Metagenomic analysis of gut microbiota in Parkinson's disease patients from Central China

Abstract
Background: Parkinson's disease (PD) is one of the most common neurodegenerative diseases, pathologic and epidemiologic studies suggest that gut microbiota may play important roles in the occurrence and progression of Parkinson's disease. However, the alterations in fecal microbiome in PD patients from Central China has not been investigated. Therefore, in this case-control study, we characterised the gut microbial community of 46 PD patients and compared it to those of healthy spouses by using metagenomic shotgun sequencing. Correlation between altered microbiota and clinical features were examined, functional pathways of gut microbiota were estimated, and potential biomarker were explored for further understaning of gut microbiota in PD. Results: Microbial communities in the feces of PD patients were notably different from those of healthy spouses at species level. Gut microbiota of patients was characterized by depletion of Prevotella_copri and Bacteroides_fragilis, while the Bacteroides_stercoris and Escherichia_coli were markedly elevated. Correlation analysis found that most identified species were negatively correlated with disease clinical features. In particular, Prevotella_copri was negatively correlated with age and UPDRS Ⅲ score. Random forest model indicated that 6 species including Prevotella_copri had good predictive value for disease. Functional analyses of the metagenomes revealed differences in microbiota metabolism. Pathways associated with superpathway of thiamin diphosphate biosynthesis, 4-aminobutanoate degradation, glucose-1-phosphate degradation and methylphosphonate degradation were significant increase in patients, while pathways associated with aromatic amino acid biosynthesis, chorismate biosynthesis, thiamin formation and pyrimidine deoxyribonucleosides salvage were significantly decrease. Functional pathways of Prevotella_copri were mainly concentrated in UMP biosynthesis, S-adenosyl-L-methionine cycle and guanosine ribonucleotides de novo biosynthesis. Conclusion: Our findings confirmed changes of gut microbiota in Chinese patients with PD. Altered microbiota had correlation with the clinical characteristics of disease, which may used as potential biomarkers. Different functional pathways of gut microbiota in PD patients will help to improve our understanding of the mechanism in disease, and targeting on gut microbiota may be one of the new therapeutic choices of PD in the future.