Orally Administered Antibiotics Vancomycin and Ampicillin Cause Cognitive Impairment With Gut Dysbiosis in Mice With Transient Global Forebrain Ischemia.
Orally Administered Antibiotics Vancomycin and Ampicillin Cause Cognitive Impairment With Gut Dysbiosis in Mice With Transient Global Forebrain Ischemia.
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DOI：
10.3389/fmicb.2020.564271
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发表时间：
2020
影响因子：
5.2
通讯作者：
Kim DH
中科院分区：
文献类型：
--
作者：
Lee KE;Kim JK;Kim DH
肠道微生物区系与神经精神疾病的发生密切相关。抗生素经常被用来预防脑缺血患者的病原体感染。为了了解预防性抗生素治疗对脑缺血患者的影响，我们观察了口服万古霉素和氨苄西林对短暂性全脑缺血(TISC)小鼠认知功能和肠道微生物区系组成的影响。TISC手术和口服万古霉素分别造成轻、中度认知功能障碍。然而，Tisc小鼠暴露于万古霉素或氨苄西林后，在Y迷宫、新物体识别和Banes迷宫任务中的认知功能严重受损。此外，它们还诱导了海马区NF-κB的激活以及小胶质细胞(NF-κB+/IBA1+和LPS+/IBA1+细胞)和凋亡细胞(caspase3+/neun+)的激活，而脑源性神经营养因子+/neun+细胞的数量减少。这些治疗还会导致结肠炎和肠道生物失调。他们增加了变形杆菌的数量，包括乡方肠杆菌。口服给予万古霉素的小鼠粪便移植加或不加Tisc和口服香方肠杆菌也显著加重了Tisc移植小鼠的认知功能障碍和结肠炎。这些发现表明，口服抗生素可以恶化脑缺血患者的认知障碍和肠道生物失调。
Gut microbiota is closely associated with the occurrence of neuropsychiatric disorders. Antibiotics are frequently used to prevent pathogen infection in patients with brain ischemia. To understand the impact of prophylactic antibiotic treatment for patients with brain ischemia, we examined the effects of orally administered vancomycin and ampicillin on cognitive function and gut microbiota composition in mice with transient global forebrain ischemia (tIsc). tIsc operation and orally gavaged vancomycin mildly and moderately caused cognitive impairment, respectively. However, the exposure of mice with tIsc to vancomycin or ampicillin severely impaired cognitive function in the Y-maze, novel object recognition, and Banes maze tasks. Furthermore, their treatments induced NF-κB activation as well as active microglia (NF-κB+/Iba1+ and LPS+/Iba1+ cells) and apoptotic (caspase 3+/NeuN+) cell population in the hippocampus, whereas the brain-derived neurotrophic factor (BDNF)+/NeuN+ cell populations decreased. These treatments also caused colitis and gut dysbiosis. They increased the population of Proteobacteria including Enterobacter xiangfangenesis. Orally delivered fecal transplantation of vancomycin-treated mice with or without tIsc and oral gavage of Enterobacter xiangfangenesis also significantly deteriorated the cognitive impairment and colitis in transplanted mice with tIsc. These findings suggest that oral administration of antibiotics can deteriorate cognitive impairment with gut dysbiosis in patients with brain ischemia.
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影响因子：
4.6
作者：
Jang HM;Lee KE;Lee HJ;Kim DH
通讯作者：
Kim DH
影响因子：
82.9
作者：
Benakis C;Brea D;Caballero S;Faraco G;Moore J;Murphy M;Sita G;Racchumi G;Ling L;Pamer EG;Iadecola C;Anrather J
通讯作者：
Anrather J
长期接触亚治疗抗生素会加重小鼠的缺血性中风结果。
影响因子：
11.1
作者：
Dong XH;Peng C;Zhang YY;Tao YL;Tao X;Zhang C;Chen AF;Xie HH
通讯作者：
Xie HH
影响因子：
3.7
作者：
Kim KA;Gu W;Lee IA;Joh EH;Kim DH
通讯作者：
Kim DH
DOI：
10.1016/j.pnpbp.2016.07.003
发表时间：
2017-10-03
影响因子：
5.6
作者：
Anttila, Jenni E.;Whitaker, Keith W.;Wires, Emily S.;Harvey, Brandon K.;Airavaara, Mikko
通讯作者：
Airavaara, Mikko