Li Suyan, Lv Jian, Li Jianguo, Zhao Zhaolong, Guo Hui, Zhang Yanni, Cheng Shichao, Sun Jianbin, Pan Hongming, Fan Shaopeng, Li Zhongxin
Second Department of Surgery, The Fourth Hospital of Hebei Medical University, 12 Jiankang Road, Shijiazhuang, Hebei 050011, PR China; Department of Emergency, Hebei General Hospital, 348 Heping Road, Shijiazhuang, Hebei 050011, PR China.
Second Department of Surgery, The Fourth Hospital of Hebei Medical University, 12 Jiankang Road, Shijiazhuang, Hebei 050011, PR China.
Neurosci Lett. 2018 Jan 1;662:98-104. doi: 10.1016/j.neulet.2017.10.008. Epub 2017 Oct 6.
The pathogenesis of sepsis associated encephalopathy (SAE) remains poorly understood. Vagus nerve plays an important role in gut-microbiota-brain axis. This study aimed to investigate whether vague nerve is a key mediator of the impact of intestinal microbiota on SAE.
Male rats were randomly divided into four groups (n=20): SHAM (SH) group, lipopolysaccharide (LPS) group, fecal microbiota transplantation (FMT) +LPS group, and vagotomy (VGX)+LPS+FMT group. The left cervical vagotomy was performed 30min before LPS administration in LPS+FMT+VGX group. LPS+ FMT and LPS+FMT+VGX groups received nasogastric infusion of feces from healthy donor three times a day. Fecal samples were collected every two days to monitor changes in microbiota composition by 16S rDNA analysis. Brain function was evaluated by behavioral tests and EEG. The levels of tumor necrosis factor alpha (TNF-α), interleukin (IL)-1β, IL-6, IL-10 in brain cortex were detected by ELISA. The expression of Iba-1 in brain cortex was assessed by immunohistochemistry and Western blot analysis.
Significant modification of microbiota composition, characterized by a profound increase of commensals in the Firmicutes phylum and depletion of opportunistic organisms in the Proteobacteria phylum, was observed in FMT groups compared to LPS group. Furthermore, we identified a reconstituted bacterial community enriched in Firmicutes and depleted of Proteobacteria. In both FMT groups the diversity of the fecal microbiota and the microbiota composition were similar to SH group. LPS mice treated with FMT demonstrated a better spatial memory and less EEG abnormalities, significantly attenuated levels of IL-1β, IL-6, TNF-α, and decreased number of Iba-1 positive microglia in the cortex, but these beneficial effects of FMT were reversed by VGX.
FMT can change intestinal microbiota in sepsis patients, and vagus nerve is a key mediator between intestinal microbiota and SAE. These findings suggest that FMT and vagus nerve are potential therapy targets for treating SAE.
脓毒症相关性脑病（SAE）的发病机制仍未完全明确。迷走神经在肠道微生物群-脑轴中发挥重要作用。本研究旨在探讨迷走神经是否是肠道微生物群对SAE影响的关键介质。
将雄性大鼠随机分为四组（n = 20）：假手术（SH）组、脂多糖（LPS）组、粪便微生物群移植（FMT）+LPS组和迷走神经切断术（VGX）+LPS+FMT组。在LPS+FMT+VGX组中，于给予LPS前30分钟进行左侧颈迷走神经切断术。LPS+FMT组和LPS+FMT+VGX组每天经鼻胃管输注来自健康供体的粪便三次。每两天收集粪便样本，通过16S rDNA分析监测微生物群组成的变化。通过行为测试和脑电图评估脑功能。采用酶联免疫吸附测定法检测大脑皮质中肿瘤坏死因子α（TNF-α）、白细胞介素（IL）-1β、IL-6、IL-10的水平。通过免疫组织化学和蛋白质印迹分析评估大脑皮质中Iba-1的表达。
与LPS组相比，FMT组的微生物群组成发生了显著改变，其特征为厚壁菌门共生菌显著增加，变形菌门机会性生物体减少。此外，我们鉴定出一个以厚壁菌门丰富、变形菌门减少为特征的重组细菌群落。在两个FMT组中，粪便微生物群的多样性和微生物群组成均与SH组相似。接受FMT治疗的LPS小鼠表现出更好的空间记忆能力和较少的脑电图异常，IL-1β、IL-6、TNF-α水平显著降低，皮质中Iba-1阳性小胶质细胞数量减少，但VGX逆转了FMT的这些有益作用。
FMT可改变脓毒症患者的肠道微生物群，迷走神经是肠道微生物群与SAE之间的关键介质。这些发现表明，FMT和迷走神经是治疗SAE的潜在治疗靶点。
