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Neurotherapeutics

, Volume 16, Issue 3, pp 741–760 | Cite as

Neuroprotection of Fasting Mimicking Diet on MPTP-Induced Parkinson’s Disease Mice via Gut Microbiota and Metabolites

  • Zhi-Lan Zhou
  • Xue-Bing Jia
  • Meng-Fei Sun
  • Ying-Li Zhu
  • Chen-Meng Qiao
  • Bo-Ping Zhang
  • Li-Ping Zhao
  • Qin Yang
  • Chun Cui
  • Xue Chen
  • Yan-Qin ShenEmail author
Original Article

Abstract

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-α and IL-1β 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.

Key Words

Parkinson’s disease fasting mimicking diet gut microbiota metabolites neuro-inflammation BDNF 

Notes

Acknowledgments

This study was supported by National Natural Science Foundation of China (81771384, 81801276), Postgraduate Research & Practice Innovation (KYCX18_1870), Public Health Research Center at Jiangnan University (JUPH201801), and national first-class discipline program of Food Science and Technology (JUFSTR20180101). We sincerely thank Dr. Stanley Li Lin’s careful revision on the manuscript.

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Supplementary material

13311_2019_719_Fig10_ESM.png (581 kb)
Supplementary Fig. 1

Changes of relative abundance of gut microbiota. (a) Relative abundance of gut microbiota changed significantly at the phylum level, based on 16S rRNA sequencing. (b) Relative abundance of gut microbiota changed significantly at the class level, based on 16S rRNA sequencing. (c) Relative abundance of gut microbiota changed significantly at the order level, based on 16S rRNA sequencing. (d) Relative abundance of gut microbiota changed significantly at the family level, based on 16S rRNA sequencing. Statistical comparison by one-way ANOVA with post hoc comparisons of LSD; data represent the means ± SEM; *p < 0.05, **p < 0.01, ***p < 0.001; n = 10 mice per group. (PNG 581 kb)

13311_2019_719_MOESM1_ESM.tif (3.6 mb)
High resolution image (TIF 3650 kb)
13311_2019_719_Fig11_ESM.png (150 kb)
Supplementary Fig. 2

Principal coordinates analysis (PCoA). (a) Principal coordinate analysis based on the Bray-Curtis similarity index of 16S rRNA sequencing. (b) Principal coordinate analysis based on the Bray-Curtis similarity index of 18S rRNA sequencing. (PNG 150 kb)

13311_2019_719_MOESM2_ESM.tif (1.1 mb)
High resolution image (TIF 1091 kb)
13311_2019_719_MOESM3_ESM.pdf (486 kb)
ESM 1 (PDF 486 kb)

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Copyright information

© The American Society for Experimental NeuroTherapeutics, Inc. 2019

Authors and Affiliations

  1. 1.Public Health Research Center at Jiangnan University, Wuxi Medical SchoolJiangnan UniversityWuxiChina

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