Parkinson’s disease (PD) is the second most prevalent neurodegenerative disease. However, it is unclear whether microbiota and metabolites have demonstrated changes at early PD due to the difficulties in diagnosis and identification of early PD in clinical practice. In a previous study, we generated A53T transgenic monkeys with early Parkinson’s symptoms, including anxiety and cognitive impairment. Here we analyzed the gut microbiota by metagenomic sequencing and metabolites by targeted gas chromatography. The gut microbiota analysis showed that the A53T monkeys have higher degree of diversity in gut microbiota with significantly elevated Sybergistetes, Akkermansia, and Eggerthella lenta compared with control monkeys. Prevotella significantly decreased in A53T transgenic monkeys. Glyceric acid, L-Aspartic acid, and p-Hydroxyphenylacetic acid were significantly elevated, whereas Myristic acid and 3-Methylindole were significantly decreased in A53T monkeys. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) (KO0131) and the oxidative phosphorylation reaction (KO2147) were significantly increased in metabolic pathways of A53T monkeys. Our study suggested that the transgenic A53T and α-syn aggregation may affect the intestine microbiota and metabolites of rhesus monkeys, and the identified five compositional different metabolites that are mainly associated with mitochondrial dysfunction may be related to the pathogenesis of PD.

帕金森病 (PD) 是第二常见的神经退行性疾病。然而，由于临床实践中早期PD诊断和识别的困难，尚不清楚早期PD时微生物群和代谢物是否表现出变化。在之前的一项研究中，我们培育了具有早期帕金森病症状的 A53T 转基因猴，包括焦虑和认知障碍。在这里，我们通过宏基因组测序分析肠道微生物群，并通过靶向气相色谱分析代谢物。肠道微生物群分析表明，A53T 猴的肠道微生物群多样性较高，与对照猴相比， Sybergistetes、Akkermansia 和Eggerthella lenta显着升高。A53T 转基因猴中普氏菌显着减少。A53T 猴中甘油酸、L-天冬氨酸和对羟基苯乙酸显着升高，而肉豆蔻酸和 3-甲基吲哚显着降低。A53T 猴的代谢途径中甘油醛-3-磷酸脱氢酶（GAPDH）（KO0131）和氧化磷酸化反应（KO2147）显着增加。我们的研究表明，转基因A53T和α-syn聚集可能影响恒河猴的肠道微生物群和代谢产物，并且确定的五种主要与线粒体功能障碍相关的组成不同的代谢产物可能与PD的发病机制有关。