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place. Apply in

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minutes at mercury.com. If

1:19

you spend a little time on health and wellness TikTok,

1:22

you can find lots of people talking

1:24

about gut health. So some are doctors,

1:26

some are scientists, some are patients, and

1:28

they'll say stuff like, You need good gut

1:30

bacteria. Sometimes they emphasize how

1:33

gut bacteria can help with gut

1:35

conditions, like irritable bowel syndrome. But

1:37

some TikTokers are making a much

1:40

bigger claim. Good and bad bacteria

1:42

living inside your gut can affect

1:44

your mental health. There are TikToks

1:46

about how gut health affects

1:48

mood disorders like anxiety and depression.

1:51

People giving testimonials about how changing their

1:53

gut health can change their life. tax,

2:00

my depression has been so much better,

2:02

and my stress has been lowered. And

2:05

while some of the suggestions for how to

2:07

improve gut health just involve eating

2:09

or drinking more fermented things.

2:12

Kimchi, kombucha, someone said sauerkraut.

2:14

Other people are recommending dietary

2:17

supplements and regimens of expensive

2:19

pills. And I will post

2:21

them here because I cannot pronounce them at

2:23

all. It's all

2:25

part of a growing gut health industry that's

2:28

already worth billions of dollars.

2:31

So I'm bird Pinkerton, and

2:33

this week on Unexplainable, I've

2:36

been trying to figure out if there's anything to these

2:38

claims. And it turns

2:40

out there is some really interesting science

2:42

here. But there are also

2:45

lots and lots of mysteries

2:47

left to solve. Big

2:50

questions like, what is a

2:52

gut feeling? And what, precisely,

2:54

is the link between

2:56

the gut and mood, or mental

2:59

health? So

3:02

we're going to take a tour of some of

3:04

the research into those questions. But

3:06

first, a quick definition of a term that's going

3:08

to come up a lot. The

3:11

gut microbiome. So that's

3:13

all the microorganisms living in our

3:15

gut. Dr. Katarina Johnson is a

3:17

biologist and gut microbiome researcher at

3:19

the University of Oxford. And

3:21

she helped me understand that mammals like

3:24

mice, chimps, dolphins, but also humans like

3:26

you and me, we have

3:28

millions of microorganisms living in our stomachs

3:30

and intestines. Bacteria

3:32

but also fungi, parasites. And

3:35

they help us break down food, they attack

3:37

the bacteria that make us sick, and they

3:39

also interact with other parts of our bodies.

3:42

They interact with our immune system,

3:44

our nervous system, our hormones. So

3:47

in many ways, our gut microbiome is almost

3:49

like the center of our physiology. So

3:52

that is the gut microbiome. And

3:54

our tour into the research about the connection

3:57

between it and mood begins in the early

3:59

2010s. when some

4:01

researchers got curious about the microbiome

4:03

and stress or anxiety. They

4:05

had noticed that a lot of people

4:07

with gut conditions like irritable bowel syndrome

4:10

had stress or anxiety. And they

4:12

wondered, was that just because gut

4:15

problems are really unpleasant? Or

4:17

was there something more at play here? Was

4:19

the gut somehow influencing

4:22

emotions? So

4:24

they designed an experiment to find out.

4:26

This experiment that Katarina ended up reading

4:28

about as part of her PhD research

4:30

years later. It was

4:32

an experiment that relied on the quirks

4:35

of lab mice. Some

4:37

mouse strains tend to

4:40

have different temperaments from other

4:42

mouse strains. In this experiment,

4:44

the researchers chose two strains

4:46

specifically for their temperamental quirks.

