Simko/Visuals Unlimited

Gut feeling. A steady diet of Lactobacillus rhamnosus (above) appears to reduce anxiety in mice.

Mind-Altering Bugs

California News Correspondent

Hundreds of species of bacteria call the human gut their home. This gut "microbiome" influences our physiology and health in ways that scientists are only beginning to understand. Now, a new study suggests that gut bacteria can even mess with the mind, altering brain chemistry and changing mood and behavior.

In recent years, researchers have become increasingly interested in how gut bacteria might influence the brain and behavior, says John Cryan, a neuroscientist at University College Cork in Ireland. So far, most of the work has focused on how pathogenic bugs influence the brain by releasing toxins or stimulating the immune system, Cryan says. One recent study suggested that even benign bacteria can alter the brain and behavior, but until now there has been very little work in this area, Cryan says.

To further investigate the mind-altering potential of benign bacteria, Cryan and colleagues at McMaster University in Canada fed mice a broth containing a benign bacterium, Lactobacillus rhamnosus. The scientists chose this particular bug partly because they had a handy supply and also because related Lactobacillus bacteria are a major ingredient of probiotic supplements and very little is known about their potential side effects, Cryan says.

In this case, the side effects appeared to be beneficial. Mice whose diets were supplemented with L. rhamnosus for 6 weeks exhibited fewer signs of stress and anxiety in standard lab tests, Cryan and colleagues report online today in the Proceedings of the National Academy of Sciences. For example, the rodents spent more time exploring narrow elevated walkways and wide-open spaces, which are scary to rodents, and they exhibited a smaller spike in stress hormone levels when the researchers put them in water. "This was really exciting because it tells us the animals are more chilled out and don't mount the same stress response," Cryan says.

In the brains of the treated mice, the researchers found changes in the activity of genes that encode portions of the receptor for the neurotransmiter GABA. GABA typically dampens neural activity, and many drugs for treating anxiety disorders target its receptors. The pattern of changes in the GABA receptors was complicated—more GABA receptors containing a certain component in some brain regions, for example, and fewer receptors with that component in other regions—but Cryan says they're consistent with an overall effect of reducing anxiety. None of these effects occurred in mice that ate a broth with no added bacteria.

The changes in GABA receptors and the antianxiety effects of L. rhamnosus disappeared when the researchers cut the vagus nerve before feeding the bacteria to mice. This nerve is a major conduit of sensory information from the gut to the brain, and this experiment shows it must be intact for L. rhamnosus to have an effect on the brain. The details of how the bacteria influence the brain through the vagus nerve still need to be elucidated, Cryan says. "That's what we have to figure out next."

"This is pioneering work," says Mark Lyte, a microbial endocrinologist at the Texas Tech University Health Sciences Center in Abilene. "It's really showing that you can alter emotional states by regulating the microbiome."

The findings "open up very exciting speculation" about using probiotics to treat mood disorders in people, says Emeran Mayer, a gastroenterologist at the University of California, Los Angeles. But Mayer says he's skeptical that the findings will translate easily from mice to people. "Personally, I think human emotional behavior is much more complex, so I don't think you'll ever find these kinds of dramatic responses." Lyte urges caution as well. "It MAY, in really big capitals, prove to be an adjunct to therapy, but there are a number of steps that need to be done."

Posted in Biology, Brain & Behavior