The Gut Microbiome in Parkinson’s Disease: A Longitudinal Study of the Impacts on Disease Progression and the Use of Device-Assisted Therapies

Abstract

BackgroundAltered gut microbiome (GM) composition has been established in Parkinson’s disease (PD). However, few studies have longitudinally investigated the GM in PD, or the impact of device-assisted therapies.ObjectivesTo investigate the temporal stability of GM profiles from PD patients on standard therapies and those initiating device-assisted therapies (DAT) and define multivariate models of disease and progression.MethodsWe evaluated validated clinical questionnaires and stool samples from 74 PD patients and 74 household controls (HCs) at 0, 6, and 12 months. Faster or slower disease progression was defined from levodopa equivalence dose and motor severity measures. 19 PD patients initiating Deep Brain Stimulation or Levodopa-Carbidopa Intestinal Gel were separately evaluated at 0, 6, and 12 months post-therapy initiation.ResultsPersistent underrepresentation of short-chain fatty-acid-producing bacteria, Butyricicoccus, Fusicatenibacter, Lachnospiraceae ND3007 group, and Erysipelotrichaceae UCG-003, were apparent in PD patients relative to controls. A sustained effect of DAT initiation on GM associations with PD was not observed. PD progression analysis indicated that the genus Barnesiella was underrepresented in faster progressing PD patients at t = 0 and t = 12 months. Two-stage predictive modeling, integrating microbiota abundances and nutritional profiles, improved predictive capacity (change in Area Under the Curve from 0.58 to 0.64) when assessed at Amplicon Sequence Variant taxonomic resolution.ConclusionWe present longitudinal GM studies in PD patients, showing persistently altered GM profiles suggestive of a reduced butyrogenic production potential. DATs exerted variable GM influences across the short and longer-term. We found that specific GM profiles combined with dietary factors improved prediction of disease progression in PD patients.

The Interplay between Gut Microbiota and Parkinson’s Disease: Implications on Diagnosis and Treatment

“…In 2021, Cilia et al showed that a shortage of Roseburia in de novo PD patients was predictive of a faster deterioration in motor, non-motor, and intellectual ability within 3 years [ 160 ]. Similar results were then obtained by Lubomski et al who reported that low levels of Barnesiella at the baseline and at 1-year follow-up were associated with a worse clinical evolution of PD [ 51 ]. Furthermore, a machine learning approach accounting for the abundance of various gut microbial species revealed that a reduction in Fusicatenibacter , Blautia and Faecalibacterium , together with an increased presence of Akkermansia , correlates with a faster progression of the disease [ 166 ].…”

“…Concerning PD, dysbiosis followed by GI symptoms and gut discomfort far precedes the onset of motor dysfunctions and it is linked to neuroinflammation, as well as to alterations in dopamine, serotonin, and kynurenine metabolism through the gut-brain axis [ 40 , 41 , 42 , 43 , 44 , 45 , 46 ] ( Figure 1 ). Similar to what has been reported in Alzheimer’s disease (AD) and aging [ 30 ], feces from PD patients are enriched in opportunistic pathogens and pro-inflammatory taxa at the expense of anti-inflammatory microbes and SCFAs-producing bacteria, especially butyrate [ 47 , 48 , 49 , 50 , 51 ]. Accordingly, meta-analysis and systematic reviews report that PD patients are characterized by an overgrowth of the genera Bifidobacterium , Lactobacillus , Akkermansia and of the opportunistic pathogens Porphyromonas and Corynebacterium , together with a decreased abundance of the SCFAs producers Prevotellaceae , Lachnospiraceae and Faecalibacterium [ 52 , 53 , 54 , 55 , 56 ].…”

The interplay between the gut-brain axis and the microbiome: A perspective on psychiatric and neurodegenerative disorders

“…Evidence from a number of research groups ( Hasegawa et al, 2015 ; Keshavarzian et al, 2015 ; Sampson et al, 2016 ; Bedarf et al, 2017 ; Hill-Burns et al, 2017 ; Aho et al, 2019 ; Romano et al, 2021 ; Lubomski et al, 2022 ; Zhu et al, 2022 ) has emerged proposing a relationship between the gut microbiota and PD. The study by Killinger et al (2018) proposed that the normal human vermiform appendix harbors pathogenic forms of α-synuclein that affect the risk of developing PD and that an appendectomy could be a potential prophylactic for initiation of PD.…”

Dopaminergic Medication Accentuates Fecal Gut Microbiome Changes in Parkinson’s Disease

“…Four longitudinal studies investigated the gut microbiome of already treated PD subjects at baseline and after one to two years. [27][28][29][30] Gut microbiome composition apparently remained stable in studies using 16S rRNA gene sequencing, whereas total fecal bacterial counts were decreased after two years in one study using quantitative reverse-transciption polymerase chain reaction (qRT-PCR) of selected taxa. Therefore, an exposure period of more than 90 days, but less than two years, seems appropriate to investigate the effect of PD medication on gut microbiome composition.…”