How chronic stress can inflame the gut

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"... Stressful events, such as losing one’s job or breaking up with a partner, often precede IBD [inflammatory bowl disease] flare-ups. [Reasearchers] have now traced that linkage. After a surge of stress, the brain sends signals to the adrenal glands, which release chemicals called glucocorticoids to the rest of the body. ...
Working in mice, they found that glucocorticoids act instead on neurons in the gut and on cells called glia that connect gut neurons to one another. ...

After being switched on by glucocorticoids, some glial cells release molecules that trigger immune cells. In turn, those immune cells release molecules that would normally be used to fight off pathogens, but in this case end up causing painful bowel inflammation.

At the same time, glucocorticoids block immature gut neurons from developing fully, the researchers found. As a consequence, these neurons produce only low levels of signalling molecules that cause gut muscles to contract. This means food moves slowly through the digestive system, which adds to the discomfort of IBD. ...
Although quick bursts of glucocorticoids seem to be anti-inflammatory, when stress becomes chronic, “the system completely shifts” and glucocorticoids take on a pro-inflammatory role ..."

From the highlights and abstract:

"Highlights

• Psychological stress leads to monocyte-mediated exacerbation of gut inflammation

• Chronic glucocorticoid signaling drives the effect of stress on IBD

• Stress induces inflammatory enteric glia that promote monocyte recruitment via CSF1

• Stress provokes transcriptional immaturity in enteric neurons and dysmotility

Summary

Mental health profoundly impacts inflammatory responses in the body. This is particularly apparent in inflammatory bowel disease (IBD), in which psychological stress is associated with exacerbated disease flares. Here, we discover a critical role for the enteric nervous system (ENS) in mediating the aggravating effect of chronic stress on intestinal inflammation. We find that chronically elevated levels of glucocorticoids drive the generation of an inflammatory subset of enteric glia that promotes monocyte- and TNF-mediated inflammation via CSF1. Additionally, glucocorticoids cause transcriptional immaturity in enteric neurons, acetylcholine deficiency, and dysmotility via TGF-β2. We verify the connection between the psychological state, intestinal inflammation, and dysmotility in three cohorts of IBD patients. Together, these findings offer a mechanistic explanation for the impact of the brain on peripheral inflammation, define the ENS as a relay between psychological stress and gut inflammation, and suggest that stress management could serve as a valuable component of IBD care."

Chronic stress can inflame the gut — now scientists know why Signals originating in the brain make their way to gut nerve cells, leading to a release of inflammatory chemicals.

The enteric nervous system relays psychological stress to intestinal inflammation (open access)

Graphical abstract