The oral microbiome of early stage Parkinson's disease and its relationship with functional measures of motor and non-motor function
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Study information
-
Quality control
- Retracted paper
- Contamination issues suspected
- Batch effect issues suspected
- Uncontrolled confounding suspected
- Results are suspect (various reasons)
- Tags applied
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
URI
Authors
Mihaila D, Donegan J, Barns S, LaRocca D, Du Q, Zheng D, Vidal M, Neville C, Uhlig R, Middleton FA
Journal
PloS one
Year
2019
Changes in the function and microbiome of the upper and lower gastrointestinal tract have been documented in Parkinson's disease (PD), although most studies have examined merely fecal microbiome profiles and patients with advanced disease states. In the present study we sought to identify sensitive and specific biomarkers of changes in the oral microbiome of early stage PD through shotgun metatranscriptomic profiling. We recruited 48 PD subjects and 36 age- and gender-matched healthy controls. Subjects completed detailed assessments of motor, cognitive, balance, autonomic and chemosensory (smell and taste) functions to determine their disease stage. We also obtained a saliva sample for profiling of microbial RNA and host mRNA using next generation sequencing. We found no differences in overall alpha and beta diversity between subject groups. However, changes in specific microbial taxa were observed, including primarily bacteria, but also yeast and phage. Nearly half of our findings were consistent with prior studies in the field obtained through profiling of fecal samples, with others representing highly novel candidates for detection of early stage PD. Testing of the diagnostic utility of the microbiome data revealed potentially robust performance with as few as 11 taxonomic features achieving a cross-validated area under the ROC curve of 0.90 and overall accuracy of 84.5%. Bioinformatic analysis of 167 different metabolic pathways supported shifts in a small set of distinct pathways involved in amino acid and energy metabolism among the organisms comprising the oral microbiome. In parallel with the microbial analysis, we also examined the evidence for changes in human salivary mRNAs in the same subjects. This revealed significant changes in a set of 9 host mRNAs, several of which mapped to various brain functions and showed correlations with some of the significantly changed microbial taxa. Unexpectedly, we also observed robust correlations between many of the microbiota and functional measures, including those reflecting cognition, balance, and disease duration. These results suggest that the oral microbiome may represent a highly-accessible and informative microenvironment that offers new insights in the pathophysiology of early stage PD.
Experiment 1
Reviewed Marked as Reviewed by Claregrieve1 on 2022/12/19
Curated date: 2021/11/14
Curator: Fcuevas3
Revision editor(s): WikiWorks, LGeistlinger, Claregrieve1, Fcuevas3, Peace Sandy
Subjects
- Location of subjects
- United States of America
- Host species Species from which microbiome was sampled. Contact us to have more species added.
- Homo sapiens
- Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
- Saliva Sailva normalis,Saliva atomaris,Saliva molecularis,Salivary gland secretion,Saliva,saliva
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Parkinson's disease IDIOPATHIC PARKINSON DIS,Idiopathic Parkinson Disease,Idiopathic Parkinson's Disease,IDIOPATHIC PARKINSONS DIS,Idiopathic PD,LEWY BODY PARKINSON DIS,Lewy Body Parkinson Disease,Lewy Body Parkinson's Disease,Paralysis agitans,paralysis agitans,PARKINSON DIS,PARKINSON DIS IDIOPATHIC,Parkinson disease,Parkinson Disease, Idiopathic,Parkinson syndrome,Parkinson's,Parkinson's disease,Parkinson's disease (disorder),Parkinson's disease NOS,Parkinson's disease NOS (disorder),Parkinson's Disease, Idiopathic,Parkinson's Disease, Lewy Body,Parkinson's syndrome,Parkinsonian disorder,Parkinsonism, Primary,Parkinsons,PARKINSONS DIS,PARKINSONS DIS IDIOPATHIC,PARKINSONS DIS LEWY BODY,Parkinsons disease,Primary Parkinsonism,parkinson's disease
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Healthy age-sex matched controls without Parkinson's disease.
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Participants with early stage Parkinson's Disease.
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Subjects included in the Parkinson’s disease (PD) group had been previously diagnosed by a neurologist and met the general diagnostic criteria for early PD.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 36
- Group 1 sample size Number of subjects in the case (exposed) group
- 48
- Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any)
- None of the participants underwent antibiotic use in the past month prior to sample collection.
Lab analysis
- Sequencing type
- 16S
- 16S variable region One or more hypervariable region(s) of the bacterial 16S gene
- Not specified
- Sequencing platform Manufacturer and experimental platform used for quantifying microbial abundance
- Illumina
Statistical Analysis
- Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
- relative abundances
- Statistical test
- Mann-Whitney (Wilcoxon)
- Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
- 0.05
- Matched on Factors on which subjects have been matched on in a case-control study
- age, sex
Alpha Diversity
- Shannon Estimator of species richness and species evenness: more weight on species richness
- unchanged
Signature 1
Reviewed Marked as Reviewed by Atrayees on 2023-7-19
Source: Table 4
Description: Significantly changed microbiota in early stage PD.
Abundance in Group 1: increased abundance in Participants with early stage Parkinson's Disease.
Revision editor(s): Fcuevas3, Claregrieve1, Atrayees
Signature 2
Reviewed Marked as Reviewed by Atrayees on 2023-7-19
Source: Table 4. Significantly changed microbiota in early stage PD.
Description: Significantly changed microbiota in early stage PD.
Abundance in Group 1: decreased abundance in Participants with early stage Parkinson's Disease.
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