Gut microbiota and metabolites of α-synuclein transgenic monkey models with early stage of Parkinson'sdisease

Background: Parkinson's disease（PD）is the second most prevalent neurodegenerative disease. Gut microbes are susceptible to various external factors (such as living environment, diet, antibiotic use), our research avoids these interferences very well. Gut microbiota affect the physiological processes of the host by regulating metabolites. However, it is unclear whether microbiota and metabolites have demonstrated changes at early stages of PD due to the difficulty to diagnose and identify early stage PD in clinical practice.Methods: In a previous study, we constructed A53T transgenic monkeys with early Parkinson's symptoms. Here we analyzed the gut microbiota by metagenomic sequencing and metabolites by untargeted chromatography, which represent the first effort to identify the association between intestinal microbiota, metabolites and early stage of PD.Results: Compared with control monkeys, the gut microbiota of A53T monkeys is more diverse. Sybergistetes and Eggerthella lenta were significantly elevated in A53T monkeys. In monkeys with early Parkinson's symptoms, Glyceric acid, L-Aspartic acid and p-Hydroxyphenylacetic acid were significantly elevated, but Myristic acid and 3-Methylindole was significantly decreased. ABC transporters are associated with two decreased metabolites. Metabolic pathways are associated with three elevated metabolites. We found KO0131 and KO2147 from metabolic pathways are related to Glycolysis.Conclusion: We identified differential gut microbiota coincides with the microbiota of the currently reported PD patients to some extent. We found these differential metabolites and KOs suggest that A53T monkeys may have Glycolysis problem, and Glycolysis problem may be associated with mitochondrial dysfunction. Our results may be a sign of early Parkinson's screening and diagnosis.