Dr. Justin Sonnenburg: How to Build, Maintain & Repair Gut Health | Huberman Lab Podcast #62
Dr. Justin Sonnenburg: How to Build, Maintain & Repair Gut Health | Huberman Lab Podcast #62
My guest this episode is Dr. Justin Sonnenburg, Professor of Microbiology \u0026 Immunology at Stanford University. Dr. Sonnenburg’s research focuses on how microbes in our gut impact our mental and physical health and how diet and your environment shape your gut microbiome. We discuss the architecture of the gut microbiome and microbiota variability in different regions of the gastrointestinal (GI) tract and how these can change in response to diet, environment or genetics. We explore the early establishment of your microbiome and how your mode of delivery into the world (C-section or not) shapes your gut. We also discuss lifestyle factors that can alter your microbiome and the integral role the gut microbiome plays in communicating to other organs, including your brain. Dr. Sonnenburg details his recent clinical study, which found that diets rich in fermented foods (but not fiber) increase microbiota diversity and reduce signals of inflammation. Additionally, we examine how foods typical in Western Diets (e.g., high fat, low fiber, processed foods) can negatively impact the gut microbiome. Throughout the episode, we discuss actionable tools from peer-reviewed clinical findings that anyone can implement, regardless of budget, in order to optimize their gut microbiome and health.
#HubermanLab #Microbiome #GutHealth
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Dr. Justin Sonnenburg Links:
Center for Microbiome Studies: https://stanford.io/3vGkdS0
Dr. Sonnenburg’s Lab: https://sonnenburglab.stanford.edu
Dr. Sonnenburg’s Published Work: https://stanford.io/3HN6eMF
Article Links:
“Gut-microbiota-targeted diets modulate human immune status”: https://bit.ly/3sLv2QI
Book Links:
“The Good Gut: Taking Control of Your Weight, Your Mood, and Your Long-Term Health”: https://amzn.to/35RQP0c
“The 4-Hour Chef: The Simple Path to Cooking Like a Pro, Learning Anything and Living the Good Life”: https://amzn.to/3hqxkP0
Other Links:
NIH Human Microbiome Project: https://hmpdacc.org
Timestamps:
00:00:00 Dr. Justin Sonnenburg, Gut Microbiome
00:02:55 The Brain Body Contract
00:04:16 AG1 (Athletic Greens), ROKA, Helix Sleep
00:08:30 What is the Gut Microbiome?
00:12:49 Gastrointestinal (GI) Tract \u0026 Microbiota Variability
00:16:00 Breast Feeding, C-Sections \u0026 Pets
00:21:56 The Human Microbiome Project at Stanford
00:26:30 Traditional vs. Industrialized Populations
00:28:58 Resilience of the Microbiome
00:35:10 Regional Differences Along Your GI Tract
00:42:04 Fasting, Cleanses \u0026 Gut Health
00:51:19 Dietary Differences
01:01:24 Simple vs. Complex Carbohydrates, Processed Foods
01:07:03 Artificial \u0026 Plant-based Sweeteners
01:12:44 Cleanses: Useful? Harmful?
01:14:50 Your Microbiome \u0026 Your Immune System
01:20:17 Dietary Fiber \u0026 Fermented Foods
01:32:13 High-Fiber vs. High-Fermented Diet; Inflammation
01:41:33 Ripple Effects of a Healthy Diet
01:45:00 Does a High-Fiber Diet Make Inflammation Worse?
01:47:22 Over Sterilized Environments
01:50:15 The Gut Microbiome’s Effect on Physiology
01:56:45 Gut-Brain Connection
01:59:30 Probiotics: Benefits \u0026 Risks
02:04:20 Prebiotics: Essential?
02:07:00 Tools for Enhancing Your Gut Microbiota
02:11:12 Dr. Sonnenburg’s Research, Zero-Cost Support, YouTube, Spotify, Apple Reviews, Sponsors, Patreon, Thorne, Instagram, Twitter, Neural Network Newsletter
Please note that The Huberman Lab Podcast is distinct from Dr. Huberman’s teaching and research roles at Stanford University School of Medicine. The information provided in this show is not medical advice, nor should it be taken or applied as a replacement for medical advice. The Huberman Lab Podcast, its employees, guests and affiliates assume no liability for the application of the information discussed.
Title Card Photo Credit: Mike Blabac - https://www.blabacphoto.com
Audio Engineering: Joel Hatstat at High Jump Media
Content
0.36 -> - Welcome to The Huberman Lab Podcast,
1.92 -> where we discuss science
and science-based tools
4.93 -> for everyday life.
5.963 -> [upbeat music]
9.33 -> I'm Andrew Huberman,
10.28 -> and I'm a professor of
neurobiology and ophthalmology
13.06 -> at Stanford School of Medicine.
14.92 -> Today my guest is Dr. Justin Sonnenburg.
17.117 -> Dr. Sonnenburg is a
professor of microbiology
19.91 -> and immunology at Stanford
School of Medicine,
22.8 -> and one of the world's leading experts
24.54 -> on the gut microbiome.
26.43 -> The gut microbiome is the
existence of trillions
29.88 -> of little microorganisms
throughout your gut,
32.74 -> and by your gut, I don't
just mean your stomach.
35.26 -> I mean your entire digestive tract.
37.61 -> Turns out we also have
a microbiome that exists
40.63 -> in our nose, in any other
location in which our body
44.37 -> interfaces with the outside world.
46.72 -> In fact, there's a
microbiome on your skin.
49.41 -> And while it might seem kind of intrusive,
51.05 -> or kind of disgusting to have
52.69 -> all these little microorganisms,
54.17 -> they can be immensely
beneficial for our health,
57.46 -> meaning our hormonal
health, our brain health
60.12 -> and our immune system function.
61.87 -> Dr. Sonnenburg teaches us
about the gut microbiome,
64.48 -> how it's organized spatially,
65.99 -> meaning which microbiota live where.
67.81 -> He teaches us about
these incredible things
69.81 -> called crypts and niches,
71.41 -> which are little caves
within our digestive tract
74.26 -> that certain microbiota take residence.
76.169 -> And at that premier real estate,
78.44 -> they're able to do incredible
things to support our health.
80.87 -> He also talks about the
things that we can all do
83.07 -> to support our microbiome
in order for our microbiome
86.264 -> to support our brain and body health.
89.42 -> Dr. Sonnenburg co-runs his
laboratory with his spouse,
92.83 -> Dr. Erica Sonnenburg, and
together they've also written
95.92 -> a terrific and highly
informative book called,
97.937 -> "The Good Gut: Taking
Control of your Weight,
100.15 -> your Mood, and your Long Term Health."
102.23 -> Even though that book was
written a few years back,
104.19 -> the information still
holds up very nicely.
106.76 -> And today he also builds
on that information,
109.6 -> informing us about recent
studies, that for instance,
112.36 -> point to the important
role of fermented foods,
115.3 -> and the role of fiber in supporting
117.25 -> a healthy gut microbiome.
119.2 -> So if you heard about the gut microbiome,
121.29 -> or even if you haven't,
122.37 -> today you're going to hear about it
123.73 -> from one of the world's leading experts.
126.17 -> He makes it immensely
clear as to what it is,
128.97 -> how it functions, and how to support it
131.23 -> for your brain and body health.
133.14 -> During today's discussion,
134.32 -> we don't just talk about nutrition.
136.15 -> We also talk about the impact
137.67 -> of behaviors and the microbiome.
140.55 -> Behaviors such as who
you touch, who you kiss,
143.13 -> who you hug, whether or
not you interact with,
145.25 -> or avoid animals,
146.95 -> whether or not those
animals belong to you,
148.95 -> or whether or not they
belong to somebody else.
150.64 -> If all that sounds a little bit bizarre,
152.173 -> you'll soon understand
that your microbiome
155.33 -> is constantly being modified
by the behavioral interactions,
158.92 -> the nutritional interactions,
160.37 -> and indeed your mood
and internal reactions
163.88 -> to the outside world.
165.109 -> This is an incredible
system. Everyone has one.
168.96 -> Everyone should know how it works,
170.25 -> and everyone should
know how to optimize it.
172.15 -> And today you're going to learn
173.72 -> all of that from Dr. Sonnenburg.
175.76 -> I'm pleased to announce that I'm hosting
177.17 -> two live events in May, 2022.
180.04 -> The first live event will take place
181.58 -> in Seattle, Washington on May 17th.
184.4 -> The second event will take place
185.72 -> in Portland, Oregon on May 18th.
188.66 -> Both are part of a series called
"The Brain-Body Contract."
191.88 -> For this series, I will discuss science,
194.01 -> so I will discuss the mechanistic science
195.68 -> around things like sleep
and focus and motivation,
198.41 -> physical performance, mental
health, physical health,
200.88 -> a large number of topics that I believe
202.74 -> many people are interested in,
204 -> and that certainly are important
205.56 -> for our health and
wellbeing, and performance.
208.05 -> In addition, I will of
course describe tools
210.34 -> and actionable items, most
of which I have not discussed
213.62 -> on The Huberman Lab
Podcast, or anywhere else.
216.097 -> Pre-sale tickets for these two events
217.83 -> go live Tuesday, Match 8th
at 10:00 a.m. Pacific Time.
221.26 -> We've made these tickets
exclusively available
223.43 -> to the listeners of The
Huberman Lab Podcast.
225.25 -> So they are password protected.
227.15 -> To find them, you can go
to hubermanlab.com/tour
230.63 -> and use the code Huberman.
232.41 -> Before we begin, I'd like to
emphasize that this podcast
235.06 -> is separate from my teaching
and research roles at Stanford.
237.84 -> It is however, part of my desire effort
239.79 -> to bring zero cost to consumer
information about science
242.4 -> and science-related tools
to the general public.
245.1 -> In keeping with that theme,
246.18 -> I'd like to thank the
sponsors of today's podcast.
248.95 -> Our first sponsor is Athletic
Greens, now called AG1.
253.1 -> I've been taking AG1 since 2012,
255.48 -> so I'm delighted that they're
sponsoring the podcast.
257.92 -> The reason I started taking AG1,
259.207 -> and the reason still take
AG1 once or twice a day
262.49 -> is that it meets all my basic,
264.31 -> foundational supplementation needs.
266.44 -> What I mean by that is
it covers any vitamin
269.44 -> and nutritional deficiencies
that I might have,
272.29 -> 'cause I'm trying to be good
about my nutrition and diet,
274.59 -> but I don't always manage to
get everything that I need,
277.5 -> and I'm sure that there
are a lot of gaps in there.
279.8 -> So it covers those gaps.
280.93 -> It also has probiotics,
and as you'll learn
284.23 -> in today's episode, and
I've talked about it
285.84 -> on previous episodes,
287.96 -> the probiotics are essential
for a healthy gut microbiome.
291.86 -> We need probiotics in order
for our microbiome to thrive,
295.46 -> and our microbiome supports
things like gut-brain health,
297.94 -> indeed things like
metabolism, mood, hunger.
300.76 -> It also that supports the immune system.
302.79 -> As you'll learn today,
304.45 -> your gut microbiome actually
manufactures neurotransmitters,
307.63 -> the very chemicals that impact
mood and brain function.
310.43 -> Athletic Greens primes your system
312.04 -> for a healthy gut microbiome,
314.23 -> something that can be achieved
315.46 -> with food and lifestyle factors,
317.12 -> but is often hard to achieve
318.72 -> with just food and lifestyle factors.
320.73 -> If you'd like to try out Athletic Greens,
322.19 -> you can go to athleticgreens.com/huberman
325.05 -> to claim a special offer.
326.4 -> They give you five free travel packs
327.483 -> that make it very easy
to mix up Athletic Greens
329.79 -> while you're on the road.
331.21 -> And a year's supply of vitamin D3 K2.
333.75 -> vitamin D3 has many important
biological functions
336.62 -> that support your media
and long term health,
338.39 -> and K2 as well is very
important for things
340.76 -> like cardiovascular health,
341.887 -> calcium regulation and so on.
344.02 -> Again, if you go to
athleticgreens.com/huberman,
346.84 -> you can claim the special offer
348.03 -> of the five free travel packs
349.56 -> and the vitamin D3 K2.
351.41 -> Today's episode is also
brought to us by ROKA.
353.764 -> ROKA makes eyeglasses and
sunglasses that I believe
356.54 -> are of the very highest quality.
358.69 -> I've spent my lifetime working
360.12 -> on the biology of the visual system,
362.06 -> and I can tell you that the
biology of the visual system
363.99 -> has a lot of mechanisms in there.
366.24 -> So that for instance, if you
move from a bright environment
368.49 -> to a dim environment, your
visual system needs to adapt.
371.77 -> One issue with a lot of
sunglasses and eyeglasses
373.93 -> is you move from one
environment to the next,
375.95 -> you have to take sunglasses
or eyeglasses off,
377.86 -> you get a glare or you have to adjust
379.72 -> because of the way that
the lenses are designed.
381.73 -> With ROKA, they've taken the
biology of the visual system
384.16 -> into account, and so you never
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386.55 -> in order to move from one
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388.86 -> They are also designed for
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391.64 -> or you can wear them for
just things like work,
394.01 -> and going out to dinner and so forth.
395.27 -> They have a terrific aesthetic,
396.33 -> they're extremely lightweight.
397.53 -> In fact, I often forget that
they're even on my face.
400.01 -> I wear sunglasses when it's very bright
401.63 -> and when I'm driving into
sunlight, I wear readers at night.
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that they're on my face.
406.973 -> They also won't slip off your face
408.71 -> if you use them when running or cycling.
410.738 -> The company was developed by two
412.34 -> all-American swimmers from Stanford.
414 -> So everything about these
sunglasses and eyeglasses
415.948 -> was developed with performance in mind,
418.42 -> in a lot of different
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421.09 -> If you'd like to try ROKA,
422.11 -> you can go to roka.com,
that's R-O-K-A .com,
425.16 -> and enter the code huberman to save 20%
427.31 -> off your first order.
428.32 -> Again, that's ROKA, roka.com,
430.5 -> and enter the code huberman at checkout.
432.64 -> Today's episode is also
brought to us by Helix Sleep.
435.28 -> Helix makes mattresses and pillows
437.254 -> that are designed for your
particular sleep needs.
440.53 -> What I mean by that is you
can go to the Helix site,
442.85 -> you can take a very brief
two or three minute quiz,
445.368 -> ask questions like do
you sleep on your side,
447.67 -> your back, your stomach,
448.72 -> do you tend to run hot or
cold through the night?
450.23 -> Maybe you don't know the
answers to those questions.
451.88 -> And then they match you to a mattress
454.63 -> that's designed for your
particular sleep needs.
457.63 -> I matched to the Dusk, D-U-S-K, mattress.
460.46 -> I like a mattress that's
not too firm, not too soft.
462.68 -> I tend to sleep on my side,
463.918 -> or sort of in the
crawling soldier position.
465.61 -> Seems to be the the most
common position I sleep in.
468.52 -> And that really works
terrifically well for me.
470.4 -> But you need to take the quiz
471.68 -> to see which mattress works best for you.
474.081 -> So if you're interested in
upgrading your mattress,
476.3 -> go to helixsleep.com/huberman,
478.41 -> take the two quiz and they'll match you
479.89 -> to a customized mattress.
481.4 -> You can figure out how to
get your optimal sleep,
483.41 -> which was talked about on this podcast
485.36 -> so many times before.
486.29 -> Sleep is the foundation of all
mental and physical health,
488.871 -> and performance in any aspect of life.
491.59 -> Sleep is key, and the
mattress you sleep on is key
494.18 -> to the sleep you get.
495.58 -> After matching you do
a customized mattress,
497.63 -> you can get up to $200
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500.57 -> and two free pillows.
501.98 -> Again, if you're interested,
502.813 -> you can go to heli sleep.com/huberman
to get up to $200 off
506.81 -> and two free pillows.
508.13 -> And now for my discussion
with Dr. Justin Sonnenburg.
511.7 -> Justin, thanks so much for being here.
513.059 -> - Great to be here.
- Yeah.
515.2 -> I am a true novice when it
comes to the microbiome,
519.83 -> so I'd like to start off
with a really basic question,
523.005 -> which is, what is the microbiome?
525.98 -> I imagine lots of little
bugs running around in my gut
530.25 -> and I don't quite like the image of that,
532.98 -> but I'm aware that our
microbiome can be good for us,
537.04 -> but we can also have an
unhealthy microbiome.
539.83 -> So if I were to look at
the microbiome at the scale
543.35 -> that I could see the meaningful things,
545 -> what would it look like, and
what's going on in there?
548.1 -> - Yeah, I mean essentially you're correct.
551.74 -> I mean, we have all of
these little microorganisms
554.09 -> running around in our gut.
555.17 -> I think, just to start off
with clarifying terminology,
560.124 -> microbiome and microbiota
quite often are referred to,
563.675 -> or used to refer to our microbial
community interchangeably,
567.13 -> and I'll probably switch
between those two terms today.
569.91 -> The other important thing to
realize is that these microbes
572.35 -> are not just in our gut, but
they're all over our body.
576.39 -> They're in our nose,
they're in our mouths,
578.71 -> they're on our skin.
580.05 -> And so basically anywhere that
the environment can get to
584.09 -> in our body, which includes
inside our digestive tract,
587.31 -> of course, is colonized with microbes.
590.05 -> And the vast majority of these
593.325 -> are in our distal gut and in our colon,
596.3 -> and so this is the gut
microbiota or gut microbiome.
599.57 -> And the density of this
community is astounding.
604.38 -> I mean, it really is.
606.86 -> If you get down to the
scale of being able to see
610.85 -> individual microbes, you start
off with a zoomed out view
615.83 -> and you see something that
looks like fecal material
618.41 -> that digest inside the
gut, and you zoom in,
622.45 -> and you start to get to
the microscopic level
624.88 -> and see the microbes.
625.964 -> They are just packed
side to side, end to end.
629.38 -> It's a super dense bacterial community,
632.12 -> almost like a biofilm,
634.247 -> something that's just made up of microbes,
636.66 -> to the point where it's
thought that around 30%
640.28 -> of fecal matter is microbes, 30 to 50%.
643.89 -> So it's an incredibly
dense microbial community,
647.99 -> we're talking of trillions
of microbial cells.
652.52 -> And all those microbial cells,
654.61 -> if you start to get to know
them, and see who they are,
658.804 -> break out in the gut probably to hundreds,
662.14 -> to 1,000 species, depending upon
664.87 -> how you define microbial species.
668.02 -> And then most of these are bacteria,
671.068 -> but there are a lot of
other life forms there.
674.06 -> There are archaea, which
are little microbes
677.61 -> that are bacterial-like,
but they're different.
680.98 -> There are eukaryotes.
683.26 -> So we commonly think of
eukaryotes in the gut
687.2 -> as something like a parasite.
690.98 -> But there are eukaryotes,
693.23 -> there are fungi, there
are also little viruses.
696.87 -> There are these bacteriophages
698.79 -> that infect bacterial cells.
702.39 -> And those actually outnumber
the bacteria, like 10 to one.
706.01 -> So they're just everywhere
there, they kill bacteria.
710.37 -> And so there's these really interesting
712.17 -> predator/prey interactions.
714 -> But overall, it's just this really dense,
716.96 -> complex, dynamic ecosystem.
719.9 -> And so, we're talking about
the human as a single species,
725.23 -> but we're also thinking of
the human as this complex,
727.55 -> integrated ecosystem of hundreds
to thousands of species,
731.68 -> interacting concert to do
all the fantastic things
735.02 -> that we know happen in the human body.
737.11 -> - Amazing. So we've got a lot of cargo.
739.94 -> Or maybe we're the cargo.
- Yeah.
741.16 -> - Who knows?
- Yeah, I mean,
742.82 -> there have been people
that have likened humans
745.53 -> to just a really elaborate
culturing flask for microbes,
748.94 -> and that we've actually been designed
752.09 -> over the course of evolution,
753.676 -> designed to just efficiently propagate
758.64 -> this microbial culture
from person to person,
761.35 -> from generation to generation.
763.03 -> So it's a different way of
thinking of the human body.
765.18 -> - Interesting.
767.39 -> I believe that our pH or the
pH of our digestive system
773.56 -> varies as you descend,
774.94 -> as you go from mouth
to throat and stomach.
778.5 -> And you said that most of the microbiota
780.86 -> are in the distal colon.
