JAD ABUMRAD: Hey, I'm Jad Abumrad.

ROBERT KRULWICH: I'm Robert Krulwich.

JAD: This is Radiolab. And today ...

ROBERT: Well, we're talking about the interior space that runs down from your mutt to your butt, and it is called ...

JAD: Your gut! Your mutt? What is that?

ROBERT: It's just an old person's word for mouth. [laughs]

JAD: Anyhow ...

ROBERT: Now as we just heard, for a very, very long time, people believed that the stomach was a place of magical transformation.

JAD: Yeah. But of course, as we know now, it's just a big muscle with acid and enzymes and stuff.

ROBERT: But if you travel a little deeper down, down below the stomach?

JAD: Yeah?

ROBERT: Then things get spooky again.

CARL ZIMMER: We just—you know, we have these sort of shadowy images of what's going on in there.

ROBERT: That's Carl Zimmer, a shadowy figure himself: a science writer.

CARL ZIMMER: Can I get some water?

ROBERT: And a frequently thirsty man.

CARL ZIMMER: My throat got a little scratchy.

ROBERT: Soren and I called him up, you know, while you were gone on paternity leave?

JAD: Yup.

ROBERT: And he told us, "You want a mystery?"

JAD: Yeah, I do.

ROBERT: Okay, then the stomach is just a warm up.

CARL ZIMMER: Oh, yeah.

ROBERT: The 25 feet of coiled, soiled, fetid tubing inside you?

JAD: You mean the intestines?

ROBERT: Yeah, yeah. That's where the real mystery lies. Because here's the riddle: the part of you that turns the world outside into you?

JAD: Yeah?

ROBERT: Isn't just you.

CARL ZIMMER: It's more like a collective.

JAD: What does he mean by that?

ROBERT: Well, if you zoom into our intestines, what you'll see is legions of tiny creatures.

CARL ZIMMER: Bacteria, viruses, fungi, protozoans.

SOREN WHEELER: And those are all little single-cell kind of guys?

CARL ZIMMER: Yeah, we're talking about non-human things inside of me.

ROBERT: How many—how many have you got, would you say?

CARL ZIMMER: Me?

ROBERT: Yeah.

CARL ZIMMER: Probably in the order of maybe a couple thousand species. So there's E coli, bacteroides fragilis, and another one, and another one, and another one.

ROBERT: It's a whole universe down there.

CARL ZIMMER: Yeah.

ROBERT: Micro bacteria, flavobacteria, versinia, diplococcus, achromobacter. Some of them you'll find in all of us.

CARL ZIMMER: And then there are just a whole bunch of other species that are rarer. Might be in one person and not in the other.

ROBERT: It's like a rainforest.

CARL ZIMMER: Oh yeah. There are ecologists now studying your gut, looking at these complicated networks of hundreds of thousands of species that are living inside of you and depending on each other or preying on each other. It's just this incredibly complicated pattern that scientists haven't figured out.

ROBERT: When you're in an embryonic—in a—what are they called? The sacs?

CARL ZIMMER: Your amniotic sac?

ROBERT: Your amniotic sac. How much bacteria do you have in and about you there?

CARL ZIMMER: You're sterile.

ROBERT: You have none?

CARL ZIMMER: No.

ROBERT: At all?

CARL ZIMMER: You're clean.

ROBERT: Huh.

CARL ZIMMER: But then as you are coming out, all of a sudden you're into this new environment: the birth canal. You're breathing, your mouth is open, stuff is coming into your mouth, it's coating your skin. There are lots of bacteria there—the vagina, the birth canal. It's a very complicated ecosystem there.

ROBERT: And right after you're born, says Carl, you meet a nurse, then some doctors. You go home, you'll play in your backyard, you'll suck on a shoe. You might eat some dirt and get licked by a dog. And by the time you're going to school, you've got ...

CARL ZIMMER: Probably about 100 trillion microorganisms.

SOREN: So 100 trillion other kinds of cells in you?

CARL ZIMMER: Yeah. So if you were to take all the bacteria in your body and just made them into one lump, it would be about three pounds.

SOREN: [laughs]

ROBERT: Oh, really?

CARL ZIMMER: Think of it as an organ. I mean, your brain's about three pounds, your heart's a pound or two. So this is another organ.

JAD: Huh.

ROBERT: In this case, it's an organ that helps you digest food. But here's the thing: this place in you which is filled with foreign critters, somehow this organ gets into your head.

JAD: What does that even mean?

ROBERT: Wait. You just wait a second. Let me introduce you to someone.

JOHN CRYAN: Hello, can you hear me?

SOREN: Yes. Yes, we can hear you.

