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

2020 ◽  
Author(s):  
Fan Zhang ◽  
Qiang Zhao ◽  
Xing Fang ◽  
Meiling Xu ◽  
Jie Tang ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Gut Microbiota ◽  
Clinical Features ◽  
De Novo ◽  
Central China ◽  
Chinese Patients ◽  
Fecal Microbiome ◽  
Potential Biomarker ◽  
Functional Pathways

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.

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

2020 ◽  
Author(s):  
Fan Zhang ◽  
Qiang Zhao ◽  
Xing Fang ◽  
Meiling Xu ◽  
Jie Tang ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Gut Microbiota ◽  
Clinical Features ◽  
De Novo ◽  
Disease Status ◽  
Central China ◽  
Fecal Microbiome ◽  
Potential Biomarker ◽  
Functional Pathways

Abstract Background: Studies have shown that gut microbiota may be involved in the occurrence and progression of Parkinson's disease (PD). Nevertheless, the alterations in fecal microbiome in PD patients from Central China have not been previously investigated, and the way in which these microbes influence PD remain unclear.Methods: We performed metagenomic shotgun analyses to investigate the gut microbiota composition of 46 Central China PD patients and their healthy spouses. The relationships between microbiota and PD clinical features were analyzed, and functional pathways were compared for further understaning the contributions of gut microbiota in PD. We also explored potential biomarker for PD diagnosis.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 Subdoligranulum_unclassified and Prevotella_copri, 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, H-Y stage, UPDRS total score 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: This study revealed the differences of gut microbiota between PD patients and their healthy spouses. Altered microbiota had correlation with the clinical characteristics of the disease, and maybe used as potential biomarkers for disease status prediction. We also observed differenct functional pathways of gut microbiota in PD patients,which may help to reveal the mechanism of disease occurrence and progression.

Does Gut Microbiota Influence the Course of Parkinson’s Disease? A 3-Year Prospective Exploratory Study in de novo Patients

2020 ◽  
pp. 1-12
Author(s):  
Roberto Cilia ◽  
Marco Piatti ◽  
Emanuele Cereda ◽  
Carlotta Bolliri ◽  
Serena Caronni ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Gut Microbiota ◽  
Cognitive Functions ◽  
Exploratory Study ◽  
Dietary Habits ◽  
De Novo ◽  
Repeated Measurements ◽  
Lower Abundance

Background: Although abnormalities in gut microbiota are hypothesized to influence the pathogenesis and clinical phenotype of Parkinson’s disease (PD), prospective studies on de novo patients are lacking. Objective: To preliminarily investigate whether gut microbiota in early untreated PD may predict motor and non-motor features progression over a 3-year period. Methods: 16S ribosomal RNA gene amplicons were sequenced on fecal samples of 39 de novo PD patients. Multiple confounders were taken into account, including dietary habits. Motor and non-motor symptoms were assessed using validated scales at baseline and followed-up yearly for 3 years. At last follow-up, a detailed neuropsychological assessment was additionally performed. A general linear model for repeated measurements— adjusted by dopaminergic therapy at follow-up— was used to investigate the relationship between bacterial taxa abundance at baseline (stratified by the median of distribution at baseline) and outcome variables. Results: Twenty-five patients were included (11 refused, 2 lost at follow-up, 1 died). Lower abundance of Roseburia (Firmicutes phylum) at baseline was associated with worse evolution of motor, non-motor and cognitive functions at 3-year follow-up. Similarly, lower abundance of Ruminococcaceae and Actinobacteria at baseline was associated with faster worsening of global cognitive functions. At follow-up, frontal lobe functions were the features most robustly associated with baseline microbial abnormalities. Conclusion: In the present exploratory study on de novo PD, we found an association between abnormal distribution of specific bacterial taxa and the progression of motor and non-motor features over a 3-year period. This proof-of-principle study supports the design of a larger observational study aiming to determine whether these differences survive multiple-comparison correction and define microbiota-specific subgroups suitable for therapeutic targeting.

