Could the microbes that inhabit our guts help explain that old idea of "gut feelings?" There's growing evidence that gut bacteria really might influence our minds.
"I'm always by profession a skeptic," says Dr. Emeran Mayer, a professor of medicine and psychiatry at the University of California, Los Angeles. "But I do believe that our gut microbes affect what goes on in our brains."
Mayer thinks the bacteria in our digestive systems may help mold brain structure as we're growing up, and possibly influence our moods, behavior and feelings when we're adults. "It opens up a completely new way of looking at brain function and health and disease," he says.
So Mayer is working on just that, doing MRI scans to look at the brains of thousands of volunteers and then comparing brain structure to the types of bacteria in their guts. He thinks he already has the first clues of a connection, from an analysis of about 60 volunteers.
Mayer found that the connections between brain regions differed depending on which species of bacteria dominated a person's gut. That suggests that the specific mix of microbes in our guts might help determine what kinds of brains we have — how our brain circuits develop and how they're wired.
Of course, this doesn't mean that the microbes are causing changes in brain structure, or in behavior.
But other researchers have been trying to figure out a possible connection by looking at gut microbes in mice. There they've found changes in both brain chemistry and behavior. One experiment involved replacing the gut bacteria of anxious mice with bacteria from fearless mice.
It worked the other way around, too — bold mice became timid when they got the microbes of anxious ones. And aggressive mice calmed down when the scientists altered their microbes by changing their diet, feeding them probiotics or dosing them with antibiotics.
To find out what might be causing the behavior changes, Collins and his colleagues then measured brain chemistry in mice. They found changes in a part of the brain involved in emotion and mood, including increases in a chemical called brain-derived neurotrophic factor, which plays a role in learning and memory.
Scientists also have been working on a really obvious question — how the gut microbes could talk to the brain.
A big nerve known as the vagus nerve, which runs all the way from the brain to the abdomen, was a prime suspect. And when researchers in Ireland cut the vagus nerve in mice, they no longer saw the brain respond to changes in the gut.
"The vagus nerve is the highway of communication between what's going on in the gut and what's going on in the brain," says John Cryan of the University College Cork in Ireland, who has collaborated with Collins.
Gut microbes may also communicate with the brain in other ways, scientists say, by modulating the immune system or by producing their own versions of neurotransmitters.
"I'm actually seeing new neurochemicals that have not been described before being produced by certain bacteria," says Mark Lyte of the Texas Tech University Health Sciences Center in Abilene, who studies how microbes affect the endocrine system. "These bacteria are, in effect, mind-altering microorganisms."
This research raises the possibility that scientists could someday create drugs that mimic the signals being sent from the gut to the brain, or just give people the good bacteria — probiotics — to prevent or treat problems involving the brain.
One group of scientists has tested mice that have behaviors similar to some of the symptoms of autism in humans. The idea is that the probiotics might correct problems the animals have with their gastrointestinal systems — problems that many autistic children also have.
In the mice, many of their autism behaviors were no longer present or strongly ameliorated with probiotics, says Paul Patterson at the California Institute of Technology in Pasadena, Calif. His research will be published soon in the journal Cell.
Experiments to test whether changing gut microbes in humans could affect the brain are only just beginning.
One team of researchers in Baltimore is testing a probiotic to see if it can help prevent relapses of mania among patients suffering from bipolar disorder.
"The idea is that these probiotic treatments may alter what we call the microbiome and then may contribute to an improvement of psychiatric symptoms," says Faith Dickerson, director of psychology at the Sheppard Pratt Health System.
"It makes perfect sense to me," says Leah, a study participant who has been diagnosed with bipolar disorder. She agreed to talk with NPR if we agreed not to use her full name. "Your brain is just another organ. It's definitely affected by what goes on in the rest of your body."
It's far too soon to know whether the probiotic has any effect, but Leah suspects it might. "I'm doing really well," she says. "I'm about to graduate college, and I'm doing everything right."