4:48

So in particular, they chose one mouse

4:50

strain that tends to be quite timid

4:53

and tends to show kind of

4:55

anxiety-like behaviors and another

4:58

mouse strain that tends to be much

5:00

more bold and exploratory. And if

5:02

you're wondering how researchers measure mouse

5:05

personalities? Obviously, it's how you can't

5:07

get inside the mind of a

5:09

mouse, but there is a range

5:11

of different tests that have been

5:13

developed over the years in kind

5:15

of like psychology and biology to

5:17

try to understand, you know, kind of

5:19

how an animal is feeling. They

5:21

can put the mice in a box with

5:23

two rooms, one dark, one full of light,

5:26

and the bolder mice are the ones that

5:28

explore more or explore more in the brighter

5:30

room, while the anxious and

5:33

timid mice stay safely in the

5:35

darkness. That's just kind of like

5:37

one example. So the experimenters had

5:40

these mice with mousy, not so

5:42

mousy personality traits, and

5:44

basically they wanted to know. If you

5:46

take the gut bacteria from this kind

5:49

of like bald mouse and all the

5:51

gut bacteria from this shy mouse, and

5:54

you swap kind of the contents

5:56

of that gut. Could you also

5:58

change how anxious or? stressy a

6:00

mouse was, would changing the

6:02

contents of the gut affect these

6:04

personality traits at all? So,

6:08

they use something called a

6:10

fecal microbiota transplant, which

6:12

we've been doing some version of for

6:14

centuries, possibly as early as the fourth

6:16

century in China. But at

6:18

the most basic level, a fecal

6:20

microbiota transplant involves taking poop from

6:22

one gut and putting it into

6:24

another. And if all goes

6:26

well, the microorganisms from the donor gut

6:29

will then spread in the recipient's gut.

6:31

So, the researchers did a version of this

6:34

process, and the end result was that they

6:36

had bold mice with

6:38

timid mouse gut microbes and

6:41

timid mice with bold mouse gut

6:43

microbes. Once

6:45

the swap was complete, they ran

6:48

their little mouse personality tests again. And

6:50

they found that if you change

6:52

the gut microbiome, it affected the

6:55

temperament of the animals. So,

6:58

the aggressive mouse becomes shyer

7:00

because it was colonized by the gut bacteria

7:02

of the shy mouse and vice versa. Now,

7:04

this wasn't like a remake of Freaky Friday,

7:06

but where Jamie Lee Curtis

7:09

and Lindsay Lohan trade guts instead

7:11

of bodies, because the personalities were

7:13

not totally swapped. It's

7:16

not like the bold mouse

7:19

becomes totally shy, but its

7:21

temperament changes more to be

7:24

more docile. And meanwhile,

7:26

the timid mice weren't suddenly

7:28

wildly bold. The shy mouse

7:30

shows less anxiety-like behavior, but

7:32

not to the total extent

7:34

of exhibiting the behavior

7:37

of the other individual,

7:39

but it becomes more like it. Still,

7:42

even without a complete

7:44

personality reversal, these

7:46

shifts in timidity and boldness

7:48

were pretty impressive, because this

7:50

study from 2011 was

7:52

one of the first to really

7:55

clearly show that behaviors could be

7:57

transferred along with a gut microbiome.

8:00

at least in mice. This is

8:02

exciting because then the implication of

8:04

that is that our gut

8:06

microbiome does contribute in some way,

8:08

we don't know how much, to

8:12

behavior. There

8:15

have since been follow-up studies also on mice,

8:18

drawing more connections between the gut

8:20

and mood disorders and stress and

8:23

personality traits. But while

8:25

we do research on mice because mice and

8:27

humans have a lot of similarities, like we have

8:29

the same kind of organs, they develop in

8:31

similar ways, mice and humans

8:34

are also very different. Mice

8:36

can't talk to therapists, for example, to

8:38

help with their emotions. So

8:41

the next question is, does the

8:43

human gut microbiome make similar contributions

8:45

to mood or emotions or stress?

8:49

Katarina says she has started to see

8:51

more research being done across species to

8:53

see if the same kinds of effects

8:55

hold up. So for example, they've taken

8:58

the gut microbiota

9:00

from humans that are

9:02

depressed, and they've then

9:04

colonized the guts of mice with

9:07

these bacteria. And

9:09

they find that the mice

9:11

show symptoms characteristic of depression

9:14

in both their physiology and

9:17

their behavior. One of the

9:19

ways that researchers measure depression in mice

9:21

is pretty controversial. They'll put them in

9:23

a tank full of water and

9:25

see how long they swim. Which is

9:27

called the forced swim test. So it's how much

9:30

the animal kind of struggles, how much motivation they

9:32

have to struggle before they give up. The

9:34

researchers found that mice that

9:36

got gut microbes from humans

9:38

with depression gave up

9:41

faster than mice with gut microbes

9:43

from humans without depression. And

9:46

then there were other interesting results.

