Stress Increases Systemic Inflammation and Anxiety in Mouse Model of IBD

Stress Increases Systemic Inflammation and Anxiety in Mouse Model of IBD 1024 606 Mary Bates, PhD

Exposure to stress did not induce a relapse in colitis in the mice.

In a new study, researchers at Nationwide Children’s Hospital and the Abigail Wexner Research Institute tested whether exposure to stress would lead to flares of intestinal inflammation in a mouse model of inflammatory bowel disease. They found stress did not exacerbate colitis in the mice, though it did increase anxiety-like behavior.

Inflammatory bowel disease (IBD) is a relapsing and remitting disease, with the reasons for relapses sometimes unclear, although stress is thought to be one factor. In addition, IBD is often associated with anxiety disorders.

The new study had two goals: to test whether stressor exposure could induce a relapse in inflammation, and to determine the impact of stress on anxiety-like behavior. To accomplish this, the researchers used a mouse model of IBD in which colitis (intestinal inflammation) is chemically induced. The team exposed the mice to a social disruption stressor while they were recovering from colitis. The researchers tested the mice for anxiety-like behavior and then measured biomarkers of inflammation in the colon, intestinal lymph nodes, blood, and brain.

Contrary to their expectations, the researchers found that stress exposure did not induce a relapse in intestinal inflammation in the mice. It did, however, increase anxiety-like behavior.

Ross Maltz, MD, a pediatric gastroenterologist at Nationwide Children’s and the study’s lead author, says the team next examined different tissues for levels of cytokines, such as interleukin 17A (IL-17A).

“We clearly showed that stressor exposure increases IL-17A in the brain, as well as in the blood and in the lymph nodes,” he says.

According to Michael Bailey, PhD, a principal investigator at The Abigail Wexner Research Institute at Nationwide Children’s and senior author of the study, the data suggest there is an immune dysregulation in the intestine, but it’s not necessarily increased inflammation.

“There may actually be some components of protective immunity that are decreased,” he says. “Overall, it looks like exposure to stress causes a dysregulation in the immune response in the intestine, which is related to increased inflammation in the intestinal lymph nodes and blood. These inflammatory responses are in turn related to inflammation in the brain and anxiety-like behavior.”

Dr. Maltz, who is also an assistant professor of clinical pediatrics at The Ohio State University College of Medicine, cautions that the mouse model of IBD they used is one of many options, and while it shares some features with human IBD, there are also differences.

“This is an acute model, rather than chronic,” he says. “It’s also a chemical-induced model versus an immune-mediated model.”

In addition to doing similar studies in other mouse models of IBD, the researchers hope to work out some of the mechanisms involved in the inflammatory response to stress.

“Our next step will be to determine whether that decrease in protective immunity in the intestine allows some intestinal bacteria to cross the intestinal barrier,” says Dr. Bailey, who is also an associate professor at The Ohio State University College of Medicine. “Based on studies in animals without IBD, we believe that bacteria crossing the intestinal barrier leads to inflammation inside the body, including the brain, that then contributes to anxiety. Identifying these mechanisms would allow us to begin developing therapies to target intestinal bacteria as a means to treat anxiety and depression in individuals with chronic diseases”.

Reference:

Maltz RM, Marte-Ortiz P, Rajasekera TA, Loman BR, Gur TL, Bailey MT. Stressor-induced increases in circulating, but not colonic, cytokines are related to anxiety-like behavior and hippocampal inflammation in a murine colitis model. International Journal of Molecular Sciences. 2022;23(4):2000. Doi: 10.3390/ijms23042000.

About the author

Mary a freelance science writer and blogger based in Boston. Her favorite topics include biology, psychology, neuroscience, ecology, and animal behavior. She has a BA in Biology-Psychology with a minor in English from Skidmore College in Saratoga Springs, NY, and a PhD from Brown University, where she researched bat echolocation and bullfrog chorusing.