肠道微生物群通过保护多巴胺能神经元的功能来缓解慢性帕金森病黑质中的炎症。
Gut microbiota relieves inflammation in the substantia nigra of chronic Parkinson's disease by protecting the function of dopamine neurons.
作者信息
Zhang Tian, Wang Tan, Chen Xinxu, Zhao Zhenqiang, Chen Zhibin
机构信息
Department of Clinical Medicine, Nanjing Medical University, Nanjing, Jiangsu 211166, P.R. China.
Department of Neurology, The First Affiliated Hospital of Hainan Medical University, Haikou, Hainan 570102, P.R. China.
出版信息
Exp Ther Med. 2022 Jan;23(1):52. doi: 10.3892/etm.2021.10974. Epub 2021 Nov 16.
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 but downregulated , , and 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.
帕金森病(PD)患者的肠道菌群组成会发生变化。然而,重塑肠道微生物组成是否能治疗PD仍有待观察。本研究在1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)诱导的C57BL/6小鼠PD模型中评估了肠道菌群在PD治疗中的作用。慢性、低剂量MPTP处理的小鼠黑质(SN)中TNF-α和IL-1β的基因表达水平上调,并导致肠道微生物紊乱。这表明慢性低剂量MPTP模型可用于评估PD早期肠道病理学进展和肠道菌群失衡。将粪便细菌移植到MPTP诱导的PD小鼠后,小鼠SN中的炎症水平降低,运动功能障碍得到缓解。值得注意的是,粪便微生物群移植(FMT)上调了PD小鼠肠道中 的丰度,但下调了 、 、 和 的丰度。此外,FMT降低了SN中微胶质细胞和星形胶质细胞的激活,并降低了SN中GSK3β、IL-1β、诱导型一氧化氮合酶和磷酸化PTEN的表达水平。总体而言,本研究表明肠道微生物功能障碍与PD的发病机制有关,并且FMT可通过抑制神经炎症来保护PD小鼠。
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