |
to the immune system as these people
link |
were increasing their gut microbiota diversity
link |
through the fermented foods.
link |
So we did this massive immune profiling
link |
and we see a couple dozen immune markers,
link |
inflammatory markers decrease over the course of the study.
link |
So we measure these at multiple time points
link |
throughout the course of the study.
link |
And there's kind of this stepwise reduction
link |
in things like interleukin-6 and interleukin-12,
link |
a variety of kind of famous inflammatory mediators.
link |
And then even if you go into the immune cells
link |
and you start looking at their signaling cascades,
link |
we see that those signaling cascades
link |
are less activated at the end of the study
link |
compared to the beginning of the study
link |
indicating an attenuation of inflammation.
link |
So kind of exactly what we would hypothesize
link |
would lead to less propensity
link |
for inflammatory disease over time.
link |
That's a huge extension of a very short study.
link |
How long was this study again?
link |
So the complete protocol I think was 14 to 17 weeks
link |
or something like that.
link |
The actual intervention phase consisted of a four-week ramp
link |
and then a six-week maintenance period.
link |
So the intervention itself was 10 weeks,
link |
but there were six weeks of really kind of
link |
hardcore high levels of fiber or fermented foods.
link |
Yeah, and I'm glad you mentioned the ramp
link |
because my experience with fermented foods
link |
is that it can be beneficial to give the system
link |
an opportunity to acclimate.
link |
I mean, if you consume a giant bowl of sauerkraut,
link |
it's not going to be the worst day and night of your life,
link |
but you'll know you did.
link |
We'll just leave it at that.
link |
And so you want to kind of acclimate to it.
link |
I'm at the point now where some people
link |
might think this is as gross,
link |
but after I exercise, I've been sweating a lot.
link |
I like the saltiness of the,
link |
I actually drink the liquid that the sauerkraut
link |
has been stewing in.
link |
And I'd like to think that I consume
link |
some fermentation that way.
link |
It's salty, it acts as kind of a post-training replenishment.
link |
But if I had done that six months ago straight off,
link |
I think it would have been pretty rough on my system.
link |
I started taking little bits of it
link |
and then adding it each day.
link |
Totally, and so both with the fermented foods and the fiber,
link |
it's well known that this kind of gradual ramping
link |
is a really important way of mitigating bloating
link |
and other kind of digestive discomfort
link |
that can happen when your microbiome reconfigures
link |
and starts fermenting more and changing community members.
link |
So you should take that ramp at your own pace.
link |
If something seems to be going wrong,
link |
just kind of level off, stay there.
link |
You know, we did this in a very delicate way
link |
to get people up to the high dose.
link |
The brine question, just a tangent here for a second.
link |
That was actually one of the products
link |
that we had people use in the fermented food phase.
link |
There's actually a product called Gut Shots,
link |
which is just the brine that they've marketed.
link |
We actually are now studying it in the lab.
link |
I just actually, before this came from a lab meeting
link |
where a GI fellow in my lab is actually putting Gut Shots,
link |
sterilized gut microbes or the fermentation microbes
link |
removed or present into mice and looking at changes
link |
in their mucosal immune system.
link |
So we're studying this in detail now
link |
because it's a rich source of lactate
link |
and a bunch of other interesting metabolites.
link |
I love that my weird behavior
link |
is inadvertently being studied at Stanford Medicine.
link |
I want to just mention something about the Gut Shots.
link |
Those are sold as a drink.
link |
Those also, just for certain listeners
link |
in different budgets, they can be very expensive
link |
if you really think about,
link |
some of them are exceedingly expensive,
link |
but what I described before
link |
with making your own kombucha is not quite brining,
link |
but the homemade sauerkraut, that protocol is out there
link |
as I mentioned in Tim's book, The 4-Hour Chef,
link |
and you get a lot of the brining from that,
link |
an almost endless amount.
link |
A cautionary note, I once went into the refrigerator
link |
and saw something similar to Gut Shot, it wasn't Gut Shot,
link |
and I drank the whole 12-ounce bottle
link |
and realized that it was 24 servings.
link |
And that's where I got my initial experience
link |
with what it is to not do a ramp-up phase.
link |
I do not recommend doing that.
link |
Some of these, it's very potent, it seems,
link |
and you can consume even a half an ounce or an ounce.
link |
I mean, very potent from the standpoint of fermentation,
link |
but also very salty.
link |
So there's a lot of effects that can-
link |
Don't do what I do, at least not at the outset.
link |
But so that is an experienced warning.
link |
So they did this, as I recall,
link |
there was a swap condition or there was a halt condition.
link |
So you did controls, right?
link |
It wasn't just comparing groups.
link |
You had individuals who were initially in one group
link |
or the other move to a different group.
