General anesthesia bullies the gut: a toxic relationship with dysbiosis and cognitive dysfunction

Perioperative neurocognitive disorder (PND) is a common surgery outcome affecting up to a third of the elderly patients, and it is associated with high morbidity and increased risk for Alzheimer's disease development. PND is characterized by cognitive impairment that can manifest acutely in the form of postoperative delirium (POD) or after hospital discharge as postoperative cognitive dysfunction (POCD). Although POD and POCD are clinically distinct, their development seems to be mediated by a systemic inflammatory reaction triggered by surgical trauma that leads to dysfunction of the blood-brain barrier and facilitates the occurrence of neuroinflammation. Recent studies have suggested that the gut microbiota composition may play a pivotal role in the PND development by modulating the risk of neuroinflammation establishment. In fact, modulation of gut microbiome composition with pre- and probiotics seems to be effective for the prevention and treatment of PND in animals. Interestingly, general anesthetics seem to have major responsibility on the gut microbiota composition changes following surgery and, consequently, can be an important element in the process of PND initiation. This concept represents an important milestone for the understanding of PND pathogenesis and may unveil new opportunities for the development of preventive or mitigatory strategies against the development of these conditions. The aim of this review is to discuss how anesthetics used in general anesthesia can interact and alter the gut microbiome composition and contribute to PND development by favoring the emergence of neuroinflammation.