ROBERT: John.

JOHN CRYAN: My name is Professor John Cryan. I'm the professor and chair of anatomy and neuroscience here at University College Cork in Ireland. And I'm a neuroscientist.

JAD: A brain guy?

ROBERT: Yep.

JOHN CRYAN: If someone told me six years ago as a neuroscientist that I'd be here talking about microbes, I would have laughed it off.

ROBERT: But to make a long story short, John found that as he was getting into neuroscience, a lot of the neuroscientists at his university in Cork, in Ireland, they were getting into bugs for reasons that will become apparent in a moment. And eventually, he got the bug for bugs, and began to work with this one particular strain of bacteria.

JOHN CRYAN: This is the lactobacillus strain.

SOREN: What was it? Lacto-something?

JOHN CRYAN: Lactobacillus, sorry. Lactobacillus rhamnosus.

ROBERT: It looks like a pill, really. Kind of a oblong thing. It's sometimes used to make yogurt.

JOHN CRYAN: We were interested in whether if you fed mice with this for a number of weeks, whether it would alter their behavioral state.

ROBERT: Meaning if you fed these mice a bunch of this bacteria, would they become very different mice?

JOHN CRYAN: Yeah.

JAD: Different mice? You mean different—fatter mice or something?

ROBERT: No, no, no, no, no. Would they change their personalities? This is like a profound change.

JAD: Because of a bacteria in their stomach?

ROBERT: Yeah.

JAD: Not in their brain?

ROBERT: No.

JAD: Just in their tummies?

ROBERT: Just in their tummy.

JAD: That's insane. That's not gonna work.

ROBERT: Well, let me tell you what he did.

JAD: All right.

ROBERT: He had two groups of mice. One of them got the lactobacillus, the others they got just normal mouse food.

JOHN CRYAN: Yeah, we fed them broth just as a control, so it didn't have any bacteria.

ROBERT: Then ...

JOHN CRYAN: We looked at how they responded to a mild water stress. And what we found was that ...

SOREN: Mild? What's a mild ...?

ROBERT: Yeah, what does that mean?

JOHN CRYAN: Sorry. Well, its water. It's water at room temperature. It's tepid water.

ROBERT: Basically, what he did is he took these two groups of mice: the bacteria mice and the no-bacteria mice, and then he would drop them into a bowl of water.

JOHN CRYAN: And all rodents are very good swimmers, but they just don't like water.

SOREN: Hmm.

ROBERT: Oh.

ROBERT: Now what he was looking for was any difference between the two groups in terms of how they dealt with this water situation.

JAD: Like, if one group squeaked more than the other or something? What does that mean?

ROBERT: Whatever. You just keep an open mind, and you wait and see what's gonna happen.

JAD: Fine.

ROBERT: So ...

JOHN CRYAN: There we go.

ROBERT: Starting with the first group—the normal ones—he dropped them in. And as you'd expect ...

JOHN CRYAN: They try and escape. They try and escape.

ROBERT: And he timed them to see how long they'd keep at it.

JAD: Okay.

ROBERT: And one minute passes.

JOHN CRYAN: They swim. They swim to the edge and all around looking for an escape.

ROBERT: Two minutes pass. Three minutes pass. But ...

JOHN CRYAN: ... about four minutes in ...

ROBERT: He says the mice start to get worn down, and then they decide at this point ...

JOHN CRYAN: There's no point, I'm giving up.

ROBERT: Which means what? The ordinary mice just go and do a dead mouse float?

JOHN CRYAN: Yeah, a dead mouse float. You know, they just gave up.

ROBERT: They don't drown?

JOHN CRYAN: No, no. They sit there.

ROBERT: They just sit there and think, "I will wait this out until it's over."

JOHN CRYAN: Exactly. It's been coined "behavioral despair."

MOUSE: I can't do this anymore.

ROBERT: That is how a normal mouse reacts to being tossed into water. It struggles for about four minutes, it gives up, and then sinks into despair. For the second group, and this is the group that ate the bacteria.

JOHN CRYAN: Yeah.

ROBERT: You also dropped them in the water?

JOHN CRYAN: Yeah, yeah, yeah. Here you go.

ROBERT: At first, he says they were just like the first group, they were swimming around frantically for one minute, two minutes, three minutes. But then at the four-minute mark, when the first group of mice had given up, these mice? They kept going.

JOHN CRYAN: They kept looking for an out.

ROBERT: Past four minutes to five minutes, six minutes.

JAD: So they're not despairing.

JOHN CRYAN: Exactly.

ROBERT: And they might have kept going on and on and on, but he then plucked them out of the water after six minutes.

