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Uncovering Biological Links Between Stress and Inflammatory Bowel Disease Flare-Ups

The word “stress” written in red by a broken red pencil.

Researchers have identified biological pathways that link stress to worsening inflammatory bowel disease (IBD) symptoms, suggesting that strategies to reduce stress could be an important component of IBD treatment. IBD, such as Crohn’s disease and ulcerative colitis, is marked by chronic inflammation in the intestines that causes debilitating symptoms. Stress is known to significantly impact inflammatory processes in the body and has been associated with triggering IBD flare-ups. The biological processes that link stress to the severity of IBD flare-ups, however, are not well understood.

In new research, scientists found that stress exacerbated intestinal inflammation in different IBD mouse models. Comparing immune cells from colon tissue of stressed and control mice with IBD, the scientists found that stressed mice had higher levels of monocytes (a type of white blood cell) that promoted inflammation. The scientists next asked: how are stress signals transmitted from the brain to the gut to cause accumulation of monocytes? Surprisingly, they found that glucocorticoids—steroid hormones historically associated with reducing inflammation—were critical for triggering the observed stress-induced gut inflammation. They found that the glucocorticoids have two effects on the enteric nervous system (ENS, the gut's nervous system). First, they activate inflammatory pathways in a subset of glial cells in the ENS. (Glia and neurons are the two main cell types in the ENS.) The glial cells in turn recruit monocytes to the gut, thereby exacerbating inflammation in the colon. Second, glucocorticoids result in more undifferentiated, or immature, neurons in the ENS. The larger proportion of undifferentiated neurons means there are less of the signals (neurotransmitters) that mature neurons release, resulting in abnormal intestinal motility (movement of content through the gut). Finally, by studying three different cohorts of people with IBD, the scientists found evidence that these pathways likely played a role in mediating the effect of stress on IBD flare-ups in people.

This study sheds light on underlying mechanisms that link stress to IBD flare-ups, identifying a key role for glucocorticoids interacting with glia in the ENS to increase the susceptibility of the gut to inflammatory triggers. It also suggests the importance of considering people’s mental health in the clinical management of IBD. Furthermore, the knowledge gained from this research may not only benefit people with IBD, but also those with other gut inflammatory diseases and other diseases that are worsened by stress.

Schneider KM, Blank N, Alvarez Y,…Thaiss CA. The enteric nervous system relays psychological stress to intestinal inflammation. Cell 186: 2823- 2838.e20, 2023.
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