Peripheral immunity is thought to be dysregulated in Parkinson's disease (PD) and may provide an avenue for novel immunotherapeutic interventions. Gut microbiota is a potential factor for modulating immunotherapy response. Considering the possibly complex role of the gut-brain axis in PD, we used a preclinical model to determine the effects of gut microbiota dynamics in mice receiving an immunotherapeutic intervention compared to controls. A total of 17 M83 heterozygous transgenic mice were used in this study. Mice in the treatment arm (N = 10) received adoptive cellular therapy (ACT) by injection, and control mice (N = 7) were injected with saline at 8 weeks of age. All mice received peripheral α-syn fibrils to hasten parkinsonian symptoms via an intramuscular injection 1 week later (9 weeks of age; baseline). Fecal pellets were collected from all mice at three time points postinjection (baseline, 6 weeks, and 12 weeks). DNA from each stool sample was extracted, and 16S rDNA was amplified, sequenced, and analyzed using QIIME2 and RStudio. Differences in the relative abundance of bacterial taxa were observed over time between groups. No significant differences in alpha diversity were found between groups at any time point. UniFrac measures of phylogenetic distance between samples demonstrated distinct clustering between groups postbaseline (p = 0.002). These differences suggest that the gut microbiome may be capable of influencing immunotherapy outcomes. Conclusively, we observed distinctly different microbiota dynamics in treated mice compared to those in the control group. These results suggest a correlation between the gut-brain axis, PD pathology, and immunotherapy.
Keywords: Parkinson’s disease; adoptive cellular therapy; alpha-synuclein; gut microbiome; gut−brain axis; mouse model.