Objective: To examine gut microbiota in the M83 mouse model of PD.

Background: Parkinson’s disease (PD) is a chronic neurodegenerative disease characterized by motor and non-motor symptoms resulting from death of dopaminergic neurons due to accumulation of misfolded alpha-synuclein (α-syn). α-syn aggregates are observed in the brain and in the periphery; enteric nervous system. We adoptively transferred pre-activated T cells from in vitro, or from immunized mice to M83 mice, which expresses the human form of the familial A53T mutant α-syn. We hypothesize that adoptive therapy will alter the composition of gut microbiota.

Method: 17 M83 mice were used in this study. Mice in the treatment arm (N=10) were injected with adoptive cellular therapy (ACT), control mice (N=7) were injected with saline all at 8 weeks of age. All mice received an intramuscular injection of alpha-synuclein fibrils in the gastrocnemius muscle one week later (9 weeks of age; baseline). Fecal pellets were collected from each mouse at three time points (baseline, 6 weeks and 12 weeks). Total bacterial DNA from each stool sample was extracted, the V1-V2 region of 16SrRNA was amplified, sequenced, and analyzed using QIIME2 and RStudio.

Results: Mice treated with ACT outsurvived controls and exhibited fewer motor deficiencies. Microbiota analyses revealed differences in relative abundance of certain phyla over time between the two groups. We observed statistically significant increases in relative abundance of Actinobacteria in the treatment group (p=0.021). Actinobacteria was significantly more abundant in the treatment group compared to controls at the timepoint following injection (p=0.022). We found no significant differences in alpha diversity (Shannon Diversity) between treatment and control groups at any timepoint. Alpha diversity measures for the treatment group demonstrated a decreasing trend over time absent in controls. Unweighted UniFrac measures of phylogenetic distance between samples demonstrated distinct clustering between all samples at baseline as well as between treatment and control mice at times 1 and 2 post-baseline (p=0.002).

Conclusion: Mice that received ACT demonstrated improved survival and behavioral measures as well as significant differences in the composition of the gut microbiome compared to controls. These results suggest an underlying relationship between the gut-brain-axis and PD pathology, with respect to ACT, which warrants further research.

« Back to MDS Virtual Congress 2020

MDS Abstracts - https://www.mdsabstracts.org/abstract/a-study-of-gut-microbiota-dynamics-in-parkinsonian-mice/