Persistence of Gut Microbiota Dysbiosis and Chronic Systemic Inflammation After Cerebral Infarction in Cynomolgus Monkeys
Persistence of Gut Microbiota Dysbiosis and Chronic Systemic Inflammation After Cerebral Infarction in Cynomolgus Monkeys
复制标题
食蟹猴脑梗死后肠道菌群失调和慢性全身炎症的持续存在
DOI：
10.3389/fneur.2019.00661
复制
发表时间：
2019-06-28
影响因子：
3.4
通讯作者：
Zeng, Jinsheng
中科院分区：
文献类型：
--
作者：
Chen, Yonghong;Liang, Jiahui;Zeng, Jinsheng
背景：脑卒中后肠道和大脑之间通过免疫介导途径的双向相互作用已被研究。然而，脑缺血后肠道微生物群和全身免疫稳态的长期影响仍不清楚。我们研究了食蟹猴脑梗死后肠道微生物群和全身炎症细胞因子的长期变化。研究方法：12只猴子成功进行了左侧大脑中动脉远端M1段闭塞（MCAO），并随机平均分配到MCAO-1.5 m、MCAO-6 m和MCAO-12 m组，分别在脑梗死诱导后1.5、6和12个月处死。四只接受假手术的猴子在12个月后被处死。分别通过16 S rDNA测序和气相色谱质谱分析肠道菌群和短链脂肪酸（SCFAs）。对横结肠进行组织学检查。采用免疫分析试剂盒检测血浆D-乳酸、连蛋白、脂多糖（LPS）、肿瘤坏死因子-α（TNF-α）、干扰素-γ（IFN-γ）和白细胞介素（IL-6）。结果如下：脑梗死后拟杆菌门和普雷沃菌属的水平显著升高，而厚壁菌门以及粪杆菌属、颤螺旋菌属和乳杆菌属的水平降低。肠源性SCFAs在脑梗死后6个月和12个月显著降低（P < 0.05）。观察肠黏膜损伤情况，采用Chiu's评分法进行评价。脑梗死后血浆D-乳酸、zonulin、LPS、TNF-α、IFN-γ、IL-6水平明显升高（P < 0.05）。脑梗死后血浆LPS、TNF-α、IFN-γ和IL-6水平升高与拟杆菌门过度生长相一致（P < 0.001）。结论：脑梗死在食蟹猴中诱导持续的宿主肠道微生物群失调、肠粘膜损伤和慢性全身性炎症。
Background: The bidirectional interaction between the gut and brain after stroke through the immune-mediated pathway has been studied. However, the long-term effects of gut microbiota and systemic immune homeostasis after cerebral ischemia remain unclear. We examined long-term changes in the gut microbiota and systemic inflammatory cytokines after cerebral infarction in cynomolgus monkeys. Methods: Twelve monkeys underwent successful distal M1 segment of the left middle cerebral artery occlusion (MCAO) and were randomly and equally assigned to the MCAO-1.5 m, MCAO-6 m, and MCAO-12 m groups, which were sacrificed 1.5, 6, and 12 months after cerebral infarction induction, respectively. Four monkeys that underwent a sham operation were sacrificed 12 months later. The gut microbiota and short-chain fatty acids (SCFAs) were analyzed by 16S rDNA sequencing and gas chromatography mass spectrometry, respectively. Histological examinations of the transverse colon were performed. Plasma D-lactate, zonulin, lipopolysaccharide (LPS), tumor necrosis factor (TNF-α), interferon (IFN)-γ, and interleukin (IL)-6 were detected by immunoassay kits. Results: The levels of the Bacteroidetes phylum and Prevotella genus were significantly increased, while the Firmicutes phylum as well as the Faecalibacterium, Oscillospira, and Lactobacillus genera were decreased after cerebral infarction. Gut-originating SCFAs were significantly decreased 6 and 12 months after cerebral infarction (P < 0.05). We observed intestinal mucosal damage, evaluated by Chiu's score. Plasma D-lactate, zonulin, LPS, TNF-α, IFN-γ, and IL-6 were significantly increased after cerebral infarction (P < 0.05). Additionally, the increases in plasma LPS, TNF-α, IFN-γ, and IL-6 after cerebral infarction coincided with overgrowth of the Bacteroidetes phylum (P < 0.001). Conclusion: Cerebral infarction induces persistent host gut microbiota dysbiosis, intestinal mucosal damage, and chronic systemic inflammation in cynomolgus monkeys.