Mayer also has been studying the effects of probiotics on the brain in humans. Along with his colleague Kirsten Tillisch, Mayer gave healthy women yogurt containing a probiotic and then scanned their brains. He found subtle signs that the brain circuits involved in anxiety were less reactive, according to a paper published in the journal Gastroenterology.
But Mayer and others stress that a lot more work will be needed to know whether that probiotic — or any others — really could help people feel less anxious or help solve other problems involving the brain. He says, "We're really in the early stages."
RENEE MONTAGNE, HOST:
This is MORNING EDITION from NPR News. Good morning, I'm Renee Montagne.
STEVE INSKEEP, HOST:
And I'm Steve Inskeep.
Today in Your Health: How the bacteria in your gut may affect your brain. Doctors have long had clues that there may be a connection between what's going on in our heads and what's going on in other parts of our bodies.
MONTAGNE: We all know, for example, that we can get pretty down when we're feeling sick and that our moods lift when we get better. Well, scientists are starting to think about this brain-body connection in a whole new way. And that's because of something we've been hearing a lot about lately: the microbes that live in the human body.
INSKEEP: Turns out you really can have a gut feeling about something, because evidence has been mounting that those microbes in the body may be important for our emotional health as well as our physical health.
NPR's Rob Stein has been exploring the role that our microbes play in our lives in a series of stories over the last few months. And in the final installment, Rob brings us this report about our microbes and our minds.
ROB STEIN, BYLINE: It's early on a Monday morning at the UCLA brain scanning center and Dr. Emeran Mayer is getting ready to peer into someone's brain.
DR. EMERAN MAYER: We're standing in the control room here. The patient is inside the scanning room, not in the scanner itself yet.
STEIN: The patient isn't really a patient at all. She's Pria Tewari, a healthy 29-year-old who volunteered for Mayer's research.
PRIA TEWARI: Growing up in India we believe that what you eat influences your thoughts.
STEIN: So she's here today to help Mayer explore this notion that the microbes that eat what we eat influence our minds.
UNIDENTIFIED WOMAN: Can you hear me OK?
STEIN: A nurse helps her get into the giant MRI brain scanner.
UNIDENTIFIED WOMAN: OK, Pria, so take a nice deep breath for me, hon. In and out through your mouth.
STEIN: Once she's settled in and the MRI is all set up, the scanning begins.
(SOUNDBITE OF MRI SCANNING)
MAYER: So the first image that was taken, that we just saw on the computer screen, will allow us to extract information regarding, it's what we call the brain signature.
STEIN: A signature of the overall structure of the brain, which Mayer hopes will help answer some provocative questions: Do the trillions of microbes that live in our bodies help mold our brains as we're growing up? Do they continue to influence our moods, behavior and feelings when we're adults? It's something, Mayer says, that has never really been explored before.
MAYER: It really happens rarely in science that you sort of stumble into an area that all of a sudden opens up this completely new frontier.
STEIN: A frontier that could help explain that old idea of gut feelings. And Mayer thinks he already has the first good clues this may be true, after analyzing about 60 volunteers like Pria.
MAYER: We found that the type of community you have, of microbes you have in your gut, is reflected in some ways in some basic architectural aspects of the brain.
STEIN: The brain connections of people whose microbes are dominated by one species of bacteria look different than those of people whose microbes are dominated by another species. That suggests that the specific mix of microbes in our guts helps determine what kinds of brains we have, how our brain circuits develop, how they're wired.
MAYER: The brain circuits obviously determine certain ways of how we perceive the world and react to the world outside of us.
STEIN: This could help explain why some people are born with brains that don't work the way they're supposed to, causing problems like autism, anxiety, depression.
MAYER: It opens up a completely new way of looking at brain function and health and disease. I think that's, you know, kind of a revolutionary concept.
STEIN: So Mayer is scanning hundreds of volunteers like Pria to see if what he's found so far holds up.
UNIDENTIFIED WOMAN: Ready to go?
STEIN: They move onto the next scan.
UNIDENTIFIED WOMAN: So your instructions for this scan are to close your eyes and rest but don't go to sleep. OK?
