0:11

I'm Beth Bennet. This is how on

0:13

earth the Cajunius Science Show. Today

0:15

is Tuesday, February 11th, 2025. Coming

0:17

up, I speak with a sea

0:20

of scientists about his recent finding

0:22

that exposure to a harmless soil

0:24

bacteria protects mice from the weight

0:26

gain and inflammation stemming from a

0:29

diet much like the average American

0:31

one. That is, high in fat and

0:33

sugar. There's

0:58

this eye-directional relationship between

1:00

obesity and inflammation, where

1:02

obesity increases inflammation, inflammation

1:04

increases obesity, and it

1:06

seems that with the

1:08

Anvaki treatment, we just

1:10

interrupted that cycle. But

1:28

first, a look at some

1:30

interesting news from Boulder in science

1:33

and a calendar item for you.

1:35

If you are a loved one is

1:37

struggling with mental health, you're

1:39

not alone. Roughly one in every

1:42

five adults experienced this according to

1:44

a 2022 CDC report. The good

1:47

news is a better state of

1:49

mind could be right in your

1:51

backyard, literally. perceived green

1:54

space exposure, that is a person's

1:56

perception of the amount and quality

1:58

of access to, and time spent

2:01

in green space may have a

2:03

significant positive effect on aspects of

2:05

mental health, according to new research

2:08

from an interdisciplinary University of Colorado

2:10

at Boulder team. Their study revealed

2:12

a strong association between perceived

2:14

green space exposure and reduced

2:16

anxiety. The relationship between green

2:19

space and mental health isn't

2:21

just about the green space

2:23

that's empirically there, which they

2:25

measured by aggregating green pixels

2:27

from aerial imagery, that's also

2:29

known as objective green space.

2:31

The scientists concluded that the

2:33

relationship is mainly influenced by

2:35

aspects of green space that

2:37

aren't well captured by objective

2:39

measures, such as the quality

2:41

and how much time someone spends

2:43

in green space and how accessible

2:46

it is. The researchers found

2:48

that perceived green space exposure

2:50

was directly linked to reduced

2:52

anxiety metrics and had a

2:55

borderline statistically significant relationship with

2:57

lower levels of depression. Meanwhile,

2:59

objective green space exposure, remember

3:01

we talked about that earlier,

3:03

bore no statistically significant association

3:06

with anxiety, depression, or stress.

3:08

In other words, when it

3:10

came to mental health and

3:12

anxiety in particular, objective green

3:14

space exposure mattered far less

3:17

than the subject's perceptions

3:19

of green space exposure.

3:21

And the researchers also

3:23

found, not surprisingly, a

3:25

positive association between socioeconomic

3:27

status and both objective

3:29

and perceived green space,

3:31

where people with higher

3:34

socioeconomic status had more

3:36

exposure. This study was

3:38

published last month in the Journal

3:41

of Environmental Psychology, but at any

3:43

time this month next, and other

3:45

times in the future, you too

3:47

can get out into green space.

4:10

If you have a preschooler who

4:12

loves natural history and what preschooler

4:14

doesn't, a twice-weekly program at the

4:17

CU Museum of Natural History gives

4:19

them the chance to play, make,

4:21

and discover in the discovery corner

4:23

of the museum. Topics range from

4:25

the small, like insects, to the

4:27

large, think dinosaurs. You can visit

4:29

the morning in the museum program

4:31

twice a month, beginning tomorrow, Wednesday,

4:33

February 12th. Register on the museum

4:35

website and remember, campus parking is

4:37

not free, so plan ahead. Christopher

4:59

Lowry is professor in the Department

5:02

of Integrated Physiology and the Center

5:04

for Microbial Exploration at the University

5:06

of Colorado Boulder. Dr. Lowry's research

5:09

program at C.U. Boulder focuses on

5:11

understanding stress-related physiology and behavior with

5:14

an emphasis on the microbiome gut

5:16

brain axis. He's working on

5:18

developing a program designed to lead

5:20

to novel microbiome-based interventions for the

5:23

prevention of anxiety disorders, mood disorders,

5:25

and trauma and stress-related disorders such

5:28

as PTSD. Welcome to the show,

5:30

Chris. I'm speaking with Professor Chris

5:32

Lowry. at the University of Colorado

5:35

in the Department of Integrative Physiology.

