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

Abstract

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.

Microbiome Changes in Humans with Parkinson’s Disease after Photobiomodulation Therapy: A Retrospective Study

“…An earlier study on 36 PD sufferers [60], using real-time PCR rather than next generation sequencing, found that lower counts of Bifidobacterium, Bacteroides, and Clostridium cluster VI were associated with a more rapid deterioration. A 3-year follow up of 25 PD sufferers found an association between the lower levels of Roseburia and Faecalibacterium and higher levels of Actinobacteria and Oscillospira with worsening motor, non-motor and cognitive symptoms [61].…”

Nuclear and Mitochondrial Genome, Epigenome and Gut Microbiome: Emerging Molecular Biomarkers for Parkinson’s Disease

“…However, structural differences between the GM of PD patients and healthy controls have been previously documented and accumulating evidence shows the abundance of certain fecal microbial taxa are differentially distributed among PD patients and healthy controls. Lactobacillus , Bifidobacterium , Verrucomicrobiaceae, and Akkermansia show an increase in PD patients while Faecalibacterium , Roseburia , Coprococcus , Blautia , Prevotella , and Prevotellaceae have lower abundances [ 261 , 262 , 263 , 264 ].…”

“…However, structural differences between the GM of PD patients and healthy controls have been previously documented and accumulating evidence shows the abundance of certain fecal microbial taxa are differentially distributed among PD patients and healthy controls. Lactobacillus, Bifidobacterium, Verrucomicrobiaceae, and Akkermansia show an increase in PD patients while Faecalibacterium, Roseburia, Coprococcus, Blautia, Prevotella, and Prevotellaceae have lower abundances [261][262][263][264]. Scheperjans et al, (2015) [265] found that the relative abundance of Prevotellaceae taxa was reduced by nearly 80% in PD patients when compared to controls, and that the abundance of four microbial taxa was able to classify PD patients with over 90% specificity.…”

“…Further, disease phenotypes such as postural instability were associated with the abundance of Enterobacteriaceae in PD patients from the same cohort. More recently, Aho et al, (2019) also found that Prevotella taxa are less abundant in faster-progressing patients [261]. Hegelmaier et al, (2020) tested dietary and enema interventions in PD patients and observed changes in the abundance of certain bacterial taxa, such as Ruminococcaceae associated with improved motor symptoms and decreased levodopa daily doses [266].…”

Role of Gastrointestinal Dysbiosis and Fecal Transplantation in Parkinson’s Disease

“…It also showed significant alteration of various functional pathways (such as those associated with xenobiotic metabolism) [ 24 ]. Two long-term observational studies addressed the correlation of gut dysbiosis and the progression of PD in the patient [ 25 , 26 ]. Both assessed the exact distribution of the gut microbiome and observed a correlation between the abnormal distribution of certain gut microflora and the progression of PD symptoms [ 25 , 26 ].…”