Gut microbiota relieves inflammation in the substantia nigra of chronic Parkinson's disease by protecting the function of dopamine neurons

肠道菌群通过保护多巴胺神经元的功能减轻慢性帕金森病黑质炎症

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作者:Tian Zhang, Tan Wang, Xinxu Chen, Zhenqiang Zhao, Zhibin Chen

Abstract

The composition of the intestinal flora of patients with Parkinson's disease (PD) can change. However, whether reshaping the gut microbial composition can treat PD remains to be seen. The present study evaluated the effect of intestinal flora in the treatment of PD in a C57BL/6 mouse PD model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Chronic, low-dose, MPTP-treated mice exhibited upregulated gene expression levels of TNF-α and IL-1β in the substantia nigra (SN) of the mice, and induced intestinal microbial disorders. This indicated that the chronic low-dose MPTP model could be used to evaluate the progress of early intestinal pathology and intestinal flora imbalance in PD. After transplantation of faecal bacteria to MPTP-induced PD mice, the level of inflammation in the SN of the mice was reduced, and motor dysfunction was alleviated. Notably, faecal microbiota transplantation (FMT) upregulated the abundance of Blautia but downregulated Anaerostipes, Bifidobacterium, ASF356 and Ruminococcus in the gut of PD mice. In addition, FMT reduced the activation of microglia and astrocytes in the SN and reduced the expression levels of GSK3β, IL-1β, inducible nitric oxide synthase and phosphorylated PTEN in the SN. Overall, the present study demonstrated that gut microbial dysfunction is associated with the pathogenesis of PD, and that FMT can protect PD mice by inhibiting neuroinflammation.

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