5:37

And he has recently been doing

5:40

some fascinating work involving the gut

5:42

microbiome, specifically using an introduced bacteria

5:44

from the soil that's giving some

5:47

really remarkable results. So Chris, do

5:49

you want to start off by

5:52

talking about what this bacteria

5:54

is and why it's doing? some

5:56

of the amazing things or why

5:58

you think it might be doing

6:01

some of the amazing things it's

6:03

doing? Yeah, I'd love to. So

6:06

we've been studying this particular type

6:08

of bacteria for about 25 years.

6:10

And my original interest in this

6:13

area was really coming from a

6:15

field of research called succindural immunology.

6:18

And essentially that's the study of

6:20

how the immune system communicates with

6:22

the brain to altered behavior and

6:25

even mental health. At that time,

6:27

we knew a lot about how

6:30

the gut signals to the brain,

6:32

but less about how the lung's

6:34

signal to the brain. And when

6:37

I was at the University of

6:39

Bristol, I became aware that there

6:42

was a group of scientists at

6:44

University College London studying this particular

6:46

bacteria and vacu. And it was

6:49

appealing for a couple of reasons.

6:51

One, it was found in soil.

6:54

And so this is the type

6:56

of bacterium we would breathing if

6:58

we're in the garden or working

7:01

on a farm, for example, and

7:03

therefore it was an ideal bacterium

7:06

to study in terms of

7:08

trying to understand how the lung

7:10

is talking to the brain. And

7:12

so that was a really simple

7:15

question in the beginning. Then we

7:17

became interested in the idea that

7:20

it may have health benefits. So

7:22

let's back up for a minute,

7:24

introduce this bacterium. It's genus is

7:27

mycobacterium and its species is vacai.

7:29

And you said it's a pretty

7:32

common and harmless bacterium, probably harmless

7:34

to most of us, but you

7:36

give it to mice in a

7:39

heat-killed form, so it would definitely

7:41

not be pathogenic in that

7:43

form. But I would guess that...

7:46

if people have heard of mycobacteria

7:48

at all, they've heard of the

7:50

pathogenic forms. So this is clearly

7:53

not that and it kind of

7:55

ties into one of the many

7:58

hypotheses about why our modern lifestyle

8:00

causes us so many problems. maybe

8:02

we haven't been exposed to enough

8:05

of this kind of bacterium, would

8:07

you say? Yeah, that's exactly the

8:10

idea. So my colleague, Graham Rook,

8:12

who was one of the scientists

8:14

that discovered this bacterium, is the

8:17

person who originated the old

8:19

friend's hypothesis. And this really is

8:21

a derivative of the hygiene hypothesis,

8:24

this idea that as we transition

8:26

from hunter gather societies to our

8:29

agricultural societies to now. our urban

8:31

societies, we've lost contact with these

8:33

types of organisms that were in

8:36

the mud and the soil and

8:38

the water. And these these were

8:41

bacteria that we were exposed to

8:43

throughout human evolution. But we also

8:45

think throughout mammalian evolution. So that

8:48

stretches back 65 million years during

8:50

a period when mammals and these

8:53

types of bacteria were co-evolving. So

8:55

there's an ancient, ancient relationship between

8:57

these soil bacteria and mammals, including

9:00

humans. So these bacteria somehow can

9:02

provide a signal from, well, you

9:05

said initially the lungs, and then

9:07

we can get into your work

9:09

with the gut microbiome that conveys

9:12

a message to the brain that

9:14

maybe... we don't need to be

9:17

as stressed about life as we

9:19

might be. And then it could

9:21

also affect the immune system. Am

9:24

I on the right track there?

9:26

Totally on the right track. So

9:29

one of the things that got

9:31

us really interested in the

9:33

potential for mental health specifically is

9:35

the very first studies we did.

9:38

We found that when we injected

9:40

the bacteria in mice, we could

9:43

see activation of serotonin neurons in

9:45

the brain. And this was this

9:47

was curious because it wasn't all

9:50

serotonin neurons. There are many different

9:52

types of serotonin neurons, but the

9:55

bacterium activated serotonin neurons that we

9:57

had previously associated with antidepressant effects.

9:59

or a more proactive coping with

10:02

stress. And this led us to

10:04

test the behavioral response to the

10:07

bacterium. We saw antech person

10:09

like behavior. About the same time,

10:11

there was a phase three clinical

10:13

trial that was done in humans

10:16

where they were injecting the same

10:18

bacterium into humans into the skin.