Structural changes of gut microbiota in Parkinson’s disease and its correlation with clinical features

2017 ◽  
Vol 60 (11) ◽  
pp. 1223-1233 ◽  
Author(s):  
Wei Li ◽  
Xiaoli Wu ◽  
Xu Hu ◽  
Tao Wang ◽  
Shan Liang ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Gut Microbiota ◽  
Clinical Features ◽  
Structural Changes

scholarly journals Serum miR-214 Serves as a Biomarker for Prodromal Parkinson’s Disease

2021 ◽  
Vol 13 ◽  
Author(s):  
Lanting Li ◽  
Jingru Ren ◽  
Chenxi Pan ◽  
Yuqian Li ◽  
Jianxia Xu ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Area Under Curve ◽  
Operating Characteristic ◽  
De Novo ◽  
Characteristic Curve ◽  
The Other ◽  
Circulating Micrornas ◽  
Potential Biomarker ◽  
Operating Characteristic Curve

Circulating microRNAs (miRNAs) have been proposed to be accessible biomarkers for Parkinson’s disease (PD). However, there is a lack of known miRNAs that can serve as biomarkers for prodromal PD (pPD). We previously identified that miR-31 and miR-214 were dysregulated in PD. The aim of this study was to explore the roles of miR-31 and miR-214 in pPD. We recruited 25 pPD patients, 20 patients with de novo PD (dnPD), 24 advanced PD (aPD) patients and 21 controls. Next, we investigated the expression of miR-31 and miR-214. Compared to controls, miR-214 was found to be significantly upregulated in pPD patients while miR-31 was significantly upregulated in aPD patients. In addition, the expression of miR-214 was lower in aPD patients compared to both dnPD or pPD patients, while the expression of miR-31 was higher in aPD patients compared to dnPD patients. In order to predict pPD via miRNA expression, the receiver operating characteristic curve was constructed and the area under curve (AUC) was calculated. For pPD prediction by miR-214, the AUC was 0.756. The optimal cut-off value of miR-214 was 0.1962, and the sensitivity and specificity were 72.0% and 76.2%, respectively. On the other hand, the AUC for aPD detection by miR-31 was 0.744. The optimal cut-off value for miR-31 was 0.0148, with a sensitivity of 87.5% and a specificity of 71.4%. In conclusion, miR-214 can distinguish pPD patients from controls and may be used as a potential biomarker for pPD diagnosis.

scholarly journals Altered gut microbiota in Parkinson's disease patients/healthy spouses and its association with clinical features

2020 ◽  
Vol 81 ◽  
pp. 84-88
Author(s):  
Fan Zhang ◽  
Liya Yue ◽  
Xing Fang ◽  
Gengchao Wang ◽  
Cuidan Li ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Gut Microbiota ◽  
Clinical Features

Functional neuroimaging and clinical features of drug naive patients with de novo Parkinson’s disease and probable RBD

2016 ◽  
Vol 29 ◽  
pp. 47-53 ◽  
Author(s):  
Dario Arnaldi ◽  
Silvia Morbelli ◽  
Andrea Brugnolo ◽  
Nicola Girtler ◽  
Agnese Picco ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Clinical Features ◽  
De Novo ◽  
Functional Neuroimaging ◽  
Drug Naïve

scholarly journals An MRI Atrophy Biomarker Predicts Global Prognosis in Early De Novo Parkinson’s Disease

2019 ◽  
Author(s):  
Yashar Zeighami ◽  
Seyed-Mohammad Fereshtehnejad ◽  
Mahsa Dadar ◽  
D. Louis Collins ◽  
Ronald B. Postuma ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
De Novo ◽  
The Other ◽  
Emission Computed Tomography ◽  
Composite Outcome ◽  
Mixed Effect ◽  
Annual Increase ◽  
Potential Biomarker ◽  
Updrs Part

