Gut microbiota and postoperative delirium: mechanistic integration of the “gut-liver-anesthesia axis” in the context of liver disease and perioperative intervention strategies

Postoperative delirium (POD) is a prevalent and clinically significant complication among older surgical patients. Despite its high incidence, the underlying pathogenesis remains incompletely understood, and effective targeted therapeutic strategies are lacking. As the largest microecosystem in the human body, the gut microbiota has been increasingly recognized for its potential role in modulating central nervous system (CNS) function and systemic inflammatory responses through the gut–brain and gut–liver axes. Accumulating evidence suggests that alterations in gut microbial composition (gut dysbiosis) may be associated with the initiation and progression of POD. Patients with pre-existing liver disease appear to be particularly vulnerable, possibly due to baseline disturbances in gut microbiota, impaired intestinal barrier function, and systemic immune dysregulation. In addition, exposure to anesthetic agents and the physiological stress of surgery may further perturb intestinal microecology, potentially contributing to a self-reinforcing cycle within a proposed gut-liver-anesthesia axis. In this narrative review, we provide a targeted synthesis of current mechanistic and clinical evidence linking the gut microbiota to POD. We further explore the potential interactions among gut dysbiosis, liver dysfunction, and perioperative anesthetic factors, with a focus on their implications for neurocognitive outcomes. Finally, we summarize emerging microbiota-targeted perioperative interventions, while emphasizing that the current evidence remains limited, heterogeneous, and largely hypothesis-generating rather than directly translatable to clinical practice.