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.

心理健康深刻影响体内的炎症反应。这在炎症性肠病（IBD）中尤其明显，在这种疾病中，心理压力与病情恶化有关。在这里，我们发现肠神经系统（ENS）在介导慢性应激对肠道炎症的加重作用中发挥着关键作用。我们发现，长期升高的糖皮质激素水平会促进肠神经胶质细胞炎症亚群的产生，该亚群通过 CSF1 促进单核细胞和 TNF 介导的炎症。此外，糖皮质激素通过 TGF-β2 导致肠神经元转录不成熟、乙酰胆碱缺乏和运动障碍。我们验证了三组 IBD 患者的心理状态、肠道炎症和运动障碍之间的联系。总之，这些发现为大脑对周围炎症的影响提供了机制解释，将 ENS 定义为心理压力和肠道炎症之间的中继，并表明压力管理可以作为 IBD 护理的重要组成部分。