IBD: We may finally know why psychological stress exacerbates gut inflammation
Stress can exacerbate inflammatory bowel disease, and now we know why
Researchers have identified a link between the brain and immune system in mice that may explain why psychological stress can exacerbate gut inflammation. The discovery could improve the treatment of chronic gastrointestinal diseases such as inflammatory bowel disease (IBD).
For years, research has shown a link between mental illness and inflammation. This link is particularly evident in IBD or other autoimmune conditions characterized by intestinal inflammation, abdominal pain, and intestinal damage. Even with treatment, people with IBD usually experience an exacerbation of symptoms when stressed.
To understand the mechanism behind this association, Christoph Theiss of the University of Pennsylvania and colleagues analyzed mice with IBD-like symptoms. For one week, the researchers placed eight animals in small test tubes for 3 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 feels stressed. The researchers then performed colonoscopies on the mice and scored inflammation and intestinal damage on a scale of 0 to 15, with higher scores indicating worse results. Mice that received the drug had an average of about 5 points, while those that did not have a score of just under 15, indicating that glucocorticoids are important in stress-induced intestinal inflammation.
The researchers then performed a genetic analysis of tissue samples taken from the colons of the animals. They found that mice with persistently elevated levels of glucocorticoids had changes in specialized nerve cells called intestinal glia. Glial cells help maintain neurons and communicate with many different cell types, and they respond to stress hormones by pumping out inflammatory molecules. Enteral glia of mice with elevated levels of glucocorticoids showed increased activity of pro-inflammatory genes.
Genetic analysis has also shown that stress alters neurons in the gut, making them less mature. “The reason this is harmful is because we need mature neurons in the gastrointestinal tract to control intestinal motility,” Theiss says. Together, these findings highlight two branches of the pathway between the brain, gut neurons, and the inflammatory immune response.
The team confirmed these findings in 63 people with IBD by collecting and analyzing tissue samples from the colons of each. Participants also completed a stress-rating questionnaire. People who experienced more stress had more gut damage and a greater increase in inflammatory markers, similar to mice.
Saurabh Mehandru of Mount Sinai Health System in New York City says these results may finally demonstrate the exact brain-gut connection that many have long believed exists in gastrointestinal disorders. “This tells clinicians that you should be looking at the patient as a whole, not just treating the symptoms of flare-ups, but also other problems that may be stress-related,” he says.
“The big question is whether the same pathway can dictate how responsive people are to different treatments,” Theiss says. If so, this could improve the treatment of IBD or lead to new targeted drugs for the condition.