“The Gut-Brain Connection: How Glucocorticoids Contribute to Inflammation in IBD”

2023-05-30 10:40:00

Thaiss and his colleagues have now traced this connection: After a wave of stress, the brain sends signals to the adrenal glands, which release certain chemical substances, so-called glucocorticoids, to the rest of the body. Initially, the researchers assumed that the glucocorticoids act directly on immune cells in the gut, which then release molecules that trigger inflammation. “It turned out, however, that there is a kind of intermediate layer,” says Thaiss. Working with mice, the group found that glucocorticoids instead act on neurons in the gut and on glial cells, which connect the gut neurons together.

Glucocorticoids: A double-edged sword when it comes to inflammation

After being activated by glucocorticoids, some glial cells release molecules that activate immune cells. These immune cells then release molecules that are normally used to fight pathogens, but in this case lead to painful intestinal inflammation. At the same time, the glucocorticoids block the development of immature gut neurons. As a result, these neurons only produce small amounts of signaling molecules that cause the gut muscles to contract. This causes food to move more slowly through the digestive system, further increasing the symptoms of IBD.

The discovery that glucocorticoids can apparently cause intestinal inflammation surprised the researchers. Because glucocorticoids are sometimes used to treat IBD. This apparent paradox may be explained by the short time span over which such treatments are typically used: although rapid bursts of glucocorticoids appear to be anti-inflammatory, the system completely shifts when stress becomes chronic. Then the glucocorticoids take on an inflammatory role, says Thaiss. Gastroenterologist and immunologist John Chang from the University of California in San Diego also considers this to be a plausible explanation.

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