link |
Or to stop and then return.
link |
Yeah, we actually just did a stop
link |
and followed them during a washout phase.
link |
And the ideal situation for dietary interventions like this
link |
are to do crossover studies, as you're suggesting.
link |
We've recently completed a ketogenic
link |
versus Mediterranean diet intervention.
link |
Were those data published yet?
link |
Not yet, but Christopher has been tweeting
link |
a lot of these data and there's a paper
link |
in revision right now.
link |
So if you go to Christopher Gardner's Twitter feed,
link |
you'll be able to find him reporting
link |
some of the early results of this study.
link |
Can you give us a snippet of, was there a superior-
link |
Just give us a, you don't have to tell us which one,
link |
but was there a superior condition
link |
of either Mediterranean versus ketogenic?
link |
So the metabolic effects of these, it's a beautiful study.
link |
I should let his group comment on that.
link |
The microbiota data we actually are just generating now.
link |
So the study that his group has put together from this
link |
is largely independent of the microbiota data.
link |
And now we're doing a more in-depth analysis
link |
and I'll have more to say about that in the future.
link |
But that- We'll return to that, yeah.
link |
But it's a super exciting study
link |
because it is one of these where people eat a certain way.
link |
And what's really beautiful about this
link |
is we even got food delivered for part of the intervention.
link |
So we had complete control over what they
link |
at least had available to eat.
link |
And then the second phase, they make the food on their own.
link |
And then we cross over and do the same thing.
link |
And so that's really like the,
link |
if you have a good enough budget,
link |
the right way to do a study like this.
link |
For this, we didn't have the time or money
link |
to do a crossover, but we did do a washout phase
link |
where people, we didn't make them stop eating whatever
link |
if they were enjoying it, but we monitored
link |
and there was some recidivism where there was a decrease
link |
in fiber fermented food.
link |
And we could see, for instance,
link |
diversity start to plateau in reverse
link |
in many of these people.
link |
So there does appear to be like a need
link |
for maintenance of the intervention
link |
to maintain the perceived health benefits
link |
that we were measuring.
link |
We will provide a link to the study in the caption.
link |
And thank you for that very clear and thorough description
link |
from one of the investigators involved in the study.
link |
It's great to go direct to the source.
link |
So anecdotally, were there improvements in mood,
link |
in resistance to colds and infection
link |
during the course of the study?
link |
And this is kind of a prelude to where I'm headed next,
link |
which is there is a tremendous amount of interest
link |
in the so-called gut brain access,
link |
but also I want to make sure that we talk about
link |
how these microbes and the conditions they're establishing
link |
in the gut are creating positive or negative health effects.
link |
I mean, actually basically how signals get out of the gut.
link |
So did people, I certainly noticed
link |
that when I'm eating more fermented foods
link |
or there's probiotics in drinks I consume and so forth,
link |
that I feel, quote unquote, air quotes,
link |
completely subjective, I feel better.
link |
I wish there was an objective measure of feeling better,
link |
but I seem to think more clearly, sleep better,
link |
mood, et cetera, and I know I'm not alone in that.
link |
And people, and anytime I've taken harsh antibiotics,
link |
I feel worse, but then again, I'm usually taking them
link |
because I'm feeling bad about something else, right?
link |
I don't take them just because.
link |
So did people say they were feeling better in any way?
link |
And if so, what did you observe?
link |
And again, we're highlighting these as anic data.
link |
You know, we, as part of this effort
link |
to look at how dietary interventions affect our health
link |
and wellbeing and so forth and microbiome and immune system,
link |
we interact with a lot of people who have like read our book
link |
or kind of have become microbiome enthusiasts
link |
and have implemented a lot of these changes
link |
in their personal life.
link |
And I hear the same thing that you're saying, Andrew,
link |
that tons of people say they have more energy,
link |
they think more clearly, they sleep better,
link |
their family is nicer to each other,
link |
like the number of crazy things.
link |
And it's really hard to uncouple like,
link |
is this because these people have taken charge now
link |
of what they're eating and just feel better in general
link |
for being in control of kind of what they're doing?
link |
Or is there this cascading set of effects
link |
that are actually impacting or kind of emanating
link |
from the gut brain axis?
link |
And so we actually implemented a bunch of questionnaires
link |
and even a cognitive test to try to get at some of this.
link |
And I should say, the list of this goes on and on.
link |
There are people who claim that their complexion improves
link |
and that their allergies,
link |
and there's probably all sorts of ripple effects.
link |
If you can affect your inflammation,
link |
we know that you can affect your cognition.
link |
We know that you can affect your skin
link |
and inflammation that's occurring on your skin.
