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 worsen gut inflammation. This discovery could improve treatments for chronic gastrointestinal conditions such as inflammatory bowel disease (IBD).
For years, studies have shown an association between mental distress and inflammation. The connection is particularly evident in IBD or other autoimmune diseases characterized by intestinal inflammation, abdominal pain, and bowel damage. Even with treatment, people with IBD often experience flare-ups of symptoms when under stress.
To understand the mechanism behind this association, Christoph Thaiss of the University of Pennsylvania and his colleagues analyzed mice with IBD-like symptoms. For a week, the researchers placed eight animals in small 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 perceives distress. 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 had, on average, a score of around 5, while those that did not had a score of just under 15, indicating that glucocorticoids are important for stress-induced gut inflammation. .
The researchers then carried out a genetic analysis of tissue samples taken from the animals’ colons. They found that mice with consistently high glucocorticoids showed changes in specialized neural cells called enteric glial cells. Glial cells help maintain neurons and communicate with many different cell types, and they respond to stress hormones by pumping out inflammatory molecules. Enteric glia from mice with elevated glucocorticoids showed increased activity in pro-inflammatory genes.
Genetic analysis has also revealed that stress alters gut neurons, making them appear less mature. “The reason this is detrimental is that we need mature neurons in the gastrointestinal tract to conduct stool and motility,” says Thaiss. Together, these results 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 and genetically analyzing colon tissue samples from each. Participants also completed a questionnaire assessing stress. People who were under more stress had more gut damage and greater increases in inflammatory markers, similar to those seen in mice.
Saurabh Mehandru of Mount Sinai Health System in New York says these findings may have finally demonstrated the exact brain-gut connection that many have long believed in gastrointestinal disorders. “This tells clinicians to look at the whole patient, not just addressing the symptoms of flare-ups, but also other issues that may be stress-related,” he says.
“The big question is whether the same pathway can dictate how responsive people are to different treatments,” says Thaiss. If so, it could improve how IBD is treated or lead to new drug targets for the disease.
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