Objective Evidence indicate that the gut microbiota of Parkinson’ s disease patients is imbalanced, but whether the Prnp-SNCA-A53T Parkinson’ s disease transgenic mouse model also has gut microbiota imbalances is unknown. This study aimed to analyze the ecological characteristics of the gut microbiota of this mouse model. Methods Illumina high-throughput sequencing technology was performed to sequence and analyze the biological information of the 16S rRNA gene V3 – V4 region of the fecal microbiota in seven female transgenic mice and 13 wild-type mice of the same sex and age. PICRUST (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States) was used to predict the differential function pathways. Results Compared with the wild-type group, the gut microbial alpha diversity of mice in the A53T group had a tendency to increase, and there were also significant differences in microbial composition and species. At the phylum level, the Actinobacteria were increased (P= 0. 0094), and the Bacteroidetes were decreased (P= 0. 0498). At the class level, the Coriobacteriia were increased (P< 0. 0001), and the Bacteroidia were decreased (P= 0. 0398). At the order level, the Coriobacteriales were increased (P<0. 0001), while the Bacteroidales (P= 0. 0398) and the Rhodobacterales were decreased ( P= 0. 0185). At the family level, the Coriobacteriaceae were increased ( P< 0. 0001), while the Bacteroidaceae (P= 0. 0277) and the Rhodobacteraceae were decreased (P= 0. 0185). At the genus level, the Eggerthella were increased ( P= 0. 0002), while the Bacteroides ( P= 0. 0277) and the Rhodobacter were decreased (P= 0. 0249). In addition, there were significant differences between the A53T group and the wild-type group in nine functional pathways, including G protein-coupled receptor, steroid hormone biosynthesis, penicillin and cephalosporin biosynthesis, ubiquinone and other terpenoid-quinone biosynthesis, toluene degradation, glycan biosynthesis and metabolism, electron transfer carriers, meiosis – yeast, and African trypanosomiasis. Conclusions This study indicated that there are imbalances in the gut microbiota of transgenic mice, as well as differences in metabolic pathways between the transgenic mice and the wild-type mice.