Neuroprotection of Fasting Mimicking Diet on MPTP-Induced Parkinson's Disease Mice via Gut Microbiota and Metabolites
Neuroprotection of Fasting Mimicking Diet on MPTP-Induced Parkinson's Disease Mice via Gut Microbiota and Metabolites
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模拟禁食饮食通过肠道微生物群和代谢物对 MPTP 诱导的帕金森病小鼠的神经保护作用
DOI：
10.1007/s13311-019-00719-2
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发表时间：
2019-07-01
影响因子：
5.7
通讯作者：
Shen, Yan-Qin
中科院分区：
文献类型：
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作者：
Zhou, Zhi-Lan;Jia, Xue-Bing;Shen, Yan-Qin
帕金森病（PD）与生活方式，特别是饮食习惯密切相关，作为疾病修饰剂已受到关注。在这里，我们报告了一个禁食模仿饮食（FMD），禁食3天，然后再喂4天，持续3个1周的周期，这加速了运动功能的保留，并减弱了1-甲基-4-苯基-1，2，3，6-四氢吡啶（MPTP）诱导的PD小鼠黑质多巴胺能神经元的损失。脑源性神经营养因子（BDNF）的水平，已知促进多巴胺能神经元的存活，在PD小鼠FMD后增加，这表明BDNF参与FMD介导的神经保护。此外，FMD减少了PD小鼠中神经胶质细胞的数量以及TNF-α和IL-1 β的释放，表明FMD还抑制了神经炎症。粪便微生物群的16 S和18 S rRNA测序表明，FMD处理调节了肠道微生物群组成的变化，包括PD小鼠中厚壁菌门、Tenericutes和后孔菌门的丰度较高，变形菌门的丰度较低。气相色谱-质谱和液相色谱-质谱分析表明，FMD对MPTP诱导的丙酸和异丁酸含量较低，而丁酸和戊酸等代谢产物含量较高。将粪便微生物群从接受FMD治疗的正常小鼠移植到经抗生素预处理的PD小鼠中，增加了受体PD小鼠中的多巴胺水平，表明肠道微生物群有助于FMD对PD的神经保护。这些研究结果表明，FMD可以通过促进有利的肠道微生物群组成和代谢产物而成为预防和治疗PD的新手段。
Parkinson's disease (PD) is strongly associated with life style, especially dietary habits, which have gained attention as disease modifiers. Here, we report a fasting mimicking diet (FMD), fasting 3 days followed by 4 days of refeeding for three 1-week cycles, which accelerated the retention of motor function and attenuated the loss of dopaminergic neurons in the substantia nigra in 1-methyl-4-phenyl-1,2,3,6-tetrathydropyridine (MPTP)-induced PD mice. Levels of brain-derived neurotrophic factor (BDNF), known to promote the survival of dopaminergic neurons, were increased in PD mice after FMD, suggesting an involvement of BDNF in FMD-mediated neuroprotection. Furthermore, FMD decreased the number of glial cells as well as the release of TNF-alpha and IL-1 beta in PD mice, showing that FMD also inhibited neuro-inflammation. 16S and 18S rRNA sequencing of fecal microbiota showed that FMD treatment modulated the shifts in gut microbiota composition, including higher abundance of Firmicutes, Tenericutes, and Opisthokonta and lower abundance of Proteobacteria at the phylum level in PD mice. Gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry revealed that FMD modulated the MPTP-induced lower propionic acid and isobutyric acid, and higher butyric acid and valeric acid and other metabolites. Transplantation of fecal microbiota, from normal mice with FMD treatment to antibiotic-pretreated PD mice increased dopamine levels in the recipient PD mice, suggesting that gut microbiota contributed to the neuroprotection of FMD for PD. These findings demonstrate that FMD can be a new means of preventing and treating PD through promoting a favorable gut microbiota composition and metabolites.