link |
So I really think that there is a basis
link |
for a lot of those anecdotes.
link |
It may just be hard to see in a short study
link |
and in a small cohort of people over a short period of time,
link |
but we didn't really see significant things
link |
associated with cognition and moods
link |
and all of the things that we were testing for,
link |
which yeah, there could be a variety
link |
of explanations for that.
link |
We also have a standardized stool measure that people use,
link |
and there was kind of less constipation,
link |
better bowel movements over the course
link |
of both of these interventions.
link |
So it did seem like bowel habits improved,
link |
which a lot of times can lead to better moods,
link |
but that we weren't able to measure that.
link |
The classic psychoanalyst would have a field day with that.
link |
What sorts of interesting things did you observe
link |
in the fiber group?
link |
Because it's clear that that group yielded
link |
some unexpected findings in both directions,
link |
things you expected to see,
link |
you didn't see as to the same amplitude
link |
as you did in the fermented food group,
link |
but I'm guessing you also saw some very interesting things
link |
in the fiber group.
link |
So we started looking at the data in more detail
link |
when we didn't see the cohort-wide response.
link |
And one of the things we observed is that
link |
in measuring all these immune parameters,
link |
there appeared to be three different groups
link |
of kind of immune responses that we were seeing.
link |
One group that got overall less inflammatory,
link |
and then two other groups that kind of had a mixed result,
link |
partly more inflammatory, partly less inflammatory
link |
in all these markers that we were looking at.
link |
And when we started digging into like what aspect
link |
of the biology of those people dictated or predicted
link |
which group they fell into,
link |
the really interesting part is the people
link |
with the highest diversity gut microbiomes
link |
to start the study were the ones that were most likely
link |
to have the decreases in inflammation.
link |
And so the data seemed to be telling us that
link |
if you start off with a diverse microbiota,
link |
maybe one that's better equipped to degrade
link |
a wide variety of dietary fiber,
link |
you're more likely to respond positively to it.
link |
If you have a very depleted gut microbiome,
link |
you're not as likely to be able to respond to it.
link |
And thinking back to that experiment
link |
that we talked about before
link |
with the multi-generational loss
link |
of fiber-fermenting microbes in mice
link |
that were fed a Western diet,
link |
it may be that many of us in the industrialized world
link |
have a microbiome that's so depleted now
link |
that even if we consume a high fiber diet,
link |
at least for a short period of time,
link |
we don't have the right microbes in our gut
link |
to degrade that fiber.
link |
And this has actually been observed by other groups,
link |
beautiful study out of University of Minnesota
link |
looking at immigrants coming to the United States.
link |
And within nine months,
link |
but certainly over the course of years,
link |
immigrants that come here lose a lot of the diversity
link |
in their gut microbiome,
link |
but a lot of the fiber-degrading capacity
link |
in their gut microbiome too.
link |
So it could be that over time,
link |
this becomes a one-way street
link |
and it's hard for us to recover the microbes
link |
that actually can degrade the fiber.
link |
And I think that this probably intersects with sanitation
link |
in our environment
link |
and the fact that we don't have access to new microbes
link |
that might help us degrade the fiber,
link |
that we actually have lost these microbes
link |
and they're in some ways irrecoverable
link |
without deliberate reintroduction
link |
of fiber-degrading microbes.
link |
I can recall from childhood,
link |
there were kids that would eat dirt and snails
link |
and stuff that just sounds totally disgusting,
link |
but kids covered with mud
link |
and that maybe not so much anymore.
link |
And certainly during the pandemic,
link |
there's been a lot more use of these hand sanitizers
link |
that prior to that, people seemed pretty spooked about,
link |
but then obviously they prioritize them.
link |
So do you, while you have children,
link |
do you encourage them to,
link |
when they were young, did you encourage them to interact
link |
with pets and dirt and stuff in the environment,
link |
provided that stuff wasn't immediately toxic?
link |
So this is really,
link |
it's a continual cost benefit analysis.
link |
I think I will say that with the pandemic now
link |
and certainly just with infectious diseases in general,
link |
it's really important to be aware of the possibility
link |
for compromising your health through the spread of germs.
link |
And so that is just, hand-washing is important
link |
and we have to be careful with the spread of germs.
link |
But I do think that the sanitization of our environment
link |
has gone overboard with various things being impregnated
link |
with antibiotics, shopping carts and things like that
link |
And it's like antibiotics and things for killing microbes
link |
And when we were raising, when our daughters were young
link |
and we were making these decisions,
link |
the calculations that we would make were really one,
link |
how likely are they to encounter a disease-causing microbe?
link |
If we've been out on a hike or in our garden,
link |
just kind of working in the dirt or whatever,
link |
maybe it's not as important to wash your hands
link |
before you have lunch,
link |
even if there's a little bit of dirt on them.