(SOUNDBITE OF MRI SCANNING)
STEIN: They want to get a picture of Pria's brain when she's doing absolutely nothing.
UNIDENTIFIED WOMAN: During that scan, did you have any pain or discomfort at all?
TEWARI: No, slight itching there.
UNIDENTIFIED WOMAN: Slight itching. OK.
STEIN: Now, the obvious question about all this is: How? How could bacteria in our bodies affect our brains? Well, the first clues came from experiments conducted in Europe and Canada.
STEPHEN COLLINS: My name is Stephen Collins. I'm a professor of medicine at McMaster University Medical School in Hamilton, Ontario, Canada.
STEIN: Collins is among the researchers who did these experiments. It's hard to study this stuff in humans. So they used mice. They did things like replace the gut bacteria of anxious mice with bacteria from fearless mice.
COLLINS: And this resulted in a change in behavior. The mice became a little bit less anxious, a little bit more gregarious.
STEIN: It worked the other way around too. The bold mice became timid when they got the microbes of anxious ones. Aggressive mice also calmed down when the scientists altered their microbes by changing their diet, feeding them probiotics, or dosing them with antibiotics.
COLLINS: We saw changes in the brain chemistry in a region called the hippocampus, which is part of the brain that's involved in emotion and mood and so forth, and found that a very important chemical called brain-derived neurotrophic factor was increased.
STEIN: Finally, these scientists figured out how the microbes in the guts of the mice were communicating with their brains - by sending signals up a big nerve known as the vagus nerve.
All this is raising the possibility that scientists could create drugs that mimic these signals. Or just give people the good bacteria - probiotics - to prevent or treat problems involving the brain.
Researchers in Baltimore, for example, are studying one probiotic. Faith Dickerson is a psychologist at the Sheppard Pratt Hospital who is leading that study.
DR. FAITH DICKERSON: The idea is that these probiotic treatments may alter what we call the microbiome and then may contribute to an improvement of psychiatric symptoms.
STEIN: Symptoms like mania in patients suffering from bipolar disorder. Patients like Leah, who ended up being hospitalized after one manic episode. We agreed not to use her full name.
LEAH: I had really bad anxiety and I took Xanax and I took too much Xanax.
STEIN: While she was recovering, Leah heard about the probiotic study and decided to volunteer.
LEAH: It makes perfect sense to me. You know, your brain is just another organ. You know, it's definitely affected by what goes on in the rest of your body.
STEIN: It's too soon to know whether the probiotic being tested in that study is helping. But Leah suspects it might be.
LEAH: It seems like, you know, maybe it helped me because, you know, I'm doing really well and like, I'm about to graduate college and I'm just, you know, doing everything right.
UNIDENTIFIED WOMAN: All righty. So we are going to move on to the final scan, OK?
STEIN: Back at UCLA, Mayer's team is almost done scanning Pria Tewari's brain.
(SOUNDBITE OF MRI SCANNING)
STEIN: While they're finishing up, Mayer explains that he's also been studying the effects of probiotics on the brain. He gave healthy women yogurt containing a probiotic and then scanned their brains, and found subtle signs that the brain circuits involved in anxiety were less reactive.
MAYER: It's the first time that it's been demonstrated in a controlled study that if you alter the gut microorganisms or microbes, that this affects the brain in a fairly profound fashion in healthy people.
STEIN: Mayer says a lot more work will be needed to know whether the probiotic they used in that study - or any probiotics - really can help people feel less anxious.
But Pria Tewari, the volunteer getting scanned today, was in that study too. She thinks maybe, just maybe, she might have noticed something. She was going for her Ph.D. at the time and thought she'd be totally stressed out.
TEWARI: I'd say I definitely, like my anxiety levels were low considering my, my own personal thing that I was going through.
STEIN: It's clear scientists still have a long way to go in all this. But the evidence that's starting to emerge suggests that we probably can't ignore the possibility that our microbes may be affecting our minds.
Rob Stein, NPR News.
INSKEEP: For more about this series including an animation about our friendly microbes - something for your microbes to think about - go to npr.org. Transcript provided by NPR, Copyright NPR.