Gut‑brain axis in anesthesia and critical illness: Molecular crosstalk and its impact on delirium and outcome (Review)

The gut‑brain axis (GBA) has emerged as a critical mediator of acute brain dysfunction, particularly postoperative delirium and sepsis‑associated encephalopathy, in surgical and critically ill patients. Anesthesia, surgical stress, and critical illness collectively disrupt gut microbiota composition and intestinal barrier integrity, leading to increased systemic translocation of microbial products. This process triggers neuroinflammation and compromises blood‑brain barrier function through defined molecular pathways, including alterations in microbe‑derived short‑chain fatty acids, tryptophan metabolites, and potent neuroimmune signaling via the LPS‑TLR4‑NF‑κB axis. The present review synthesizes current evidence on the molecular crosstalk within the GBA, highlighting how perioperative and intensive care interventions drive dysbiosis and subsequent neurological sequelae. Furthermore, it evaluates promising GBA‑targeted therapeutic strategies, including dietary modulation, biotherapeutics and pharmacological interventions, are evaluated for their potential to mitigate delirium and improve long‑term cognitive outcomes. A deeper understanding of these mechanisms is essential for developing novel preventive and therapeutic approaches in vulnerable patient populations.