10:21

They were testing the idea that

10:23

it could be beneficial in cancer.

10:25

And it didn't prolong life

10:27

in these cancer patients. But

10:30

it did improve quality of

10:32

life scores. And so that

10:34

included things like increased overall

10:36

emotional health, increased cognitive function,

10:38

decreased pain, and decreased nausea.

10:40

And of course we reason

10:42

this must be because somehow

10:44

this bacteria is talking to

10:46

the brain and altering the

10:48

brain in a way that's

10:50

improving these mental and cognitive

10:52

functions. So this makes sense,

10:55

you know, that different elements

10:57

of our environment, including our

10:59

internal environment, talk to the

11:01

brain and tell us what's

11:03

going on. I'm happy with

11:05

that idea. But what kind

11:07

of mechanism do you think

11:09

is at work here? How

11:11

does that signal arrive? And

11:13

then what is it doing

11:15

in the brain? We know

11:17

that one of the common

11:20

features of these old friends,

11:22

in other words microbes that

11:24

have anti-inflammatory, immunregulatory properties. They

11:26

share in common the ability

11:28

to communicate with our mean

11:30

cells. And they're particularly good

11:32

at communicating with macrophages and

11:34

dendritic cells, which are part

11:36

of our innate immune system.

11:38

And you can think of

11:40

the dendritic cell as a

11:42

teacher. It's playing a role

11:45

where it's teaching naive T

11:47

cells, which is part of

11:49

our acquired immune system, training

11:51

those, teaching those T cells

11:53

to differentiate into. regulatory T-cells

11:55

that have anti-inflammatory effects. And

11:57

back he seems to be...

11:59

talking to the teachers, which

12:01

then train the students to

12:03

become anti-inflammatory. And then those

12:05

T-saws, because they have a

12:07

very long half-life, they can

12:10

provide protection against inflammation for

12:12

long periods of time. And

12:14

in fact, in our preclinical

12:16

studies, we see that we

12:18

can see beneficial behavioral effects

12:20

that last at least a

12:22

month after... treatment with the

12:24

bacterium. And so this really

12:26

points to the long-term amino

12:28

regulation that's occurring. So I'm

12:30

really glad you mentioned the

12:32

anti-inflammatory properties and I want

12:35

to come back to that

12:37

because I'm really interested in

12:39

that. I think it is

12:41

the basis for or at

12:43

least the inflammation, at least

12:45

at the chronic level, was

12:47

the basis for so much

12:49

of what goes wrong with

12:51

us. But before I go

12:53

there, let me ask you,

12:55

and this is a very

12:58

hypothetical question because I love

13:00

the evolutionary aspect of this

13:02

idea. So we have these

13:04

old friends in bacteria, and

13:06

do they somehow signal to

13:08

us that we're in a

13:10

good environment, one that can,

13:12

you know, protect us or

13:14

at least not harm us?

13:16

Yeah, I love where you're

13:18

going with this question. It's

13:20

not something that comes up

13:23

very often, but we started

13:25

to think of bacteria as

13:27

components of our environment in

13:29

the place that we live

13:31

in at a particular point

13:33

in time. And some bacteria,

13:35

it seems like, and backy

13:37

are essentially physiological signals that

13:39

tell us that we're in

13:41

a safe environment. And that

13:43

would mean that there's abundant

13:45

resources, food and water, and

13:48

maybe that's a good time

13:50

for reproduction and growth. And

13:52

so there's very little inflammation,

13:54

there's very little anxiety, there's

13:56

very little social avoidance, etc.

13:58

But then there are other

14:00

types of bacteria that are

14:02

predominantly pro-inflammatory, and many of

14:04

these can actually cause disease.

14:06

And we may encounter these

14:08

types of bacteria. throughout mammalian

14:10

evolution when we are in

14:13

situations where maybe there's a

14:15

drought, maybe there's not abundant

14:17

food and water, you know,

14:19

mammals are eating more, decaying

14:21

flesh, carrying in, etc. And

14:23

that in a sense, those

14:25

bacteria are danger signals. They

14:27

increase inflammation because we're at

14:29

greater risk of being exposed

14:31

to pathogenic bacteria, so that's

14:33

adaptive. But they also increase,

14:35

we know inflammation increases anxiety

14:38

and even depression. In fact,

14:40

inflammation is recognized as a

14:42

risk factor for anxiety disorders,

14:44

mood disorders like depression and

14:46

also trauma-related disorders like PTSD.