784.44 -> Are there distinct forms
of microbiota all along
786.8 -> the length of the digestive tract,
788.79 -> and within these other interfaces
with the outside world?
792.67 -> - Totally. Yeah.
793.503 -> So it starts with our
teeth and in our mouth,
795.86 -> and saliva, there's a oral microbiota.
799.63 -> These microbial species are very different
802.31 -> than the ones that you find
in the digestive tract.
804.67 -> They're usually built to
deal with oxygen very well.
810.243 -> They're in an area that is
exposed to a lot of oxygen,
813.65 -> they of course see different
nutrients than, for instance,
816.19 -> the colonic bacteria would see.
818.11 -> And they grow quite often
in mats that live on teeth.
822.71 -> So they're very structured in terms of...
827.305 -> And not moving around a lot.
829.87 -> So they're very, fairly stationary.
832.22 -> As you move down the digestive tract,
833.83 -> there are microbes in
esophagus in our stomach,
836.23 -> but those communities are not very dense,
839.6 -> and actually not very well studied.
841.19 -> We know of a very...
843.46 -> There's a very famous stomach bacteria
845.44 -> known as Helicobacter pylori,
847.142 -> which can cause stomach ulcers
and cause gastric cancer
850.94 -> in some less frequent situations.
855.43 -> But this is
859.195 -> a very different set of
microbes, they have to be adapted
863.73 -> to a different environment,
in the stomach especially,
865.69 -> incredibly acidic environment.
867.91 -> But also very different in terms
869.25 -> of their ability to interact
with other microbes,
872.13 -> just because the
communities are less dense,
874.06 -> they're less dynamic, there's
less nutrients that stay there
877.86 -> and passage through the community.
880 -> So a lot of times those communities
882.17 -> are reliant upon nutrients
derived from the host,
885.18 -> as opposed to nutrients
derived from our diet.
887.49 -> As you move down out of the stomach,
889.02 -> into the small intestine,
890.17 -> you start to see these communities,
892.21 -> which are the ones that are
becoming more well-studied.
895.355 -> Small intestine is still
a bit of a black box,
898.18 -> just because it's hard to access.
899.77 -> And so there's some really
cool technologies out there
901.94 -> for using, for instance,
capsules to do sampling
905.597 -> as the capsule passes
through the digestive tract,
909.07 -> so that we have a better
idea of what's going on
910.82 -> in the small intestine.
912.08 -> And then you get to the colon,
and this is the community
915.44 -> that's just so incredibly
densely packed, doing a ton of...
920.27 -> There's a ton of metabolic
activity happening there,
922.995 -> and a bunch of interaction with the host.
926.35 -> And that's the community
that's really the best studied.
931.44 -> Part of the reason for
that is because stool
934.56 -> is so easy to obtain
compared to, for instance,
937.06 -> something in the stomach
or small intestine.
939.17 -> And that stool is fairly
representative, we know,
942.5 -> from studies that have been done
943.87 -> using colonoscopies and so forth.
945.64 -> Stool is fairly representative
947.24 -> of what's happening in the colon.
949.12 -> So dense, super exciting community,
951.69 -> but also the best studied,
952.86 -> just because it's the easiest to access
955.347 -> in the lower digestive tract.
957.38 -> - Very interesting.
959.93 -> I imagine these microbiota
have to get in there
962.29 -> at some point, are
microbiota seen in newborns?
965.948 -> In other words, where do they come from?
968.5 -> And dare I ask, what direction
do they enter the body?
972.16 -> Or is it from multiple directions?
974.79 -> - Yeah, yeah. Great question.
976.29 -> So one of the burning questions
that we can come back to
978.87 -> at the end of this, is where
does our microbiota come from?
981.12 -> Because it is this kind of
983.49 -> existential question in the field,
985.22 -> like where is this
community assembling from?
988.42 -> And the reason that it's
such an interesting question
990.97 -> is that, a fetus, when it's in the womb,
995.46 -> that's actually a sterile environment.
997.84 -> There have been some
studies that have looked
999.53 -> at whether there are microbes in the womb,
1001.91 -> and microbes colonizing
the fetus at that point.
1005.165 -> There's some debate about this,
1006.68 -> but overall it looks like that's not a big
1008.78 -> part of the equation of
microbial colonization.
1011.47 -> And so each time I'm an infant is born,
1014.93 -> it's this new ecosystem.
1016.8 -> It's like an island
rising up out of the ocean
1018.9 -> that has no species on it,
1020.26 -> and suddenly there's this land rush
1021.778 -> for this open territory.
1024.93 -> And so we know that infants go through
1029.53 -> this really complex process
of microbiota assembly
1033.37 -> over the first days, weeks,
months, years of life.
1036.47 -> And then you get into
switching to solid food,
1040.76 -> two to three years of age.
1042.88 -> There are some changes in
childhood, adolescence,
1046.17 -> working into adulthood.
1047.59 -> But that first zero to one year
1052.58 -> is a super dynamic time
with really kind of
1056.53 -> stereotypical developmental changes
1058.49 -> in the gut microbiota, that
appear to have the possibility
1062.25 -> of going wrong and causing
problems for infants
1066.54 -> in some instances.
1068.02 -> But if you step away
from that extreme side
1071.73 -> of things going wrong,
1073.15 -> there also were a lot of
different trajectories
1076.24 -> that developmental process can take,
1077.87 -> because our microbiota is
so malleable and so plastic,
1081.98 -> and those trajectories can be affected
1083.84 -> by all sorts of factors in early life.
1086.4 -> So an example is whether an infant is born
1089.17 -> by C-section or born vaginally.
1091.92 -> We know from beautiful work
that's been done in the field
1095.03 -> that infants that are born by C-section
1098.26 -> actually have a gut microbiota that looks
1102.57 -> more like human skin than it does
1106 -> like either the birth canal,
the vagina microbiota,
1110.69 -> or the mother's stool microbiota.
1115.28 -> Babies that are born
through the birth canal
1117.22 -> have initial colonization
of vaginal microbes
1120.98 -> and of stool microbes from their mother.
1123.22 -> And so just these first days,
1124.85 -> whether you're born by C-section
1126.2 -> or through natural childbirth,
1128.53 -> your gut microbiota looks very different.
1131.09 -> And then compound on top of that,
1133.1 -> whether you're breast fed or formula fed,
1135.47 -> whether your family has a
pet or doesn't have a pet,
1138.49 -> whether you're exposed to antibiotics,
1140.617 -> there are all these factors that really
1143.17 -> can change that developmental process,
1145.75 -> and really change your microbial identity,
1147.82 -> eventually in life.
1149.36 -> The reason that the field is
paying really close attention
1154.75 -> to this and studying this right now
1156.25 -> is because we know from animal studies,
1160.486 -> that depending upon the microbes
that you get early in life,
1165.68 -> you can send the immune
system or metabolism
1170.24 -> of an organism or other
parts of their biology
1172.652 -> in totally different
developmental trajectories.
1175.58 -> So what microbes you're
colonized with early in life
1179.14 -> can really change your biology,
1180.327 -> and we can come back to that later, but-
1181.97 -> - Yeah, we should.
1183.83 -> - Getting back to that original question
1185.26 -> of where do your microbes come from,
1187.42 -> you'd think because you're born
1189.3 -> through your mother's birth canal,
1190.84 -> or exposed to her skin microbes,
1192.57 -> that a lot of your microbes
would come from your mother,
1195.75 -> but it actually turns out that,
1197.285 -> we can certainly detect that signal,
1199.45 -> we certainly see maternal
microbes in the infant,
1202.73 -> but there are a lot of
microbes that are coming
1204.83 -> from other places, surfaces, other people,
1208.64 -> perhaps other caregivers, but
perhaps strangers as well.
1212.25 -> So we acquire our microbes
from a variety of sources.
1216.224 -> The first ones are from our mom,
1218.51 -> or from our caregivers from the hospital,
1220.64 -> but then we add to that tremendously
1222.79 -> over the first year or so of life.
1224.68 -> - Incredible, you even said pets.
1227.06 -> So if there's a dog in the
home or a parakeet in the home,
1233.33 -> clearly they have a microbiome also,
1235.08 -> and potentially the child
is deriving microbiota
1238.28 -> species from those pets, correct?
1240.67 -> - Exactly, yeah.
1241.503 -> And so the best studies
that have been done
1246.14 -> have just looked at pets in
the household as a factor,
1248.88 -> and whether that changes
the group of infants
1252.84 -> that have a pet to look slightly different
1255 -> than the group of infants
that don't have a pet.
1257.51 -> And then the question is,
1258.61 -> what is the pet doing to
change those microbes?
1261.27 -> And some of it is probably
actually contributing,
1263.92 -> direct members of the microbiota.
1265.503 -> Actually, I have a dog,
that dog occasionally
1270.39 -> will lick my mouth without
me paying attention,
1273.58 -> and that's probably introducing microbes.
1275.675 -> We also know that pets
are down in the dirt,
1280.19 -> they're outside, they're being exposed
1283.75 -> to a lot of environmental microbes.
1285.72 -> And so just pets serving as a conduit
1290.12 -> for a bunch of microbes
that we wouldn't otherwise
1293.17 -> come in contact with is
a possibility as well.
1296.31 -> - Well, we will return to pets,
and in particular your dog,
1299.862 -> an amazing dog, by the way.
1301.31 -> I met your dog just the other day,
1303.25 -> and I had to force myself,
1304.48 -> I had to pry myself away from...
1306.227 -> It's a Havanese, right?
- Havanese.
1307.73 -> - [Andrew Huberman] Incredible.
What is your dog's name?
1308.968 -> - Louis. Louis Pasteur.
1310.64 -> - Louis Pasteur.
- Yeah, yeah.
1311.86 -> - How appropriate.
1313.39 -> Amazing dog, what a personality
1315.15 -> on that dog.
- Yeah.
1317.836 -> - The issue that I think
1319.514 -> a lot of people are probably wondering is,
1322.76 -> what is a healthy microbiome?
1325.015 -> What is it supporting?
1327.05 -> We hear that you need a healthy microbiome
1329.96 -> to support the immune
system or metabolism,
1331.9 -> or even the gut-brain axis.
1334.01 -> How do we define a healthy,
versus a unhealthy microbiome?
1337.72 -> Some people might know
the unhealthy microbiome
1339.85 -> is dysbiosis is the word that
I encounter in the literature.
1343.66 -> But given that there's so
many species of microbiota,
1346.213 -> and given that I think we
probably each have a signature
1349.4 -> pattern of microbiota,
1350.854 -> how do we define healthy
versus unhealthy microbiota?
1354.04 -> Is there a test for this?
1356.63 -> Later we'll talk about technologies
for testing microbiota.
1358.697 -> There are a lot of companies now,
1361.05 -> a lot of people sending
stool samples in the mail.
1364.38 -> Never look at the Postal
Service the same way again,
1366.18 -> but it's out there and
it's getting analyzed.
1369.38 -> So how should I think about this?
1370.81 -> I can think about things like heart rate,
1372.89 -> heart rate variability, BMI,
all sorts of metrics of health.
1377.96 -> How should I think about the microbiota?
1379.75 -> How do I know if my microbiome
is healthy or unhealthy?
1382.1 -> - Yeah, it's a million
dollar question right now
1384.75 -> in the field, and there's
a lot of different ways
1386.641 -> of thinking about that, and I
can talk about some of those.
1388.34 -> But I would say that there
are sessions at conferences,
1393.42 -> there are review articles
being commissioned.
1395.28 -> There are all sorts of thought
pieces about this right now,
1398.28 -> like what is a healthy microbiota?
1399.95 -> What are the features that define it?
1402.26 -> And I think before diving into this,
1405.01 -> the important thing to realize
is, it's a complex topic.
1411.227 -> Context matters a lot.
1413.28 -> What's healthy for one
person or one population
1415.45 -> may not be healthy for
another person or population.
1418.76 -> And the microbiota is malleable.
1423.57 -> It's plastic, it changes
our human biology,
1428.59 -> which I think is, how we think
about health quite often,
1432.72 -> BMI and longevity, reproductive success,
1436.37 -> however you want to define it.
1439.38 -> It certainly can accommodate a variety
1443.81 -> of configurations of gut
microbiota, and we don't have...
1448.03 -> It's really hard to untangle
all of the different factors
1452 -> of what could be very healthy,
1454.03 -> versus a little bit less healthy.
1456.092 -> So I will say that there's
no single answer to this,
1458.76 -> but there's some really
important considerations.
1460.92 -> And perhaps the best way
to start talking about this
1463.66 -> is to go back to the inception
1467.2 -> of the Human Microbiome Project,
1468.68 -> which was this program that NIH started.
1471.42 -> They invested a lot of money in 2008, 2009
1474.604 -> for really propelling the field
of gut microbiome research.
1481.57 -> It was becoming evident at that point
1483.81 -> that this was not just a
curiosity of human biology,
1486.37 -> that it was probably really
important for our health.
1488.61 -> And they had all this
wonderful sequencing technology
1491.64 -> from the Human Genome Sequencing Project,
1494.34 -> and with the human genome
completed that point,
1496.64 -> they started turning that technology
1498.17 -> to sequencing our gut microbes.
1499.61 -> And it's important to contextualize
1501.89 -> the amount of information that
they're trying to document,
1505.52 -> the collective genome of our
gut microbes is on the order
1509.89 -> of 100 to 500 times larger
than our human genome.
1515.04 -> So it's just in terms
of the number of genes.
1517.44 -> So it's just this vast number of genes,
1520.03 -> and then if you start getting into
1521.42 -> some of the fine variation,
it's scales by 10 to a 100 fold.
1524.94 -> So really a huge amount information
1527.2 -> they're trying to document.
1528.18 -> And so it was a wonderful investment,
1531.93 -> and it continues to pay
dividends to this day.
1534.544 -> But one of their goals of that
project was to try to define
1537.78 -> what a healthy microbiome is,
versus a diseased microbiome
1541.23 -> in different contexts.
1542.19 -> And so they started enrolling
a bunch of healthy people
1545.72 -> and a bunch of people with, for instance,
1547.09 -> inflammatory bowel disease
and other diseases.
1549.47 -> And the idea was, let's
document those microbiomes.
1552.725 -> What microbes are there,
what genes are there?
1555.41 -> And then we can start to get a sense of,
1557.05 -> what are the commonalities
of the healthy people,
1560 -> and how can that go wrong in
these different disease states?
1568.75 -> There were some answers from that,
1570.56 -> but through those studies,
1573.47 -> we really started to get the image
1574.95 -> that there is this
tremendous individuality
1577.59 -> in the gut microbiome.
1578.97 -> And so it's really hard to
start drawing conclusions
1586.34 -> after initial pass of that project,
1588.44 -> of what is a healthy microbiome?
1590.59 -> But the other thing that
we started to realize
1592.7 -> at the same time, there
were studies going on
1595.325 -> documenting the gut microbiome
of traditional populations
1599.43 -> of humans, hunter-gatherers,
rural agricultural populations.
1603.68 -> And those studies were really mind-blowing
1606.89 -> from the perspective of all
these people are healthy,
1609.93 -> they're living very different lifestyles,
1612.45 -> and their microbiome doesn't look anything
1614.65 -> like a healthy American microbiome.
1617.57 -> - So does that mean that the
healthy American microbiome
1620.81 -> is healthy, but only in
the context of living
1625.55 -> in the United States and
consuming what's consumed here?
1629.05 -> Or is it that there is a
superior microbiome signature,
1632.095 -> somewhere in our history
or currently in the world?
1634.84 -> - Yeah, I think that's kind
of a big question right now.
1639.53 -> I think there's a great quote
from Dobzhansky that says,
1644.057 -> "Nothing in biology makes sense,
1645.66 -> except in the light of evolution."
1647.53 -> And these traditional
populations are all modern people
1651.916 -> living on the planet now,
1653.99 -> but their lifestyle does represent
the closest approximation
1659.37 -> to how our ancestors, early humans lived.
1663.34 -> And so those microbiomes,
1666.07 -> and now we know from
sequencing of paleofeces,
1668.92 -> the microbiome of these
traditional populations
1671.14 -> is more representative of the microbiome
1675.2 -> that we evolved with,
that potentially shaped
1678.11 -> our human genome.
1679.43 -> And so one possibility is
that in industrialized world,
1685.33 -> we have a different microbiome
from traditional populations,
1688.417 -> and that microbiome is well-adapted
1690.5 -> to our current lifestyle,
and therefore healthy
1693.05 -> in the context of an
industrialized society.
1695.05 -> And there probably are
elements of that that are true.
1697.72 -> But another possibility is
that this is a microbiome
1700.74 -> that's gone off the rails,
1701.947 -> that it is deteriorating in
the face of antibiotic use,
1706.75 -> and all the problems associated
1710.55 -> with an industrialized diet, Western diet.
1714.01 -> And that even though the
Human Microbiome Project
1719.19 -> documented the microbiome
of healthy people,
1722.56 -> healthy Americans, that what they really
1724.87 -> may have been documenting
there is a perturbed microbiota
1728.38 -> that's really predisposing
people to a variety
1731.75 -> of inflammatory and metabolic diseases.
1734.9 -> - It reminds me, as a neurobiologist,
1737.779 -> was weaned in the landscape
of so-called critical periods,
1741.45 -> where early life environment
very strongly shapes the brain.
1747.07 -> And so many studies were
done on animals raised
1749.28 -> in traditional cages with a
water bottle and some food,
1751.53 -> maybe a few other animals
of the same species.
1754.2 -> And then people came along and said, wait,
1756.2 -> normally these species in
the wild would have things
1758.52 -> like things to climb over
and things to go through,
1760.62 -> and you provide those very basic elements,
1762.72 -> and all of a sudden the
architecture of neural circuits
1765.08 -> looks very different, and you realize
1766.28 -> that were studying a deprived condition.
1768.773 -> And earlier you actually referred to,
1770.7 -> if I understood correctly,
to critical periods
1773.41 -> for gut microbiome development.
1776.43 -> Is it fair to say that
there are critical periods?
1779.69 -> Meaning, if let's say my...
1781.3 -> Let's aim it at me.
1782.133 -> If my gut microbiome was dysbiotic,
1786.35 -> it was off early in
life, can I rescue that
1790.26 -> through proper conditions and exercise?
1792.6 -> Or is there some sort of fixed pattern
1795.34 -> that's going to be hard
for me to escape from?
1797.22 -> - Yeah, there's a big
field that's emerging now
1800.88 -> that we refer to as kind of reprogramming
1804.29 -> the gut microbiome.
1805.33 -> And I think if we want
to conceptualize humans
1809.13 -> as this aggregate human microbial biology,
1813.268 -> most people have heard of CRISPR,
1815.827 -> and the ability to potentially
change our human genome
1819.13 -> in ways that correct genetic problems.
1823.22 -> That's a wonderful technology,
and has kind of put
1828.1 -> on the table genetic
engineering for cur disease,
1831.007 -> but it's much easier to change
gut microbes for a problem,
1835.01 -> just because that community is malleable.
1839 -> The issue that I think
we're seeing in the field
1843.4 -> is that microbiomes quite often,
1847.13 -> whether they're diseased or healthy,
1849.28 -> exist in stable states.
1850.9 -> They kind of tend towards this
well that has gravity to it
1856.09 -> in a way, biological gravity,
1858.04 -> where it's really hard to dislodge
1860.78 -> that community from that state.
1862.7 -> So even individuals, for
instance, that get antibiotics.
1866.52 -> You take oral antibiotics,
1869.13 -> the community takes this huge hit.
1871.12 -> We know that a bunch of microbes die,
1873.059 -> the composition changes.
1875.39 -> And that represents a
period of vulnerability
1878.29 -> where pathogens can come in and
take over and cause disease.
1880.98 -> But if that doesn't happen,
the microbiota kind of works
1884.68 -> its way back to something
that is not exactly like,
1887.51 -> but similar to the
pre-antibiotic treatment.
1890.695 -> We know with dietary perturbations,
1893.981 -> quite often you'll see
a really rapid change
1897.04 -> to the gut microbiome.
1898.33 -> And then it's almost like a
memory where it snaps back
1901.26 -> to something that's very
similar to the original state,
1904.51 -> even though the diet remains different.
1906.9 -> And so there's this incredible,
1908.82 -> what we refer to as resilience
of the gut microbiome,
1911.191 -> and resistance to change,
1914 -> or at least resistance to
establishing a new stable state.
