Orthopedics of Chinese Medicine, The Fourth Affiliated Hospital of Guangxi Medical University, Liuzhou, 545000, People's Republic of China.
Department of Acupuncture, Heilongjiang Academy of Chinese Medical Sciences, Harbin, 150036, People's Republic of China.
J Neuroinflammation. 2023 May 19;20(1):117. doi: 10.1186/s12974-023-02782-1.
New data are accumulating on gut microbial dysbiosis in Parkinson's disease (PD), while the specific mechanism remains uncharacterized. This study aims to investigate the potential role and pathophysiological mechanism of dysbiosis of gut microbiota in 6-hydroxydopamine (6-OHDA)-induced PD rat models.
The shotgun metagenome sequencing data of fecal samples from PD patients and healthy individuals were obtained from the Sequence Read Archive (SRA) database. The diversity, abundance, and functional composition of gut microbiota were further analyzed in these data. After the exploration of the functional pathway-related genes, KEGG and GEO databases were used to obtain PD-related microarray datasets for differential expression analysis. Finally, in vivo experiments were performed to confirm the roles of fecal microbiota transplantation (FMT) and upregulated NMNAT2 in neurobehavioral symptoms and oxidative stress response in 6-OHDA-lesioned rats.
Significant differences were found in the diversity, abundance, and functional composition of gut microbiota between PD patients and healthy individuals. Dysbiosis of gut microbiota could regulate NAD anabolic pathway to affect the occurrence and development of PD. As a NAD anabolic pathway-related gene, NMNAT2 was poorly expressed in the brain tissues of PD patients. More importantly, FMT or overexpression of NMNAT2 alleviated neurobehavioral deficits and reduced oxidative stress in 6-OHDA-lesioned rats.
Taken together, we demonstrated that dysbiosis of gut microbiota suppressed NMNAT2 expression, thus exacerbating neurobehavioral deficits and oxidative stress response in 6-OHDA-lesioned rats, which could be rescued by FMT or NMNAT2 restoration.
在帕金森病（PD）中，肠道微生物失调的新数据不断积累，但其具体机制尚不清楚。本研究旨在探讨 6-羟多巴胺（6-OHDA）诱导的 PD 大鼠模型中肠道微生物失调的潜在作用和病理生理机制。
从序列读取档案（SRA）数据库中获取 PD 患者和健康个体粪便样本的鸟枪法宏基因组测序数据。进一步分析这些数据中肠道微生物的多样性、丰度和功能组成。在探索与功能途径相关的基因后，使用 KEGG 和 GEO 数据库获取与 PD 相关的微阵列数据集进行差异表达分析。最后，进行体内实验以确认粪便微生物移植（FMT）和上调的 NMNAT2 在 6-OHDA 损伤大鼠神经行为症状和氧化应激反应中的作用。
PD 患者和健康个体之间的肠道微生物多样性、丰度和功能组成存在显著差异。肠道微生物失调可调节 NAD 合成途径，影响 PD 的发生和发展。作为 NAD 合成途径相关基因，NMNAT2 在 PD 患者的脑组织中表达水平较低。更重要的是，FMT 或过表达 NMNAT2 可缓解 6-OHDA 损伤大鼠的神经行为缺陷和减少氧化应激。
综上所述，我们证明了肠道微生物失调抑制 NMNAT2 的表达，从而加剧 6-OHDA 损伤大鼠的神经行为缺陷和氧化应激反应，而 FMT 或 NMNAT2 的恢复可对此进行挽救。
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