Gut Microbiota Diversity Analysis And Biomarker Identification In Patients With Parkinson's Disease

Background: Parkinson's disease(PD) is one of the most common neurodegenerative diseases.Current studies suggest that Parkinson's disease may originate from the gut,and imbalance of gut microbiota may plays an important role in the occurrence and progression of Parkinson's disease.There are few studies on the alteration of gut microbiota in Parkinson's disease patients in China,and the subjects included are mainly patients and healthy people.The results may be affected by differences in dietary habits.The aim of this study was to analyze the characteristics of gut microbiota in Chinese patients with Parkinson's disease,to compare the differences of structural composition and functional pathways of gut microbiota between Parkinson's disease and healthy people.In additionally,we also attempted to explore the correlation between altered microbiota and clinical characteristics of disease,and further screen out gut microbiota that may be used as biomarkers for Parkinson's disease.Methods: 63 patients with Parkinson's disease and 137 healthy controls(63 spouses of the patients and 74 healthy people of matched age)were included in the study.Fecal samples were collected and microbial DNA was extracted.Illumina Hiseq2500 high-throughput sequencing platform was used for high-throughput sequencing of the V4 variable region of bacterial 16 S r RNA.The raw data was processed by QIIME2 software,and the gut microbiota was annotated with reference to the Greengenes database.Statistical methods were used to analyze the different relative abundance of gut microbiota between three groups,and PCo A and ANOSIM were used to examine the structural differences of gut microbiota.Biomarkers of gut microbiota were found by LEf Se analysis,and the predictive ability to diseases was evaluated by random forest model.Spearman correlation analysis was used to screen the microbiota associated with Parkinson's disease,and generalized linear model was used to analyze the correlation between the screened microbiota and the clinical characteristics of the disease.Based on the KOs number of KEGG database,the functional pathways affected by altered gut microbiota were analyzed.Results: We observed significant increases in microbiota diversity in PD patients,and structural composition of gut microbiota from PD patients was significantly changed compared with that of the spouse and healthy control group.The relative abundance of Firmicutes,Ruminococcaceae and Akkermansia in Parkinson's disease patients was significantly increased,while the relative abundance of Bacteroidetes,Prevotellaceae and Prevotella was significantly decreased,and the ratio of Firmicutes to Bacteroidetes was significantly increased in PD patients.Lef Se analysis found that Actinobacteria,Verrucomicrobiaceae,and Akkermansia were the most important biomarkers on the Phylum,Family,and Genus levels,respectively,which were able to distinguish PD patients from spouses and healthy controls.The random forest model indicated that 5 families and 7 genera of altered gut microbiota had good predictive value for diseases.Correlation analysis showed significant relationship between gut microbiota and clinical features of PD at family and genus levels.At the family level,Desulfovibrionaceae had a significant positive correlation with the duration of disease.Veillonellaceae had significant negative correlation with H-Y stage,while Desulfovibrionaceae and Methanobacteriaceae had significant positive correlation with H-Y stage.Moreover,Alcaligenaceae had positive correlation with both UPDRS total scores and UPDRS ? scores.Most genera were positively correlated with PD duration and H-Y stage.Sutterella was positively correlated with UPDRS total score and UPDRS III score,while Anaerostipes was only positively correlated with UPDRS III score.Among non-motor symptoms,Erysipelotrichaceae,Streptococcaceae and Streptococcus were positively correlated with constipation,Actinomyces was negatively correlated with dysosmia.We also found Alistipes was positively related to family history.However,we did not find any significant correlation between microorganisms and sleep disorder or pesticide expose.PICRUSt functional analyze found pathways associated with Transcription and Lipid Metabolismwere significant increased in patients,while pathways associated with Energy Metabolism and Carbohydrate Metabolism(TCA cycle)were significantly decrease.Conclusion: Our study further confirmed the significant changes in microbial diversity and abundance in Chinese PD patients,and these changes had a significant correlation with the clinical features of PD.Additionally,we also discovered specific gut microbes as potential biomarkers for PD in China.Targeting on gut microbiota may be one of the new therapeutic choices of PD.