14:48

inflammation is associated with so

14:50

many chronic issues. And in

14:52

one of your recent papers,

14:54

you injected the heat-killed form

14:56

of the bacteria into an

14:58

inbred strain of mouse, and

15:00

you found that that protected

15:03

them against some of the

15:05

adverse, i.e. inflammatory effects of

15:07

our terrible Western diet, our

15:09

sad, standard American diet. So

15:11

could you talk a little

15:13

bit about how you give

15:15

mycist diet and what they...

15:17

typically exhibit on that diet

15:19

and how the bacteria protect

15:21

them. Yeah, so this is

15:23

a fascinating study. We really

15:25

set out to determine whether

15:28

we could prevent the effects

15:30

of this Western diet on

15:32

neuroinclamation, so inflammation in the

15:34

brain, and also anxiety, because

15:36

our previous work could show

15:38

that this type of diet,

15:40

of course, induces inflammation in

15:42

the body, but also in

15:44

the brain in the form

15:46

of neuroinclamation. And it also

15:48

induces anxiety like behaviors. And

15:51

so we knew from previous

15:53

studies that Ambachie is very

15:55

effective at preventing this kind

15:57

of, if you will, stress-induced

15:59

inflammation, neuro-inclamation, and anxiety. And

16:01

so that was our context.

16:03

And Ambachie did decrease their

16:05

inflammation. markers of neuroimclamation and

16:07

anxiety as expected. But then

16:09

we were completely surprised because

16:11

the animals that were given

16:13

the Western diet, they were

16:16

about 16% heavier than animals

16:18

on a healthy controlled diet

16:20

at the end of this

16:22

study. They had increased visceral

16:24

out of paucity so they

16:26

were becoming obese or overweight

16:28

and had obesity. And what

16:30

we found is the animals

16:32

that were on the high-fat

16:34

diet, a sugar diet, this

16:36

typical Western diet, but given

16:38

them, they gained no additional

16:41

weight, no excessive weight compared

16:43

to animals that got a

16:45

healthy diet. And it completely

16:47

prevented any weight gain or

16:49

visual out of opacity in

16:51

the animals that were on

16:53

a high-fat diet. You know,

16:55

having worked with mice for

16:57

many years, my first response

16:59

is to think, well, mice

17:01

are not little people. But...

17:03

given that this is really

17:06

a great thing to follow

17:08

up on and especially given

17:10

that you you decided to

17:12

look at the microbiome and

17:14

you found that the and

17:16

vacu didn't affect the composition

17:18

of the gut microbiome so

17:20

something else there's some other

17:22

mechanism for that weight loss.

17:24

Yeah so we think and

17:26

vacu particularly when we inject

17:28

it as we did in

17:31

this study it's interacting directly

17:33

with the immune system. And

17:35

so one of the things

17:37

that this unhealthy diet does

17:39

from many many years of

17:41

research by others is that

17:43

it induces a type of

17:45

leaky gut phenomenon where contents

17:47

of the gut looming food

17:49

and bacteria and other microbes

17:51

can actually breach the barrier

17:53

or the gut barrier and

17:56

get into the body. When

17:58

that happens you have an

18:00

inflammatory response which is adaptive

18:02

and That's what the immune

18:04

system is designed to do

18:06

in part. But if that

18:08

leaky got and you know

18:10

this kind low-grade inflammation persists.

18:12

That's what can drive all

18:14

of these negative physical and

18:16

mental health outcomes. And we

18:19

know, for example, in obesity,

18:21

obesity has a bidirectional relationship

18:23

with inflammation. As obesity increases,

18:25

there's cell death within the

18:27

fat tissue that induces monocytes.

18:29

another type of immune cell

18:31

to traffic into the adipose

18:33

tissue and differentiate in the

18:35

macrophages that are really angry.

