15:07 PM

Does your gut hold the key to your mind?

Researchers delving into the link between bacteria and brain

Michelle Roley-Roberts and her husband, Ryan, know a lot more about what’s living inside their guts than most.

The Hilliard couple agreed recently to let researchers inspect the bacteria in their intestines in hopes of better understanding the increasingly clear connection between the human mind and intestinal tract.

Researchers at The Ohio State University and Nationwide Children’s Hospital want to answer questions about what biological differences could contribute to changes in the gut and in cellular-level communication between the gut and the brain.

“This is a really hot area in terms of behavior research, and right now we know relatively little. There’s so much to learn about how the gut and the immune system and the brain interact,” said Jan Kiecolt-Glaser, lead researcher and director of Ohio State’s Institute for Behavioral Medicine Research at the Wexner Medical Center Researchers around the world are exploring the gut/brain axis in the quest for knowledge about mood disorders such as depression, neurodegenerative diseases including Alzheimer’s and chronic conditions such as Crohn’s disease.

The work is based on communications between the enteric nervous system – a network of neurons that run the gastrointestinal tract and are sometimes called “the second brain” – and the central nervous system. The scientists want to better understand the influence of bacteria and other gut microbes on those cellular-level conversations.

Kiecolt-Glaser has built an international reputation on understanding how stress – and stress reduction – shapes human health. In recent years, as she heard more and more from her colleagues about the potential importance of the microbiome, she became fascinated with its role in this relationship.

This is a really hot area in terms of behavior research, and right now we know relatively little. There’s so much to learn about how the gut and the immune system and the brain interact.
Jan Kiecolt-Glaser

In the current study, married couples present an opportunity to unearth important information, she said.

“We have a really nice paradigm where there’s likely overlap on a variety of influences including diet, exercise, pets, smoking and alcohol use,” Kiecolt-Glaser said.

But it’s the differences between one partner and the other that might hold the most interest, she said.

“When we look at couples and compare stress levels, we might see important differences. And when we evaluate all of the couples, it’s possible we’ll be able to identify some patterns,” Kiecolt-Glaser said.

The researchers are working with a company called uBiome to analyze fecal samples provided by couples in the study. They aim to analyze 175 couples in all.

“Overall, the greater the diversity of bacteria in your gut, the better your health. We know that exercise, diet and stress can all have an effect on the gut,” said Kiecolt-Glaser. “And some small studies have suggested that depression can affect the microbiome.”

In a recent study, she and her colleagues found that married people who fight nastily are more likely to suffer from a leaky gut – a problem that unleashes bacteria into the blood and can drive up disease-causing inflammation.

Everything from eating sauerkraut to sleeping with your canine best friend has an influence on the complex mix of bacteria that make up a human microbiome. It can change from day to day, and stress, illness and other factors can reshape the gut landscape.

The outside factors that influence the bacterial makeup of the gut are more similar in people who live together because they tend to eat similar things and interact with similar environments – at least when they’re at home.

Roley-Roberts, for instance, doesn’t eat meat (just fish) and does the majority of cooking at home so her husband eats a mostly vegetarian diet as well. When he’s at work, he might grab a turkey sandwich, but he’s eating like his wife most of the time. They have no children, but do live with two cats – Mr. Booters and Mr. Popodopolous. And they’ve been married for two years and lived together for more than a decade.

But they also have different exposures. Roberts works at OhioHealth Doctors Hospital in environmental services; his wife is a postdoctoral researcher at Ohio State’s Nisonger Center.

For the study, the husband and wife independently answered questions about their relationship, including about how often they fight, and what their fights are like. They reported what they ate in the last 24 hours. Researchers analyzed fecal samples to analyze their gut bacteria.

The research is underway, so neither the participants nor the scientists know any details about what trends will emerge. But Roley-Roberts and Roberts each have already received a report about their individual microbiome analysis.

