According to research from the Perelman School of Medicine at the University of Pennsylvania, which was recently published in Cell, cells involved with the communication between stress responses in the brain and inflammation in the gastrointestinal (GI) tract have been identified in animal models for the first time.
The enteric nervous system (ENS), a semi-autonomous neural system located within the gastrointestinal (GI) tract, receives stress signals from the central nervous system (CNS) via glial cells, which support neurons. These psychological stress signals can cause inflammation and exacerbate symptoms of inflammatory bowel disease (IBD).
IBD, also known as Crohn’s disease and ulcerative colitis, is an illness that affects 1.6 million people in the United States and is characterized by GI tract inflammation and symptoms include chronic diarrhea, abdominal pain, and bloody feces. Prolonged inflammation can also lead to permanent damage to the GI tract. Current treatments consist of anti-inflammatory drugs, immune suppressants, dietary changes, and steroids.
“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.
In the study, researchers found that, like humans, mice with IBD developed severe symptoms when stressed. The adrenal cortex, which releases the glucocorticoids steroid hormones that trigger the physiological reactions to stress throughout the body, was found to be the source of the initial stress response signals.
This finding highlights the importance of psychological evaluations in patients being treated for IBD, as well as to inform treatment protocols. 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.
Professor Maayan Levy
The discovery that neurons and glia in the ENS reacted to persistently high glucocorticoid levels raises the possibility that these hormones are what mediates intestinal inflammation and stress perception in the brain.
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.”
Researchers stress the need for additional study into the biology of enteric glial cells and the functions they serve in the body’s multiple regulatory systems, including the interaction between the neurological and immune systems.
