Stress can lead to flare-ups of inflammatory bowel disease, and now we know why
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Researchers have identified a pathway between the mouse brain and immune system that may explain why psychological stress exacerbates intestinal inflammation. This finding may improve treatments for chronic gastrointestinal diseases such as inflammatory bowel disease (IBD).
Over the years, research has shown a link between emotional distress and inflammation. This association is particularly evident in IBD and other autoimmune diseases characterized by intestinal inflammation, abdominal pain, and intestinal damage. Even with treatment, it is common for people with IBD to experience flare-ups of symptoms when stressed.
To understand the mechanisms behind this association, Christoph Theis and his colleagues at the University of Pennsylvania 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. Mice were then treated with chemical irritants for 7 days to induce IBD-like symptoms.
Three mice were given hormone-blocking drugs called glucocorticoids. Glucocorticoids send signals to the body that the brain produces when it senses pain. The researchers then performed colonoscopies on the mice and rated intestinal inflammation and intestinal damage on a scale of 0 to 15, with higher scores indicating worse outcomes. Drug-treated mice scored an average of about 5, while untreated mice scored slightly below 15, indicating the importance of glucocorticoids in stress-induced enteritis. It has been shown.
The researchers then performed genetic analysis on tissue samples taken from the animals’ colons. They found that mice with persistently elevated glucocorticoids had changes in specialized nerve cells called intestinal glia. Glial cells help maintain neurons and communicate with different cell types and respond to stress hormones by releasing inflammatory molecules. Enteric glia from mice with increased glucocorticoids showed increased activity of proinflammatory genes.
Genetic analysis also reveals that stress alters neurons in the gut, making them appear less mature. “The reason it’s harmful is that you need mature neurons in your GI tract to facilitate bowel movement and motility,” says Theis. Taken together, these findings highlight his two branches of pathways between the brain, gut neurons, and the inflammatory immune response.
The research team tested these findings by collecting and genetically analyzing colon tissue samples from all 63 IBD patients. Participants also completed a questionnaire assessing stress. People who experienced more stress had greater intestinal damage and greater increases in inflammatory markers, similar to those seen in mice.
Saurab Mehandle of the Mount Sinai Health System in New York said these results may finally prove the precise connection between the brain and the gut that many have long believed exists in gastrointestinal ailments. said. “This teaches clinicians that they need to look at their patients holistically, treating not just symptom flare-ups, but other problems that may be stress-related,” he said. say.
“The big question is whether the same pathway might determine people’s degree of responsiveness to different treatments,” says Theis. If so, it may lead to improved treatments for IBD or new drug targets for this condition.
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