link |
If they've been in a public playground
link |
where maybe there's other kids with germs
link |
or maybe even chemicals like pesticides
link |
and herbicides that are being used,
link |
maybe it's more important than to wash your hands.
link |
Certainly if you've been in the grocery store
link |
or on the subway, probably a good idea to wash your hands.
link |
So I think you really need to think about
link |
kind of the context of it.
link |
And exposure to microbes from the environment
link |
is likely an important part of educating our immune system
link |
and keeping the proper balance in our immune system.
link |
And it's just a matter of figuring out
link |
the right way to do that safely.
link |
And it may be that the fermented food result that we saw
link |
is a way of tapping into those same pathways,
link |
kind of an environmental exposure to microbes that's safe.
link |
I'd like to touch on how signals get from the gut
link |
to the rest of the body.
link |
And we probably don't have time to go into all the systems
link |
that benefit from having a diverse microbiome
link |
or a healthy microbiome,
link |
but we talked about the immune system.
link |
There's active signaling and transport from the gut
link |
all along its length, as far as I know,
link |
into the bloodstream and to other organs and tissues.
link |
So for the immune system, it seems straightforward.
link |
You could reduce the amount or number
link |
of inflammatory cytokines like IL-6 and so forth,
link |
maybe increase the anti-inflammatory cytokines
link |
like IL-10 and others.
link |
But we know there's a gut-brain axis of neurons
link |
that literally talk in both directions
link |
between brain and gut.
link |
But let's say I'm eating my fermented foods,
link |
I'm doing all the right things and my gut is diverse
link |
and I have all the goodies at all the right places.
link |
How is it that the fact that those microbiota are thriving
link |
is conveyed to the rest of the body?
link |
Because they're in there doing their thing
link |
and I don't know that they have a mind,
link |
but they're probably not thinking of taking care of me,
link |
Andrew, but I get feel better
link |
or I might get sick less often
link |
or combat any illness more quickly.
link |
How is that actually happening?
link |
I mean, is it that the microbiota stay restricted
link |
to the gut, but the signaling molecules
link |
are all in a downstream way
link |
are making good or bad things happen?
link |
Or is there some sort of direct recognition
link |
at the body level or are there cells in the body
link |
that are responding to, ah, the gut microbiome is healthy
link |
and therefore I can make more of the good stuff
link |
and less of the bad stuff, so to speak.
link |
You're right, it's super complex.
link |
There's a huge array of ways that our body perceives
link |
both the microbes and the molecules that they produce
link |
in our gut and the molecules they produce
link |
are of course a product of what microbes are there
link |
and then what they receive as kind of metabolic inputs,
link |
what we're eating and what other microbes are present
link |
in the environment providing molecules to them.
link |
So, you know, it's this complex matrix,
link |
but probably the simplest place to start
link |
is just the immune system.
link |
We have an immune system that the vast majority
link |
of immune cells in our body are located in our gut
link |
just because there's such a dense population
link |
of microbes there that have,
link |
we consider them beneficial microbes,
link |
but they're only beneficial if they're in the right spot
link |
As soon as they mislocalize,
link |
we know that they can become opportunistic pathogens.
link |
And so the immune system really playing an important role
link |
to keep them in place is essential for the system
link |
not moving into a disease space.
link |
The immune system has a variety of ways
link |
of monitoring what microbes are there.
link |
There are actually specialized structures in the gut
link |
known as Peyer's patches that actually take up microbes.
link |
They actually allow microbes to transit
link |
into this population of immune cells
link |
in a very controlled way
link |
so that that set of immune cells becomes educated
link |
as to what microbes are just on the other side
link |
Wow, it's kind of like a border patrol.
link |
So they bring them in, they fingerprint them,
link |
and then have kind of this set of responses
link |
ready to go if needed.
link |
There are other cells known as dendritic cells,
link |
special types that actually send long arms,
link |
these processes out into the lumen of the gut
link |
and do the same thing.
link |
Take up microbes, bring them back in and sample them.
link |
In addition to these direct sampling mechanisms,
link |
the cells that line the gut have a huge array of receptors,
link |
specialized proteins that perceive patterns
link |
that the molecular patterns that the microbes make.
link |
So things like endotoxin, lipopolysaccharide,
link |
just the cell wall of the bacteria.
link |
We have specialized receptors that recognize those.
link |
If those signals become too profound
link |
or if they're perceived in the wrong place,
link |
that can stimulate an inflammatory response.
link |
So there's all these ways of kind of monitoring
link |
the membership and where it is and how close it is.
link |
But then there's this whole other set of ways
link |
of perceiving metabolic activity
link |
and what's happening in the gut.
