The vagus nerve connects the brain region called the amygdala (red; artist’s illustration) to nerves for the Brunner’s glands in the gut.Credit: Sebastian Kaulitzki/Science Photo Library
Stress can make people feel sick, and bacteria in the gut might be to blame, according to a study1 in mice. The research suggests that a stressed brain directly shuts down specific glands in the gut, affecting gut bacteria and the body’s broader immune system.
The study “is a technical tour de force”, says neuroscientist John Cryan at University College Cork in Ireland, who reviewed the study. Most work on the gut–brain connection has focused on how bacteria affect the brain, so Cryan welcomes research into how psychological states can exert ‘top-down’ control of bacteria. “It’s a really cool part of the puzzle”, he says. The research was published on 8 August in Cell.
Gut–brain chitchat
Researchers have long known that the gut and brain ‘talk’ to each other. Under stress, the brain spurs the release of hormones that can trigger gut conditions such as inflammatory bowel disease. And certain bacteria in the gut can release chemical signals that affect the brain and behaviour.
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But the neural communication pathways are less understood. To find out more, neuroscientist Ivan de Araujo at the Max Planck Institute for Biological Cybernetics in Tübingen, Germany, and his colleagues focused on small organs called Brunner’s glands that are found in the walls of the small intestine. Little is known about these glands, other than that they produce mucus and contain numerous neurons.
De Araujo’s team found that removing the Brunner’s glands of mice made the animals more susceptible to infection. It also raised markers of inflammation, a flood of immune chemicals and cells that can damage tissues. The team saw a similar effect in humans: people who’d had tumours removed from the part of the gut containing Brunner’s glands had higher levels of white blood cells — a marker of inflammation — than people who’d had tumours removed from other areas.
Housekeeping bacteria
Closer analysis showed that removing the Brunner’s glands from mice eliminates bacteria in the Lactobacillus genus, which live in the small intestine. In a healthy gastrointestinal tract, Lactobacilli stimulate production of proteins that act as grout between the cells lining the gut, keeping most of the gut’s contents inside while allowing certain nutrients to enter the bloodstream. But when Lactobacilli are gone, the gut becomes ‘leaky’ and “things that shouldn’t cross into the blood do so”, de Araujo says. The immune system attacks these foreign molecules, causing the inflammation and illness seen in mice without Brunner’s glands.
The researchers then examined the glands’ neurons. They found that the neurons connect to fibres in the vagus nerve, a communications pathway between the gut and the brain. These fibres run directly to the brain’s amygdala, which is involved in emotion and stress response.
Placing mice with intact Brunner’s glands under chronic stress had the same effect as removing the glands: Lactobacillus levels fell, and inflammation increased. This suggested that stress had shut down the Brunner’s glands.
Lines of communication
Asya Rolls, a neuroimmunologist at the Technion — Israel Institute of Technology in Haifa, is impressed by the direct line between the brain, Brunner’s glands, bacteria and immune system. “The specificity of the connection is amazing,” she says. But she cautions that the pathways in mice might not be identical to those in humans.
“This paper is pretty inspiring,” says Christoph Thaiss, a microbiologist and neuroscientist at the University of Pennsylvania in Philadelphia. Understanding the specific pathways that connect the brain and gut, he says, could help researchers to study questions such as why some people are more resilient to stress than others.
De Araujo says the study could have implications for treating stress-related disorders such as inflammatory bowel disease. His group is now studying whether chronic stress affects this pathway in infants, who receive their Lactobacillus through breast milk. “We are excited about the idea that these glands are important for normal development and immune function early in life,” de Araujo says.
