Intraoperative intestinal ischemia-reperfusion injury aggravates postoperative delirium by remodeling gut microbiota

Postoperative delirium, is a notable and serious complication after surgery, commonly extending hospitalization by 2-3 days. In a cohort of 167 patients, elevated serum intestinal fatty acid binding protein (I-FABP) was identified as an independent risk factor for postoperative delirium. Complementary experiments conducted in murine models demonstrated that intestinal ischemia-reperfusion injury induced behaviors analogous to delirium, accompanied by disruption of the intestinal barrier and gut dysbiosis predominantly characterized by Enterobacteriaceae overgrowth. Fecal microbiota transplantation from healthy donors effectively restored the microbial homeostasis, improved cognitive performance, and preserved hippocampal synaptic integrity. Multiomics analyses further revealed that microbiome dysbiosis triggered intestinal expression of indoleamine-2,3-dioxygenase 1 (IDO1), leading to systemic accumulation of L-kynurenine. This accumulation activated microglia, leading to aberrant synaptic phagocytosis and consequent cognitive decline.