“It tells you about what bacteria you have and whether it’s helpful or non-helpful, or rare, compared to other people of your gender and age group with similar diets,” she said.

“As a pescatarian, I could look and compare myself with people who are strict vegans or who are vegetarian.”

Most interesting to Roley-Roberts was the presence in her gut of a microbe that has been linked to overweight and obesity.

“I exercise a lot, and I still struggle more with weight than Ryan does,” she said. “Just based on my gut bacteria, it might be harder for me to keep weight off.”

For his part, Roberts was interested to see that he had much more rare bacteria than his wife.

“I don’t know if it’s genetic, or what I ate as a kid or what, and I don’t know if it’s a good thing or a bad thing,” he said, laughing.

Kiecolt-Glaser envisions a day when concrete knowledge about the good guys and bad guys of the microbiome could lead to interventions such as dietary changes or probiotics that could improve health problems, including depression.

The possibilities have many scientists intrigued – and hopeful.

Tamar Gur, an assistant professor of psychiatry and behavioral health, neuroscience and obstetrics and gynecology at Ohio State, has in recent years become fascinated by the brain-gut connection and how it might apply to her investigations involving pregnant women and their babies.

In a recent study in mice, Gur and her colleagues found that prenatal exposure to a mother’s stress contributes to anxiety and cognitive problems that persist into adulthood, a phenomenon that could be explained by lasting changes in the microbiome.

“I think this type of research could allow us to pinpoint mechanisms for health problems and dream up interventions to stop them. This area of research has just exploded in recent years and I don’t think it’s a flash in the pan. I’ve learned too much about the influence of the microbiome to believe that,” Gur said.

She’s particularly interested in how the microbiome might interact with the brain in stressed pregnant women, potentially leading to preterm birth – the leading cause of infant death. Gur is currently working on a study evaluating stress and the microbiome during pregnancy and hopes to also study use of a probiotic during pregnancy.

“My goal is to find a way to offer moms interventions that can benefit both them and their babies,” Gur said.

The possibility that dietary changes or some other approach to disrupting or bolstering the bacterial makeup of the gut wasn’t even on her radar until 2013, when she learned about the work Mike Bailey was doing at Nationwide Children’s, Gur said.

Bailey, an associate professor of microbial infection and immunity at Ohio State and a researcher in the Center for Microbial Pathogenesis at Nationwide Children’s, is working on the married couples research with Kiecolt-Glaser. He also recently partnered with Lisa Christian, a member of Ohio State’s Institute for Behavioral Medicine Research, on work that found a link between toddlers’ gut microbes and temperament.

Bailey was thinking about the complex microbial community inside the gut decades before it was a topic that jammed meeting rooms at medical and scientific conferences – well before “probiotic” and “prebiotic” were words used to sell the virtues of dietary supplements and yogurt.

Bailey said he’s especially interested in understanding how changes in the gut after stressful events can alter the immune system, potentially clearing the way for disease. Another focus is pinpointing the microbes’ path from gut to spleen, where they can hamper normal, healthy immune function.

Bailey is also excited about the potential to find ways to optimize probiotics so that they are more effective against particular ailments, including irritable bowel syndrome.

When he started out, Bailey said, studying gut microbes involved taking a small fecal sample and putting it in a slide, seeing which bacteria grew and counting how many of them showed up. Technological advances in recent years have allowed scientists to examine the genetics of hundreds of species of gut microbes at once, propelling the science forward.

“We’re getting a clearer and more comprehensive picture of the microbiota and now we’re talking about understanding bacterial communities,” he said.

There’s a lot of ground to cover. While many individuals – and companies – are eager to talk about diet and supplements as ways to fend off disease, “we just don’t have a good enough understanding about the way the body responds,” Bailey said.

There’s much to discover, as well, about how the bacteria in our intestinal tracts contribute to how we metabolize medications, he said.

“So far the push has been to understand which bacteria are in our guts and in what proportions. But that’s a very small part of the story. These bacteria have a tremendous number of functions.”