SOREN: The thing that's kind of strange is worrying and scurrying about and panicking, that all seems like what it is to be a mouse. And you're saying that a bacteria in the gut can change that?

JOHN CRYAN: Yeah.

JAD: Wait a second, Soren. Okay, fine. There seems to be a difference between these two groups, but how do you know? How does John know that the bacteria had anything to do with it?

ROBERT: Well, he didn't just stare at the mice, he looked at their mouse chemistry.

JOHN CRYAN: By looking at the stress hormones. And we measured the ...

ROBERT: And what he found is that in the first group, the mice that quit and despaired ...

JOHN CRYAN: We got about a hundred-fold increase in corticosterone levels.

ROBERT: That's the hormonal version of "Ahh!"

JOHN CRYAN: Exactly!

ROBERT: And in that first group, when he dropped them in the water, their blood flooded with this one. Which initially, it's not a bad thing because a mouse has to act, but all-out panic isn't great for a little mouse, and after a couple of minutes of hormone coursing through the veins, the mouse just burns out and shuts down. But in the second group of mice, now these are the mice that ate the bacteria ...

JOHN CRYAN: We found that in the mice fed the lactobacillus ...

ROBERT: They—well, first of all, they had half as much of that stress hormone.

JOHN CRYAN: Half.

ROBERT: And they had another chemical suddenly in the mix.

JOHN CRYAN: We found very, very distinct changes in the receptors for GABA in a variety of brain regions.

JAD: GABA?

JOHN CRYAN: GABA.

JAD: What's GABA?

ROBERT: Well, he says you can think of it as the opposite of a stress hormone.

JOHN CRYAN: It basically is there to shut down the brain, stop things, inhibit, make us more relaxed, chilled out.

ROBERT: And he thinks what's happening is that, in these mice that ate the bacteria, they hit the water, the stress hormones come online, but before things get too intense, in comes GABA and GABA just goes, "Shh." And as a result, these mice ...

JOHN CRYAN: They're chilled out, they're relaxed. They're not afraid.

ROBERT: They never panic, they never burn out, and they never fall into despair.

JOHN CRYAN: They behave like as if they were on Valium.

JAD: So somehow the mice—the gut bacteria of the mice are sending Valium to the brain. Is that what he's saying?

ROBERT: That's what he's saying, yeah.

JAD: But you haven't—he hasn't said anything about bacteria yet. I mean, it's a long distance. Gut down here, brain up here.

ROBERT: Well, let me—wait. Look, John told me that if you look inside a mouse's body, you will find a giant nerve.

JOHN CRYAN: The vagus nerve.

ROBERT: That runs ...

JOHN CRYAN: ... between the gut and the brain.

JAD: Oh, you mean like a phone line?

JOHN CRYAN: Exactly.

ROBERT: And he thought, "Well, maybe they chemically tickle one end of the line, send a "Shh" signal up to the brain, which then makes the GABA." Now in order to prove this, he thought, "Why don't I just cut the line?"

JOHN CRYAN: Basically sever the vagus nerve.

JAD: Oh, because then if the bacteria are the ones doing it, if he cuts the phone line, they won't be able to do it anymore, and then the mice should go back to normal.

JOHN CRYAN: Exactly. So in collaboration with my colleagues in McMaster in Ontario ...

ROBERT: He got some mice.

JOHN CRYAN: We fed them the bacteria again.

ROBERT: But this time before throwing them into the pool, he cut the nerve.

JAD: And?

JOHN CRYAN: We found that all of the changes that we had seen ...

ROBERT: The swimming forever, the not giving up ...

JOHN CRYAN: ... and the neurochemical changes in the brain ...

ROBERT: ... the GABA "Shh" making them so calm ...

JOHN CRYAN: ... were completely absent.

JAD: Oh!

ROBERT: You cut out the highway and then the communication, the brainy changes ...

JOHN CRYAN: Stop.

ROBERT: Totally.

JOHN CRYAN: Totally.

SOREN: Huh.

JAD: When they cut the nerves the mice went back to being quitters?

ROBERT: Yep.

JAD: Oh!

ROBERT: You have to be convinced now.

JAD: Okay, I'm convinced.

ROBERT: Right?

JAD: So here's my question, though.

ROBERT: Yeah?

JAD: This is a mouse we're talking about. This is just a mouse.

ROBERT: Mm-hmm.

JAD: Does this have anything to say about us? I mean, is there any connection to make?

ROBERT: Well, I asked Carl that question.

CARL ZIMMER: There was one study that—where was it? Oh, you know what?

JONAH LEHRER: So this was a clinical trial actually done in France last year.