18:37

They release all kind of

18:39

joycide kinds and they're there

18:41

to kind of clean things

18:44

up and you know trying

18:46

to come back to some

18:48

kind of homeyesthetic state. And

18:50

so there's this bidirectional relationship

18:52

between obesity and the inflammation

18:54

where obesity increases inflammation, inflammation,

18:56

And it seems that with

18:58

the Anbaki treatment, we just

19:00

interrupted that cycle. In other

19:02

words, by preventing the inflammation,

19:04

we prevented any weight gain

19:06

and we prevented the increase

19:09

in obesity. So that's fascinating

19:11

because you didn't deter the

19:13

leaky gut. And that's the

19:15

thing about inflammation. It's something

19:17

good that's, we've got too

19:19

much of a good thing

19:21

and it's causing all these

19:23

downstream problems. To develop this

19:25

technology so that we can

19:27

provide. these mycobacteria for use

19:29

in nutritional supplements or even

19:31

as food ingredients. And it

19:34

seems like we don't need,

19:36

you know, a lot of

19:38

exposure. We just need some

19:40

exposure that might mimic, you

19:42

know, what we traditionally experienced

19:44

during hunter-gatherer times. We did

19:46

do a study where we

19:48

kind of tested hygiene hypothesis

19:50

or with friends hypothesis. in

19:52

the context of psychiatry and

19:54

I'd like to talk about

19:56

this study because it is

19:59

it is fascinating and what

20:01

we did is we brought

20:03

20 young men around 20

20:05

to 24 years of age

20:07

that had grown up on

20:09

farms in Germany. These were

20:11

farms with farm animals and

20:13

then we also brought in

20:15

20 young men that grew

20:17

up in cities of at

20:19

least 100,000 people and did

20:21

not have pets at home.

20:24

We know that there's a

20:26

big difference in the risk

20:28

of allergic asthma based on

20:30

what's called the farm effect.

20:32

In other words, if you

20:34

grow up on a farm,

20:36

you get protection from allergic

20:38

asthma as an adult. This

20:40

has been highly replicated. And

20:42

we thought that if that's

20:44

the case, then we should

20:47

also see a difference in

20:49

the inflammatory response to purely

20:51

psychological stress in humans. And

20:53

that's exactly what we found.

20:55

We found that people that

20:57

grew up in cities. had

20:59

a much exaggerated inflammatory response

21:01

to a purely psychological stress

21:03

exposure, whereas the people that

21:05

grew up on farms returned

21:07

to normal more quickly and

21:09

had an attenuated inflammatory response.

21:12

So the point of that

21:14

I think is that, you

21:16

know, if we're a person

21:18

that grew up in a

21:20

city, in an urban environment,

21:22

we have this. intensity for

21:24

inappropriate or exaggerated inflammation, even

21:26

to day-to-day stressors that might

21:28

occur in our normal everyday

21:30

lives. Yeah, I think that's

21:32

so true that and more

21:34

and more people are recognizing

21:37

that that we have higher

21:39

levels of stress living in

21:41

urban environments and you know,

21:43

there's more emphasis on being

21:45

in nature that so-called nature

21:47

bathing, the lovely Japanese term,

21:49

you know, gardening or even

21:51

having pets would probably expose

21:53

you to more of these

21:55

potentially protective bacteria. All of

21:57

those things, we know that

21:59

having a pet during the...

22:02

years of life, life, a

22:04

dog, for example, can protect

22:06

against the allergic airway, inflammation

22:08

as an adult, being outdoors

22:10

can be certainly has been

22:12

shown to be able being

22:14

exposed to the bright light

22:16

and being outdoors can improve

22:18

sleep quality, it also can

22:20

improve mental health outcomes. And

22:22

so we don't. We don't

22:24

claim that we know all

22:27

the mechanisms that are involved

22:29

in being outdoors and being

22:31

in nature, but it's a

22:33

really powerful effect. And so

22:35

maybe we shouldn't question about

22:37

question about exactly how it's

22:39

working. But I love it

22:41

that you tested it. You

22:43

know, you took these young

22:45

men and you tested that

22:47

hypothesis and. We're going to

22:49

have to leave it there.

22:52

Unfortunately, I'm not going to

22:54

get time to talk to

22:56

you about cancer. Maybe we

22:58

can do that on another

23:00

occasion. But thank you so

23:02

much for talking and congratulations

23:04

on your startup company. Thank

23:06

you, Beth. I really appreciate

23:08

your time. That was Professor

23:10

Christopher Lowry, talking about his

23:12

recent work with Michael bacteria

23:15

and Vachai, a harmless soil

23:17

dweller that can protect mice

23:19

and possibly us humans from

23:21

numerous stressors, including a harmful

23:23

diet. I'll link to his

23:25

recent paper on the role

23:27

of the bacteria in preventing

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