We’ve all experienced the physical tension of stress at one point or another. Some feel this tension in their neck, resulting in stress-induced headaches, or their chest, which can cause heart palpitations. Many feel the effects of stress in their gut, as seen in cases of IBS and IBD.
In fact, numerous studies show that IBD patients experience an elevation of disease severity when suffering a stressful life event. The impact of psychological distress on quality of life, disease progression, and treatment adherence is so pronounced it is now included in the clinical guidelines for IBD treatment.
Still, we knew little of the mechanisms tying stress to IBD flares – until a study this year discovered an unexpected connection between stress and gastrointestinal symptoms that may pave the way to improved treatment outcomes and quality of life for IBD patients.
The Brain-Gut Connection
In the 2023 study, researchers gave mice a chemical that erodes the protective layer of the gut to stimulate IBD, then placed a portion of them under stressful conditions. The mice under stress showed at least a twofold increase in IBD severity.
The increased severity was tied to a stress hormone pathway that links stress perception in the brain to inflammatory processes in the digestive tract – the glucocorticoid signaling pathway.
The glucocorticoid signaling pathway refers to the release of glucocorticoid from the adrenal gland when we are exposed to stress triggers. Glucocorticoids are able to cross the blood-brain barrier and activate glucocorticoid receptors throughout the body, including the intestines.
The researchers found the release of glucocorticoid was directly triggering gut inflammation, opposing the long-standing assumption it should have the opposite effect. It is now suspected glucocorticoid release is only anti-inflammatory during short-term, acute stress while exerting the opposite effect under long-term, chronic stress.
Can Stress Cause IBD?
At the heart of this pathway lie neurons and enteric glial cells, which are specialized neurons found in the intestinal wall containing glucocorticoid receptors.
Apparently, when enteric glial cells are under chronic glucocorticoid exposure, they become pro-inflammatory by turning into eGAPS cells. The eGAPS cells send out signals to draw immune monocytes (a type of white blood cell) into the intestines. The monocytes then release TNF signals, causing no small degree of inflammation, intestinal cell damage, and pain.
The chronic release of stress signals also causes a decline in healthy, mature neurons and an increase in immature neurons. The immature neurons are not able to excrete an enzyme called acetylcholine (ACh), which is vital for the healthy movement of food through the digestive tract, and is an important regulator of inflammation.
The overproduction of glucocorticoids may additionally reduce tight junction expression, which leads to intestinal barrier permeability and is closely associated with the progression of IBD.
A New Avenue for Future IBD Treatments
The above findings suggest that stress management may play a vital role in the future of IBD treatment.
Studies have already established that psychological intervention can improve treatment efficacy and quality of life in IBD patients. Cognitive Behavioral Therapy is especially beneficial for both UC and CD patients, improving not only anxiety and low mood but also disease activity.
Supplements to Reduce Stress Hormones
Certain herbal compounds may also alleviate the impact of stress on the digestive system by inhibiting the hypothalamic-pituitary-adrenal axis (HPA). The HPA is our main stress response system, responsible for moderating hormone signals, including glucocorticoid, to keep the body in a state of balance.
Studies show that dysregulated HPA activity can be alleviated by some adaptogenic herbs, which are able to counteract stress signals. Ashwagandha, for example, is believed to have an attenuating effect on the HPA axis activity, reducing the force of its impact.
Future treatment of IBD will likely incorporate drugs and adaptogens to moderate these stress hormones, ultimately improving response to treatment and quality of life.
Tessa Eskin
