“微生物-肠-脑”轴在术后认知功能障碍中的作用及干预研究

“微生物-肠-脑”轴的生理功能逐渐受到医学界重视，麻醉手术后严重的并发症-术后认知功能障碍（POCD）与肠道微生物关系的研究罕见报道。我们前期研究发现POCD不仅与脑功能异常相关，而且肠道菌群的组成及功能异常亦参与其中，同时观察到POCD与肠嗜铬细胞合成神经递质5-羟色胺异常有关。据此，我们推测：“微生物-肠-脑”轴可能参与到POCD的发病机制中。本项目拟选择16S rRNA测序、宏基因组学及代谢组学分析等对比POCD易感与非易感型肠道菌群组成和功能及其代谢物的异同，借助无菌小鼠观察POCD易感与非易感型肠道菌群移植对其影响，并研究肠道菌群的优化及改善对POCD的治疗作用，同时探索迷走神经和肌肉在POCD中的作用，揭示“菌群-肠嗜铬和上皮细胞-迷走神经与肌肉-脑”轴在POCD发病中的作用及治疗意义。为探索肠道菌群检测用于POCD辅助诊断和POCD预防和治疗新措施提供重要科学依据。

The physiological role of “microbiota-gut-brain” axis has attracted increasing scientific attentions. The relationship between gut microbiota and postoperative cognitive dysfunction (POCD), a severe complication after anesthesia and surgery, has rarely been reported. Our previous studies showed that the underlying mechanisms of POCD are not only associated with the abnormal brain function, but also related to the abnormalities in the composition and function of gut microbiota. Additionally, we also observed that the occurrence of POCD was potentially attributed to the dysfunctional synthesis of neurotransmitter serotonin in the enterochromaffin cells. Based on this, we speculated that the “microbiota-gut-brain” axis may underlie the pathogenesis of POCD. We therefore intended to compare the gut microbiota and its metabolites between POCD susceptible and unsusceptible via 16S rRNA sequencing, metagenomics and metabonomics analysis. We also aimed to observe the effects of transplantation of gut microbiota, originated from POCD susceptible and unsusceptible mice, on germ-free mice. Furthermore, we designed to investigate the beneficial effects of gut microbiota optimization on POCD, further investigating the specific role of vagus nerve and muscle in POCD, therefore revealing the key role of “gut microbiota-enterochromaffin and epithelial cells-vagus nerve and muscle-brain”, a physiological axis, in the pathogenesis and therapeutic mechanisms of POCD. Finally, our findings would provide important scientific values for auxiliary diagnosis of POCD and exploring new alternatives for the prevention and treatment of POCD by detection of gut microbiota.