From dysbiosis to postoperative neurocognitive disorders: The anesthesia-disrupted microbiota-gut-brain axis

Postoperative neurocognitive disorders (PND) remains a prevalent and debilitating complication in older surgical patients, with accumulating evidence implicating gut microbiota dysbiosis as a contributing factor. Anesthesia and surgical stress are known to disrupt intestinal microbial ecosystems, but the precise mechanisms by which these perturbations translate into central nervous system pathology are not fully understood. The gut-brain axis has emerged as a critical biological conduit, yet a comprehensive synthesis of the microbial, metabolic, and neuroinflammatory pathways linking perioperative dysbiosis to cognitive decline is lacking.

This narrative Review synthesizes current clinical and preclinical evidence on the role of the anesthesia-disrupted microbiota-gut-brain axis in PND. Specifically, we seek to: (1) characterize how anesthetics and surgical stress alter gut microbial composition and function; (2) delineate the downstream translocation of microbial metabolites (e.g., short-chain fatty acids, indole derivatives, bile acids) and endotoxins, and their contribution to central neuroinflammation via the kynurenine pathway, microglial activation, and blood-brain barrier disruption; (3) identify specific microbial taxa and metabolites with potential as peripheral biomarkers for postoperative cognitive outcomes; and (4) critically evaluate emerging microbiota-targeted preventive strategies.