An experiment in mice showed that elevated levels of glucocorticoids under chronic stress trigger processes in the enteric nervous system that exacerbate inflammation and disrupt gut motility.
The scale of the problem—and a long-standing mystery
Inflammatory bowel disease (IBD) remains one of the serious challenges for gastroenterology. As of 2017, 6.8 million people worldwide were living with these disorders. Clinicians have long noted that chronic stress noticeably worsens the course of the disease, but the specific biological mechanism behind this link remained unclear.
A new study, the results of which were published in the journal Cell, sheds light on the molecular chain of events linking stress to a flare-up of intestinal inflammation.
What the Aachen team found
A group led by physician and researcher Kai Markus Schneider of RWTH Aachen University found that glucocorticoids—natural hormones that the body releases into the bloodstream in stressful situations—act on cells of the enteric nervous system (ENS). The result is increased intestinal inflammation and disruption of normal gut function.
The ENS is often called the body’s “second brain” because it contains its own network of millions of neurons and glial cells that regulate digestion autonomously. It was this system that turned out to be the target of stress hormones.
How the experiment was set up
The study design involved several stages. First, the scientists used a chemical agent to induce intestinal injury in mice, creating an IBD model. Then half of the animals were exposed to stress by restraining their movement for 7–10 days. The control group had the same IBD model but lived without additional stress. Comparing the two groups allowed the researchers to isolate the contribution of stress to the worsening.
The findings were unambiguous: in mice experiencing chronic stress, intestinal inflammation was significantly more pronounced than in the control animals.
Glucocorticoids were the key link
“There are several pathways by which the stress response can spread to the gut,” Schneider noted. The release of glucocorticoids, he said, is one of the key ones. When the researchers experimentally increased the level of these hormones, inflammation in IBD intensified. When, on the other hand, glucocorticoid levels were reduced, the negative effect of stress on inflammation could be prevented. This bidirectional effect confirmed the causal role of the hormones in the mechanism described.
Glial cells switched on pro-inflammatory programs
At the cellular level, the picture looked as follows. Under stress, enteric glial cells—the nervous system’s “support staff” in the gut—changed their gene expression profile. Pro-inflammatory signaling pathways were activated, which attracted more white blood cells into intestinal tissue, thereby exacerbating the inflammatory process.
In parallel, the scientists recorded another important change. Stress increased the proportion of immature neuronal precursors relative to mature neurons in the ENS. This shift disrupted coordinated contractions of the intestinal wall—that is, it impaired motility—which clinically manifests as slowed digestion or digestive disturbances.
Why stress management is discussed in IBD care
The data obtained point to the practical importance of combating stress in the comprehensive management of patients with inflammatory bowel disease. As Schneider emphasized, stress management is an essential part of IBD therapy. In his view, it is important for patients to discuss available forms of psychological support with their doctor and not be afraid to seek such help to reduce stress levels.
Stress can be caused by a whole range of factors—problems at work and in one’s personal life, worries about finances or political events. In recent years, an increasingly common problem has been stress related to gambling. This is largely because it has become more accessible.We found confirmation of this fact here, on the website about the Ice Fishing live show. The authors point out that there are more and more online casinos, which means that gambling has become much easier. In addition, new projects are becoming increasingly fast-paced, which increases the frequency of losses that can cause stress, including chronic stress.
Independent assessment and open questions
Keith Sharkey, a gastrointestinal physiologist at the University of Calgary who was not involved in the study, praised the work. According to him, it provides a detailed mechanistic explanation of exactly how stress affects the gut.
At the same time, Sharkey drew attention to an aspect that for now remains outside the scope of the study. Stress responses differ markedly between men and women, and sex hormones play an important role in protection against colitis. This direction requires separate verification, and its results could substantially refine our understanding of the mechanism.