Stress can lead to flare-ups of inflammatory bowel disease, and now we know why
Shutterstock/Sorapop Udomsri
Researchers have identified a pathway between the brain and the immune system in mice that may explain why psychological stress can exacerbate intestinal inflammation. The finding could improve treatments for chronic gastrointestinal conditions such as inflammatory bowel disease (IBD).
For years, studies have shown a link between mental health problems and inflammation. The connection is especially evident in IBD or other autoimmune diseases characterized by intestinal inflammation, abdominal pain and intestinal damage. Even with treatment, people with IBD often experience symptom flare-ups when they are stressed.
To understand the mechanism behind this association, Christoph Thais at the University of Pennsylvania and colleagues analyzed mice with IBD-like symptoms. For a week, the researchers placed eight animals in small tubes for three hours a day to induce stress. They then treated the mice with a chemical irritant for seven days to induce IBD-like symptoms.
Three mice were given a drug to block hormones called glucocorticoids, which the brain signals the body to produce when it senses fear. The researchers then performed a colonoscopy on the mice and rated intestinal inflammation and intestinal damage between 0 and 15, with higher scores indicating worse outcomes. Mice that received the drug averaged a score around 5, while those without had a score just under 15, indicating that glucocorticoids are important for stress-induced intestinal inflammation.
The researchers then performed a genetic analysis of tissue samples collected from the animals’ colons. They found that mice with persistently elevated glucocorticoids had changes in specialized neural cells called enteric glia. Glial cells help maintain neurons and communicate with many different types of cells, and they respond to stress hormones by pumping out inflammatory molecules. The enteric glia of mice with elevated glucocorticoids showed increased activity in proinflammatory genes.
Genetic analysis also revealed that stress changes neurons in the gut, making them appear less mature. “The reason this is harmful is because we need mature neurons in the GI tract to stimulate bowel movements and motility,” says Thaiss. Together, these findings highlight two branches of a pathway between the brain, gut neurons, and the inflammatory immune response.
The team validated these findings in 63 people with IBD by collecting tissue samples from each person’s colon and genetically analyzing them. Participants also completed a questionnaire to rate stress. People who experienced more stress had more intestinal damage and greater increases in inflammatory markers, similar to those seen in mice.
Saurabh Mehandru at Mount Sinai Health System in New York says these results have finally revealed the exact brain-gut connection that many have long believed existed in gastrointestinal disorders. “It tells clinicians that you need to look at the patient as a whole, treat not just the symptoms of flare-ups, but also other issues that may be related to stress,” he says.
“The big question is whether the same pathway could determine people’s susceptibility to different treatments,” says Thaiss. If so, it could improve the way IBD is treated or lead to new drug targets for the condition.
Subjects: