Wednesday, June 28, 2023

Mechanisms that link psychological stress to the exacerbation of gut inflammation.

Schneider et al. describe one mechanism by which psychological stress deteriorates our health  -  the enteric nervous system relays psychological stress to intestinal inflammation. Here is their abstract:  


• 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
Mental health profoundly impacts inflammatory responses in the body. This is particularlyapparent 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.

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