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

Abstract

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.