Extracellular vesicles from Akkermansia muciniphila block NACHT, LRR, and PYD domains-containing protein 3 inflammasome activation to promote cognitive recovery in aged mice under sevoflurane anesthesia

The gut-brain axis plays a significant role in maintaining cognitive health. Akkermansia muciniphila -derived extracellular vesicles (Akk.m-EVs) improve postoperative cognitive dysfunction (POCD) induced by intestinal ischemia-reperfusion, but their role in elderly POCD is unclear. Therefore, this study investigates whether Akk.m-EVs affect POCD in elderly patients by mediating intestinal barrier dysfunction. Akk.m-EVs were obtained via ultracentrifugation. Sevoflurane (sevo; 3%) was used to induce POCD in mouse models. The cognitive function of mice was assessed by novel objective recognition and Morris water maze tests. Levels of proinflammatory cytokines in hippocampal tissues were detected by ELISA. The NACHT, LRR, and PYD domains-containing protein 3 (NLRP3) inflammasome activation was analyzed by, while tight junction proteins were detected by immunofluorescence western blot. Akk.m-EVs elevated exploration time, percentage of time spent exploring, identification index for novel objects, decreased escape latency, and enhanced the frequency of crossing the initial platform in sevo-induced POCD mice, highlighting the potential of Akk.m-EVs in improving cognitive, memory, and spatial learning abilities in POCD mice. In addition, Akk.m-EV treatment decreased inflammatory response and suppressed NLRP3 inflammasome activation in hippocampal tissues of POCD mice, accompanied by elevated zona occludens 1 and occludin protein levels in colonic tissues, suggesting that Akk.m-EVs reduced neuroinflammation and improved intestinal barrier disorder. Akk.m-EVs ameliorate POCD in elderly patients by decreasing neuroinflammation and improving intestinal barrier dysfunction, providing a theoretical basis for the development of prevention and treatment strategies for POCD based on probiotic extracellular vesicles.