Peripheral to central: Exploring the neural, endocrine, and immune pathways of the gut-brain axis in postoperative neurocognitive dysfunction

Perioperative neurocognitive dysfunction (PND), a common complication associated with anesthesia and surgery, has garnered considerable interest regarding its underlying mechanisms. However, the precise pathways through which PND develops remain incompletely understood. Accumulating evidence suggests that dysfunction of the microbiota-gut-brain axis (MGBA) plays a pivotal role in the pathogenesis of PND. Accordingly, this article reviews current advances in the understanding of MGBA-mediated mechanisms contributing to PND, with a focus on neurological, endocrine, and immune pathways. Specifically, we discuss the involvement of the sympathetic, vagal, and enteric nervous systems, neuroinflammation within the central nervous system, the stress response and glucocorticoid signaling, microbial metabolites, and specific inflammatory factors and signaling pathways in the development of PND. Furthermore, targeting the gut microbiota may represent a promising therapeutic strategy for PND. This review aims to provide insights beneficial to both clinical management and future research on PND.