1918.04 -> So that doesn't mean it's hopeless
1919.7 -> to change an unhealthy microbiome
to a healthy microbiome,
1924.19 -> but it does mean that we
need to think carefully
1926.39 -> about restructuring
these communities in ways
1930.88 -> where we can achieve a new
stable state that will resist
1934.067 -> the microbial community
getting pulled back
1936.83 -> to that original state.
1938.2 -> And one of the really
simplest and nicest examples
1942.814 -> of this an experiment that
we performed with mice,
1949.63 -> where we were feeding
mice a normal mouse diet,
1952.698 -> a lot of nutrients there
for the gut microbiota,
1955.51 -> things like dietary fiber.
1957.21 -> And we switched those mice, half the mice,
1960.74 -> to a low fiber diet.
1962.38 -> And we were basically asking the question
1964.57 -> that if you switch to kind
of a Western-like diet,
1967.75 -> a low fiber, higher fat diet,
1969.93 -> what happens to the gut microbiota?
1971.74 -> And we saw the microbiota
change, it lost diversity.
1974.93 -> It was very similar to what
we see in the difference
1978.66 -> between industrialized and
traditional populations.
1981.34 -> But when we brought back a healthy diet,
1983.95 -> a lot of the microbes
returned, it was fairly...
1987.75 -> There was this kind of
memory where it went back
1990.13 -> to very similar to its original state.
1992.41 -> The difference is that
when we put the mice
1994.96 -> on the low fiber, high fat diet,
1997.3 -> and then kept them on that
for multiple generations,
2001.14 -> we saw this progressive deterioration
2003.56 -> over the course of generations
2005.2 -> whereby the fourth generation,
2007.07 -> the gut microbiome was a fraction
of what it originally was.
2011.71 -> Let's say 30% of the species only remained
2015.07 -> something like 70% of the
species had gone extinct,
2018.2 -> or appeared to have gone extinct.
2020.42 -> We then put those mice back
onto a high fiber diet,
2023.124 -> and we didn't see recovery.
2025.35 -> So in that case, it's a situation
where a new stable state
2029.17 -> has been achieved.
2030.082 -> In that case, it's
probably because those mice
2032.44 -> don't actually have access
2033.988 -> to the microbes that they've lost.
2036.31 -> And we actually know that we
did the control experiment
2039.57 -> of mice on a high fiber
diet for four generations.
2042.73 -> They maintain all their microbes.
2044.28 -> If we take those fourth generation mice
2046.74 -> with all the diversity
and do a fecal transplant
2049.54 -> into the mice that had
lost their microbes,
2051.97 -> but had been returned
to a high fiber diet,
2053.834 -> all of the diversity was reconstituted.
2056.581 -> So your question of like,
2059.53 -> how do we establish new stable states?
2061.59 -> How do we get back to a healthy microbiota
2063.42 -> if we have taken a lot of antibiotics,
2065.55 -> or have a deteriorated microbiota,
2067.152 -> it's probably a combination
of having access
2069.96 -> to the right microbes.
2071.44 -> And we can talk about what
that access looks like.
2073.91 -> It may look like
therapeutics in the future.
2075.57 -> There are a lot of companies
working on creating cocktails
2077.85 -> of healthy microbes.
2078.92 -> But it'll be a combination of
access to the right microbes
2082.53 -> and nourishing those microbes
with the proper diet.
2086.93 -> - Very interesting.
2087.763 -> This multi-generational
study reminds me of something
2089.68 -> that I was told early in my training,
2091.488 -> which was that it takes a long
time for a trait to evolve,
2096.21 -> but not a long time for traits to devolve.
2099 -> - Yeah, exactly.
2100.24 -> - Which generally is true
of human behavior too,
2104.35 -> although it depends.
2106.161 -> We can all do better, nonetheless.
2107.757 -> - [Justin Sonnenburg] Very interesting.
2108.75 -> - So I have a puzzle
or a bit of a conundrum
2114.31 -> around this notion of
species of microbiota.
2117.54 -> So if the pH, if the acidity
2121.129 -> differs along the digestive tract,
2123.77 -> but is more or less fixed
for a given location, right?
2126.11 -> I mean, unless something's really off,
2127.31 -> the pH of the stomach is
within a particular range,
2129.92 -> and the intestines and so forth.
2132.55 -> And certain microbiota
thrive at a given station,
2136.98 -> a given location along
the digestive tract,
2139.53 -> and the pH is sort of fixed more or less.
2143.59 -> I'm trying to figure out,
2145.58 -> what is allowing certain microbiota
2147.95 -> to stay in a given location?
2149.97 -> Why don't they migrate up or down?
2151.7 -> So are they pH sensitive,
2152.99 -> and that's what they're
selecting for along the tract?
2156.31 -> And I'm also trying to figure
out how these changes in food
2161.09 -> so robustly change the microbiome.
2163.44 -> The way you describe it
almost makes it sound
2165.03 -> like food is the variable
that's going to dictate
2167.85 -> the quality of the microbiome,
2169.78 -> although I'm sure there
are other factors as well.
2171.96 -> And then in the back of my mind,
2173.46 -> I don't know that I want
to ask this question,
2175.25 -> but I really want to ask this question,
2176.7 -> which is, where are they in there exactly,
2179.77 -> and why don't they all get flushed out?
2181.71 -> Right?
- Right.
2182.61 -> - If 30% of fecal matter is microbiota,
2187.5 -> then where are they living?
2189.39 -> Are they along the lining,
and the little microvilli
2193.73 -> of the intestine, and
what are they attaching to
2196.564 -> and interacting with?
2198.17 -> we know there are neurons in there,
2200.74 -> especially within the stomach,
2201.94 -> there's a lot of work now being done
2203.68 -> on the gut neurons and how they signal
2205.9 -> to the brain and so forth.
2207.38 -> But who are they talking to in terms
2209.35 -> of the host cells?
- Yeah.
2212.43 -> - Because if it's just from food,
2214.09 -> I imagine that they're in
there having their good time,
2216.1 -> or not, and then some are
getting flushed out or not,
2219.97 -> but how do they actually stay in there?
2221.89 -> - Yeah.
- Who are they attaching to?
2223.43 -> What are they talking about?
What are they doing for fun?
2225.85 -> - Yeah.
- And so forth.
2226.683 -> - Yeah, yeah. Super interesting.
2228.33 -> So I'll come back to
the attachment question,
2231.79 -> and kind of why they don't get washed out,
2233.75 -> 'cause this is a super
fascinating question.
2235.83 -> And I think your initial point of like,
2239.389 -> the kind of regional
differences in what's happening
2243.41 -> in terms of physiology, biochemistry
2245.44 -> along the length of the
gut is really interesting.
2247.65 -> There certainly is a pH gradient
2249.32 -> along the length of the gut.
2250.59 -> There is actually
bicarbonate that's secreted
2253.68 -> into the small intestine to
try to neutralize stomach acid.
2257.38 -> There also is bile that's secreted.
2259.511 -> That creates a different
chemical environment in there,
2262.82 -> bio-loving bacteria that kind of live
2265.49 -> in that region of the gut.
2267.03 -> And then there is a nutrient gradient,
2271.18 -> just because as food leaves the stomach,
2275.27 -> a lot of the simple
nutrients are absorbed.
2278.38 -> And so you might see microbes
in the small intestine,
2281.86 -> for instance, that are better
at consuming simple sugars,
2284.72 -> but you won't find many
microbes in the colon like that,
2287.22 -> because all the simple sugars
2288.43 -> have been depleted at that point.
2290.28 -> And then the immune system
is a big factor as well.
2293.597 -> And the immune system is incredibly active
2296.39 -> in the small intestine.
2298.31 -> The small intestine is
this really interesting
2300.17 -> challenge for the host, because
it's a tissue that's been...
2302.87 -> Its purpose is mainly absorptive.
2304.756 -> And so there has to be
flow of a lot of things,
2310.41 -> a lot of nutrients from
the luminal contents
2315.09 -> into host cells.
2316.7 -> And so that means the barrier
can't be as fortified.
2320.68 -> And so the immune system
is incredibly active
2324.34 -> in the small intestine to
make sure that microbes
2326.83 -> aren't getting so close, and
if they are getting close,
2329.91 -> there's a response to
them to put them back
2331.86 -> in their right location.
2335.417 -> And then along this whole kind
of architecture of the gut,
2341.056 -> there's the longitudinal gradients,
2344.01 -> things like pH and so forth.
2346.012 -> And I should say that pH starts
to drop again in the colon,
2349.5 -> because a lot of those
microbes are fermenting things
2352.21 -> and producing acids.
2353.83 -> And so you actually end up
with the pH starting to drop,
2357.93 -> not as low as the stomach,
but starting to drop again
2359.857 -> if there's a lot of fermentation
happening in the colon.
2363.83 -> In addition, you also have a gradient
2365.73 -> from the host surface epithelium
2368.74 -> out to the middle of the gut.
2371.66 -> And that is likely the key for
what is retained in the gut
2378.16 -> and how the community isn't washed out.
2381.16 -> So lining the gut, we
have epithelial cells.
2384.62 -> In the small intestine,
they're largely absorbative.
2386.625 -> In the colon, there's a
lot of mucus production.
2390.257 -> And we also see this
in the small intestine,
2393.62 -> and this mucus lining is this
substance that we secrete,
2398.47 -> largely made of carbohydrate actually.
2401 -> And the purpose of that
is to keep microbes
2404.96 -> in the right spot and to allow nutrients
2408.93 -> and water to be absorbed
in the small intestine
2411.84 -> and large intestine.
2412.68 -> And so it's this mesh
work that is supposed
2415.27 -> to keep out large things
like back to and lead,
2417.51 -> and small things like nutrients.
2420.84 -> That mucus layer is, it
turns over more slowly
2426.38 -> than the luminal contents passing by.
2429.44 -> And so if a microbe learns to
hold onto that mucus layer,
2434.11 -> it can actually resist the flow
of the contents of the gut.
2439.71 -> And so there there's
many microbes in the gut
2442.36 -> that are not just good
at attaching to mucus,
2444.58 -> but also good at nibbling
on it, at eating it.
2448.36 -> And there are these bacteria,
2449.95 -> like Akkermansia
muciniphila, mucus-loving.
2453.108 -> One of its main things it
does is actually eat mucus
2456.58 -> in the gut, that's its lifestyle.
2458.127 -> And so there's an incredible
gradient of activity
2464.06 -> from the host tissue,
2465.2 -> working your way out to
the middle of the gut.
2467.26 -> What's amazing is some microbes actually
2469.35 -> do penetrate past the mucus,
2471.11 -> and there are these invaginations
2473 -> in the intestine known as crypts,
2475.2 -> actually where the stem cells live
2476.996 -> that produce the epithelium,
2478.96 -> and there are microbial communities
2480.79 -> that can form in those crypts.
2482.72 -> And we don't know completely
what their function is,
2484.973 -> but we've done some studies
that appear to indicate
2487.86 -> that if you can localize to a crypt,
2490.62 -> you've hit the jackpot as a microbe
2492.882 -> for being able to maintain
dominance in the gut.
2496.48 -> So if you sit in the crypt
and something similar to you,
2500.38 -> another microbe that's similar
to you, comes into the gut,
2502.92 -> you can actually exclude that microbe.
2505.39 -> And the thinking is that
it can't find a spot
2509.39 -> to resist being washed out of the gut.
2512.08 -> So there probably are these little niches
2514.08 -> close to host tissue in the mucus
2515.93 -> that are absolutely essential
2517.454 -> for resisting getting washed out
2520.284 -> with the flow of all the contents.
2522.92 -> - Incredible.
2524.52 -> That raises a question about two things
2526.65 -> that are reasonably popular.
2528.99 -> One is this notion of cleanses,
from either direction.
2533.11 -> People will consume things by mouth to try
2535.06 -> and cleanse their digestive tract.
2537.15 -> This there's a long history of this.
2538.57 -> I'm not recommending this.
2540.3 -> There's differing
opinions on whether or not
2541.9 -> this is good or bad.
2543.05 -> And the other is fasting
or time-restricted feeding.
2546.95 -> The reason I ask about
time-restricted feeding,
2549.82 -> is my understanding is
that after a prolonged
2552.97 -> period of fasting, there's
some auto-absorption
2556.59 -> or digestion of one's own digestive tract,
2560.91 -> that then gets renewed.
2561.9 -> In other words, you're testing and stomach
2563.83 -> start eating its own lining to some extent
2565.76 -> in the absence of food.
2567.16 -> So what do we know about cleanses?
2569.27 -> Oh, and then I suppose there's cleanses
2570.5 -> from the other direction too, right?
2571.91 -> Which, less popular, but I've
never run the statistics,
2575.78 -> but certainly exist out there.
2580.46 -> What's the idea about cleanses and fasting
2583.75 -> as it relates to the
health or the dysbiosis
2586.21 -> of the microbiota?
2587.54 -> - Yeah, there hasn't been a
lot of high quality science
2590.76 -> in this area, and so it's
really hard to conclude
2592.9 -> whether these are good for
health or bad for health.
2595.327 -> I think the fasting...
2599.05 -> We're in a really interesting situation
2601.194 -> in the industrialized world,
2603.12 -> because we have so many problems
2604.75 -> associated with our digestive tract,
2606.52 -> and that probably has to do
with our highly processed diet
2610.16 -> and perhaps having a microbiota
2611.85 -> that's fairly perturbed as well.
2614.02 -> And so,
2617.66 -> whether doing things like
this are good or bad,
2624.385 -> it's really hard to define,
because we may be starting off
2628.33 -> in a fairly bad state anyway.
2630.43 -> There's so many diseases
that we're dealing with,
2633.28 -> metabolic syndrome,
inflammatory bowel disease,
2636.14 -> that just put a massive
portion of the population
2640.43 -> in a very different category
than people that are thinking
2643.88 -> about how do I maintain health,
how do I live a long life,
2647.84 -> from starting off in what we consider
2650.04 -> a fairly healthy state.
2651.53 -> And so things like fasting
and a lot of other therapies
2656.94 -> that have been developed in the field,
2659.092 -> I think ketogenic diet may
be in this category as well.
2663.73 -> There can be tremendous benefits
in terms of their impact
2668.6 -> in the context of metabolic syndrome,
2670.89 -> and for people that are battling
2673.313 -> eating a continual bad diet
or something like that.
2677.537 -> - And adherence.
2678.75 -> I think one of the one of the
reasons for the popularity
2681.15 -> of intermittent fasting,
time-restricted feeding,
2685.6 -> and what do they call them now?
2688.44 -> Exclusion diets, where you
entire entirely exclude meat,
2691.39 -> or you entirely exclude
plants or whatever it is,
2693.44 -> is that adherence is sometimes
easier in the all or none.
2698.185 -> As neurobiologists, we think
of it as a go, no-go circuitry.
2700.97 -> It's harder to make decisions,
2704.59 -> nuanced decisions often,
about food than it is
2706.78 -> to just eliminate entire
categories of food.
2709.47 -> Not eating, for many people-
- Yeah.
2711.49 -> - Is easier than eating smaller portions.
2713.604 -> - Yeah, yeah.
2715.077 -> Yeah, and-
- Yeah.
2716.69 -> So some of it, I think,
2717.523 -> is neurobiological and psychological.
2719.2 -> - Absolutely.
2720.05 -> And we've had gastroenterology
fellows in our lab
2722.64 -> that come in and we kind of...
2724.53 -> I think that to kind of
slice through the nuance
2728.1 -> of all this, there's a very simple recipe
2730.15 -> and a really well
accepted, broad definition
2733.11 -> of what a healthy diet is.
2734.54 -> kind of the Mediterranean
diet, plant-based diet is...
2739.03 -> There's just a ton of data
that particularly people
2741.78 -> of European ancestry, but
there's a pretty broad acceptance
2745.885 -> that if you eat mostly
plants, for most people,
2749.41 -> that's going to be very
healthy, to the point where...
2752.849 -> A wonderful colleague of
ours, Christopher Gardner,
2755.53 -> who's studied diet his whole life,
2758.95 -> trying to establish
what a healthy diet is.
2760.93 -> And people was giving advice,
I saw him giving advice
2763.23 -> to a dietician who is
trying to get all the rules
2766.573 -> of what she should be
recommending to people
2770.47 -> that she deals with that are
interested in a healthy diet.
2772.88 -> And she said, so the number
one, I'm going to say,
2774.92 -> plant-based fiber is
probably super important,
2777.877 -> and that should be very high on the list.
2780.08 -> And she goes on to number
two and he said, stop.
2783.38 -> He said, if people do number one well,
2786.58 -> you don't need to know any other rules.
2788.54 -> I mean, it's basically
like if you can have
2790.84 -> a high fiber, plant-based diet,
2793.48 -> for most people, at least,
2794.829 -> talking about the bucket of people
2796.36 -> that are already in a healthy state,
2798.2 -> you don't really need to
think about other things,
2799.87 -> because you can't eat too much meat,
2801.35 -> you can't eat too many sweets.
2802.59 -> You've already eaten a huge
amount of plant-based fiber.
2805.384 -> Your gut is full, you're
not going to be hungry.
2809.46 -> And it kind of takes care of worrying
2812.04 -> about what should I eat or
what, what shouldn't I eat.
2814.29 -> Just eat a ton of whole
grains, legumes, vegetables,
2819.993 -> fruit that's high fiber
based, not high sugar.
2822.59 -> - Does it completely exclude
meat, and fish and dairy?
2825.66 -> - And he was saying people can
add their own spins on this.
2829 -> But I think that the main
rule is just start off with...
2832.777 -> And it kind of gets back to,
2834.18 -> to Michael Pollan's mantra,
2837.63 -> eat food, not too much, mostly plants.
2840.03 -> I think if you stick
with these simple rules,
2842.95 -> and don't overthink,
like, should I have this?
2844.951 -> Can I eat eggs? Can I eat...
2847.11 -> Just kind of stick to these simple rules,
2848.76 -> it makes it very approachable.
2850.44 -> But I agree, so these
gastroenterology fellows
2852.65 -> that we've had in our lab say that they...
2854.57 -> It's really hard.
2855.403 -> We kind of say to them,
2856.63 -> why won't you give this dietary advice
2858.56 -> that's really well-known.
2859.75 -> And they just said, well,
it's, it's really hard
2861.71 -> to get people to change their diet,
2863.364 -> unless you're doing either
a go, no-go sort of thing,
2867.21 -> or eliminating something.
2869.03 -> So if carrots are giving you
problems, don't eat carrots.
2872 -> And that's a very simple,
easy instruction to follow,
2875.53 -> but doesn't really deal
with the root problem
2878.94 -> of why can't you eat carrots,
2880.89 -> because you should be able to eat carrots.
2882.75 -> Most people can eat carrots.
2884.16 -> And so I think that we...
2890.36 -> Yeah, when we're thinking
about things like fasting,
2895.28 -> and all these different dietary regimes
2898.15 -> and cleanses that people do,
2900.73 -> we have to step back for
a moment and say, okay,
2902.61 -> well, what are really the big,
2905.23 -> high level rules that we should take home?
2907.62 -> And then if you are experiencing problems,
2909.85 -> and you want to think about
how to deal with them,
2911.59 -> it's good to go to an
evidence-based method
2913.289 -> where there's actually data to back it up.
2915.91 -> The data in the field really
shows that with like fasting,
2920.57 -> particularly if you go to
animals that hibernate,
2923.51 -> or things like that, where
there's really extended fasts,
2925.7 -> you actually have a microbiota come up
2928.972 -> that blooms in the absence
2931.445 -> of food coming in through diet
2933.969 -> that's really good at eating mucus.
2936.961 -> So you have bacteria
that's that specialize
2941.13 -> in eating nutrients derived from the host,
2943.23 -> because there's no other
nutrients to live on.
2945.56 -> Now, whether this is good
or bad, we don't know.
2948.42 -> But it seems like the
consumption of mucus in excess
2955.44 -> is a problem from the
standpoint of microbes
2958.99 -> getting too close to host tissue
and inciting inflammation,
2961.68 -> which is what we see in animal models
2963.28 -> when we deprive of dietary fiber.
2965.77 -> We see these mucus
utilizers become abundant,
2968.46 -> and inflammatory markers start to come on.
2970.737 -> So fasting short term
might be fine, probably.
2975.24 -> There's definitely benefits
that are seen metabolically.