link |
And you mentioned before this direct,
link |
these cell types that express taste receptors in the gut
link |
and have ways of sampling dietary components.
link |
They're those same types of analogous cells in our gut
link |
that are perceiving metabolites produced by the microbiota
link |
so that our bodies can perceive
link |
what sort of metabolic activity is going on.
link |
And then in addition to that,
link |
there's this tremendously important enteric nervous system
link |
that's sending signals back to the brain,
link |
dictating things like motility.
link |
Do I get rid of what's in here?
link |
Do I move it along quickly?
link |
What actually is happening?
link |
Do I need to interact with immune cells?
link |
So there's this really complex array of interactions
link |
between the different cell types.
link |
And then a lot of the cells that are in the gut
link |
perceiving all of these signals,
link |
a lot of the immune cells can actually get up and leave.
link |
They can get into the blood cycle through
link |
and then home to other regions of the mucosal surfaces
link |
so that mucosal surfaces are educated broadly
link |
against what's passing through our gut.
link |
So there's a variety of ways of cells communicating.
link |
And then a lot of the molecules that the microbiota makes
link |
can actually make their way into the bloodstream directly.
link |
And so the array of molecules is still being defined.
link |
We're trying to figure out what all these chemicals are.
link |
We've mentioned the short chain fatty acids,
link |
but those are just the tip of the iceberg.
link |
They're really interesting compounds
link |
like indole derivatives and phenols
link |
and derived from amino acids metabolized by gut microbes
link |
taken up into the bloodstream.
link |
And then we further metabolize these.
link |
They become kind of co-microbe host metabolites,
link |
and then they can go on and bind to different receptors
link |
throughout our body, anywhere our bloodstream has access to
link |
and start to trigger signaling cascades.
link |
Is it known whether or not any of those molecules
link |
are small enough to cross the blood-brain barrier?
link |
Because the hypothesis and the current thinking
link |
is that neurotransmitters manufactured in the gut
link |
and signaling along the gut-brain axis,
link |
literally neurons talking back and forth electrically
link |
from brain to gut and gut to brain
link |
is what regulates things like mood
link |
or at least in animal models.
link |
And there are some emerging human studies improvement
link |
of symptoms in autism spectrum disorders,
link |
maybe even in ADHD.
link |
What I'm basically saying here is there is some evidence
link |
emerging that improving the gut microbiome
link |
can improve outcomes in psychiatric
link |
and developmental disorders.
link |
But what you're telling me is that the microbiota themselves
link |
are manufacturing chemicals that can make it
link |
into the bloodstream, and therefore I'm asking
link |
if those chemicals can move from the bloodstream
link |
into the brain directly.
link |
It may not be a gut-brain axis via neurons.
link |
It actually could just be seepage of serotonin
link |
into the brain or acetylcholine into the brain
link |
And the biology of most of these molecules
link |
is not well understood, but certainly in like
link |
cerebrospinal fluid that's been analyzed,
link |
you can perceive these microbial metabolites.
link |
So they are there.
link |
That's the answer.
link |
Some of them are getting across the barrier.
link |
But so really interesting thing is I think a lot
link |
of these molecules are, if they're experienced
link |
at high enough doses, are toxic or have toxic properties.
link |
We know that a lot of these metabolites
link |
when they make their way into the bloodstream
link |
eventually are excreted through the kidneys and urine.
link |
So actually we can monitor the metabolism
link |
that's going on in your gut by actually looking
link |
at the metabolites that are present in your urine
link |
because many of those originated in your gut
link |
from your gut microbes.
link |
But people with kidney disease whose kidneys
link |
filtering processes not functioning properly
link |
actually build up high levels of many of these metabolites
link |
into the bloodstream, and that can lead
link |
to more of these molecules making it
link |
across the blood-brain barrier.
link |
And in fact, some of the transporters in the kidney
link |
that are responsible for shuttling these molecules
link |
out into urine are also found at the blood-brain barrier
link |
for shuttling the molecules back into the bloodstream
link |
if they do get across.
link |
And we know that like mental fog is a big,
link |
one of the big symptoms of kidney disease
link |
potentially because a lot of these metabolites
link |
accumulate in blood and then make their way
link |
across the blood-brain barrier into, yeah,
link |
the central nervous system.
link |
I'm glad you mentioned mental fog.
link |
A few years back there were some reports,
link |
some scientific reports and as a consequence in the media
link |
that excessive intake of pill-form probiotics
link |
could create mental fog.
link |
I don't know if that ever took hold.
link |
And it raises a general question about pill-form probiotics.
link |
I took them for a few years just thinking
link |
that would be good for my gut microbiome,
link |
and then I switched to the fermented food thing
link |
but largely as a consequence of the work
link |
that you and Chris published.
