Gut Microbial Alteration in MPTP Mouse Model of Parkinson Disease is Administration Regimen Dependent

Parkinson Disease (PD) is one of the most common neurodegenerative disorders characterized by loss of dopaminergic neurons involved in motor functions. Growing evidence indicates that gut microbiota communicates with the brain known as the gut-brain axis (GBA). Mitochondrial toxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is commonly used in animal studies to investigate the GBA in PD. Various MPTP administration regimens are performed in PD mouse models involving one to multiple injections in 1 day or one injection per day for several days. The aim of this study is to investigate if the impact of MPTP on gut microbiota differs depending on the administration regimen. C57BL/6 mice were treated with acute or subchronic regimens of MPTP. Motor functions were assessed by open-field, catalepsy, and wire hanging tests. The cecum and the brain samples were obtained for microbiota and gene expression analyses, respectively. MPTP administration regimens differed in their ability to alter the gut microbiota. Firmicutes and Bacteroidota were both increased in subchronic mice while did not change and decreased, respectively, in acute mice. Verrucomicrobiota was elevated in acute MPTP mice but dropped in subchronic MPTP mice. Muribaculaceae was the predominant genus in all groups but acute mice. In acute mice, Akkermansia was increased and Colidextribacter was decreased; however, they showed an opposite trend in subchronic mice. These data suggest that MPTP mouse model cause a gut microbiota dysbiosis in an administration regimen dependent manner, and it is important to take consideration of mouse model to investigate the GBA in neurodegenerative diseases including PD. GRAPHICAL ABSTRACT: [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10571-023-01319-7.