2977.94 -> In terms of what it means
for long term health
2980.51 -> from the standpoint of the gut microbiota,
2982.33 -> I would say we don't have
the answer to that yet.
2984.72 -> In terms of the cleanses and
the flushes and all this,
2988.84 -> personally, I think it's a terrible idea.
2991.07 -> I mean, we know that if...
2993.752 -> In studies that are being
done now to reprogram
2996.62 -> the gut microbiota to install
2998.06 -> a completely new microbial community,
3000.36 -> the first step is to wash away
3002.5 -> the resident microbial
community that's there.
3004.9 -> So if you're in the process of acquiring
3007.06 -> a really good microbiota
and you know how to do that,
3009.76 -> then flushing everything out is great.
3012.17 -> Otherwise, what is happening
is you're kind of leaving
3016.11 -> rebuilding of the community
to chance, like what is it?
3019.61 -> And so what microbes
are going to colonize?
3023.24 -> Who's going to take up space
3024.38 -> after you do this flush or cleanse?
3026.61 -> And I think it's a little bit
3030.1 -> like playing Russian Roulette.
3031.21 -> You may end up with a
good microbial community
3034.07 -> in there afterwards, you may not.
3036.07 -> You certainly want to pay close attention
3037.71 -> to what you're eating while you're doing
3039.9 -> the reconstitution of the community
3041.38 -> after you do something like that.
3043.09 -> - Yeah.
3043.933 -> Thank you for that.
3045.18 -> I know a lot of people are interested
3046.55 -> in these kinds of elimination diets.
3048.47 -> And intermittent fasting/
time-restricted feeding
3052.04 -> seems to be getting
some traction, in part,
3053.7 -> because at some level we are
all doing this when we sleep.
3057.81 -> Most of us aren't eating
while we sleep anyway,
3059.75 -> and adjusting the numbers
seems more accessible
3063.83 -> for a lot of people.
3064.663 -> We have a lot of colleagues at Stanford
3065.71 -> who I know happen to of that regimen,
3068.95 -> or a time-restricted feeding regimen,
3070.79 -> but also who follow the more
traditional meal spacing
3075.42 -> as well, of course.
3077.694 -> One of the things that I wonder about
3080.34 -> as we talk about primarily
plant-based with some,
3083.163 -> what did you say the Pollan thing was?
3085.09 -> It was eat mostly plants
and then maybe some meat,
3088.86 -> but not too much, or not
3090.1 -> too much...
- Yeah, eat food,
3090.933 -> mostly plants, not too much.
- Got it.
3092.94 -> - Or sorry, eat food, not
too much, mostly plants.
3095.13 -> - Got it.
3098.953 -> I hear this again and again.
3100.46 -> I know there are a number of
people who do seem to do well
3103.507 -> on a lower carbohydrate, and
even some people who report
3108.24 -> feeling much better on a really strictly,
3111.6 -> almost meat, organ-only diet.
3113.54 -> And the only reason I raise is not...
3115.55 -> I don't participate in...
3116.95 -> I'm one of those omnivores that out there,
3121.08 -> I do eat some meat and
I do eat plants as well.
3124.56 -> But the reason I raise
this is that earlier
3126.77 -> you were talking about communities
3129.07 -> that may have microbiota
that are healthier than ours,
3133.39 -> or at least different than ours.
3135.01 -> And there are communities in the world
3136.486 -> that subsist largely on animal products,
3140.62 -> or for which unprocessed animal products
3143.5 -> are considered the richest-nutrient foods
3145.95 -> in those communities.
3147.13 -> Protein is very scarce in...
3149.225 -> Ancestrally, protein was more scarce,
3151.94 -> so eggs and meat and things of that sort.
3153.73 -> So could there be a genetic component?
3155.42 -> In other words, if we
fast forward 10 years
3157.149 -> and we actually can make sense
3158.88 -> of all this human genome stuff,
3160.31 -> are we going to find that someone
who has Scandinavian roots,
3165.171 -> or somebody who has South American roots,
3167.22 -> or somebody had descended
from a different tribe,
3169.74 -> will do better on one
particular diet versus another,
3172.59 -> and thereby, or I should say,
and in parallel with that,
3176.36 -> that their gut microbiome
3177.51 -> will have different signatures that are...
3179.29 -> So your microbiome might thrive on plants
3182.08 -> and mine might thrive on organ meats.
3184.23 -> And as I say this, I'm not a
big consumer of organ meats.
3186.518 -> I'm just laying this
out for sake of example.
3189.33 -> - Yeah.
3190.5 -> Yeah, great.
3191.84 -> So,
3194.58 -> a few notes, the first one
has to do with carbohydrates
3198.93 -> and restriction of carbohydrates,
3200.34 -> and some people feeling healthier
3201.79 -> when they cut carbohydrates out.
3203.79 -> My guess is...
3205.79 -> This is my theory to be tested,
3209.825 -> that people feel better
cutting carbohydrates out,
3213.36 -> because the diet that we
eat in the United States
3217.5 -> and in industrialized countries,
3219.124 -> the carbohydrates are largely crap.
3222.29 -> - Processed.
- They're processed.
3223.476 -> - Right.
- It's like starch,
3224.85 -> simple sugar.
3226.39 -> It's things that contribute
to glycemic index.
3229.13 -> It's these sugars that we eat.
3232.21 -> They make it to our small intestine,
3233.867 -> they get chopped up into simple sugars,
3236.76 -> absorbed into our bloodstream,
3238.17 -> and we have a ton of glucose then
3239.81 -> coursing through our
veins, which we know is bad
3242.44 -> and can lead to things like diabetes.
3245.75 -> If the carbohydrates that were in our diet
3248.92 -> were complex carbohydrates, dietary fiber,
3252.81 -> and we like to refer to
the subset of dietary fiber
3255.65 -> that the microbiota can actually access
3258.09 -> as microbiota-accessible carbohydrates.
3261.56 -> And the reason that we like that term
3262.96 -> is it has the word carbohydrate in it.
3264.84 -> And it's to point out that
not all carbs are bad,
3268.28 -> it's just, there are bad carbs or carbs,
3270.434 -> or carbs that are bad if you consume them
3272.1 -> in too high quantity,
3273.14 -> things like table sugar
and simple starches,
3276.422 -> but there are good carbs as well.
3278.5 -> And these microbiota-accessible
carbohydrates
3280.93 -> are the complex ones that we can't digest,
3283 -> and fuel our got microbiota,
3286.2 -> our gut microbiota can ferment them.
3290.931 -> I think we probably
all would be better off
3295.61 -> with less of the carbs that
we're typically served,
3299.03 -> but most of us, and probably
the vast majority of us
3303.054 -> would be better off by
consuming a lot more carbs
3306.82 -> that were complex, that
we're microbiotic-accessible.
3309.7 -> And I'll come back to why that's important
3311.62 -> in terms of our biology.
3312.68 -> There's some mechanisms
that are known as to why
3315.6 -> those complex carbohydrates
are so important
3317.47 -> for our health, for most of us.
3320.494 -> I think this aspect of human
genetic adaptation to diet
3323.86 -> is super interesting.
3325.45 -> And then layer on top
of that got microbiota
3328.326 -> adaptation to diet, which
is another layer of this
3331.41 -> that is also fascinating.
3333.2 -> It's very clear that over
very short periods of time,
3335.85 -> humans can adapt to
differences in their diet,
3338.61 -> lactase persistence as kind of
3340.25 -> the classic example of this.
3341.83 -> Just over the past 10,000 years,
3345.439 -> certain groups of humans have adapted
3349.03 -> to being able to consume
dairy by taking this enzyme,
3353.67 -> lactase, that normally is just expressed
3355.7 -> in most of the world's
population early in life
3357.831 -> to be able to metabolize
lactose in breast milk.
3362.562 -> By extending the expression
of that throughout life,
3365.87 -> now you can consume milk
for your whole life.
3369.08 -> And so that is an example
of specific populations
3372.5 -> of human genome,
genetically adapting to diet
3376.66 -> in a very short period of time.
3377.96 -> And there are other examples
of this, and undoubtedly,
3380.4 -> this has happened throughout the world
3382.49 -> to various aspects of diets.
3383.78 -> So certainly it's important to remember
3386.11 -> that there will be different diets
3390.01 -> that are better for different groups,
3391.93 -> based on what genes you harbor and have
3395.9 -> in your human genome.
3397.49 -> The other aspect on top of that is that,
3401.57 -> there are good examples
of the gut microbiome
3406.42 -> adapting to cultural differences in diet.
3409.11 -> And the classic example of this
3410.619 -> is the degradation of seaweed.
3414.04 -> So we know that most
Americans, if you eat sushi,
3417.89 -> and there's nori there and
you eat some of the seaweed,
3422.938 -> it has a dietary fiber
in it known as porphyrin.
3426.92 -> That porphyrin will shoot
through most of us untransformed.
3430.2 -> Inert substance.
3431.478 -> It'll do other things like retain water,
3433.61 -> and serve as kind of
something like cellulose,
3435.69 -> not be fermented at a high level.
3438.82 -> If somebody from Southeast Asia
3440.32 -> that's always consumed seaweed,
3443.2 -> and is part of a culture
that consumes seaweed,
3445.56 -> eats seaweed, they have a gut microbe
3447.897 -> that can now metabolize porphyrin.
3451.21 -> And so there are these very
specific gene transfer events
3454.57 -> where the genes for
breaking down porphyrin
3457.47 -> have been imported into the microbiome
3460.834 -> of many people in Southeast Asia to...
3465.39 -> We can think of it as
helping digest porphyrin,
3467.52 -> but it's really just a
microbe that's found a niche,
3470.14 -> found a way to make a living in the gut
3472.44 -> by consuming something that's
common in the diet there.
3475.48 -> So there are these different layers,
3476.73 -> there are human genetic adaptations,
3478.24 -> and there are microbiome
adaptations that are cultural,
3480.776 -> and based on people's geographic location.
3483.98 -> But there's no escaping the fact
3487.35 -> that for much of human evolution,
3489.65 -> the vast majority of people
that are on this planet
3493.79 -> had ancestors that were
hunter-gatherers, foraging,
3498.65 -> consuming huge quantities
of plant material,
3502.12 -> just because that's what was there.
3504.37 -> And so one of the groups that we study,
3506.24 -> the Hadza hunter-gatherers in Africa,
3508.65 -> and I should take a moment
just to say that our research,
3513.974 -> and research of many people
in our field and other fields
3516.82 -> rely on study of indigenous communities.
3519.96 -> And it's really important to
think of these communities,
3523.67 -> as our equals, they're
modern people on the planet.
3528.53 -> They have interesting
lifestyles that are informative
3530.9 -> with regard to certain
aspects of human biology,
3534.53 -> but in many cases, they also are
3537.66 -> leading a vulnerable existence.
3539.92 -> And so we really take great
care in our research program,
3542.64 -> and it's important for people to realize
3544.23 -> that these populations
take part in our research,
3547.37 -> because they're wonderful
research partners.
3549.66 -> And we need to be mindful
of kind of thinking
3552.35 -> about how, yeah, both we talk
about them and use our data
3557.032 -> that has been gained through
their generous contribution
3561.08 -> to our research program.
3562.72 -> The Hadza hunter-gatherers,
it's estimated,
3564.69 -> consume on the order 100 to 150 grams
3567.7 -> of dietary fiber per day,
3569.349 -> and that's in stark contrast
to the typical American
3572.91 -> that consumes about 15 grams.
3575.52 -> So somewhere, a seven to tenfold decrease
3578.299 -> in the main nutrient that
feeds are got microbiome
3581.672 -> in the American diet.
3583.73 -> The Hadza are one example.
3588.01 -> There are many different
foraging populations,
3590.74 -> but the vast majority of these populations
3593.558 -> consume huge amounts of dietary fiber,
3596.72 -> because plants are the
reliable, consistent source.
3600.46 -> If you, as a hunter-gatherer go on a hunt,
3603.91 -> usually that hunt is unsuccessful.
3606.44 -> I think the data that one out
of 20 hunts are successful
3610.97 -> in landing actually
big game for the Hadza.
3613.74 -> They have birds that they
shoot and small animals,
3617.53 -> but quite often, day after day,
3619.84 -> they're relying upon berries,
tubers, baobab fruit.
3625.14 -> They're relying on the
plants in their environment.
3627.6 -> And actually if you go
to the data and look
3630.74 -> at what their fruit food preferences are,
3633.37 -> their food preferences are
actually meat and honey.
3635.93 -> So they don't eat a high fiber
diet because they love fiber.
3639.38 -> They eat a high fiber diet,
3640.53 -> because that's what's
available and consistent
3643.183 -> for them to survive.
3645.84 -> But our brains are wired
for caloric density.
3649.01 -> And so if you took a Hadza
and put them in a restaurant
3651.69 -> in the United States,
3652.91 -> they would make the same
crappy decisions that we make,
3655.24 -> because we all want sugar
and fat and calories.
3659.51 -> It's how our brain is wired.
3661.44 -> - And protein and fat
for brain development,
3663.77 -> as far as we know, right?
3664.76 -> So it sounds like the Hadza,
3666.84 -> I hope I'm pronouncing that correctly,
3668.35 -> you said would prefer
to eat meat and honey,
3672.06 -> but they happen to consume
a lot of plant fiber
3675.57 -> as a consequence of what's available.
3678.753 -> One of the questions I have
as it relates to all of this,
3683.54 -> is it sounds to me like
there is no question
3689.02 -> from the pure vegan all the
way to the extreme opposite,
3694.63 -> which would be pure meat diet,
3697.055 -> that avoiding processed
foods is a good idea.
3700.15 -> - Yeah.
- Or heavily processed foods,
3702.19 -> in general and I mean, not
that the occasional consumption
3705.42 -> is necessarily bad.
3707.9 -> But whether or not one is thinking
3710.41 -> about one macronutrient
profile or another,
3712.48 -> it sounds like consuming processed foods
3714.82 -> is just bad for the microbiome.
3716.73 -> Can we say that categorically?
3718.54 -> For sure, yeah, yeah.
- Okay.
3719.412 -> - Absolutely.
3720.554 -> - So you're a low carb person,
you're a zero carb person,
3722.71 -> you're extreme vegan, no meat.
3724.54 -> Whether or not you're
all meat, organ meat.
3726.56 -> Sounds to me as if the number one thing,
3730.15 -> maybe even, dare I say above
Chris's point about plants,
3734.84 -> although I'm not going to challenge
Chris Gardner on nutrition,
3737.29 -> I would be way outside
the lane lines to do that.
3740.21 -> But is it to avoiding processed foods?
3742.54 -> - Yeah.
- Is paramount.
3743.96 -> - Yeah, and I think that's
completely compatible
3746.08 -> with what Christopher was saying.
3747.02 -> He was saying, if you
prioritize getting a huge amount
3750.11 -> of whole, plant-based food
with a lot of fiber first,
3755.01 -> you're not going to have room
3756.05 -> for eating a lot of processed food.
3757.281 -> - [Andrew Huberman] Yeah, yeah.
3758.114 -> - So it's kind of the same
as avoiding processed food.
3760.13 -> So I think that those are
exactly the same rule,
3762.35 -> and I think that you're exactly right.
3764.437 -> And we can break down...
3766.194 -> There's a lot of data of
why different components
3768.46 -> of processed food are so bad for us,
3770.06 -> and so bad for our microbiome.
3771.5 -> And I can talk about a
few examples of that.
3773.73 -> But the flip side of this
is this mechanism of...
3777.84 -> And again, thinking about the
spectrum of a plant-based diet
3781.09 -> versus a meat-based diet.
3783.122 -> There's a lot of data to tell us
3787.36 -> that a meat or ketogenic, or high fat diet
3790.65 -> may have big benefits in terms
3793.25 -> of short term metabolic health.
3794.64 -> That's typically how people
think about that diet.
3796.871 -> There's also a lot of heart disease
3798.77 -> that's linked with that as well.
3800.02 -> There's good literature for that,
3801.21 -> which is something for people
to look at and be aware of.
3805.08 -> The plant-based diet, if you're
eating a bunch of complex
3809.069 -> fibers that feed your gut microbiota,
3811.89 -> your gut microbiota
produces these substances
3814.72 -> called short-chain fatty
acids, things like butyrate.
3817.52 -> And it's known that these
short-chain fatty acids
3820.22 -> play really essential components,
3821.647 -> both in terms of fueling
colonocytes, enforcing the barrier,
3825.65 -> keeping inflammation low,
regulating the immune system,
3828.23 -> regulating metabolism.
3829.84 -> And so a lot of people
think of dietary fiber
3833.49 -> as this inert substance
that passes through,
3835.55 -> makes this feel full
maybe for a little bit,
3837.41 -> but we get hungry afterwards right away.
3839.16 -> If you're eating a lot of fiber
3840.44 -> that's feeding your gut microbiota,
3841.822 -> your gut microbiota is just
producing this vast array
3845.738 -> of fermentation end products
3848.53 -> that then get absorbed
into our bloodstream,
3851.02 -> and have all of these
tremendous, cascading effects
3853.57 -> that appear to be largely
beneficial on our biology.
3857.14 -> And so to think about that
paradigm of simple carbs,
3859.93 -> versus complex carbs, in
the case of simple carbs,
3862.63 -> you end up with high blood sugar,
3864.1 -> something that will spike your insulin,
3866.78 -> and have all kinds of
weird, metabolic effects.
3869.44 -> In the case of complex carbohydrates,
3871.145 -> you'll end up with very low blood sugar,
3874.11 -> because most of those
have low glycemic index
3876.138 -> and a bunch of short-chain fatty acids
3878.44 -> that are having regulatory roles.
3879.9 -> So just to round out that topic,
3882.89 -> I think there is a reason to think that,
3885.131 -> maybe not appropriate for
absolutely everyone out there,
3888.48 -> but I think the vast majority of people,
3891.2 -> particularly given the statistics
of what we know people eat
3894.1 -> in the United States and in
industrialized countries,
3896.92 -> most people would reap
tremendous health benefits
3899.76 -> from eating more whole,
plant-based dietary fiber.
3903.65 -> Now, processed foods, I
think, is this other dimension
3906.38 -> where you have all of
these weird chemicals,
3908.22 -> artificial sweeteners, weird fats,
3911.757 -> a lot of refined, simple nutrients.
3914.63 -> The simple nutrients we've talked about,
3916.13 -> but we know that for instance,
artificial sweeteners
3918.56 -> can have a massive negative
impact on the gut microbiome
3921.27 -> and can lead us towards
metabolic syndrome, actually.
3924 -> There's been beautiful work
3925.43 -> out of the Weizmann Institute on this.
3927.25 -> And then emulsifiers,
3928.73 -> these compounds that are
put in processed foods
3930.877 -> to help them maintain shelf stability
3934.23 -> so things don't separate.
3935.61 -> And so all the the moisture content
3939.27 -> is retained appropriately.
3941.6 -> Many of these are known to
disrupt the mucus layer,
3945.09 -> and as soon as you start
disrupting that barrier,
3947.3 -> that can lead you in the
direction of inflammation
3949.308 -> and in animal models,
3950.98 -> we know that can lead towards
metabolic syndrome as well.
3953.42 -> So there's components of
processed food, that are,
3957.42 -> when studied in isolation known to have
3959.25 -> a direct negative impact on
gut biology in the microbiota.
3962.447 -> - Yeah, the mention of artificial
sweeteners interesting.
3965.586 -> I confess it's a third rail on...
3969.15 -> Talking about artificial sweeteners,
3969.983 -> there are two camps it
seems, or at least two camps.
3973.75 -> One that say artificial sweeteners
3975.7 -> are not detrimental at all.
3977.24 -> Another that says
they're very detrimental,
3978.71 -> mainly based on the mouse studies.
3980.03 -> And then there are people
in the middle that are...
3981.8 -> I put myself in that category.
3982.7 -> I drink the occasional diet soda,
3985.04 -> I don't consume them in large volume,
3986.55 -> but I'm sort of in the middle there.
3989.45 -> And so I just throw that out there,
3990.93 -> because I know immediately
people are jumping on that,
3993.88 -> but I will just mention
there's some recent data
3996.028 -> out of Diego Bohorquez's
lab at Duke University
3998.78 -> that the neurons that
live in the gut mucose
4000.27 -> of these neuro pod cells
can actually distinguish
4003.16 -> between artificial and true sweet...
