Study discovers cells linking chronic psychological stress to inflammatory bowel disease

Pennsylvania [US], June 9 : Cells involved in the connection between stress reactions in the brain and inflammation in the gastrointestinal (GI) tract have been discovered in animal models for the first time, according to research from the University of Pennsylvania's Perelman School of Medicine.

The study's findings were just published in Cell. Glial cells, which support neurons, transmit stress signals from the central nervous system (CNS) to the enteric nervous system (ENS), a semi-autonomous neural system within the gastrointestinal (GI) tract. These psychological stress signals might promote inflammation and aggravate inflammatory bowel disease (IBD) symptoms.

IBD, which refers to two disorders - Crohn's disease and ulcerative colitis - that are characterised by inflammation of the GI tract and can produce symptoms such as recurrent diarrhoea, stomach discomfort, and bloody stools, affects an estimated 1.6 million Americans today. Prolonged inflammation can potentially cause irreversible damage to the gastrointestinal tract. Anti-inflammatory medications, immune suppressants, dietary modifications, and steroids are now used as therapies.

"Clinicians have long observed that chronic stress can worsen IBD symptoms, but until now, no biological connection has been identified to explain how the digestive system knows when someone is stressed," said senior author Christoph Thaiss, PhD, an assistant professor of Microbiology.

Researchers discovered that mice with IBD exhibited severe symptoms when stressed, just as humans. They followed the first stress response signals to the adrenal cortex, which releases glucocorticoidssteroid chemicals that trigger the body's physiological reactions to stress. The researchers discovered that neurons and glia in the ENS responded to chronically high glucocorticoid levels, indicating that they constitute the connection between brain stress perception and intestine inflammation.

While glucocorticoids typically have an anti-inflammatory effect in the body, the researchers found that when glia in the ENS were exposed to the steroid hormones for a prolonged period, such as during chronic stress, they attract white blood cells to the GI tract that increase inflammation. The researchers also found that when exposed to chronic stress, the neurons in the ENS in the GI tract stop functioning as they normally do, which can lead to impaired bowel movements and exacerbated IBD symptoms.

Thaiss and collaborators verified the connection between psychological stress and IBD symptoms in humans using the UK Biobank and a patient cohort from the IBD Immunology Initiative at Penn Medicine. They found that the in patients with an IBD diagnosis, the level of reported stress correlated with an increased severity of IBD symptoms.

"This finding highlights the importance of psychological evaluations in patients being treated for IBD, as well as to inform treatment protocols," said Maayan Levy, PhD, an assistant professor of Microbiology and co-senior author of the study. "One of the most common treatments for IBD flare-ups is steroids, and our research indicates that in patients with IBD who experience chronic stress, the efficiency of this treatment could be impaired."