link |
But what's the thought about probiotics
link |
for the typical person that's not recovering
link |
from a round of antibiotics
link |
or that has been prescribed them?
link |
I've heard that the species of microbiota
link |
that they proliferate might not be the species
link |
that we want to proliferate,
link |
but I've also heard that maybe that doesn't matter.
link |
So what's your general stance?
link |
They can be quite expensive also.
link |
I know I've been talking about expense law today,
link |
but I always want to take into account
link |
that people are showing up to the table
link |
with a variety of budgets.
link |
And probiotics are one of the more expensive
link |
supplements out there.
link |
You can quickly get into the several hundreds of dollars
link |
per month if you're getting the quote unquote
link |
best quality ones.
link |
And if they're actually causing brain fog,
link |
then I'm not sure I'd want to use them.
link |
And there's a ton of snake oil out there.
link |
I mean, there's just people know that they,
link |
I think that many of these companies are aware
link |
that they can pray off of people's fears
link |
and get a lot of money from them
link |
with absolutely no data to back up
link |
that their probiotic is doing anything.
link |
So I think the first thing to say is buyer beware
link |
because it's a supplement market.
link |
It's largely unregulated.
link |
And that means that there are a lot of bad products
link |
out there and a lot of products that,
link |
even though they're not intended to be bad,
link |
just don't have great quality control.
link |
There have been several studies that have taken
link |
off the, over the counter,
link |
just kind of off the shelf probiotics.
link |
Surveyed what's in there based on sequencing
link |
and shown that they, what is in there
link |
does not match what's on the label.
link |
And that's true of many supplements
link |
and unfortunately supplement companies.
link |
This is something we get into on the podcast a lot there.
link |
There are reputable brands and they go through
link |
a lot of work to get things right.
link |
And there are many that just for whatever reason,
link |
it just doesn't match what's listed.
link |
And so there are places that probiotic companies
link |
can send their product to have it independently validated.
link |
So you want to look for that sort of validation
link |
There also are names that are just very well known
link |
their reputations are on the line.
link |
So they probably invest a little bit more
link |
in quality control than maybe some of the other
link |
lesser known names.
link |
But there's a huge range of data on probiotics
link |
and I think the thing that we kind of recommend
link |
is try to find good products and then experiment
link |
for yourself and see if you can find something
link |
that works for you.
link |
I know people who have experienced constipation
link |
and don't want to change their diet
link |
and have found a probiotic that helps them with that.
link |
If you can find that right mix, great.
link |
I would say that the data right now
link |
is not overwhelmingly positive for what probiotics
link |
do to the gut microbiota.
link |
So there have been some nice studies looking at
link |
the impact of probiotics on recovery
link |
after antibiotic treatment and it appears to slow down
link |
the recovery of the mucosal microbiota.
link |
And some other studies that have,
link |
where the big signal isn't seen, as you might hope,
link |
with a probiotic that's supposed to treat
link |
a different disease.
link |
There have been meta-analysis that do suggest
link |
in certain instances recovery from antibiotics
link |
that there, even though it may cause your microbiota
link |
to recover more slowly, that it may actually prevent
link |
diarrheal disease, recovery from viral diarrhea,
link |
probiotics may help.
link |
But because there's such a huge range of products
link |
and because each person is their own little caper
link |
when it comes to the microbiome, it's really hard
link |
to know whether there are great products
link |
for a given indication.
link |
The really good advice that I've heard is try to find
link |
a study that supports in a really well-designed study,
link |
and this is very hard for people who aren't scientists
link |
to evaluate, but so if you're experiencing
link |
a medical problem or wanna consult a doctor,
link |
that might be helpful, but finding a study
link |
where a specific probiotic has successfully done
link |
whatever it is you're looking for and then sticking
link |
with that probiotic is really the best recipe
link |
as a place to start in this space, I think.
link |
And what about prebiotics?
link |
Is there a number of reasons why I can imagine
link |
that prebiotics would be beneficial?
link |
Which essentially, you're pushing the fiber system,
link |
which we talked a lot about today.
link |
Yeah, yeah, absolutely.
link |
The studies that have been done on prebiotics,
link |
it's really kind of a mixed bag of results.
link |
There have been studies done with purified fibers
link |
where you actually see microbiota diversity plummet
link |
over the course of the study because you get
link |
a very specific bloom in a small number of bacteria
link |
that are good at using that one type of fiber,
link |
and that's at the expense of all the other microbes
link |
that are in the gut.
link |
And so it's really hard to replicate with purified fiber
link |
what you'd get, for instance, at a salad bar
link |
in terms of the array of complex carbohydrates
link |
that you would be exposing your microbiota to.