4006.74 -> Sugar versus artificial sweeteners.
4009.401 -> They send different
patterns of neural signals
4012.26 -> up to the brain, and the brain circuitry
4014.44 -> seems strongly impacted.
4015.81 -> So I think that as the data emerge,
4017.65 -> we're hearing more and more of
these artificial sweeteners.
4020.39 -> Either are problematic
or at least are signaling
4023.01 -> different events in the gut.
4025.93 -> I do want to make sure that we distinguish
4028.532 -> artificial sweeteners
4030.12 -> from non-caloric plant-based sweeteners.
4032.997 -> - Yeah.
- And this is based
4034.27 -> on a mistake that I've
made over and over again
4036.01 -> on the podcast where
I'll just kind of lump
4038.23 -> artificial sweeten into one big category,
4041.145 -> and then I'll mention stevia.
4043.19 -> So what about plant-based sweeteners
4044.97 -> that are not artificial,
4046.59 -> they weren't manufactured in a laboratory,
4048.14 -> like saccharin or sucralose, or aspartame?
4050.848 -> Do we know anything about plant-based,
4053.13 -> non caloric sweeteners or
low caloric sweeteners?
4056.7 -> - Very little.
4057.6 -> A lot of those have a lot
more bang for the buck.
4061.21 -> They're incredibly sweet,
4062.54 -> so it takes a really small amount for them
4064.41 -> to trigger a huge amount of sweetness.
4066.33 -> And so it's, depending upon
the mechanism of action
4070.787 -> by which these sweeteners
that are not sugar
4074.022 -> are impacting our biology.
4077.4 -> It may be that those are
actually less negative
4082.27 -> or more healthy than the
ones that are artificial,
4085.82 -> just because it requires
less of them in the food
4088.51 -> for us to perceive that sweet taste.
4090.32 -> It may also be that because they're...
4092.46 -> I don't think that everything
is that's natural is better,
4095.05 -> necessarily than things
that are artificial,
4097.073 -> but it may be that because of
kind of evolutionary exposure
4101.37 -> to these compounds in our diet,
4103.092 -> historically there are, I think,
4105.23 -> traditional populations that
use these, for instance,
4107.58 -> to sweeten different foods,
that our bodies just know
4113.44 -> how to deal with those compounds better
4115.08 -> than the ones that are synthetic.
4116.781 -> But I think the studies
still need to be done.
4119.98 -> - Do you actively avoid
artificial sweeteners?
4122.5 -> Sucralose, aspartame, saccharin?
4124.78 -> You personally.
- Yeah.
4126.85 -> So I do, I avoid them, but I'm not...
4132.04 -> So I work closely with my
wife, Erica, as you know.
4135.97 -> We were in the lab together
and we wrote this book,
4140.477 -> "The Good Gut," where we
kind of document our journey
4143.52 -> in changing our lifestyle,
dietary habits, choices we make
4147.42 -> based on the research as
we've gotten to know it
4149.31 -> in the gut microbiota
over the past 15 years.
4151.84 -> And I think that one of the
lessons that we've learned
4157.97 -> is that just doing things in moderation
4161.57 -> makes it a lot easier,
and doing things slowly
4165.25 -> makes it a lot easier.
4166.2 -> So there are very few rules that I have
4169.63 -> that are hard and fast.
4170.73 -> I'm a pretty flexible eater.
4172.6 -> I don't believe that having a diet Coke
4175.5 -> will somehow cascade into
some terrible disease
4179.31 -> or something like that.
4180.86 -> I try to avoid them, I don't
really like the flavor of them.
4183.51 -> I'm super sensitive to
the nuances of the flavor,
4187.11 -> even with the stevia and mogrosides
4189.5 -> from monk fruit and stuff like that.
4190.815 -> The off flavors are really
hard for me to deal with.
4195.895 -> But also in this journey
of changing our diet...
4198.83 -> Like when we started off
in microbiome research,
4201.54 -> I was in the habit of in the
afternoons having a sweet,
4204.27 -> a muffin or a cookie,
or something like that.
4206.4 -> And when we started to realize
that we should be eating
4209.77 -> less sweets and eating more dietary fiber,
4212.201 -> this was an incredibly
difficult change for me to make.
4214.96 -> I was just wired to kind of crave this-
4218.31 -> - Classic scientist.
4219.92 -> Scientists love the pastry in
the afternoon and the coffee.
4222.505 -> - Yeah, yeah.
- And in the old days
4224.06 -> it used to be a cigarette too.
4225.71 -> - Right, exactly.
- When I started my training,
4227.103 -> a lot of people still smoked
4229.12 -> - Yeah, right.
4229.953 -> - And it was only during
my post-doctoral training
4232.21 -> that they eliminate smoking on campuses,
4233.97 -> and productivity took
a trough for a while,
4237.061 -> until these people developed other tools
4239.31 -> to focus their attention.
- Exactly, exactly.
4242.37 -> So there is this kind of need,
4244.24 -> and then once you have
an ingrained behavior,
4246.08 -> and maybe things that are addictive,
4247.44 -> it becomes incredibly
difficult to break that habit.
4250.499 -> And so I would say, gradually
over the course of like,
4255.721 -> five or more years, we
have migrated our diet
4260.85 -> away from sweet foods to
things that are less sweet.
4265.86 -> And it's been a journey,
it's been a slow process,
4269.247 -> but we've gotten to the point now
4270.94 -> where we've just retrained our pallets.
4272.8 -> And it's amazing how this happens now,
4275 -> where I'll have something
that is something
4278.27 -> that I would've used to have like daily.
4280.77 -> And it's unpalatable.
4282.84 -> I just can't deal with
the sweetness of it.
4284.94 -> And I certainly avoid
artificial sweeteners,
4288.97 -> but I also avoid just
sweet things in general
4291.48 -> that have sugar in them,
just because they now,
4294.33 -> was originally, I was
trying to be disciplined
4298.55 -> and trying to change my diet,
4299.58 -> but now they just don't taste good to me.
4301.31 -> - Yeah, likewise,
4302.143 -> I completely lost my appetite for sugar
4304.8 -> at the turn of the last year,
4306.02 -> and I don't know how to
explain it, but the way I...
4308.874 -> Even though I don't have
a mechanistic explanation,
4311.65 -> I say I like sweet people, I
don't like sweet food anymore.
4314.47 -> I just don't.
4315.4 -> I have not lost my
appetite for fatty foods.
4318.34 -> I love cheese and certain meats for me,
4322.45 -> I blame my Argentine lineage is,
4325.03 -> is I gravitate towards them.
4327.25 -> But in any case, avoiding processed foods,
4330.53 -> probably avoiding sugars, emulsifiers,
4332.95 -> these kinds of things.
4333.783 -> And for people listening or watching,
4335.85 -> we're not setting up strict guidelines.
4337.8 -> We're just bouncing around the carnival
4341.67 -> that is the microbiome and nutrition,
4344.17 -> because I think that we
hear this everywhere,
4347.45 -> eat this, don't eat that, or
this is best for microbiome,
4349.9 -> or worse for microbiome.
4350.76 -> But I'm hearing fiber again and again,
4352.64 -> so we're going to come back to fiber,
4353.764 -> but I want to make sure
that we close the hatch
4356.75 -> on this issue of fasting and cleansing.
4358.774 -> Based on your answer
earlier, it sounds to me like
4361.69 -> it is not necessary to
do a cleanse or fast
4365.16 -> prior to an attempt to
repopulate the microbiome.
4368.66 -> In other words, if I want to
make my microbiome healthier,
4371.27 -> it sounds like I don't
have to try and flush
4373.35 -> all the current microbiota
out of there first,
4376.31 -> is that correct?
4377.143 -> - Yeah, it's a very good question,
4379.24 -> and I don't mean to
suggest that those things
4380.544 -> are known to be terrible.
4383.84 -> Or I would just say, the
studies haven't been done.
4386.461 -> And to me, wiping out
this microbial community,
4390.448 -> unless it's done with some sort of...
4393.59 -> Unless it's done in an informed way,
4395.3 -> and we don't really have the information
4396.78 -> for how that would be done.
4398.1 -> It just seems like playing
the lottery a little bit.
4401.74 -> - Okay.
- And so I think...
4403.95 -> I don't want to say that those are...
4405.02 -> It may be that when the study is done,
4406.87 -> those are shown to be amazing,
4408.53 -> but I just don't think we have
the data to know that yet.
4410.69 -> So it's somewhat of an arbitrary thing.
4413.08 -> If somebody out there feels
way better when they do this,
4417 -> and are not experiencing problems with it,
4419.083 -> then maybe it's the right thing for them.
4421.02 -> But I certainly can't say that
it's something great to do.
4424.175 -> I can't imagine a future
where as the microbiome
4428.77 -> gets incorporated into
this emerging paradigm
4431.43 -> of precision health, you go into a clinic,
4434.19 -> somebody types your microbiome and says,
4436.15 -> oh, there's this huge,
massive misconfiguration.
4439.38 -> You have all these engrafted bacteria
4441.69 -> that are residents in your gut microbiome
4443.583 -> that are sending out molecules
4446.12 -> that are not good for your health.
4447.73 -> It would be good if we do
a mass-reprogramming of it.
4450.66 -> The way that we do that
is we flush your gut,
4453.68 -> and we actually give a
light antibiotic treatment
4456.11 -> to try to kill everything that's there.
4458.08 -> And then we repopulate
with this other consortium
4461.48 -> of microbes that we've
studied and know are healthy,
4464.16 -> know are compatible
with your human genome,
4465.993 -> and can be reinforced with a diet
4468.136 -> that we know is good for you.
4469.676 -> We'll install those microbes,
4471.71 -> we'll help you along
in the diet so you know
4474.084 -> how to nourish those microbes,
4476.4 -> and that will be the way
that will reconfigure
4478.47 -> your gut microbiome.
4479.41 -> So I can't imagine a future
where that sort of flushing,
4482.89 -> or cleansing is part of something
for repopulating the gut.
4486.7 -> But right now it seems a
little half-baked to me.
4489.89 -> Yeah.
- Great.
4491.97 -> I'd love to talk about
fiber and fermented foods,
4494.96 -> because you and Chris had a really,
4498.5 -> what I think is a really
interesting and exciting paper
4501.66 -> at the end of last year about
comparing the inflammatome,
4506.389 -> so inflammatory markers of people who ate
4510.19 -> a certain amount of fiber,
4511.31 -> or a certain amount of
these fermented foods.
4514.59 -> This study is amazing for several reasons,
4516.71 -> but almost as amazing as how diverse
4521.36 -> the interpretation of this
study was in the media.
4524.69 -> If ever there was a study
that was kind of hijacked
4528.85 -> by different priority schemes out there-
4531.81 -> - Yeah.
- It's this study.
4533.56 -> So you performed the study with Chris,
4536.5 -> and your postdocs, and
graduate students and staff.
4539.35 -> What are the major conclusions
and what sorts of directives,
4542.68 -> if any, emerged from this study?
4544.57 -> And I'll just preface
this again by saying,
4546.82 -> if I wasn't clear, some news report said,
4550.257 -> "Ah, this means fiber is not important."
4552.68 -> - Yeah.
- And then others said,
4554.145 -> this means fermented foods
and fiber are important.
4557.49 -> And others said, fermented
foods are the thing,
4560.12 -> and the only thing.
4561.42 -> It was all over the place.
- Yep.
4563.414 -> - And one of the reasons for
doing this podcast at all
4566.99 -> is so that we can go straight
4568.41 -> to the people who perform the work.
4570.728 -> - Fantastic.
- And even though
4571.561 -> I'm certainly not an expert in microbiome,
4573.67 -> to give you the opportunity
to share with me,
4575.8 -> and me to ask the kinds
of questions that have...
4577.96 -> I have zero agenda.
4579.02 -> I do like sauerkraut, I do
drink the occasional kombucha.
4585.27 -> I do like low sugar, not so
sweet forms of fermented foods.
4589.24 -> So I would be delighted if
fermented foods are good for me,
4591.58 -> but I have no stake in the
fermented and food industry.
4594.55 -> - Yeah, absolutely.
- Yeah.
4595.63 -> - Yeah, yeah. Great.
4597.68 -> Yeah, wonderful, and
an important note there
4600.17 -> is the one you pointed out,
4601.52 -> that this is an incredible collaboration
4603.07 -> with Christopher Gardner's lab,
4604.37 -> and a bunch of people.
4606.84 -> Erica Sonnenburg helped lead
this study, and then tons of,
4609.9 -> like you were saying, postdoc staff
4611.5 -> and other people at Stanford,
4613.85 -> and then wonderful participants
4615.2 -> that were part of this study.
4617.36 -> So a huge team effort.
4619.88 -> Let me tell you, before
I dive into that study,
4621.7 -> let me take a step back,
because I think the reason
4623.89 -> that we did this study, and
kind of Christopher's group,
4626.98 -> and our group has started
to pursue this line
4631.27 -> of looking at dietary interventions
4633.45 -> and how they impact our microbiome,
4634.91 -> how they impact human biology,
4637.203 -> goes back to this kind of
epiphany that we we had
4642.07 -> while studying the gut microbiome.
4643.59 -> Because I think when we started
studying it at Stanford,
4646.54 -> we were thinking about it as this
4648.21 -> kind of newly appreciated
aspect of our biology,
4650.9 -> almost like finding an organ
that we didn't know was there,
4654.913 -> and starting to think about
like all the drug targets
4657.9 -> that were there.
4658.733 -> Can we go in with small molecule drugs,
4660.37 -> and think of ways to
manipulate this community
4661.912 -> to ameliorate disease?
4663.801 -> And this is largely the
mindset of Western medicine,
4667.4 -> and largely born out of the
era of infectious disease.
4670.35 -> You wait for an infection to
start a bacterial infection,
4673.61 -> you treat with antibiotics,
4674.85 -> and that's the way medicine is practiced,
4676.88 -> and that's become less
successful over time,
4679.82 -> as we've moved into this
era of inflammatory,
4683.373 -> Western diseases, and with the exception
4687.53 -> of the current pandemic
that's sweeping the world,
4691.605 -> largely moved out of the
era of infectious diseases,
4695.07 -> at least infectious bacterial diseases,
4697.29 -> that this paradigm of waiting
for diseases to appear,
4701.23 -> and come into the clinic is
not really very effective
4705.05 -> in the context of
inflammatory, Western diseases,
4707.84 -> autoimmune diseases, metabolic syndrome,
4709.906 -> heart diseases, and inflammatory disease.
4712.3 -> The list goes on and on.
4713.92 -> And so we started to
think a lot about like,
4717.96 -> how can we get out in front of this?
4719.39 -> How can we think about preventative ways
4722.28 -> of dealing with this crisis of metabolic
4725.35 -> and inflammatory diseases?
4726.791 -> And this tremendous,
beautiful body of literature
4730.15 -> started to come forward in
the field about 10 years ago
4733.567 -> that showed that the gut
microbiome is absolutely critical
4737.9 -> to modulating our immune status.
4739.77 -> So if you change the microbiome,
4741.75 -> you can fundamentally change
how the immune system operates.
4745.47 -> And we know that the immune system
4747.27 -> is at the basis of a lot of these disease,
4751.24 -> inflammatory, chronic diseases.
4753.48 -> And so it brought up this
possibility that maybe the fact
4756.82 -> that we're not nourishing
this community well enough,
4759.76 -> maybe the fact that it's
deteriorated over time
4763.823 -> due to all of the things that go along
4765.52 -> with an industrialized lifestyle,
antibiotics and so forth.
4769.76 -> Maybe we have a microbiome right now
4772.66 -> in the industrialized
world that is setting
4774.95 -> our immune system at a set
point, simmering inflammation
4778.34 -> that's driving us towards
these inflammatory diseases.
4781.49 -> And wouldn't it be wonderful
if we could figure out how to
4786.73 -> use diet specifically, but
just kind of learn the rules
4790.27 -> of how to reconfigure both the composition
4792.99 -> and function of our gut microbiome,
4794.84 -> so that inflammation was
different in our bodies,
4798.35 -> so that each one of us was less likely
4800.618 -> to go on and to develop
an inflammatory disease,
4803.3 -> leading to better longevity and health
4806.429 -> over the course of our life.
4808.41 -> And so we were studying this
in actually in mouse models,
4814.42 -> and realizing that we really needed
4817.55 -> to start doing human studies.
4819.04 -> We needed to start studying
microbiome in humans,
4823.29 -> and because we were studying diet,
4825.187 -> we knew that this was
something we could go in
4827.34 -> and do right away.
4828.173 -> We didn't have to apply
for FDA approval for a drug
4830.89 -> before we could do a human study,
4832.49 -> we could just start doing
human dietary interventions,
4834.866 -> longitudinally monitoring
the immune system,
4838.206 -> and the microbiome, and starting
to put the pieces together
4841.99 -> of what is it in diet that can change
4843.79 -> our microbiome in a healthy way,
4845.5 -> help us define what a
healthy microbiome is,
4848.26 -> and monitor the immune
system in great detail.
4851.34 -> And so there were really two
critical components of this,
4853.83 -> in addition to our microbiome expertise.
4856.11 -> One was Christopher Gardner's group.
4858.035 -> We wanted to do these human studies,
4860.54 -> but we're absolutely terrified of humans.
4863.08 -> We work with mice. Humans
are terrifying in many ways.
4866.75 -> - But they house themselves,
you don't have to pay-
4868.47 -> - That's true.
- You don't have to pay
4869.303 -> for their housing.
- That's true.
4870.9 -> - For those that can afford
housing, of course, yeah.
4873.484 -> - Yeah, sadly, just for that
portion of the population.
4878.19 -> So Christopher's group were,
4879.27 -> they were our masters at
working with human populations.
4881.97 -> And then the other wonderful
thing that we have at Stanford
4884.47 -> is this Human Immune Monitoring Center
4886.106 -> run by Mark Davis and Holden Maecker.
4888.69 -> They started this beautiful
center for allowing people
4892.7 -> to do immunology in humans.
4895.37 -> Critical element, because
a lot of the mouse studies
4897.78 -> don't translate well to humans.
4899.18 -> So if you can do the studies in humans,
4900.634 -> similar to how we were
thinking about the microbiome,
4903.185 -> you learn something that you
know is relevant to humans.
4905.97 -> And so having that immune
profiling capability
4909.05 -> where we can monitor hundreds to thousands
4911.797 -> of different parameters
in the immune system,
4914.45 -> longitudinally in people,
from a blood draw,
4917.09 -> and not just know if CRP
goes up or if interleukin-6
4920.55 -> goes up or down, but to be
able to see all these facets
4923.43 -> of the immune system change in concert,
4925.32 -> as we're changing the microbiome with diet
4927.5 -> was really a key component of this.
4929.45 -> And so our flagship study,
supported by wonderful donors.
4933.726 -> So this actually isn't
funded by typical foundations
4937.35 -> and national institutes of health,
4938.59 -> it was funded by philanthropy.
4941.48 -> We wanted to understand if we put people
4944.04 -> on a high fiber diet,
4946.04 -> how would that affect their
microbiome immune system?
4948.27 -> And if we put them on a high food diet,
4950.77 -> a diet rich in live microbes
and all the metabolites
4953.66 -> that are present from
fermentation and foods,
4956.36 -> how would that change
microbiome in immune system?
4958.54 -> - Could you give us some examples
4959.66 -> of what those diets look like?
4960.76 -> And were you changing their basal diet,
4962.551 -> or were you just adding things on top
4964.53 -> of what they were already eating?
4966.876 -> 'Cause it's hard to change people's diets.
4969.39 -> - It's very hard.
- And then you have to trust
4970.56 -> that they actually do it and
they're not sneaking, and-
4974.03 -> - Totally, yeah.
4976.979 -> We started this center for
human microbiome studies
4979.5 -> at Stanford for doing
a lot of these studies,
4981.274 -> and a portion of the studies,
we do focus on supplements,
4984.74 -> probiotics, microbes
delivered in pill form.
4987.94 -> Prebiotics, which are
purified forms of fiber.
4991.87 -> And in those cases, we actually
can have placebo groups,
4996.59 -> because it's more like a drug study,
4999.34 -> and we don't change people's diets.
5002.13 -> So we can just administer this
on top of what they're doing.
5004.89 -> So in a way, they're
a lot more controlled,
5006.77 -> but it's not food.
