Regulation of neurotoxicity in the striatum and colon of MPTP-induced Parkinson's disease mice by gut microbiome.

Increasing evidence suggests the role of gut-microbiota-brain axis in the pathogenesis of Parkinson's disease (PD). The objective of this study was to examine whether repeated administration of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) can influence the neurotoxicity in the striatum and colon, and the composition of gut microbiota and short-chain fatty acids (SCFAs) in feces of adult mice. MPTP caused the reduction of dopamine transporter (DAT) and tyrosine hydroxylase (TH) in the striatum, and increases in phosphorylated α-synuclein (p-α-Syn) in the striatum and colon. There was a negative correlation between the expression of TH in the striatum and the expression of p-α-Syn in the colon, suggesting a role of gut-brain communication. MPTP caused abnormalities in the α- and β-diversity of gut microbiota in the mice. Furthermore, the relative abundance of the genus Faecalicatena in the MPTP-treated group was significantly lower than that of control group. Interestingly, there was a positive correlation between the genus Faecalicatena and the expression of TH in the striatum. Moreover, MPTP did not alter the levels of SCFAs in feces samples. However, there was a positive correlation between the relative abundance of the genus Faecalicatena and propionic acid. The data suggest that MPTP-induced increases in colonic p-α-Syn expression might be associated with dopaminergic neurotoxicity in the striatum via gut-microbiota-brain axis.