Aims: Postoperative cognitive dysfunction (POCD) is the decline in cognitive function of the central nervous system after anesthesia/surgery. The present study explored whether anesthesia/surgery altered gut microbiota and fecal metabolites, examining their associations with risk factors of cognitive dysfunction in aged mice. Methods: Sixteen-month-old C57BL/6 mice underwent abdominal surgery under isoflurane anesthesia to establish an animal model of POCD. The Morris water maze test (MWMT) was used as an indicator of memory after surgery. The effects of anesthesia/surgical interventions on gut microbiota, fecal metabolites, hippocampus, and serum levels of inflammatory factors were examined. Results: The anesthesia/surgery induced more serious POCD behavior, increasing brain IL-6 and IL-1β levels than sham control mice. The relative abundance of bacterial genera Bacteroidales_unclassified, Mucispirillum, and Clostridiales_unclassified declined, whereas that of Escherichia-Shigella, actinomyces, Ruminococcus_gnavus_group and Lachnospiraceae_FCS020_group were enriched after anesthesia/surgery compared to the baseline controls. Liquid chromatography-mass spectrometry (LC-MS) showed that the metabolites differed between post anesthesia+surgery (post_A+S) and baseline samples and were associated with the fecal metabolism of tryptophan, kynurenic acid, N-oleoyl γ-aminobutyric acid (GABA), 2-indolecarboxylic acid, and glutamic acid. Furthermore, the differential metabolites were associated with alterations in the abundance of specific bacteria. These results indicate that POCD intervention may be achieved by targeting specific bacteria associated with neurotransmitter metabolism. Conclusions: A transient cognitive disturbance induced by anesthesia/surgery may be associated with unfavorable alterations in gut microbiota and fecal metabolites, thereby contributing to POCD development. Keywords: gut microbiota, metabolomics, gut-brain axis, postoperative cognitive dysfunction, neurotransmitter

中文翻译：

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麻醉/手术对肠道菌群和粪便代谢物的影响及其与认知功能障碍的关系

目的：术后认知功能障碍（POCD）是麻醉/手术后中枢神经系统认知功能的下降。本研究探讨了麻醉/手术是否会改变肠道微生物群和粪便代谢物，检查它们与老年小鼠认知功能障碍风险因素的关联。方法：16个月大的C57BL/6小鼠在异氟醚麻醉下进行腹部手术，建立POCD动物模型。莫里斯水迷宫试验（MWMT）被用作手术后记忆的指标。研究了麻醉/手术干预对肠道微生物群、粪便代谢物、海马和炎症因子血清水平的影响。结果：麻醉/手术诱导了更严重的 POCD 行为，与假手术对照小鼠相比，脑 IL-6 和 IL-1β 水平增加。与基线对照相比，在麻醉/手术后，拟杆菌属_未分类、粘螺旋菌属和梭菌属_未分类的细菌属的相对丰度下降，而埃希氏菌-志贺氏菌、放线菌、瘤胃球菌_gnavus_组和毛螺菌科_FCS020_组的相对丰度增加。液相色谱-质谱 (LC-MS) 表明，麻醉后 + 手术后 (post_A+S) 和基线样品的代谢物不同，并且与色氨酸、犬尿氨酸、N-油酰 γ-氨基丁酸 (GABA) 的粪便代谢有关)、2-吲哚羧酸和谷氨酸。此外，差异代谢物与特定细菌丰度的改变有关。这些结果表明，可以通过靶向与神经递质代谢相关的特定细菌来实现 POCD 干预。结论：麻醉/手术引起的短暂认知障碍可能与肠道微生物群和粪便代谢物的不利改变有关，从而促进 POCD 的发展。关键词：肠道微生物群，代谢组学，肠脑轴，术后认知功能障碍，神经递质