9:48

The animals that were colonized with

9:50

the gut microbiota of people who

9:52

were depressed, will so show a

9:54

more pro-inflammatory kind of profile that

9:56

means their immune system was more

9:59

eagerly. was reacting to more things

10:01

in their environment, seeing more stuff

10:03

as threats. And humans

10:05

with depression can also have more active immune

10:07

systems, just like these mice. So

10:09

there were kind of changes also at the

10:11

physiological level that seemed to match, or you

10:14

might expect. All of which

10:16

suggests that gut microbiomes might play

10:18

some role in depression, even in

10:20

humans. But this study

10:22

was also done in mice. So

10:24

then, like the next obvious

10:26

thing is to wonder, okay, so

10:28

what about fecal microbiota transplants in

10:31

humans? Would those affect people's moods

10:33

too? Katarina has

10:35

looked at the research into this, such as

10:37

it is. Like she says that fecal microbiota

10:39

transplants are pretty rare

10:41

in humans. They're generally safe,

10:44

but they can have side

10:46

effects. And they're usually only

10:48

used to treat severe intestinal

10:50

issues like Clostridium difficile, or

10:52

C. diff. So this

10:54

is an infection of nasty gut

10:56

bacteria, and it can be really

10:58

hard to get rid of even

11:00

faithful. Still, even though Clostridium difficile

11:02

patients don't have fecal microbiota transplants

11:04

specifically to alter their mood, researchers

11:07

have started to look and see if there's

11:09

an effect to their mood from the transplants.

11:12

There's also been some interesting observations in

11:14

these patients that had had the fecal

11:16

transplant for Clostridium difficile. And

11:18

then they found that it emigrated other

11:20

conditions that they had, for example, depression,

11:23

chronic fatigue. And there have been

11:25

some small papers detailing case studies

11:27

for other conditions. Like there

11:30

was one where a few patients with

11:32

irritable bowel syndrome had fecal transplants. And

11:34

they found that the fecal transplant

11:37

improved their kind of psychiatric symptoms.

11:39

Including depression. Now, it

11:41

is possible that if someone gets

11:43

a transplant and it helps with their IBS or their

11:45

C. diff, they're less tired or

11:47

less depressed because they're not struggling with

11:50

severe stomach problems anymore. Obviously,

11:52

these are just small trials and

11:54

there's not enough evidence. It's very

11:56

early days and there's

11:58

still many unknowns of fecal transplants.