ABSTRACTBackgroundCommonly used neuroimaging biomarkers in Parkinson’s disease (PD) are useful for diagnosis but poor at predicting outcomes. We explored whether an atrophy pattern from whole-brain structural MRI, measured in the drug-naïve early stage, could predict PD prognosis.Methods362 de novo PD patients with T1-weighted MRI (n=222 for the main analysis, 140 for the validation analysis) were recruited from the Parkinson’s Progression Markers Initiative (PPMI). We investigated a previously identified PD-specific network atrophy pattern as a potential biomarker of disease severity and prognosis. Progression trajectories of motor function (MDS-UPDRS-part III), cognition (Montreal Cognitive Assessment (MoCA)), and a global composite outcome measure were compared between atrophy tertiles using mixed effect models. The prognostic value of the MRI atrophy measure was compared with 123I ioflupane single photon emission computed tomography, the postural-instability-gait-disturbance score, and cerebrospinal fluid markers.FindingsAfter 4.5 years follow-up, PD-specific atrophy network score at baseline significantly predicted change in UPDRS-part III (r=-0.197, p=0.003), MoCA (r=0.253, p=0.0002) and global composite outcome (r=-0.249, p=0.0002). Compared with the 3rd tertile (i.e. least atrophy), the tertile with the highest baseline atrophy (i.e. the 1st tertile) had a 3-point annual faster progression in UPDRS-part III (p=0.012), faster worsening of posture-instability gait scores (+0.21 further annual increase, p<0.0001), faster decline in MoCA (−0.74 further annual decline in MoCA, p=0.0372) and a +0.38 (p=0.0029) faster annual increase in the global composite z-score. All findings were replicated in a validation analysis using 1.5T MRI. By comparison, the other biomarkers were limited in their ability to predict prognosis either in the main or validation analysis.InterpretationA PD-specific network atrophy pattern predicts progression of motor, cognitive, and global outcome in PD, and is a stronger predictor of prognosis than any of the other tested biomarkers. Therefore, it has considerable potential as a prognostic biomarker for clinical trials of early PD.

Association of the Non-Motor Burden with Patterns of Striatal Dopamine Loss in de novo Parkinson’s Disease

2020 ◽  
Vol 10 (4) ◽  
pp. 1541-1549
Author(s):  
Seok Jong Chung ◽  
Sangwon Lee ◽  
Han Soo Yoo ◽  
Yang Hyun Lee ◽  
Hye Sun Lee ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
De Novo ◽  
Early Stage ◽  
Striatal Dopamine ◽  
Motor Deficits ◽  
Dopamine Depletion ◽  
Severe Motor ◽  
Severe Group ◽  
Striatal Dopamine Depletion

Background: Striatal dopamine deficits play a key role in the pathogenesis of Parkinson’s disease (PD), and several non-motor symptoms (NMSs) have a dopaminergic component. Objective: To investigate the association between early NMS burden and the patterns of striatal dopamine depletion in patients with de novo PD. Methods: We consecutively recruited 255 patients with drug-naïve early-stage PD who underwent 18F-FP-CIT PET scans. The NMS burden of each patient was assessed using the NMS Questionnaire (NMSQuest), and patients were divided into the mild NMS burden (PDNMS-mild) (NMSQuest score <6; n = 91) and severe NMS burden groups (PDNMS-severe) (NMSQuest score >9; n = 90). We compared the striatal dopamine transporter (DAT) activity between the groups. Results: Patients in the PDNMS-severe group had more severe parkinsonian motor signs than those in the PDNMS-mild group, despite comparable DAT activity in the posterior putamen. DAT activity was more severely depleted in the PDNMS-severe group in the caudate and anterior putamen compared to that in the PDMNS-mild group. The inter-sub-regional ratio of the associative/limbic striatum to the sensorimotor striatum was lower in the PDNMS-severe group, although this value itself lacked fair accuracy for distinguishing between the patients with different NMS burdens. Conclusion: This study demonstrated that PD patients with severe NMS burden exhibited severe motor deficits and relatively diffuse dopamine depletion throughout the striatum. These findings suggest that the level of NMS burden could be associated with distinct patterns of striatal dopamine depletion, which could possibly indicate the overall pathological burden in PD.

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