Gut Bacteria Might Guide The Workings Of Our Minds

by ROB STEIN

November 18, 2013 3:07 AM

Illustration by Benjamin Arthur for NPR

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.

Credit: Benjamin Arthur for NPR

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.

“The mice became less anxious, more gregarious,” says Stephen Collins of McMaster University in Hamilton, Ontario, who led a team that conducted the research.

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 calledbrain-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 couldtalk 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.”

Chowing Down On Meat, Dairy Alters Gut Bacteria A Lot, And Quickly

by MICHAELEEN DOUCLEFF

December 11, 2013 1:34 PM

To figure out how diet influences the microbiome, scientists put volunteers on two extreme diets: one that included only meat, egg and cheese and one that contained only grains, vegetables and legumes.

Morgan Walker/NPR

Looks like Harvard University scientists have given us another reason to walk past the cheese platter at holiday parties and reach for the carrot sticks instead: Your gut bacteria will thank you.

Switching to a diet packed with meat and cheese — and very few carbohydrates — alters the trillions of microbes living in the gut, scientists report Wednesday in the journal Nature.

The change happens quickly. Within two days, the types of microbes thriving in the gut shuffle around. And there are signs that some of these shifts might not be so good for your gut: One type of bacterium that flourishes under the meat-rich diet has been linked to inflammation and intestinal diseases in mice.

“I mean, I love meat,” says microbiologist Lawrence David, who contributed to the study and is now at Duke University.

“But I will say that I definitely feel a lot more guilty ordering a hamburger … since doing this work,” he says.

Scientists are just beginning to learn about how our decisions at the dinner table — or the drive-through — tweak our microbiome, that is, the communities of bacteria living in our bodies. But one thing is becoming clear: The critters hanging out in our intestine influence many aspects of our health, including weight, immunity and perhaps evenbehavior.

And interest in studying the links between diet and the human microbiome is growing. Previous research in this field had turned up tantalizing evidence that eating fiber can alter the composition of gut bacteria. But these studies had looked at diets over long periods of times — months and even years. David and his colleagues wanted to know whether fiber — or lack of it — could alter gut bacteria more rapidly.

To figure that out, the researchers got nine volunteers to go on two extreme diets for five days each.

The first diet was all about meat and cheese. “Breakfast was eggs and bacon,” David says. “Lunch was ribs and briskets, and then for dinner, it was salami and prosciutto with an assortment of cheeses. The volunteers had pork rinds for snacks.”

Then, after a break, the nine volunteers began a second, fiber-rich diet at the other end of the spectrum: It all came from plants. “Breakfast was granola cereal,” David says. “For lunch, it was jasmine rice, cooked onions, tomatoes, squash, garlic, peas and lentils.” Dinner looked similar, and the volunteers could snack on bananas and mangoes.

“The animal-based diet is admittedly a little extreme,” he says. “But the plant-based diet is one you might find in a developing country.”

David and the team analyzed the volunteers’ microbiomes before, during and after each diet. And the effects of all that meat and cheese were immediately apparent.

“The relative abundance of various bacteria species looked like it shifted within a day after the food hit the gut,” David says. After the volunteers had spent about three days on each diet, the bacteria in the gut even started to change their behavior. “The kind of genes turned on in the microbes changed in both diets,” he says.

In particular, microbes that “love bile” — the Bilophila — started to dominate the volunteers’ guts during the animal-based diet. Bile helps the stomach digest fats. So people make more bile when their diet is rich in meat and dairy fats.

A study last year found that blooms of Bilophila cause inflammation and colitis in mice. “But we didn’t measure levels of inflammation in our subjects,” David says. “That’s the next step.”

Instead, he says, his team’s data support the overall animal model that Bilophila promotes inflammation, which could ultimately be controlled by diet.

“Our study is a proof of concept that you can modify the microbiome through diet,” David says. “But we’re still a long ways off from being able to manipulate the community in any kind of way that an engineer would be pleased about.”

Even just classifying Bilophila as “bad bacteria” is a tricky matter, says Dr. Purna Kashyap, a gastroenterologist at the Mayo Clinic in Minnesota.

“These bacteria are members of a community that have lived in harmony with us for thousands of years,” says Kashyap, who wasn’t involved in the study. “You can’t just pick out one member of this whole team and say it’s bad. Most bacteria in the gut are here for our benefit, but given the right environment, they can turn on us and cause disease.”

Nevertheless, Kashyap thinks the Nature study is exciting because the findings unlock a potentially new avenue for treating intestinal diseases. “We want to look at diet as a way of treating patients,” Kashyap says. “This study shows that short-term dietary interventions can change microbial composition and function.”

Of course, figuring out exactly how to do that will take much more research.

“The paper has made the next leap in the field,” Kashyap says. “With discovery comes responsibility. Once you make this big finding, it needs to be tested appropriately.”