MPTP induced Parkinson's disease in mouse: potential association between neurotransmitter disturbance and gut microbiota dysbiosis

Recent studies have revealed significant roles of the neurotransmitters and gut microbiota along the gut-brain axis in Parkinson's disease (PD), however, the potential mechanisms remain poorly understood. In the current study, 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP) induced a characteristic PD neurobehavior changes accompanied by increased α-synuclein, apoptotic protein Bim, cleaved caspase-3 and decreased expression of tyrosine hydroxylase (TH). Meanwhile, the tryptophan (TRP) and tyrosine (TYR) neurotransmitter metabolites involving kynurenine (KYN), serotonin (5-HT) and dopamine (DA) pathways were significantly changed in serum. Furthermore, the step-limited enzymes which responsible for the key metabolic pathways of these neurotransmitters were obviously dysregulated. The 16S rRNA gene sequence results indicated that the abundance and diversity of the microbiota were obviously decreased in MPTP treated mice, the presence of Ruminococcus, Parabacteroides and Parasutterella families were obviously increased while Coriobacteriaceae, Flavonifractor, Lachnospiraceae, Lactobacillaceae and Rikenellaceae abundance was markedly decreased. The connectivity between the gut microbiota and neurotransmitter metabolism revealed that the gut microbiota dysbiosis was associated with the disturbance of the DA, KYN and 5-HT metabolic pathways. Therefore, our results provide the evidence that the gut-microbiota-brain axis disturbance may play an important role in PD development, and targeting this axis might provide a promising therapeutic strategy for PD. Key Words: gut-microbiota-brain axis; gut microbiota dysbiosis; neurotransmitter metabolism; Parkinson's disease.