5008.31 -> When you start doing food studies,
5009.95 -> you can't do a placebo group,
5011.49 -> 'cause people know what they're eating.
5013.03 -> And the other problem is that
5016.297 -> it's really hard to just change one thing,
5019.41 -> because as soon as you
start adding something,
5021.71 -> people usually eliminate something else.
5023.53 -> So the idea was to
basically give these people
5026.84 -> simple instructions for in the
case of the high fiber diet,
5030.66 -> just increasing plant-based fiber.
5033.37 -> So can you eat more whole
grains, more legumes,
5035.78 -> more vegetables, nuts, get
the fiber up in the range of,
5040.15 -> from 15 to 20 grams per day,
up to over 40 grams per day.
5044.38 -> So can you double or more the amount
5047.14 -> of fiber that you eat per day,
5048.768 -> knowing that that would
have a tremendous impact
5052.3 -> on a lot of other facets of their diet.
5055.08 -> They eat less meat, animal-based protein,
5060.177 -> less animal-based fats
as a product of this.
5063.113 -> I will say that getting
back to Christopher's rule
5067.58 -> for a healthy diet, a lot of
the macro nutrient changes
5071.91 -> that we saw in their diet were consistent
5075.21 -> with healthy changes in diet.
5077.99 -> Less saturated fat, less
animal-based protein,
5081.17 -> more plant-based protein.
5082.59 -> So a lot of changes that are known
5085.55 -> to be beneficial came in concert
with just telling people,
5088.67 -> eat a high fiber diet, high
plant-based fiber diet.
5093.02 -> The people that were eating
the high fermented food diet,
5098.37 -> they were instructed to basically eat
5102.151 -> foods that you could
buy at a grocery store
5104.76 -> that were naturally fermented
and contain live microbes.
5107.95 -> And so this largely
consisted of yogurt, kefir,
5113.52 -> sauerkraut, kimchi, some
fermented vegetables,
5118.78 -> brined, fermented vegetables.
5120.08 -> - Pickles.
- Pickles, things like that.
5123.78 -> One of the things that
I think is a pitfall
5125.89 -> in choosing fermented foods is,
5127.447 -> you can go down the canned food aisle
5129.85 -> and there's this huge section of pickles,
5132.43 -> and jars that are canned.
5134.45 -> Those are not fermented foods.
5136.32 -> Those are are cucumbers that
they've put in a acidic acid
5139.15 -> and vinegar to reconstitute
that fermented flavor,
5143.1 -> but there's no live
microbes involved in that.
5145.7 -> And even sauerkrauts in
the canned food aisle,
5147.94 -> even if they were naturally fermented,
5149.76 -> quite often they're not.
5150.62 -> Quite often they're
just brined in vinegar.
5154.15 -> But even if they are naturally fermented,
5156.02 -> all the microbes are
killed prior to canning
5158.83 -> or during the process of canning.
5161.394 -> So what we use for this study
5162.82 -> and if you want to have
live fermented foods
5164.7 -> that contain live microbes,
you need to buy those
5166.87 -> out of the refrigerated
section, essentially.
5170.78 -> - And I'm really glad
you pointed this out,
5172.938 -> because you can find sauerkraut
5175.3 -> on the non-refrigerated shelf,
that is indeed non fermented.
5181 -> A lot of fermented that
are available in the US
5184.81 -> can be high in sugar.
5186.77 -> So was there any instruction
as to getting people
5190.02 -> to make sure that they
were consuming yogurts
5192.35 -> that weren't loaded with sugar?
5194.45 -> - Yep.
- Or did you let them just
5195.97 -> select for the stuff in the
cold section that is fermented?
5200.956 -> - No, super important point.
5202.379 -> We instructed people to
eat non-sweetened yogurts.
5207.123 -> I think a huge pitfall in this
area is you can have a yogurt
5211.19 -> loaded with bacteria, kind of
the base of what's healthy,
5214.65 -> and then a ton of like
artificial flavoring
5217.35 -> and sugar loaded on top of that.
5219.02 -> Manufacturers put a ton
of sugar in after the fact
5221.92 -> to kind of mask the sour
taste fermented foods,
5224.47 -> which is hard for some people
to become accustomed to.
5227.41 -> When we were switching
to more fermented foods,
5229.91 -> our daughters were young at that point,
5231.67 -> we would take plain yogurt,
5233.61 -> which they didn't like just neat,
5237.08 -> we would mix in a little
maple syrup or honey,
5240.12 -> just a little bit, and
gradually we would reduced that
5242.68 -> over time to the point where
they're pallet adjusted,
5245.64 -> and now they just really
like plain yogurt.
5248.62 -> But it is, I think, getting
used to that sour flavor
5252.201 -> is difficult, but people
really should try to stay away
5255.1 -> from those fermented foods
that are loaded with sugar.
5257.81 -> And that's what we instructed
people in this study.
5260.14 -> - And beer was not included.
5261.87 -> - Right.
- The number of people
5263.19 -> that asked, when I did a
brief thing on social media
5266.17 -> about this study, and
hopefully I got it right.
5268.1 -> I think I did.
5269.69 -> But people just ask about beer.
5271.19 -> I'm not a drinker, so for me,
beer has no appeal anyway.
5276.06 -> But beer is fermented, correct?
5280.09 -> But were they instructed to
avoid beer or to drink beer?
5283.16 -> - Just to go with their
normal dietary habits,
5285.32 -> but that did not count
as a fermented food.
5287.85 -> - And kombucha was, as I recall-
5289.29 -> - Kombucha was, and kombucha can have
5290.78 -> small amounts of alcohol in it.
5295.85 -> Yeah, kombucha actually
was one of the major things
5297.813 -> that people drank during,
5299.85 -> or consumed during the
fermented food phase.
5302.42 -> And the deal with beer
5307.06 -> is that there may be beneficial properties
5310.69 -> of the microbial communities
in naturally fermented beer,
5313.16 -> but most of the beer that we buy, again,
5314.73 -> is canned and filtered, and
there's no live microbes there.
5318.13 -> So very different than
if you siphon it off
5320.84 -> of your home brew and drink it, probably,
5322.86 -> than if you buy it in a store.
5324.54 -> - I will get to the results of
the study in just one moment.
5327.37 -> But I want to say, a
lot of people shy away
5329.64 -> from the high quality fermented foods,
5331.99 -> because they can be quite costly.
5334.01 -> And I'll just refer people to a resource
5336.3 -> in Tim Ferriss's book, "The 4-Hour Chef,"
5338.74 -> he actually gives an excellent recipe
5340.39 -> for making your own sauerkraut,
5341.65 -> which basically involves
cabbage and water and salt,
5346.58 -> but you have to do it properly,
5348.03 -> because you can grow some,
not necessarily lethal,
5351.67 -> but some somewhat dangerous bacteria
5353.96 -> if you don't scrape off
the top layer properly,
5356.07 -> but he gives beautiful instructions
5357.48 -> for how to do this in vats.
5358.89 -> We've started doing this
at home now, actually,
5361.08 -> is we got a, just ceramic vat.
5362.75 -> And you can make large amounts
of truly fermented sauerkraut
5366.66 -> just from cabbage water and salt,
5368.93 -> if you're willing to follow the protocol.
5370.518 -> And if you're interested in science,
5372.07 -> that protocol looks a
lot like what you'll do
5374.02 -> for most of your graduate career,
5375.88 -> except maybe some sequencing too.
5377.84 -> So anyway, just to
refer people to a source
5379.71 -> that's very low cost.
5381.34 -> - Yeah.
- Compared to buying
5382.55 -> the high quality, fermented foods.
5383.73 -> Even kombuchas, for some
people, it's like $5 a bottle-
5387.41 -> - Totally.
- Only this much.
5388.63 -> And if you consume liquids
the way I consume them,
5390.71 -> that's just the the start, so-
5393.315 -> - Yeah.
5394.83 -> But if you can get your hands on a SCOBY,
5396.94 -> kombucha is another one
that's super simple.
5399.12 -> - You can grow your own.
5399.953 -> - You can just make your own,
5401.06 -> and it's super easy to do.
5402.51 -> I make it, I constantly have a batch
5404.65 -> of kombucha going at home.
5407.286 -> It's a SCOBY, a symbiotic
community of bacteria and yeast.
5412.007 -> You brew tea, you add sugar to
it, and you put the SCOBY in,
5415.58 -> and you wait a week or two,
depending upon the temperature,
5418.24 -> and then you just move the
SCOBY or over to a new batch,
5422.87 -> and you your old, what the
SCOBY was in is kombucha,
5425.56 -> and it's wonderful.
5426.57 -> - I love it, I would love it
if members of this audience
5428.67 -> would start to make their
own kombucha and sauerkraut.
5431.416 -> I've been having so much fun.
5433.25 -> I don't do it, but it's done in our home.
5437.32 -> I don't go anywhere near
the food production,
5439.047 -> and it's for everyone's benefit.
5442.22 -> So how much fermented
food were they consuming?
5446.34 -> 'Cause you mentioned the number
5447.52 -> of grams approximately of fiber,
5450.649 -> but was it in servings, ounces?
5454.2 -> How many times a day? Early day, late day?
5456.45 -> - Right, yeah.
5457.283 -> So we had a wonderful dietician
instructing people for this,
5462.12 -> and her name's Dalia Perelman,
5463.67 -> and she really was the key and is the key
5465.47 -> for many of our studies
5466.303 -> for getting people to eat differently.
5468.19 -> And the general instructions
were for people to eat
5472.09 -> as much fermented foods as
possible, more is better.
5474.81 -> And the reason is that
with this initial study,
5478.08 -> we really wanted to maximize our chance
5480.31 -> of seeing a signal if there was
5481.94 -> something biological going on,
5483.5 -> with the idea that if
the dose was excessive
5487.175 -> and not easily achievable by
a lot of people in the end,
5490.27 -> we can go back and and say, okay,
5492.36 -> this is the point at which we
lose the biological signal.
5494.877 -> But people during the height
of the intervention phase,
5498.66 -> the intervention phase was six weeks,
5500.81 -> during the height of that,
5501.887 -> were up over six servings, on average,
5504.78 -> per day of fermented foods.
5506.27 -> So kind of two servings at each meal.
5508.62 -> And the ounces or weight or size,
5512.159 -> it really depended on what
the fermented food was.
5515.36 -> And we just told them to stick
5516.67 -> to what was a recommended
dose on the package
5519.82 -> that they were buying,
5521.92 -> For kombucha, it'd be like
a six to eight ounce glass.
5524.836 -> Sauerkraut like a half cup,
or something like that,
5527.337 -> and same with yogurt.
5528.72 -> - Great. So what were the results?
5532.54 -> - Yeah, so the results
astounded us in a way,
5537.17 -> but then thinking more deeply,
5539.21 -> and it'll be evident
even after I explain it
5541.846 -> in the context of this conversation,
5544.66 -> likely why we saw the results we saw.
5547.72 -> The results were astounding
because our hypothesis
5551.36 -> going into this was
that the high fiber diet
5553.94 -> was going to give the massive signal.
5555.6 -> We know that this is the big
deficiency in the Western diet.
5560 -> All the mouse studies have
told us that high fiber
5562.5 -> really leads to a much
healthier microbiota,
5564.06 -> it can lead to positive
changes in the immune system.
5567.09 -> And in fact, even when we had a limited...
5569.18 -> We had wonderful donor support,
5570.46 -> but still a limited amount of money
5571.77 -> when we started this study.
5573.76 -> My lab was really very
eager to do the high fiber
5577.829 -> part of this really well,
5580.28 -> and Christopher kind of
had to twist our arms
5582.57 -> to do the fermented food side of it.
5584.64 -> And we thought it was
kind of quirky and neat,
5587.59 -> live microbes should be
exciting, let's try it.
5590.89 -> So we put that in and it turns out
5592.92 -> that we were very thankful
that he twisted our arms,
5595.54 -> because it was that
high fermented food arm
5598.45 -> that really gave us the big signal.
5600.12 -> Even though our hypothesis
was that the high fiber
5602.89 -> was going to lead to more short-chain
5604.38 -> fatty acids produced in the
gut, more diverse microbiota,
5608.814 -> less inflammation in the immune system,
5611.41 -> we didn't see that across the cohort.
5613.51 -> We actually saw very
individualized responses
5617.05 -> to the dietary fiber,
5618.51 -> and I'll come back to
what those responses were.
5620.78 -> The big signal really was
in the fermented food group.
5624.2 -> We saw all the things
that you would hope to see
5626.88 -> in a Western microbiota in western human.
5629.82 -> We saw this increase
in microbiota diversity
5632.4 -> over the course of the six weeks
5633.7 -> while they were consuming
the fermented foods.
5635.665 -> And we can't always say that
higher diversity is better
5641.32 -> when it comes to our
microbial communities.
5643.34 -> We know there are cases for
instance, bacterial vaginosis,
5646.24 -> where higher diversity is actually
5647.73 -> indicative of a disease state,
5650.33 -> but we know in the context of the gut,
5653.63 -> and for people living in
the industrialized world,
5656.43 -> higher diversity is generally better.
5659.31 -> We know that there's a
spectrum of diversity.
5661.43 -> People with higher diversity
generally are healthier.
5664.54 -> If you can push your diversity higher,
5666.2 -> you're in better shape.
5667.34 -> And so we saw that increase in diversity.
5669.64 -> And then the major question is,
5670.85 -> what happened to the immune system
5672.34 -> as these people were increasing
5674.29 -> their gut microbiota diversity
through the fermented foods?
5677.866 -> So we did this massive immune profiling,
5681.5 -> and we see a couple dozen immune markers,
5685.06 -> inflammatory markers decrease
over the course of the study.
5688.97 -> So we measured these
at multiple time points
5691.97 -> throughout the course of the study,
5692.95 -> and there's kind of this
set stepwise reduction
5695.8 -> in things like interleukin-6,
and interleukin-12,
5700.18 -> a variety of famous
inflammatory mediators.
5703.79 -> And then even if you go
into the immune cells
5706.28 -> and you start looking at
their signaling cascades,
5708.77 -> we see that those signaling
cascades are less activated
5712.12 -> at the end of the study compared
5713.44 -> to the beginning of the study,
5714.83 -> indicating in attenuation of inflammation.
5717.074 -> So kind of exactly what
we would hypothesize
5720.67 -> would lead to less propensity
5722.47 -> for inflammatory disease over time.
5724.78 -> That's a huge extension
of a very short study and-
5728.37 -> - How long was this study again?
5729.47 -> - So the complete protocol
I think was 14 to 17 weeks,
5733.97 -> or something like that.
5735.09 -> The actual intervention phase
consisted of a four week ramp
5738.89 -> and then a six week maintenance period.
5741.33 -> So the intervention itself was 10 weeks,
5743.23 -> but there were six weeks
of really kind of hardcore,
5745.76 -> high levels of fiber or fermented foods.
5748.81 -> - Yeah, and I'm glad
you mentioned the ramp,
5751.23 -> 'cause my experience with
fermented foods is that you,
5754.88 -> it can be beneficial to give the system
5756.6 -> an opportunity to act acclimate.
5757.78 -> I mean, if you consume a
giant bowl of sauerkraut,
5761.1 -> it's not going to be the worst
day and night of your life,
5763.1 -> but you'll know you did.
5764.833 -> - Totally.
- We'll just leave it at that.
5766.52 -> And so you want to kind
of acclimate to it.
5768.7 -> - Absolutely.
- I'm at the point now where,
5770.564 -> some people might think this is gross,
5772.25 -> but after I exercise,
I've been sweating a lot,
5775.15 -> I like the saltiness of the...
5776.66 -> I actually drink the
liquid that the sauerkraut
5780.1 -> has been stewing in, and I get,
5782.99 -> I like to think that I consume
some fermentation that way,
5786.78 -> it's salty, it as kind of a
post-training replenishment.
5790.88 -> But if I had done that six
months ago, straight off,
5794.45 -> I think it would've been
pretty rough on my system.
5796.33 -> I started taking little bits of it
5797.93 -> and then adding it each day.
5799.09 -> - Totally, and so both
with the fermented foods
5800.687 -> and the fiber, it's well known
5802.44 -> that this kind of gradual ramping
5804.42 -> is a really important way
of mitigating bloating,
5808.1 -> and other digestive
discomfort that can happen
5811.01 -> when your microbiome reconfigures
5812.7 -> and starts fermenting more,
and changing community members.
5815.59 -> So you should take that
ramp at your own pace.
5818.65 -> If something seems to be going wrong,
5820.22 -> just kind of level off, stay there.
5822.09 -> We did this in a very delicate way
5823.5 -> to get people up to the high dose.
5825.13 -> The brine, just a tangent
here for a second,
5829.919 -> that was actually one of the products
5832.015 -> that we had people use in
the fermented food phase.
5836.373 -> There's actually a
product called Gut Shots,
5838.58 -> which is just bring that they've marketed.
5841.275 -> We actually are now
studying it in the lab.
5844.43 -> I just actually, before
this came from a lab meeting
5847.29 -> where a GI fellow in my lab
is actually putting Gut Shots,
5851.26 -> sterilized gut microbe, or the
fermentation microbes removed
5858.77 -> or present into mice
and looking at changes
5862.09 -> in their mucosal immune system.
5864.32 -> So we're studying this in detail now,
5866.1 -> because it's a rich source of lactate
5868.516 -> and a bunch of other
interesting metabolites.
5871.11 -> - I love that my weird behavior
5872.46 -> is inadvertently being
studied at Stanford Medicine.
5876.51 -> I want to just mention
something about the Gut Shots.
5879.38 -> Those are sold as a drink.
5882.12 -> Those also, just for certain
listeners in different budgets,
5884.53 -> they can be very expensive
if you really think about...
5886.74 -> Some of them are exceedingly expensive.
5888.76 -> But what I described before
with making your own kombuchas,
5893.17 -> it's not quite brining, but
the homemade sour sauerkraut,
5896.361 -> that protocol is out there, as I mentioned
5898.5 -> in Tim's book, "The 4-Hour Chef."
5900.87 -> And you get a lot of
the brining from that,
5903.57 -> an almost endless amount.
5905.23 -> A cautionary note, I once
went into the refrigerator
5908.48 -> and saw something similar to
Gut Shot, it wasn't Gut Shot.
5911.31 -> And I drank the whole 12 ounce bottle,
5913.86 -> and realized that it was 24 servings.
5916.19 -> And that's where I got
my initial experience
5919.34 -> with what it is to not do a ramp up phase.
5921.34 -> - Yeah.
I do not recommend
5922.47 -> doing that.
5923.303 -> Some of these, it's very potent, it seems,
5925.37 -> and you can consume even a
half an ounce or an ounce.
5927.842 -> - Yeah, I mean, very
potent from the standpoint
5930.41 -> of fermentation, but also very salty.
5932.09 -> So there's a lot of effects that can....
5934.24 -> Yeah.
- Yeah, don't do what I do,
5935.824 -> - Yeah.
- At least not at the outset.
5939.421 -> So that is an experienced warning.
5942.524 -> So they did this, as I recall,
5944.37 -> there was a swap condition or
there was a halt condition.
5946.97 -> So you did controls, right?
5948.74 -> It wasn't just comparing groups.
5950.1 -> You had individuals in who
were initially in one group
5953.07 -> or the other moved to a
different group, correct?
5957.46 -> Or to stop and then return.
5958.68 -> - Yeah, we actually just did a stop
5960.62 -> and followed them during a washout phase.
5962.267 -> And the ideal situation for
dietary interventions like this
5966.95 -> are to do crossover studies,
as you're suggesting.
5969.672 -> We've recently completed a ketogenic
5972.57 -> versus Mediterranean diet intervention-
5974.43 -> - Are those data published yet?
5975.89 -> - Not yet, but Christopher's been Tweeting
5977.4 -> a lot of these data and
5978.35 -> there's a paper in revision right now.
5979.79 -> So if you go to Christopher
Gardner's Twitter feed,
5983.22 -> you'll be able to find him reporting
5985.78 -> some of the early results of this study.
5988.147 -> - Can you give us a snippet
of, was there a superior...
5990.61 -> Just give us a, you don't
have to tell us which one,
5992.68 -> but was there a superior condition
5995.8 -> of either Mediterranean versus ketogenic?
5997.79 -> - So the metabolic effects of
these, it's a beautiful study.
6002.5 -> I should let his group comment on that.
6004.42 -> The microbiota data we actually
are just generating now.
