Department of Epidemiology, College of Public Health and Health Professions and College of Medicine, University of Florida, Gainesville, Florida 32611, United States.
Emerging Pathogens Institute, University of Florida, Gainesville, Florida 32611, United States.
ACS Chem Neurosci. 2020 Oct 21;11(20):3267-3276. doi: 10.1021/acschemneuro.0c00386. Epub 2020 Oct 2.
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 ( = 10) received adoptive cellular therapy (ACT) by injection, and control mice ( = 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 ( = 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.
外周免疫被认为在帕金森病（PD）中失调，可能为新的免疫治疗干预提供途径。肠道微生物群是调节免疫治疗反应的潜在因素。考虑到肠道-大脑轴在 PD 中可能具有复杂的作用，我们使用临床前模型来确定接受免疫治疗干预的小鼠与对照组相比肠道微生物群动态的影响。本研究共使用了 17 只 M83 杂合转基因小鼠。治疗组（n = 10）的小鼠通过注射接受过继细胞治疗（ACT），对照组（n = 7）的小鼠在 8 周龄时注射生理盐水。所有小鼠在 1 周后（9 周龄；基线）通过肌肉内注射接受外周α-突触核蛋白纤维以加速帕金森病症状。所有小鼠在注射后三个时间点（基线、6 周和 12 周）收集粪便样本。从每个粪便样本中提取 DNA，并使用 QIIME2 和 RStudio 对 16S rDNA 进行扩增、测序和分析。组间观察到细菌分类群相对丰度随时间的差异。在任何时间点，组间 alpha 多样性均无显著差异。样本之间系统发育距离的 UniFrac 测量值表明基线后组间存在明显聚类（p = 0.002）。这些差异表明肠道微生物组可能能够影响免疫治疗结果。总之，我们观察到与对照组相比，治疗组小鼠的肠道微生物组动态明显不同。这些结果表明肠道-大脑轴、PD 病理学和免疫治疗之间存在相关性。
