A growing body of evidence implies that gut microbiota was involved in pathogenesis of Parkinson’s disease (PD), but the mechanism is still unclear. The aim of this study is to investigate the effects of antibiotics pretreatment on the 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP)-induced PD mice. In this study, vancomycin pretreatment was given by gavage once daily with either vancomycin or distilled water for 14 days to mice, then mice were administered with MPTP (20 mg/kg, i.p) for four times in one day to establish an acute PD model. Results show that vancomycin pretreatment significantly improved motor dysfunction of mice in pole and traction tests. Although vancomycin pretreatment had no effect on dopamine (DA) or the process of DA synthesis, it inhibited the metabolism of DA by suppressing the expression of striatal monoamine oxidase B (MAO-B). Furthermore, vancomycin pretreatment reduced the number of astrocytes and microglial cells in the substantia nigra pars compacta (SNpc) to alleviate neuroinflammation, decreased the expression of TLR4/MyD88/NF-κB/TNF-α signaling pathway in both brain and gut. Meanwhile, vancomycin pretreatment changed gut microbiome composition and the levels of fecal short chain fatty acids (SCFAs). The abundance of Akkermansia and Blautia increased significantly after vancomycin pretreatment, which might be related to inflammation and inhibition of TLR4 signaling pathway. In summary, these results demonstrate that the variation of gut microbiota and its metabolites induced by vancomycin pretreatment might decrease dopamine metabolic rate and relieve inflammation in both gut and brain via the microbiota-gut-brain axis in MPTP-induced PD mice.

Graphical Abstract

The neuroprotection of vancomycin pretreatment on MPTP-induced Parkinson's disease mice

The alterations of gut microbiota and SCFAs induced by vancomycin pretreatment might not only improve motor dysfunction, but also decrease dopamine metabolism and relieve inflammation in both brain and gut via TLR4/MyD88/NF-κB/TNF-α pathway in MPTP-induced PD mice.

中文翻译：

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万古霉素预处理 MPTP 诱导的帕金森病小鼠通过抑制大脑和肠道炎症发挥神经保护作用

越来越多的证据表明肠道微生物群参与帕金森病（PD）的发病机制，但其机制仍不清楚。本研究的目的是探讨抗生素预处理对1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)诱导的PD小鼠的影响。本研究先用万古霉素或蒸馏水对小鼠进行万古霉素预处理，每日一次灌胃，连续14天，然后给予小鼠MPTP（20mg/kg，ip），每日4次，建立急性PD模型。 。结果表明，万古霉素预处理显着改善了小鼠在杆和牵引测试中的运动功能障碍。尽管万古霉素预处理对多巴胺（DA）或DA合成过程没有影响，但它通过抑制纹状体单胺氧化酶B（MAO-B）的表达来抑制DA的代谢。此外，万古霉素预处理减少黑质致密部（SNpc）星形胶质细胞和小胶质细胞的数量以减轻神经炎症，降低大脑和肠道中TLR4/MyD88/NF-κB/TNF-α信号通路的表达。同时，万古霉素预处理改变了肠道微生物组组成和粪便短链脂肪酸（SCFA）水平。万古霉素预处理后Akkermansia和Blautia丰度显着增加，可能与炎症反应和抑制TLR4信号通路有关。总之，这些结果表明，万古霉素预处理诱导的肠道微生物群及其代谢物的变化可能会降低多巴胺代谢率，并通过微生物群-肠-脑轴减轻 MPTP 诱导的 PD 小鼠肠道和大脑的炎症。

图形概要

万古霉素预处理对MPTP致帕金森病小鼠的神经保护作用

万古霉素预处理引起的肠道菌群和 SCFA 的改变不仅可以改善 MPTP 诱导的 PD 小鼠的运动功能障碍，还可以通过 TLR4/MyD88/NF-κB/TNF-α 通路降低多巴胺代谢并减轻大脑和肠道炎症。