6007.29 -> So the study that his group
has put together from this
6010.96 -> is largely independent
of the microbiota data.
6013.737 -> - Right.
- And now we're doing
6014.99 -> a more in depth analysis,
and I'll have more to say
6017.01 -> about that the future.
6017.99 -> - We'll return to that, yeah.
6019.086 -> - But it's a super exciting study,
6020.7 -> because it is one of these
where people eat a certain way.
6023.958 -> And what's really beautiful about this
6026.22 -> is we even got food delivered
for part of the intervention.
6029.67 -> So we had complete control
6031.47 -> over what they at least
had available to eat.
6034.43 -> And then the second phase,
6035.75 -> they make the food on their own.
6040.55 -> And then we cross over
and do the same thing.
6043.229 -> And so that's really like,
6045.187 -> if you have a good enough budget,
6047.08 -> the right way to do a study like this.
6048.26 -> For this, we didn't have the time or money
6051.72 -> to do a crossover, but
we did do a washout phase
6054.45 -> where people, we didn't make
them stop eating, whatever,
6057.59 -> if they were enjoying
it, but we monitored.
6059.34 -> And there was some recidivism
6060.56 -> where there was a decrease
in fiber fermented food.
6063.1 -> And we could see, for instance,
6064.81 -> diversity start to plateau and reverse
6066.85 -> in many of these people.
6068.09 -> So there does appear to
be a need for maintenance
6071.41 -> of the intervention to maintain
6073.98 -> the perceived health benefits
that we were measuring.
6076.832 -> - Great.
6077.711 -> We will provide a link to
the study in the caption,
6080.23 -> and thank you for that very
clear and thorough description,
6083.389 -> from one of the investigators
involved in the study.
6087.61 -> It's great to go direct to the source.
6090.304 -> Anecdotally, were there movements in mood,
6094.75 -> in resistance to colds and infection
6098.42 -> during the course of the study?
6099.508 -> And this is kind of a prelude
to where I'm headed next,
6103.15 -> which is there is a
tremendous amount of interest
6105.28 -> in the so-called gut-brain axis.
6106.64 -> But also I want to make
sure that we talk about
6108.872 -> how these microbes and the
conditions they're establishing
6112.26 -> in the gut are creating positive
or negative health effects.
6115.88 -> I mean, basically how
signals get out of the gut.
6118.27 -> - Totally. Yeah.
6119.13 -> - So I certainly notice
that when I'm eating
6121.61 -> more fermented foods,
or there's probiotics
6123.67 -> in drinks I consume and so forth,
6125.53 -> that I feel quote, unquote, air quotes,
6128.01 -> completely subjective, I feel better.
6129.82 -> - Yeah.
6130.872 -> - I wish there was an objective
measure of feeling better.
6134.77 -> But I seem to think more
clearly, sleep better,
6139.02 -> mood, et cetera, and I
know I'm not alone in that.
6141.18 -> And any time I've taken harsh
antibiotics, I feel worse,
6145.81 -> but then again, I'm usually taking them
6147.07 -> because I'm feeling bad
about something else, right?
6149.04 -> I don't take them just because.
6150.69 -> So did people say they were
feeling better in any way?
6153.55 -> And if so, what did you have observe?
6154.95 -> And again, we're highlighting
these as anecdata.
6157.598 -> - Yeah, totally.
6158.68 -> We, as part of this effort to look at
6164.28 -> how dietary interventions
affect our health and wellbeing,
6168.74 -> and so forth, and
microbiome immune system,
6171.56 -> we interact with a lot of
people who have read our book,
6175.84 -> or kind of have become
microbiome enthusiasts.
6179.62 -> And have implemented
a lot of these changes
6181.88 -> in their personal life.
6182.713 -> And I hear the same thing
that you're saying, Andrew,
6184.87 -> that tons of people say
they have more energy.
6187.66 -> They think more clearly,
they sleep better,
6189.77 -> their family is nicer to each other,
6191.85 -> like the number of crazy things.
6193.336 -> And it's really hard to uncouple, like,
6195.56 -> is this because these
people have taken charge now
6198.57 -> of what they're eating and
just feel better in general
6200.45 -> for being in control
of what they're doing,
6203.23 -> or is there this cascading set of effects
6206.69 -> that are actually impacting our...
6209.646 -> Kind of emanating from the gut-brain axis.
6211.906 -> And so we actually implemented
a bunch of questionnaires
6216.264 -> and even a cognitive test to
try to get at some of this.
6220.54 -> And I should say, the list
of this goes on and on.
6224.04 -> There are people who claim
that their complexion improves,
6226.29 -> and that their allergies...
6228.1 -> And there's probably all
sorts of ripple effects.
6230.28 -> If you can affect your inflammation,
6232.467 -> we know that you can
affect your cognition,
6234.7 -> we know that you can affect your skin
6237.97 -> and inflammation that's
occurring on your skin.
6240.178 -> So I really think that there is a basis
6242.81 -> for a lot of those anecdotes.
6244.62 -> It may just be hard to
see in a short study
6247.482 -> and in a small cohort of people
over a short period of time,
6253.12 -> but we didn't really
see significant things
6257.4 -> associated with cognition and
moods and all of the things
6261.466 -> that we were testing for which, yeah,
6265.35 -> there could be a variety
of explanations for that.
6267.393 -> We also have a standardized
stool measure that people use,
6274.24 -> and there was less constipation,
6278.15 -> better bowel movements over the course
6280.17 -> of both of these interventions.
6281.31 -> So it did seem like bowel habits improved,
6284.24 -> which a lot of times can
lead to better moods,
6286.77 -> but that we weren't able to measure.
6288.75 -> - That the classic psychoanalyst
6290.6 -> would have a few field day with that.
6293.26 -> What sorts of interesting
things did you observe
6295.485 -> in the fiber group?
6296.56 -> Because it's clear that that group yielded
6299.03 -> some unexpected findings
in both directions.
6302.52 -> Things you expected to see, you didn't see
6304.236 -> to the same amplitude as you did
6306.15 -> in the fermented food group,
6307.28 -> but I'm guessing you also saw
some very interesting things
6309.81 -> in the fiber group.
6310.91 -> - Totally, yeah.
6311.894 -> So we started looking at
the data in more detail
6314.85 -> when we didn't see the
cohort-wide response.
6317.85 -> And one of the things we
observed is that in measuring
6320.87 -> all these immune parameters,
6322.04 -> there appeared to be
three different groups
6323.853 -> of immune responses that we were seeing.
6327.683 -> One group that got
overall less inflammatory,
6331.26 -> and then two other groups that
kind of had a mixed result,
6334.62 -> partly more inflammatory,
partly less inflammatory
6337.13 -> in all these markers
that we were looking at.
6339.14 -> And when we started digging
into like, what aspect
6343.37 -> of the biology of those people
6347.26 -> dictated or predicted
which group they fell into,
6350.94 -> the really interesting part is the people
6352.67 -> with highest diversity gut
microbiomes to start the study
6356.26 -> were the ones that were
most likely to have
6359.694 -> the decreases in inflammation.
6363.52 -> And so data seemed to be
telling us that if you start off
6369.19 -> with a diverse microbiota,
maybe one that's better equipped
6371.767 -> to degrade a wide
variety of dietary fiber,
6376.67 -> you're more likely to
respond positively to it.
6378.94 -> If you have a very
depleted gut microbiome,
6381.43 -> you're not as likely to
be able to respond to it.
6383.44 -> And thinking back to that
experiment that we talked about
6385.57 -> before with the multi-generational loss
6388.05 -> of fiber-fermenting microbes in mice
6390.398 -> that were fed a Western diet,
6394.31 -> it may be that many of us
in the industrialized world
6398.37 -> have a microbiome that's so depleted now,
6400.99 -> that even if we consume a high fiber diet,
6403.95 -> at least for a short period of time,
6405.6 -> we don't have the right
microbes in our gut
6407.58 -> to degrade that fiber.
6408.413 -> And this has actually been
observed by other groups,
6410.75 -> beautiful study out of
University of Minnesota,
6413.07 -> looking at immigrants,
coming to the United States.
6415.485 -> And within nine months,
6417.9 -> but certainly over the course of years,
6419.95 -> immigrants that come here lose
6421.9 -> a lot of the diversity
in their gut microbiome,
6425.297 -> but a lot of the fiber-degrading capacity
6428.01 -> in their gut microbiome too.
6429.25 -> So it could be that over time,
6431.03 -> this becomes a one way street,
6432.93 -> and it's hard for us to recover microbes
6436.116 -> that actually can degrade the fiber.
6438.02 -> And I think that this probably intersects
6440.04 -> with sanitation in our environment,
6441.547 -> and the fact that we don't have access
6443.393 -> to new microbes that might
help us degrade the fiber.
6447.2 -> That we actually have lost these microbes,
6450.237 -> and they're in some ways irrecoverable
6452.76 -> without deliberate reintroduction
6454.45 -> of fiber-degrading microbes.
6455.84 -> - I can recall from childhood,
6456.96 -> there were kids that would eat dirt.
6458.9 -> - Yeah.
- And snails and stuff.
6460.557 -> That just sounds totally disgusting,
6462.55 -> bu kids covered with mud
maybe not so much anymore.
6467.246 -> And certainly during the pandemic,
6469.25 -> there's been and a lot more
use of these hand sanitizers,
6472.13 -> that prior to that, people
seemed pretty spooked about,
6474.38 -> but then obviously they prioritized them.
6479.52 -> Well, you have children.
6480.41 -> Do you encourage them to...
6482.89 -> When they were young, did you
encourage them to interact
6485.75 -> with pets and dirt and-
6487.396 -> - Absolutely, yeah.
- Stuff in the environment,
6489.97 -> provided that stuff
wasn't immediately toxic?
6492.06 -> - Exactly. So this is really...
6493.78 -> It's a continual cost-benefit
analysis, I think.
6498.84 -> I will say that with the pandemic now,
6502.25 -> and certainly just with
infectious diseases in general,
6505.73 -> it's really important to
be aware of the possibility
6510.66 -> for compromising your health
through the spread of germs.
6513.27 -> And so that is just, hand
washing is important,
6516.05 -> and we have to be careful
with the spread of germs.
6519.773 -> But I do think that the
sanitization of our environment
6526.807 -> has gone overboard with various things
6531.31 -> being impregnated with antibiotics,
6533.507 -> shopping carts and things
like that, and toothbrushes.
6537.208 -> It's like antibiotics
6539.078 -> and things for killing
microbes are everywhere.
6543.96 -> And when we were raising...
6547.12 -> When our daughters were young
6548.11 -> and we were making these decisions,
6550.28 -> the calculations that we
would make were really one,
6555.32 -> how likely are they to encounter
a disease-causing microbe?
6559.05 -> If we've been out on a
hike or in our garden,
6562.062 -> just kind of working in
the dirt or whatever,
6564.86 -> maybe it's not as important
to wash your hands
6566.88 -> before you have lunch,
6567.8 -> even if there's a little
bit of dirt on them.
6569.88 -> If they've been in a public playground
6571.49 -> where maybe other kids with germs,
6574.7 -> or maybe even chemicals like pesticides
6577.23 -> and herbicides that are being used,
6579.646 -> maybe it's more important
than to wash your hands.
6582.414 -> Certainly if you've been
in the grocery store
6584.66 -> or on the subway, probably a
good idea to wash your hands.
6587.84 -> So I think you really need to think
6589.16 -> about kind of the context of it.
6592.65 -> Exposure to microbes from the environment
6596.21 -> is likely an important part of
educating our immune system,
6600.13 -> and keeping the proper balance
6601.39 -> in our immune system.
6602.223 -> And it's just a matter of figuring out
6603.571 -> the right way to do that safely.
6605.62 -> And it may be the fermented
food result that we saw
6608.19 -> is a way of tapping into
those same pathways,
6610.42 -> kind of an environmental
exposure to microbes that's safe.
6613.38 -> - Interesting.
6614.72 -> I'd like to touch on how signals get
6617.1 -> from the gut to the rest of the body.
6619.03 -> And we probably don't have time to go
6621.61 -> into all the systems that benefit
6623.26 -> from having a diverse microbiome
or healthy microbiome.
6626.35 -> But we talked about the immune system.
6629.655 -> There's active signaling
and transport from the gut,
6632.99 -> all along its length, as far as I know,
6634.66 -> into the bloodstream, into
other organs and tissues.
6637.08 -> So for the immune system,
it seems straightforward.
6641.72 -> It could reduce the amount or number
6643.85 -> of inflammatory cytokines,
like IL-6 and so forth,
6646.56 -> maybe increase the
anti-inflammatory cytokines,
6649.13 -> like IL-10 and others.
6651.67 -> But we know there's a
gut-brain access of neurons
6654.13 -> that literally talk in both directions
6655.89 -> between brain and gut.
6657.2 -> But let's say I'm eating
my fermented foods,
6659.9 -> I'm doing all the right things,
6661.19 -> and my gut is diverse and
I have all the goodies
6664.76 -> at all the right places.
6666.47 -> How is it that fact that
those microbiota are thriving
6671.86 -> is conveyed to the rest of the body?
6674.513 -> Because they're in
there doing their thing,
6676.28 -> and I don't know that they have a mind,
6678.01 -> but they're probably not thinking
6678.98 -> of taking care of me, Andrew.
6680.73 -> But I feel better, or I
might get sick less often,
6685.08 -> or combat any illness more quickly.
6687.93 -> How is that actually happening?
6690.11 -> Is it that the microbiomes
stay restricted to the gut,
6693.419 -> but the signaling molecules
are all downstream,
6697.47 -> in a downstream way, are making
good or bad things happen?
6700.61 -> Or is there some sort
of direct recognition
6703.44 -> at the body level, or are
there cells in the body
6705.84 -> that are responding to, ah,
the gut microbiome is healthy,
6708.66 -> and therefore I can make
more of the good stuff,
6711.59 -> and less of the bad stuff, so to speak.
6713.32 -> - Yeah, great.
6715.585 -> You're right, it's super complex.
6717.47 -> There's a huge array of ways
6719.48 -> that our body perceives both
the microbes and the molecules
6724.57 -> that they produce in our gut,
6725.94 -> and the molecules they
produce are, of course,
6727.9 -> a product of what microbes are there,
6729.42 -> and then what they receive
as kind of metabolic inputs,
6732.37 -> what we're eating and what other microbes
6734.36 -> are present in the environment,
providing molecules to them.
6737.62 -> So, it's this complex matrix, but we...
6742.03 -> Probably the simplest place to start
6744.03 -> is just the immune system.
6745.26 -> We have an immune system that,
6748.32 -> the vast majority of
immune cells in our body
6750.49 -> are located in our gut,
6751.75 -> just because there's
such a dense population
6755.19 -> of microbes there that have...
6757.617 -> We consider them beneficial microbes,
6761.44 -> but they're only beneficial if they're
6762.84 -> in the right spot in the gut.
6764.08 -> As soon as they mislocalize,
6765.8 -> we know that they can become
opportunistic pathogens.
6768.76 -> And so the immune system really
playing an important role
6771.86 -> to keep with them in place
is essential for this system
6776.3 -> not moving into a disease space.
6778.97 -> The immune system has a variety of ways
6781.17 -> of monitoring what microbes are there.
6782.733 -> They're actually specialized
to structures in the gut
6785.867 -> known as peyer's patches that
actually take up microbes.
6790.86 -> They actually allow microbes to transit
6794.37 -> into this population of immune cells
6798.299 -> in a very controlled way,
6800.77 -> so that that set of immune
cells becomes educated
6803.73 -> as to what microbes are just
6805.41 -> on the other side of the barrier.
6806.8 -> - Wow, kind of like a border patrol.
6808.9 -> - Exactly, yeah.
6809.87 -> So they bring them in,
they fingerprint them,
6813.068 -> and then have kind of
this set of responses
6819.43 -> ready to go if needed.
6821.36 -> - [Andrew Huberman] Amazing.
6822.39 -> - There are other cells
known as dendritic cells,
6824.97 -> special type types that
actually send long arms,
6828.75 -> these processes out into
the lumen of the gut,
6831.63 -> and do the same thing, take up microbes,
6833.96 -> bring them back in and sample them.
6835.704 -> In addition to these
direct sampling mechanisms,
6839.15 -> the cells that line the gut
have a huge array of receptors,
6843.05 -> specialized proteins,
that perceive patterns,
6846.76 -> molecular patterns that the microbes make.
6850.12 -> So things like endotoxin
lipopolysaccharide,
6853.61 -> just the cell wall of the bacteria.
6856.72 -> We have specialized receptors
that recognize those.
6859.58 -> If those signals become too profound,
6861.76 -> or if they're perceived
in the wrong place,
6864.67 -> that can stimulate an
inflammatory response.
6866.76 -> So there's all these ways of
monitoring the membership,
6869.88 -> and where it is and how close it is.
6872.08 -> But then there's this
whole other set of ways
6875.76 -> of perceiving metabolic activity,
6877.93 -> and what's happening in the gut.
6879 -> And you mentioned before,
6881.474 -> these cell types, that express
taste receptors in the gut
6886.21 -> and have ways of sampling
dietary components.
6888.98 -> They're the same types of,
or analogous cells in our gut
6894.745 -> that are perceiving metabolites
produced by the microbiota
6898.62 -> so that our bodies can perceive
6900.61 -> what sort of metabolic
activity is going on.
6903.38 -> And then in addition to that,
6905.78 -> there's this tremendously
important nervous system
6910.61 -> that's sending signals back to the brain,
6913.22 -> dictating things like motility.
6915.67 -> Do I get rid of what's in here?
Do I move it along quickly?
6918.49 -> What actually is happening?
6920.69 -> Do I need to interact with immune cells?
6923.21 -> So there's this really complex array
6924.99 -> of interactions between
the different cell types.
6928.47 -> And then a lot of the
cells that are in the gut,
6931.78 -> perceiving all of these signals,
6933.33 -> a lot of the immune cells can
actually get up and leave.
6937.13 -> They can get into the
blood, cycle through,
6939.55 -> and then home to other regions
of the mucosal surfaces,
6944.36 -> so that mucosal surfaces
are educated broadly
6948.47 -> against what's passing through our gut.
6951.27 -> So there's a variety of
ways of cells communicating,
6955.86 -> and then a lot of the molecules
that the microbiota makes
6960.62 -> can actually make their way
into the bloodstream directly.
6964.1 -> And so the array of molecules
is still being defined,
6968.61 -> we're trying to figure out
what all these chemicals are.
6971.53 -> We've mentioned the
short-chain fatty acids,
6973.29 -> but those are just the tip of the iceberg.
6975.37 -> They are really interesting compounds
6977.23 -> like indole derivatives and phenols,
6982.559 -> derived from amino acids,
metabolized by gut microbes,
6986.48 -> taken up into the bloodstream.
6988.2 -> And then we further metabolize these,
6990.44 -> they become kind of
co-microbe host metabolites,
6993.93 -> and then they can go on and bind
6995.77 -> to different receptors
throughout our body,
6998.11 -> anywhere our bloodstream has access to,
7000.36 -> and start to trigger signaling cascades.
7003.36 -> - Is it known whether or
not any of those molecules
7005.42 -> are small enough to cross
the blood-brain barrier?
7007.97 -> Because the hypothesis it
and the current thinking
7011.72 -> is that neurotransmitters
manufactured in the gut,
7015.54 -> and signaling along the gut-brain axis,
7017.71 -> literally neurons talking
back and forth electrically
7020.58 -> from brain to gut and gut to brain
7022.47 -> is what regulates things like mood,
7023.777 -> or at least in animal models.
7025.37 -> And there are some emerging human studies,
7027.38 -> improvement of symptoms in
autism spectrum disorders,
7031.41 -> maybe even in ADHD.
7032.82 -> What I'm basically saying here
7033.73 -> is there is some evidence emerging
7036.48 -> that improving the gut microbiome
7038.14 -> can improve outcomes in psychiatric
7040.62 -> and developmental disorders.
7042.33 -> But what you're telling me is
that the microbiota themselves
7046.15 -> are manufacturing chemicals
7047.44 -> that can make into the bloodstream.
7048.76 -> And therefore I'm asking
if those chemicals
7050.77 -> can move from the bloodstream
into the brain directly.
7053.39 -> It may not be a gut-brain
axis via neurons.
7057.37 -> It actually could just be seepage
7058.75 -> of serotonin into the brain,
7060.527 -> or acetylcholine into the
brain for that matter.
