Does Gut Microbiota Influence the Course of Parkinson's Disease? A 3-Year Prospective Exploratory Study in de novo Patients.
Aged
Cognitive Dysfunction
/ etiology
Disease Progression
Dysbiosis
/ diagnosis
Executive Function
/ physiology
Feces
Female
Follow-Up Studies
Gastrointestinal Microbiome
Humans
Male
Middle Aged
Parkinson Disease
/ diagnosis
Prognosis
Proof of Concept Study
Prospective Studies
RNA, Ribosomal, 16S
Sequence Analysis, RNA
Parkinson’s disease
de novo
gut microbiota
prognosis
prospective study
Journal
Journal of Parkinson's disease
ISSN: 1877-718X
Titre abrégé: J Parkinsons Dis
Pays: Netherlands
ID NLM: 101567362
Informations de publication
Date de publication:
2021
2021
Historique:
pubmed:
19
12
2020
medline:
16
11
2021
entrez:
18
12
2020
Statut:
ppublish
Résumé
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. To preliminarily investigate whether gut microbiota in early untreated PD may predict motor and non-motor features progression over a 3-year period. 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. 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 33337387
pii: JPD202297
doi: 10.3233/JPD-202297
doi:
Substances chimiques
RNA, Ribosomal, 16S
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM