Electroacupuncture modulates gut microbiota in mice: A potential target in postoperative cognitive dysfunction

The detailed mechanism of inflammation in postoperative cognitive dysfunction (POCD) is unclear. This study aimed to determine whether electroacupuncture (EA) ameliorates POCD by modulating gut microbial dysbiosis. Compared to the control group, mice in the EA group were treated at the acupoints Zusanli (ST36), Quchi (L111), Baihui (GV20), and Dazhui (GV14) 1 week before appendectomy. Novel object recognition and the Morris water maze tests were used to assess learning and spatial reference memory deficits, whereas hippocampus samples and stool samples were collected for central inflammatory tests and 16S-rRNA sequencing of intestinal flora, respectively. In amyloid precursor protein/presenilin 1 (APP/PS1) mice, EA enhanced spatial memory and learning deficits. The fecal microbial community was altered in APP/PS1 mice in the absence of EA following surgery. Among them, Coprococcus and Bacteroidetes were more abundant in the EA groups than in the control groups; however, Actinobacteriota, Helicobacteraceae, and Escherichia/shigella constitute the minor bacterial colonization in the EA groups. Furthermore, we found a significant negative correlation between Firmicutes and escape latency (Pearson correlation coefficient - 0.551, p < 0.01) and positive correlation between Proteobacteria and escape latency (Pearson correlation coefficient 0.462, p < 0.05). Electron microscopy revealed signs of blood-brain barrier (BBB) impairments and immunofluorescence images showed glial cells activated in the hippocampus of APP/PS mice without EA, and serum diamine oxidase levels were increased in these mice; whereas EA treatment significantly relieved the above pathological changes. Our findings implied that EA decreases hippocampal inflammation of APP/PS1 by upregulating benificial gut microbiota, reducing BBB and intestinal barrier dysfunction, thus alleviates postoperative cognitive dysfunction. This may provide a novel target in POCD management.术后认知功能障碍(POCD)中枢炎症的详细机制尚不清楚。本研究旨在确定电针刺激 (EA) 是否通过调节肠道微生物菌群失调来改善 POCD。本实验将接受手术的淀粉样前体蛋白/早老素 1 (APP/PS1)和同窝野生小鼠各20只, 随机分为非电针组(WT-C和APP/PS1-C)和电针组(WT-E和APP/PS1-E)。与非电针组相比, 电针组小鼠在阑尾切除术前一周分别在足三里(ST36)、曲池(L111)、百会(GV20)和大椎(GV14)穴位进行电针。新物体识别和莫里斯水迷宫测试用于评估小鼠学习和空间参考记忆缺陷, 而海马样本和粪便样本分别用于中枢炎症因子测试和 16S-rRNA 测序评估肠道微生物菌群。结果发现:在APP/PS1小鼠中, 电针组改善了空间记忆和学习缺陷。非电针组APP/PS1 小鼠术后的粪便微生物群落发生了改变。电针组的粪球菌和拟杆菌属较非电针组明显增加, 而放线菌、螺杆菌科和大肠杆菌/志贺氏菌表达则显著低于非电针组。此外, 我们发现厚壁菌与逃逸潜伏期之间存在显著负相关(皮尔逊相关系数 - 0.551, p < 0.01), 变形杆菌与逃逸潜伏期呈正相关(皮尔逊相关系数0.462, p < 0.05)。电镜显示非电针组APP/PS1小鼠血脑屏障 (BBB)明显 受损, 免疫荧光图像显示其海马神经胶质细胞被激活, 血清二胺氧化酶水平升高; 而电针治疗显著缓解了上述病理改变。综上所述, 电针通过上调有益的肠道微生物群、减轻血脑屏障和肠道屏障损伤来降低海马炎症反应, 从而改善APP/PS1 小鼠术后认知功能障碍。因此针灸有望为 POCD 提供一种新的防治方法。.