ROBERT: That's Jonah Lehrer, who regularly reports about things neurological for us and others. And he knew about the study too.

JONAH LEHRER: Yeah, so they fed people just massive doses of probiotics.

JAD: Does "probiotic" mean the good ones versus the bad ones?

JONAH LEHRER: Yeah, probiotics are the good gut bacteria.

ROBERT: They're in yogurt and things like that. So these guys in France, they gave these people packets, like, sugar-sized packets of powder. And inside the packets, there are two different kinds of bugs.

CARL ZIMMER: Lactobacillus helveticus and bifidobacterium longum.

SOREN: Mm. Two of my favorites.

CARL ZIMMER: Oh yeah. Well, you should like them, because they gave them to people.

JONAH LEHRER: And they showed a fairly dramatic reduction in their basal anxiety levels.

CARL ZIMMER: They became less stressful and had less anxiety.

ROBERT: Because when they took them to high diving boards and threw them off, instead of screaming, they—how do you test these things?

CARL ZIMMER: I see the Hopkins symptom checklist. I see the Hopkins ...

ROBERT: Basically, they did a little survey and asked questions.

JONAH LEHRER: "How distressed do you feel?" They took levels of stress hormone.

CARL ZIMMER: And a 24-hour urinary-free cortisol.

JONAH LEHRER: So they had some quantitative measures, and ...

ROBERT: People who took those probiotics said they felt less angry, less anxious and less depressed.

JAD: Wow! So the gut bugs have us on a chain too.

CARL ZIMMER: Yes.

ROBERT: Hmm. Huh.

CARL ZIMMER: Because we—one thing to remember is our mood, a lot of the way our mood is set is through serotonin.

SOREN: That's like when they do antidepressant drugs, it's the serotonin reuptake something.

CARL ZIMMER: Right. Yeah, so you're controlling the amount of serotonin that's going in and out of your neurons. Right. You have very little serotonin in your brain, but it makes a huge difference. You have a huge supply of serotonin in your gut.

JONAH LEHRER: 80 percent of all the serotonin in your body is in your gut.

JAD: Really?

CARL ZIMMER: Yeah, and the bacteria can be feeding on that stuff. And it could be that they ...

ROBERT: You have an oil well of happiness in your gut, and if you get the right pump, you could feel happy more of the times.

CARL ZIMMER: One possibility.

ROBERT: Jad, when you and I are sitting around feeling all stressed and anxious, or if we're just happy and gay in the old sense of the word.

JONAH LEHRER: Now we know this mood is shadowed, influenced and shaped by the bacteria you have in your intestine.

CARL ZIMMER: The kinds of studies that show this effect, they've all happened in the past couple years. And that's it. Period. But there's this judged review, it was in the Proceedings of the National Academy of Sciences. It was just kind of commenting on a couple of these studies and saying, "Hmm. Let's think about which bacteria we should focus on for psychological treatments. Let's think about how we can treat people's psychological disorders with bacteria this way. Let's just think about it."

SOREN: This is in the Proceedings of the National Academy of the Sciences. They're talking about treating psychological disorders with yogurt.

CARL ZIMMER: Yeah. Medicinal yogurt in the future.

SOREN: But medicinal as in Prozac.

CARL ZIMMER: Sure!

SOREN: Medicinal as in whatever they give to people with schizophrenia.

CARL ZIMMER: Well, I don't know. I mean, who knows what will work and what won't work, but it's something that people are saying, "We need to look into this."

JONAH LEHRER: There's something for me a little poetic about the fact that a lot of our moods come from the same organ that produces [bleep]. I mean, I haven't put my finger on what's poetic about that, but it does make a little bit more sense when you step back and think about this from the perspective of evolution that our biggest decisions way back when were what to eat. "Is this gonna kill me and make me sick? Is this food spoiled?" So it makes sense that the part of the body which can detect that is also intimately connected with decision-making systems that have to do with "This is gonna make me happy", or this is "I should fear this and not eat this."

JAD: Hmm.

JONAH LEHRER: So as outlandish as it seems that the self is connected with the part of the body that produces [bleep], it also has a little bit of engineering logic to it.

ROBERT: Special thanks to Carl Zimmer. His latest book is called Science Ink. It's a description of tattoos that people get on scientific themes, and you can see them on their arms, their legs, thighs, and embarrassing places.

JAD: Yes. And thanks also to Jonah Lehrer, whose new book is called Imagine: How Creativity Works.

ROBERT: And you see their creativity on their nose, thighs, cheeks and embarrassing places.

JAD: Speaking of embarrassing places, we're going to go to one right now. We'll be right back.

 

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