The impact of Parkinson's disease-associated gut microbiota on the transcriptome revealed by fecal microbiota transplantation

Parkinson's disease (PD) is a common neurodegenerative disease in middle-aged and elderly people, and many studies have confirmed that the disorder of gut microbiota is involved in the pathophysiological process of PD. Fecal microbiota transplantation (FMT) has been considered as an important treatment for PD to reconstruct the gut microbiota. However, the mechanism of FMT treatment for PD is still lacking, which requires further exploration and can facilitate the application of FMT. In this study, to investigate the impact of PD-associated gut microbiota on host transcriptome, we established various PD models with FMT in the model organism Drosophila followed by integrative data analysis of microbiome and transcriptome. We found that there were significant differences in the gut microbiota of conventional Drosophila colonized from PD patients compared to those transplanted with fecal samples from healthy controls. We further constructed rotenone-induced PD models in Drosophila followed by FMT in different groups. Microbial analysis by 16S rDNA sequencing showed that gut microbiota from normal Drosophila could affect bacterial structure of PD. Moreover, transcriptome analysis suggested that gut microbiota influenced gene expression patterns of PD. Further experimental validations confirmed that lysosome and neuroactive ligand-receptor interaction are the most significantly influenced functional pathways by PD-derived gut microbiota. In summary, our study reveals the influence of PD-derived gut microbiota on host transcriptome and helps better understanding the interaction between gut microbiota and PD through gut-brain axis. The present work will facilitate the understanding of the mechanism underlying PD treatment with FMT in clinical practice.