Researchers have identified a pathway between the brain and the immune system in mice that may explain why psychological stress can worsen gut inflammation. The finding could improve treatments for chronic gastrointestinal conditions like inflammatory bowel disease (IBD).
For years, studies have shown an association between mental distress and inflammation. The connection is especially apparent in IBD or other autoimmune conditions characterised by gut inflammation, abdominal pain and intestinal damage. Even with treatment, people with IBD commonly experience symptom flare-ups when stressed.
To understand the mechanism behind this association, Christoph Thaiss at the University of Pennsylvania and his colleagues analysed mice with IBD-like symptoms. For one week, the researchers placed eight animals inside small tubes for 3 hours a day to induce stress. They then treated the mice with a chemical irritant for seven days to bring on 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 gut inflammation and intestinal damage between 0 and 15, with higher scores indicating worse outcomes. Mice given the drug had, on average, a score around 5, whereas those without had a score slightly below 15, indicating glucocorticoids are important for stress-induced gut 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 specialised 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 pro-inflammatory genes.
Genetic analysis also revealed that stress alters neurons in the gut, making them appear less mature. “The reason why this is detrimental is because we need mature neurons in the gastrointestinal tract to drive bowel movement 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 and genetically analysing tissue samples from everyone’s colons. Participants also completed a questionnaire assessing 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 may have finally demonstrated the exact connection between the brain and gut that many have long believed existed in gastrointestinal disorders. “It tells clinicians that you have to look at the patient as a whole, not just treat the symptoms in flare-ups, but also other problems that may be stress related,” he says.
“The big question is whether the same pathway might dictate people’s degree of responsiveness to different treatments,” says Thaiss. If so, it could improve how IBD is treated or lead to new drug targets for the condition.
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