7063.7 -> - Totally, yeah.
7067.383 -> The biology of most of these molecules
7071.13 -> is not well understood,
7072.07 -> but certainly in like
cerebral spinal fluid
7074.43 -> that's been analyzed,
7076.92 -> you can perceive these
microbial metabolites,
7079.54 -> so they are there.
- That's the answer, yeah.
7081.076 -> Some of them are getting
across the barrier.
7083.4 -> - But so a really interesting thing is,
7085.08 -> I think a lot of these molecules are,
7088.426 -> if they're experienced
at high enough doses,
7091.38 -> are toxic or have toxic properties.
7094.36 -> We know that a lot of these metabolites,
7097.63 -> when they make their way
into the bloodstream,
7098.925 -> eventually are excreted
through the kidneys in urine.
7101.76 -> So actually we can monitor the metabolism
7103.86 -> that's going on in your
gut by actually looking
7106.26 -> at the metabolites that
are present in your urine,
7108.22 -> because many of those
originated in your gut,
7111.69 -> from your gut microbes.
7113.06 -> But people with kidney disease,
7115.001 -> whose kidneys' filtering processes
7117.59 -> is not functioning properly,
7119.24 -> actually build up high levels
of many of these metabolites
7123.95 -> into the bloodstream,
7126.05 -> and that can lead to
more of these molecules
7130.43 -> making it across the blood-brain barrier.
7132.76 -> And in fact, some of the
transporters in the kidney
7136.06 -> that are responsible for
shuttling these molecules
7138.41 -> out into urine, are also
founded the blood-brain barrier
7141.509 -> for shuttling the molecules
back into the bloodstream
7144.56 -> if they do get across.
- Incredible.
7146.24 -> - And we know that mental
fog one of the big symptoms
7150.37 -> of kidney disease, potentially
because a lot of these
7154.019 -> metabolites accumulate in blood,
7156.27 -> and then make their way
across the blood-brain barrier
7159.14 -> into, yeah, the central nervous system.
7161.4 -> - Amazing. I'm glad you
mentioned mental fog.
7163.2 -> A few years back, there were some reports,
7166.806 -> some scientific reports and
as a consequence in the media,
7170.1 -> that excessive intake
of pill-form probiotics
7173.87 -> could create mental fog.
7175.59 -> I don't know if that ever took hold.
7177.99 -> And it raises a general question
about pill form probiotics.
7182.06 -> I took them for a few years,
7183.42 -> just thinking that would be
good for my gut microbiome,
7185.53 -> and then I switched to
the fermented food thing,
7187.36 -> largely there's a consequence of the work
7190.1 -> that you and Chris published.
7192.198 -> But what what's the
thought about probiotics
7195.5 -> for the typical person
that's not recovering
7197.28 -> from a round of antibiotics
7198.602 -> or that has been prescribed them?
7202.064 -> I've heard that the species of microbiota
7206.41 -> that they proliferate
might not be the species
7210.04 -> that we want to proliferate,
7211.36 -> but I've also heard that
maybe that doesn't matter.
7213.43 -> So what's your general stance?
7214.55 -> They can be quite expensive.
7216.05 -> - Yeah.
- Also,
7216.883 -> I know I've been talking
about expense a lot today,
7218.41 -> but I always want to take into account
7219.6 -> that people are showing up to the table
7222.88 -> with a variety of budgets,
and probiotics are one
7225.35 -> of the more expensive
supplements out there.
7227.19 -> You can quickly get into the
several hundreds of dollars
7229.46 -> per month if you're
getting the quote, unquote,
7232.56 -> best quality ones.
- Right.
7234.176 -> - And if they're actually
causing brain fog,
7235.81 -> then I'm not sure I'd want to use them.
7237.86 -> - No, completely.
7238.707 -> And there's a ton of snake oil out there.
7239.916 -> People know that they...
7242.01 -> I think many of these companies are aware
7245.84 -> that they can prey off of people's fears
7247.5 -> and get a lot of money from
them with absolutely no data
7250.16 -> to back up that their
probiotic is doing anything.
7253.63 -> So I think the first thing
to say is buyer beware,
7256.7 -> because it's a supplement
market, it's largely unregulated.
7260.01 -> And that means that there
7261.1 -> are a lot of bad products out
there, and a lot of products
7264.56 -> that even though they're
not intended to be bad,
7267.62 -> just don't have great quality control.
7269.43 -> There have been several
studies that have taken
7271.73 -> off the over the counter,
7273.81 -> just kind of off the shelf probiotics,
7275.72 -> surveyed what's in there
based on sequencing
7278.99 -> and shown what is in there
7282.56 -> does not match what's on the label.
7284.68 -> - And that's true of many supplements,
7286.22 -> and unfortunately supplement companies.
7287.815 -> This is something we get
into on the podcast a lot.
7289.54 -> There are reputable brands and
they go through a lot of work
7292.782 -> to get things right, and there are many
7295.65 -> that just for whatever reason,
7297.88 -> it just doesn't match what's listed.
7299.49 -> - Exactly, and so there are
places that probiotic companies
7304.81 -> can send their product to have
it independently validated.
7308.28 -> So you want to look for that sort
7310.24 -> of validation on a product.
7312.104 -> There also are names that
are just very well-known,
7315.48 -> and their reputations are on the line,
7322.27 -> so they probably invest a little
bit more in quality control
7325.12 -> than maybe some of the
other, lesser-known names.
7328.56 -> But there's a huge range
of data on probiotics.
7334.26 -> And I think, the thing that
we kind of recommend is,
7339.433 -> try to find good products and
then experiment for yourself
7342.96 -> and see if you can find
something that works for you.
7344.81 -> I know people who have experienced
7346.241 -> constipation and don't
want to change their diet,
7351.08 -> and have found a probiotic
that helps them with that.
7353.87 -> If you can find that right mix, great.
7356.8 -> That's wonderful.
7358.47 -> I would say that the data right now
7360.83 -> is not overwhelmingly positive
for what probiotics do
7366.85 -> to the gut microbiota.
7368.61 -> So there have been some
nice studies looking
7370.21 -> at the impact of probiotics on recovery
7372.99 -> after antibiotic treatment.
7375.02 -> And it appears to slow down the recovery
7376.88 -> of the mucosal microbiota.
7378.77 -> And some other studies that
have where the big signal
7385.32 -> isn't seen, as you might hope,
7387.48 -> with a probiotic that's supposed
7389.05 -> to treat a different disease.
7390.4 -> There have been
metaanalysis that do suggest
7392.89 -> in certain instances, recovery
from antibiotics that there,
7397.69 -> even though it may cause your microbiome
7399.72 -> to recover more slowly,
7400.83 -> that it may actually
prevent diarrheal disease,
7404.16 -> recovery from viral diarrheas,
probiotics may help.
7407.44 -> But because there's such
a huge range of products,
7410.01 -> and because each person
is their own little caper
7413.07 -> when it comes to the microbiome,
7414.321 -> it's really hard to know
whether there are great products
7419.53 -> for a given indication.
7421.1 -> The really good advice that
I've heard is try to find
7425.31 -> a study that supports in...
7428.76 -> A really well designed
study, and this is very hard
7431.13 -> for people who aren't
scientists to evaluate.
7433.55 -> But so if you're experiencing
a medical problem,
7436.19 -> or want to consult a doctor,
that that might be helpful.
7440.54 -> But finding a study where
a specific probiotic
7443.32 -> has successfully done whatever
it is you're looking for,
7447.09 -> and then sticking with that probiotic
7449.131 -> is really the best recipe
as a place to start
7452.47 -> in this space, I think.
7453.303 -> - And what about prebiotics?
7454.56 -> Is there are a number of
reasons why, I can imagine,
7457.56 -> that prebiotics would be beneficial?
7460.27 -> Which essentially it's, you're
pushing the fiber system,
7463.88 -> which we've talked a lot about today.
7465.13 -> - Yeah, yeah, absolutely.
7469.1 -> The studies that have
been done on prebiotics,
7473.45 -> it's really kind of a
mixed bag of results.
7477.71 -> There have been studies
done with purified fibers
7481.17 -> where you actually see
micro biodiversity plummet
7483.78 -> over the course of the study,
7484.83 -> because you get a very specific bloom
7487.82 -> in a small number of
bacteria that are good
7489.82 -> at using that one type of fiber.
7492.16 -> And that's at the expense
of all the other microbes
7494.33 -> that are in the gut.
7495.31 -> And so it's really hard to
replicate with purified fiber
7499.75 -> what you'd get, for
instance, at a salad bar,
7501.76 -> in terms of the array
of complex carbohydrates
7504.455 -> that you would be exposing
your microbiota to.
7506.87 -> And I think the kind of
7511.87 -> broad view of this in the field
7513.77 -> is that consuming a
broad variety of plants,
7517.555 -> and all the diverse fiber
that comes with that
7521.58 -> is probably better in fostering diversity
7523.64 -> in your microbiota than purified fibers.
7526.21 -> Now, there are, again,
7528.23 -> a lot of people who benefit
from purified fibers,
7530.78 -> either for GI motility or for
other aspects of GI health,
7535.7 -> problems that they've been experiencing.
7537.46 -> Again, I think it's the type of thing
7538.75 -> where you have to try to find the thing
7541.24 -> that's right for you.
7542.166 -> But there also are studies that suggest
7546.4 -> that if you layer rapidly
fermentable fibers
7550.91 -> on top of a Western diet,
you actually can result
7555.47 -> in weird metabolism
happening in your liver,
7558.71 -> because you have this incredibly
rapid fermentation of fiber
7561.7 -> along with a lot of fat
coming into the system.
7564.75 -> At least that's the theory.
7566.76 -> And in a mouse study that was
published a few years ago,
7569.85 -> they actually see that
a subset of the mice
7571.86 -> develop hepatocellular
carcinoma when they're fed
7575.17 -> a high dose prebiotic-
- Liver cancer.
7577.466 -> - Liver cancer, a on
top of a Western diet.
7581.23 -> So whether that's
representative of human biology,
7583.96 -> we don't know,
7584.98 -> but purified fibers are
definitely very different,
7588.638 -> both in terms of the
diversity of structures,
7590.97 -> but also in terms of how rapidly
7593.58 -> they're fermented in the gut.
7594.79 -> Because if you are eating plants,
7598.136 -> the complex structures there
really slow the microbes down
7601.69 -> in terms of fermentation, and
you end up with a slow rate
7604.37 -> of fermentation over the
length of your colon,
7606.9 -> as opposed to this big burst
of fermentation that can happen
7610.06 -> if you eat something
that is highly soluble
7612.93 -> and easily accessed by the microbes.
7616.04 -> - Interesting, so I guess,
7617.26 -> is it fair to come back to this idea?
7618.87 -> Try and avoid processed foods,
7620.796 -> the highly palatable foods,
7623.28 -> they're all sometimes super
highly palatable foods.
7625.45 -> They're now called,
7626.51 -> that are packed with
hidden sugars, emulsifiers.
7628.52 -> So it sounds like some fiber is good,
7631.808 -> and despite the outcome of the study,
7634.01 -> you identified that if you have
7635.39 -> the appropriate microbiota background,
7638.473 -> then one will even better to the fiber,
7641.76 -> maybe a longer ramp up
phase for those folks,
7644.62 -> and then the fermented foods.
7646.55 -> 'Cause there's no reason
why you can't do both.
7648.08 -> And as we've talked about before,
7649.71 -> a lot of fermented foods have fiber.
7651.84 -> So you can kill two birds with one stone.
7653.77 -> - Totally.
7654.603 -> And it could be that the
diversity increase that we saw
7656.74 -> in the high fermented food
group could be something
7659.55 -> that would aid the high fiber group.
7661.85 -> And so now we're planning
another study coming up
7663.936 -> where we're doing high
fiber, high fermented food,
7666.84 -> and then fiber plus fermented food,
7668.52 -> just to see if there's a
synergistic effect there.
7669.947 -> - Great, I want to enroll, seriously.
7673.11 -> Although I guess I'm biased,
7674.22 -> 'cause I was sort of know
where you're trying to..
7676.096 -> Well, is it blood draws that you use
7678.62 -> to measure the inflammatome?
7680.21 -> - Exactly, so we do blood draws-
7681.29 -> - [Andrew Huberman] Blood draws don't lie,
7682.966 -> so that's good.
- Yep, yep, right.
7683.96 -> - So you've covered a tremendous
amount of information,
7686.9 -> and I'm incredibly grateful.
7688.15 -> This was a area of biology,
7689.89 -> that despite having learned
a lot about through papers
7692.27 -> and going to talks and
reading articles in the media
7696.24 -> has remained somewhat
mysterious to me until today.
7699.11 -> You've given us a very vivid picture
7700.76 -> of how this system works.
7703.47 -> Where can people find out more
7704.78 -> about the work that you're doing?
7706.34 -> We can certainly provide links,
7707.546 -> and your wife who co-run your lab,
7711.59 -> you have a book on this topic.
7712.97 -> So could you tell us about the book,
7714.07 -> where we can learn more
about Sonnennburg Lab
7715.763 -> and the work that you're doing?
7717.47 -> Maybe people will even try and enroll
7719.41 -> in some of these studies.
7720.34 -> - Yeah, fantastic, yeah.
7721.21 -> It'd be great if we could
get people to enroll.
7723.12 -> We're always looking for
willing participants.
7727.08 -> Yeah, so Erica, my wife and I wrote a book
7729.8 -> called "The Good Gut," and
that really was a response
7734.61 -> to how we were changing our lives
7737.1 -> in response to being in the field,
7738.72 -> being very familiar with the research.
7740.7 -> Seeing that a lot of our friends
7741.84 -> that weren't studying that got microbiome,
7743.39 -> but were very well informed,
many of them scientists,
7746.09 -> were not doing the same
things we were doing.
7748.114 -> And it was very clear that it was just
7750.35 -> the lack of information funneling out
7753.564 -> of the field to other people.
7756.414 -> And so we were wanted to make
that accessible to people
7759.61 -> who are not microbiome scientists.
7761.61 -> There's also a really interesting story.
7763.27 -> We were at a conference site that just has
7765.42 -> scientific conferences all summer long,
7767.57 -> week after week, after
week, different fields.
7770.03 -> And so it's people that work there
7771.67 -> that are just dealing
with these new groups
7773.35 -> coming in week after week and the week,
7774.822 -> we were there for a microbiome conference,
7778.879 -> people that work in the dining comments
7782.62 -> came up to us and they said,
7783.453 -> "What group is this? This is weird."
7785.35 -> And we're like, "What's weird?"
7786.33 -> And they said, "We can't
keep the salad bar stocked."
7788.588 -> And it was very clear
that nobody was doing
7791.43 -> what we were doing until we'd
go to a microbiome conference
7794.01 -> and then everybody was
doing the same stuff
7795.93 -> that we were doing.
7796.91 -> And so anyway, we wrote this book to talk
7799.46 -> about our personal journey
and the science in the field,
7801.978 -> and yeah, just to lay
a foundation for people
7805.93 -> if they want to start
thinking about these changes.
7807.95 -> And then in terms of
connecting with our research,
7811.72 -> certainly there's the Center
for Human Microbiome Studies
7814.28 -> at Stanford, which is
kind of our home base
7816.67 -> for doing a lot of these
dietary and interventions.
7818.66 -> We list the studies there,
7820.072 -> give more information on what we're doing.
7822.083 -> And then we have a lab website too
7824.25 -> that people can go to and
read more about our research.
7827.39 -> Yeah, and we're always looking
7829.57 -> for participants for our studies.
7831.13 -> - Great, well, we will provide links
7832.74 -> to all of those sources.
7833.936 -> And I just want to say, thank
you so much for sharing with us
7837.91 -> your knowledge for the incredible
work that you and Erica,
7841.21 -> your wife and Chris do,
and are continuing to do.
7845.75 -> I think this is an area that,
when I started my training,
7848.86 -> I heard a little bit about microbiota,
7851.83 -> and I always just thought that are people
7852.85 -> that work on infectious
disease and all the bad stuff.
7855.38 -> So it's interesting and,
and really important
7859.39 -> that people realize that we're
carrying all this vital cargo
7862.32 -> and we need to take care of the cargo
7863.9 -> so it can take care of us.
7865.195 -> So thank you so much for your time
7867.59 -> and for the work you do, and
I hope we can do it again.
7870.01 -> - Thanks Andrew. This
was a great conversation.
7871.895 -> - Terrific.
7872.98 -> Thank you for joining me
today for my discussion
7874.81 -> with Dr. Justin Sonnenburg,
all about the gut microbiome
7877.84 -> and how to optimize your
gut microbiome for health.
7880.775 -> Please check out the
Sonnenburg Lab webpage,
7883.52 -> that's Sonnenburg, spelled
S-O-N-N-E-N-B-U-R-G-L-A-B
7889.417 -> .stanford.edu.
7890.98 -> That's sonnenburglab.stanford.edu.
7894.29 -> They often recruit for studies
7896.27 -> exploring how different
aspects of nutrition
7898.5 -> impact the got microbiome,
7899.94 -> much as we discussed
during today's episode.
7902.57 -> Please also check out the
book that he and his wife,
7905.01 -> Dr. Erica Sonnenburg wrote,
called "The Good Gut."
7907.61 -> It's readily available
on all the usual sites,
7909.75 -> such as Amazon and so forth.
7911.43 -> If you're learning from and
are enjoying this podcast,
7913.68 -> please subscribe to our YouTube channel.
7915.38 -> That's a terrific zero-cost
way to support us.
7918.13 -> In addition, please
subscribe to the podcast
7920.41 -> on Apple and Spotify.
7922.1 -> And on Apple, you have the
opportunity to leave us
7924.37 -> up to a five star review.
7925.93 -> You can also leave a comment
on Apple, if you like.
7928.5 -> The best place to leave us
comments and feedback, however,
7930.87 -> is on our YouTube channel
in the comment section.
7933.309 -> There you can suggest
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7935.89 -> to cover in future episodes,
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7941.03 -> that you've heard or
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7943.508 -> Please also check out the sponsors
7945.4 -> mentioned at the beginning
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7947.37 -> that's the best way to
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7950.08 -> We also have a Patreon, it's
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7954 -> and there you can support the podcast
7955.76 -> at any level that you like.
7957.33 -> On many episodes of the
Huberman Lab Podcast,
7959.16 -> including today, we discuss supplements.
7961.169 -> While supplements are certainly
not necessary for everybody,
7964.16 -> many people derive
tremendous benefit from them
7966.44 -> for things like sleep and focus,
7968.27 -> and indeed gut microbiome support.
7970.739 -> The one issue with supplements, however,
7972.81 -> is that many of the
supplement companies out there
7974.939 -> do not independently
test their supplements.
7977.55 -> So there isn't tremendous
confidence in all supplements
7980.815 -> that they contain the
amounts of the ingredients
7983.62 -> that are listed on the bottle,
7984.88 -> and that the quality of the ingredients
7986.46 -> is where it should be.
7987.62 -> For that reason we've
partnered with Thorne,
7989.33 -> that's Thorne, T-H-O-R-N-E,
because Thorne supplements
7992.7 -> are known to have the very
highest levels of stringency
7995.12 -> with respect to the
quality of the supplements
7997.768 -> and the amounts of the supplements
listed on their bottles
8000.803 -> list what's actually in the
containers, which is essential.
8004.516 -> If you'd like to see the
Thorne supplements that I take,
8006.84 -> you can go to Thorne, T-H-O-R-N-E,
8008.577 -> .com/u/huberman, and you can get 20% off
8013.2 -> any of the Thorne supplements
that are listed there.
8015.45 -> Also, if you navigate
deeper into the Thorne site
8017.72 -> through that portal,
thorne.com/u/huberman,
8020.67 -> you can also get 20% off
any of the other supplements
8023.41 -> that Thorne makes.
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8028.98 -> There I cover topics about
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8034.6 -> much of which is separate and unique
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8039.67 -> it is called The Neural
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8046.38 -> actionable takeaways in particular.
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8050.531 -> You can look in the menu,
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8065.74 -> So thank you once again for joining me
8067.26 -> for today's discussion
about the gut microbiome,
8069.63 -> and last, but certainly not least,
8071.458 -> thank you for your interest in science.
8073.564 -> [upbeat music]
Source: https://www.youtube.com/watch?v=ouCWNRvPk20