link |
And I think the kind of broad view of this in the field
link |
is that consuming a broad variety of plants
link |
and all the diverse fiber that comes with that
link |
is probably better in fostering diversity in your microbiota
link |
than purified fibers.
link |
Now, there are, again, a lot of people who benefit
link |
from purified fibers, either for GI motility
link |
or for other aspects of GI health problems
link |
that they've been experiencing.
link |
Again, I think it's the type of thing
link |
where you have to try to find the thing
link |
that that's right for you.
link |
But there also are studies that suggest
link |
that if you layer rapidly fermentable fibers
link |
on top of a Western diet, you actually can result
link |
in weird metabolism happening in your liver
link |
because you have this incredibly rapid fermentation of fiber
link |
along with a lot of fat coming into the system.
link |
At least that's the theory.
link |
And in a mouse study that was published a few years ago,
link |
they actually see that a subset of the mice
link |
develop hepatocellular carcinoma
link |
when they're fed a high dose prebiotic liver cancer
link |
on top of a Western diet.
link |
So whether that's representative of human biology,
link |
we don't know, but purified fibers
link |
are definitely very different,
link |
both in terms of the diversity of structures,
link |
but also in terms of how rapidly they're fermented
link |
in the gut, because if you are eating plants,
link |
the complex structures there really slow the microbes down
link |
in terms of fermentation and you end up
link |
with a slow rate of fermentation
link |
over the length of your colon,
link |
as opposed to this big burst of fermentation
link |
that can happen if you eat something
link |
that is highly soluble and easily accessed by the microbes.
link |
Interesting. So I guess,
link |
is it fair to come back to this idea,
link |
trying to avoid processed foods,
link |
the highly palatable foods,
link |
they're all sometimes super highly palatable foods
link |
they're now called that are packed
link |
with hidden sugars, emulsifiers.
link |
So it sounds like some fiber is good.
link |
And despite the outcome of the study,
link |
you identified that if you have the appropriate microbiota,
link |
then you will background,
link |
then one will respond even better to the fiber,
link |
maybe a longer ramp up phase for those folks.
link |
And then the fermented foods,
link |
because there's no reason why you can't do both.
link |
And as we've talked about before,
link |
a lot of fermented foods have fiber.
link |
So you can kill two birds with one stone.
link |
Totally. And it could be that the diversity increase
link |
that we saw in the high fermented food group
link |
could be something that would aid the high fiber group.
link |
And so now we're planning another study coming up
link |
where we're doing high fiber, high fermented food,
link |
and then fiber plus fermented food,
link |
just to see if there's a synergistic effect there.
link |
Great. I want to enroll.
link |
Seriously, although I guess I'm biased
link |
because I sort of know where you're trying to,
link |
well, is it blood draws that you use
link |
to measure the inflammatome?
link |
Exactly. So we do blood draws like for two weeks.
link |
So you've covered a tremendous amount of information
link |
and I'm incredibly grateful.
link |
This was a area of biology that,
link |
despite having learned a lot about through papers
link |
and going to talks and reading articles in the media,
link |
has remained somewhat mysterious to me until today.
link |
You've given us a very vivid picture
link |
of how this system works.
link |
Where can people find out more
link |
about the work that you're doing?
link |
We can certainly provide links.
link |
And you and your wife who co-run your lab,
link |
you have a book on this topic.
link |
So could you tell us about the book
link |
where we can learn more about the Sonnenberg Lab
link |
and the work that you're doing?
link |
Maybe people will even try and enroll
link |
in some of these studies.
link |
Yeah, it'd be great if we could get people to enroll.
link |
We're always looking for willing participants.
link |
Yeah, so Erica, my wife and I wrote a book
link |
called The Good Gut.
link |
And that really was a response
link |
to how we were changing our lives
link |
in response to being in the field,
link |
being very familiar with the research,
link |
seeing that a lot of our friends
link |
that weren't studying the gut microbiome,
link |
but were very well-informed,
link |
many of them scientists,
link |
were not doing the same things we were doing.
link |
And it was very clear that it was just
link |
the lack of information funneling out of the field
link |
And so we wanted to make that accessible
link |
to people who are not microbiome scientists.
link |
There's also a really interesting story.
link |
We were at a conference site
link |
that just has scientific conferences all summer long,
link |
week after week after week, different fields.
link |
And so it's people that work there
link |
that are just dealing with these new groups
link |
coming in week after week.
link |
And the week we were there for a microbiome conference,
link |
people that work in the dining commons came up to us
link |
and they said, what group is this?
link |
And we're like, what's weird?
link |
And they said, we can't keep the salad bar stocked.
