Chronic stress adds fuel to gut flame

Inflammatory bowel diseases (IBD) is characterized by chronic inflammation of the gastrointestinal tract, which can lead to dysfunctions of the intestines associated with pain and body weight loss, and requires effective treatments. Evidence from both preclinical animal and clinical human observations suggests that IBD can be exacerbated by chronic stress. However, the mechanism that links chronic stress to intestinal inflammation remains largely elusive. Using a comprehensive set of mouse genetic models, pharmacologic interventions and sequencing analysis, a recent study systematically investigated the pathway that mediates chronic stress in inducing responses of inflammation in the intestine, and revealed an increased action of glucocorticoid, a known stress-induced blood hormone, as the key mediator in initiating the IBD inflammation. Convincing evidence was presented to argue that the intestinal inflammation and dysmotility in IBD are mediated by direct glucocorticoid action on enteric glia cells and enteric neurons, respectively. These findings, on one hand, identified a heightened stress-induced hypothalamus-pituitary-adrenal (HPA) action in causing IBD, but on the other hand, in consideration of the known glucocorticoid's anti-inflammatory effects, revealed the complexity nature of glucocorticoid action in mediating inflammatory responses.