Are you a worrier? Low on energy? You might be able to blame your state of mind on the bugs in your gut. Researchers studying behavior and gene activity in mice have found that these microbes appear to help shape brain development. If the findings translate to humans, they could lead to new ways to treat depression, anxiety, and other mental disorders.
Twenty years ago, people would have laughed at the suggestion that gut microbes could influence brain function, says immunologist Sven Pettersson of the Karolinska Institute in Stockholm. But in the past decade, researchers have come to appreciate that the bacteria living in and on our bodies—collectively called the human microbiome —play a role in how our bodies work, affecting everything from allergies  to obesity .
Pettersson began to suspect a mind-microbe link 5 years ago when he and genomicist Shugui Wang of the Genome Institute of Singapore found through gene-expression studies that gut microbes regulated the activity of a gene important to the production of serotonin, a key brain chemical. He then initiated a collaboration with Karolinska Institute neurobiologist Rochellys Diaz Heijtz to assess behavioral differences between germ-free mice—which have been bred to lack any microbial partners—and mice with intact gut bacteria. The researchers also dissected out major regions of the brain and measured gene activity in each region in both types of animals.
The team found differences in activity and anxiety levels. Germ-free mice spent more time roaming about an open arena than other mice did. They were also more daring. When placed in a box with light and dark compartments, most mice tend to seek refuge in the dark sections—but not the germ-free mice. That indicates that they are less anxious than normal mice, the researchers report  online today in the Proceedings of the National Academy of Sciences. Pettersson and his colleagues also found that exposing germ-free mice to gut microbes during pregnancy made the resulting offspring less active and more anxious, further showing a role for the microbiome in shaping behavior.
Heijtz, Pettersson, and colleagues then analyzed the chemistry and gene activity in the brains of these mice. They found that germ-free mice broke down brain chemicals associated with anxiety, such as noradrenaline and dopamine, faster than did the other mice. In all, activity levels of dozens of genes in the brain were distinct between the two types of mice, they report. Two genes associated with anxiety were less active in the germ-free mice, for example.
The presence of microbes also reduced the amounts of two proteins important to nerve-cell maturation, suggesting how the microbiome leads to the differences in behavior. During pregnancy, gut microbes may release chemicals that affect fetal brain development, the researchers say.
How these results might translate into therapies for mental illness is still uncertain. But the findings point to “clear effects of the microbiome on brain development and behavior,” says John Bienenstock, an immunologist at McMaster University in Hamilton, Canada, whose own work has found behavioral differences between germ-free and other mice. “It never occurred to me that microflora would have anything to do with brain development,” adds Bryan Kolb, a neurobiologist at the University of Lethbridge in Canada who has studied brain development for 35 years. “It tells us that neurodevelopmental disorders [such as schizophrenia] may be profoundly influenced by the microflora in the gut.”