link |
And it was very clear that nobody was doing
link |
what we were doing until we'd go to a microbiome conference.
link |
And then everybody was doing the same stuff
link |
that we were doing.
link |
And so anyway, we wrote this book
link |
to talk about our personal journey
link |
and kind of the science in the field.
link |
And yeah, just to lay a foundation for people
link |
if they wanna start thinking about these changes.
link |
And then in terms of kind of connecting with our research,
link |
certainly there's the Center for Human Microbiome Studies
link |
at Stanford, which is kind of our home base
link |
for doing a lot of these dietary interventions.
link |
We list the studies there,
link |
give more information on what we're doing.
link |
And then we have a lab website too
link |
that people can go to and read more about our research.
link |
Yeah, and we're always looking
link |
for participants for our studies.
link |
Great, well, we will provide links to all of those sources.
link |
And I just wanna say thank you so much
link |
for sharing with us your knowledge
link |
for the incredible work that you and Erica,
link |
your wife and Chris do and are continuing to do.
link |
I think this is an area that when I started my training,
link |
I heard a little bit about microbiota
link |
and I always just thought those are people
link |
that work on infectious disease and like all the bad stuff.
link |
So it's interesting and really important
link |
that people realize that we're carrying all this vital cargo
link |
and we need to take care of the cargo
link |
so it can take care of us.
link |
So thank you so much for your time and for the work you do.
link |
And I hope we can do it again.
link |
This was a great conversation.
link |
Thank you for joining me today
link |
for my discussion with Dr. Justin Sonnenberg,
link |
all about the gut microbiome
link |
and how to optimize your gut microbiome for health.
link |
Please check out the Sonnenberg Lab webpage.
link |
That's Sonnenberg spelled S-O-N-N-E-N-B-U-R-G-L-A-B
link |
That's sonnenberglab.stanford.edu.
link |
They often recruit for studies exploring
link |
how different aspects of nutrition impact
link |
the gut microbiome,
link |
much as we discussed during today's episode.
link |
Please also check out the book that he and his wife,
link |
Dr. Erica Sonnenberg wrote called The Good Gut.
link |
It's readily available on all the usual sites,
link |
such as Amazon and so forth.
link |
If you're learning from and are enjoying this podcast,
link |
please subscribe to our YouTube channel.
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That's a terrific zero cost way to support us.
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please subscribe to the podcast on Apple and Spotify.
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you have the opportunity to leave us up to a five-star
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You can also leave a comment on Apple if you like.
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The best place to leave us comments and feedback,
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however, is on our YouTube channel in the comment section.
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There, you can suggest topics that you'd like us to cover
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Please also check out the sponsors mentioned
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That's the best way to support this podcast.
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We also have a Patreon.
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It's patreon.com slash Andrew Huberman,
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and there you can support the podcast
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at any level that you like.
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On many episodes of the Huberman Lab Podcast,
link |
we discuss supplements.
link |
While supplements are certainly not necessary for everybody,
link |
many people derive tremendous benefit from them
link |
for things like sleep and focus,
link |
and indeed gut microbiome support.
link |
The one issue with supplements, however,
link |
is that many of the supplement companies out there
link |
do not independently test their supplements.
link |
So there isn't tremendous confidence in all supplements
link |
that they contain the amounts of the ingredients
link |
that are listed on the bottle,
link |
and that the quality of the ingredients
link |
is where it should be.
link |
For that reason, we've partnered with Thorne,
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that's Thorne, T-H-O-R-N-E,
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because Thorne supplements are known
link |
to have the very highest levels of stringency
link |
with respect to the quality of the supplements
link |
and the amounts of the supplements listed on their bottles
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lists what's actually in the containers,
link |
which is essential.
link |
If you'd like to see the Thorne supplements that I take,
link |
you can go to thorne.com slash the letter U slash Huberman,
link |
and you can get 20% off any of the Thorne supplements
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that are listed there.
link |
Also, if you navigate deeper into the Thorne site
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through that portal, thorne.com slash U slash Huberman,
link |
you can also get 20% off any of the other supplements
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that Thorne makes.
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If you're not already following Huberman Lab
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on Instagram and Twitter, please do so.
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There I cover topics about science and science-based tools,
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some of which overlap with the content of this podcast,
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much of which is separate and unique
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We also have a newsletter.
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It is called the Neural Network Newsletter.
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Once a month, we put out short summaries of podcast episodes
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You can sign up for that by going to hubermanlab.com.
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You can look in the menu,
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You can download previous newsletters
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The privacy policy is made very clear at hubermanlab.com.
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So thank you once again for joining me
link |
for today's discussion about the gut microbiome.
link |
And last, but certainly not least,
link |
thank you for your interest in science.
link |
I'll see you in the next one.