How Stress Inflames the Gut
In mice, chronically high levels of stress hormones worsen bowel inflammation.
In 2017, 6.8 million people worldwide were affected by inflammatory bowel disease (IBD), a group of disorders that causes prolonged intestinal inflammation.1 Scientists knew that chronic stress worsens IBD symptoms, but how exactly that happens was unclear.
In a recent Cell publication, Kai Markus Schneider, a physician scientist at RWTH Aachen University, and his colleagues reported that naturally occurring hormones secreted during stressful events, glucocorticoids, affect cells in the enteric nervous system (ENS) to cause intestinal inflammation and bowel problems.2
To investigate how stress worsens IBD symptoms, the team gave mice a chemical that damages their guts to simulate IBD and then stressed half of them by restricting their movement for seven to ten days. Stressed IBD mouse models showed increased inflammation compared to IBD mouse models without stress.
“There are different pathways that can propagate the stress response into the guts,” Schneider explained. The release of glucocorticoids is one of them. When the researchers modulated glucocorticoid levels, they found that elevated levels worsened IBD inflammation, whereas reducing the levels prevented that effect.
Since glucocorticoids affect neuronal cells, the team next investigated how stress changed the gene expression in ENS cells. When stressed, enteric glia cells showed increased proinflammatory pathways, which worsened bowel inflammation by attracting more white blood cells. The team also found that stress increased the proportion of precursor-like neurons relative to mature neurons in the ENS, a shift that impaired the bowel’s movements.
Keith Sharkey, a gastrointestinal physiologist at the University of Calgary who was not involved in the research, said that the study provides a detailed mechanistic explanation for how stress affects the bowels. He also expressed curiosity about sex differences in those findings. “There is a clear difference in the way male and female [subjects] respond to stress, and we know that sex hormones are important in protection against colitis.”
The findings might point to ways to improve patient care, Schneider added. “Stress management is also essential for the management of IBD. We should offer this to patients, and patients should not be afraid to ask for psychological support to reduce stress levels.”