Table_2_Multi-Omics Integration in Mice With Parkinson’s Disease and the Intervention Effect of Cyanidin-3-O-Glucoside.DOCX

BackgroundParkinson’s disease (PD) is a multifactorial degenerative disease of the central nervous system, which affects mostly older adults. To date, research has focused on the progression of PD. Simultaneously, it was confirmed that the imbalances in gut microbiota are associated with the onset and progression of PD. Accurate diagnosis and precise treatment of PD are currently deficient due to the absence of effective biomarkers.MethodsIn this study, the pharmacodynamic study of cyanidin-3-O-glucoside in PD mice was used. It intends to use the “imbalance” and “balance” of intestinal microecology as the starting point to investigate the “gut-to-brain” hypothesis using metabolomic-combined 16S rRNA gene sequencing methods. Simultaneously, metabolomic analysis was implemented to acquire differential metabolites, and microbiome analysis was performed to analyze the composition and filter the remarkably altered gut microbiota at the phylum/genera level. Afterward, metabolic pathway and functional prediction analysis of the screened differential metabolites and gut microbiota were applied using the MetaboAnalyst database. In addition, Pearson’s correlation analysis was used for the differential metabolites and gut microbiota. We found that cyanidin-3-O-glucoside could protect 1-methyl-4-phenyl-1,2,3,6− tetrahydropy ridine (MPTP)-induced PD mice.ResultsMetabolomic analysis showed that MPTP-induced dysbiosis of the gut microbiota significantly altered sixty-seven metabolites. The present studies have also shown that MPTP-induced PD is related to lipid metabolism, amino acid metabolism, and so on. The 16S rRNA sequencing analysis indicated that 5 phyla and 22 genera were significantly altered. Furthermore, the differential gut microbiota was interrelated with amino acid metabolism, and so on. The metabolites and gut microbiota network diagram revealed significant correlations between 11 genera and 8 differential metabolites.ConclusionIn combination, this study offers potential molecular biomarkers that should be validated for future translation into clinical applications for more accurately diagnosing PD. Simultaneously, the results of this study lay a basis for further study of the association between host metabolisms, gut microbiota, and PD.

背景帕金森病（PD）是一种多因素导致的神经系统退行性疾病，主要影响老年人群。截至目前，研究主要集中于PD的进展。同时，研究表明肠道微生物群的失衡与PD的发生和发展密切相关。由于缺乏有效的生物标志物，目前对PD的准确诊断和精确治疗尚显不足。方法在本研究中，利用氰苷-3-O-葡萄糖苷在PD小鼠中的药效学进行了研究。本研究旨在以肠道微生态的“失衡”与“平衡”为切入点，运用代谢组学结合16S rRNA基因测序方法来探究“肠-脑”假说。同时，通过代谢组学分析获取差异代谢物，并运用微生物组学分析在门/属水平上对显著改变的肠道微生物群进行组成分析和筛选。随后，利用MetaboAnalyst数据库对筛选出的差异代谢物和肠道微生物群进行代谢途径和功能预测分析。此外，采用皮尔逊相关分析方法对差异代谢物和肠道微生物群进行了相关性分析。我们发现氰苷-3-O-葡萄糖苷可以保护1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）诱导的PD小鼠。结果代谢组学分析显示，MPTP诱导的肠道微生物群失调显著改变了六十七种代谢物。本研究还显示，MPTP诱导的PD与脂质代谢、氨基酸代谢等相关。16S rRNA测序分析表明，五个门和二十二个属发生了显著改变。此外，差异肠道微生物群与氨基酸代谢等相关。代谢物和肠道微生物群网络图揭示了十一属与八种差异代谢物之间的显著相关性。结论综合来看，本研究提供了潜在的分子生物标志物，这些标志物应经过验证，以便在未来转化为临床应用，从而更准确地诊断PD。同时，本研究为探讨宿主代谢、肠道微生物群与PD之间的关联奠定了基础。