12:00

But still, research like this was

12:02

intriguing to Katarina. So

12:04

she decided she wanted to do a

12:07

study of her own and one that

12:09

would not be limited to people with

12:11

intense gastrointestinal issues. Her

12:13

plan was to take a bunch of human

12:15

gut microbiomes and look at the personalities of

12:17

the people that they belong to to

12:19

see if she could spot any connections between the

12:22

two. So she gathered more than

12:24

600 participants. She collected

12:26

information about their diet, their lifestyle, their

12:28

life history, gave them a series of

12:31

questionnaires to figure out how social and

12:33

anxious they were, how big their social

12:35

network was. And

12:38

then she gathered the most important

12:40

data of all. So people sent

12:42

a stool collection kit in the

12:44

post. And so they take

12:46

their sample and then they post it as

12:48

soon as they can afterwards. And I was

12:50

working with a company to actually do

12:52

the kind of like sequencing. Katarina had all

12:55

that poop sent to a lab, which helped

12:57

her identify which microbes were in each sample,

12:59

how many, how many different kinds, which

13:02

meant that Katarina finally had a sense of

13:04

which types of microorganisms each person had in

13:07

their gut and how diverse their guts were,

13:10

and also a sense of how social

13:12

these people were and how

13:14

anxious and stressed. Now

13:16

she just had to crunch all this

13:18

data together and look for patterns. I

13:21

found that sociable people have

13:23

a high abundance of

13:25

certain types of bacteria. So

13:29

we know from animal studies that the

13:31

gut microbiome can affect how likely they

13:33

are to interact socially. So the fact

13:35

that I find that these specific

13:38

gut bacteria are also

13:41

differentially abundant in humans in

13:44

relation to their social behavior

13:47

does suggest that the gut microbiome may

13:49

contribute to variations in social behavior that

13:51

we see in the general population as

13:54

well. She also found

13:56

a link between those traits and how

13:58

diverse a person's gut was. So more

14:00

diverse. was linked to less anxiety, more

14:02

sociability, but it is

14:05

possible that, for example, social people

14:07

end up seeing more people swapping

14:10

bacteria with them, and that is

14:12

what leads to a more diverse

14:14

microbiome. We almost each have like

14:16

almost our own personal microbial cloud,

14:18

and we were always transmitting microbes

14:20

between us. Katerina's work is another

14:23

piece in a growing research argument that

14:25

the gut really does seem to be

14:28

connected to mood and personality, not

14:31

just in mice, but also in humans. But

14:35

knowing that the gut plays a role doesn't

14:38

really answer why it plays a

14:40

role, or how. Like, how

14:43

could microorganisms down in the intestines

14:45

of all places connect

14:48

to boldness in mice or

14:50

socialness in humans? Why

14:52

would our poop have any connection

14:54

to depression? Hmm,

14:58

yeah, that's like kind of the killer

15:00

question, like how does our gut microbiome

15:02

really affect our brain? Support

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18:05

Podcasts. Well,

18:12

Bill, now you know why

18:14

you feel so bad. You

18:16

mistreated your stomach all day long.

18:20

No wonder you have a — Unexplainable

18:22

from Vox. There's

18:24

a growing body of evidence suggesting

18:26

that the microbes in the mammalian

18:28

gut are having some kind of

18:30

an effect on mood and personality

18:32

traits, mice but also humans. So

18:35

the next question is, how? And

18:38

the answer might lie in

18:40

something called the enteric nervous system.

18:43

People often call me the father

18:45

of the enteric nervous system, and

18:47

I say, I'm not the father of the

18:50

— I swear paternity to Perry, Dana,

18:52

and Timothy, my three children, and

18:54

no further. So

18:56

I didn't discover the enteric nervous

18:59

system. I popularized it.

19:02

Dr. Michael Gershon, father of Perry,

19:04

Dana, and Timothy, longtime

19:06

gut researcher and popularizer of

19:09

the enteric nervous system. And

19:12

in case his popularizing efforts have not

19:14

yet reached you, the enteric nervous system

19:16

is the idea that the mammal gut

19:18

has a brain of its own almost,

19:21

like a whole separate division of the

19:23

nervous system that's sometimes referred

19:25

to as a second brain because

19:27

it has an unusual number of

19:29

nerve cells. In humans,

19:32

there are hundreds of millions of

19:35

nerve cells in the gut. That's

19:37

a lot less than the billions of

19:39

neurons in your head brain, which means

19:42

that your gut nerve cells are probably

19:44

not teasing out the nuances of Russian

19:46

philosophy, for example. But

19:48

Michael has been trying to work out what

19:50

exactly they are doing ever since his early

19:52

research days. And because I'm

19:55

old, that was a long time ago. It was not that

19:57

long ago. It was back in the 1960s. and

30:00

to solve problems in new and exciting

30:02

ways. So why does it feel so threatened?

30:05

With new technological advances that can create

30:07

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30:09

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Tune into Saving Creativity, a special series

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from The Gray Area sponsored by Canva.

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You can find it on The Gray

30:23

Area feed wherever you get your podcasts.

30:27

And we're back with Canva Presents

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Secret Sounds Work Edition. Caller,

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guess this sound. It's

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a mouse click. So close! That's

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actually publishing a website with Canva

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Docs. Next caller. Definitely

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