A Pilot Microbiota Study in Parkinson's Disease Patients versus Control Subjects, and Effects of FTY720 and FTY720-Mitoxy Therapies in Parkinsonian and Multiple System Atrophy Mouse Models

Study information

Reviewed Marked as Reviewed by Chloe on 2024-5-6

study design

case-control

Citation

PMID PubMed identifier for scientific articles.

31561385

DOI Digital object identifier for electronic documents.

https://doi.org/10.3233%2FJPD-191693

URI

Authors

Vidal-Martinez G, Chin B, Camarillo C, Herrera GV, Yang B, Sarosiek I, Perez RG

Journal

Journal of Parkinson's disease

Year

2020

Keywords:

FTY720, FTY720-Mitoxy, Microbiota, Parkinson’s disease, multiple system atrophy, transgenic mouse models

BACKGROUND: Parkinson's disease (PD) and multiple system atrophy (MSA) patients often suffer from gastrointestinal (GI) dysfunction and GI dysbiosis (microbial imbalance). GI dysfunction also occurs in mouse models of PD and MSA. OBJECTIVES: To assess gut dysfunction and dysbiosis in PD subjects as compared to controls, identify potential shared microbial taxa in humans and mouse models of PD and MSA, and to assess the effects of potential therapies on mouse GI microbiota. METHODS: In this human pilot study, GI function was assessed by fecal consistency/frequency measured using the Bristol Stool Form Scale and GI transit time assessed using Sitzmarks pills and abdominal radiology. Human and mouse microbiota were analyzed by extracting fecal genomic DNA followed by 16S rRNA sequencing. RESULTS: In our PD patients genera Akkermansia significantly increased while a trend toward increased Bifidobacterium and decreased Prevotella was observed. Families Bacteroidaceae and Lachnospiraceae and genera Prevotella and Bacteroides were detected in both humans and PD mice, suggesting potential shared biomarkers. In mice treated with the approved multiple sclerosis drug, FTY720, or with our FTY720-Mitoxy-derivative, we saw that FTY720 had little effect while FTY720-Mitoxy increased beneficial Ruminococcus and decreased Rickenellaceae family. CONCLUSION: Akkermansia and Prevotellaceae data reported by others were replicated in our human pilot study suggesting the use of those taxa as potential biomarkers for PD diagnosis. The effect of FTY720-Mitoxy on taxa Rikenellaceae and Ruminococcus and the relevance of S24-7 await further evaluation. It also remains to be determined if mouse microbiota have predictive power for human subjects.

Experiment 1

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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: Feces Cow dung,Cow pat,Droppings,Dung,Excrement,Excreta,Faeces,Fecal material,Fecal matter,Fewmet,Frass,Guano,Matières fécales@fr,Merde@fr,Ordure,Partie de la merde@fr,Piece of shit,Porción de mierda@es,Portion of dung,Portion of excrement,Portion of faeces,Portion of fecal material,Portion of fecal matter,Portion of feces,Portion of guano,Portion of scat,Portionem cacas,Scat,Spoor,Spraint,Stool,Teil der fäkalien@de,Feces,feces

Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology

Group 0 name Corresponds to the control (unexposed) group for case-control studies: Healthy controls

Group 1 name Corresponds to the case (exposed) group for case-control studies: Parkinson’s disease

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: Patients diagnosed with Parkinson’s disease (confirmed by a neurologist) between 35 and 95 years of age.

Group 0 sample size Number of subjects in the control (unexposed) group: 13

Group 1 sample size Number of subjects in the case (exposed) group: 9

Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any): 2 weeks

Lab analysis

Sequencing type: 16S

16S variable region One or more hypervariable region(s) of the bacterial 16S gene: V3-V4

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

MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?: No

Signature 1

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Reviewed Marked as Reviewed by Chloe on 2024-5-6

Curated date: 2024/03/08

Curator: Flo

Revision editor(s): Flo, Scholastica, WikiWorks

Source: Table 1 (Column A)

Description: Relative abundance of gut microbial taxa in pilot studies of human PD.

Abundance in Group 1: increased abundance in

NCBI	Quality Control	Links
Akkermansia
Verrucomicrobiaceae

Revision editor(s): Flo, Scholastica, WikiWorks

Experiment 2

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Differences from previous experiment shown

Subjects

Host species Species from which microbiome was sampled. Contact us to have more species added.: Mus musculus

Group 0 name Corresponds to the control (unexposed) group for case-control studies: Wild Type mice

Group 1 name Corresponds to the case (exposed) group for case-control studies: Parkinsonian mice

Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group: 10-month old transgenic (Tg) parkinsonian mice that expresses A53T mutant human alpha-synuclein (a-Syn) in neurons

Group 0 sample size Number of subjects in the control (unexposed) group: 2

Group 1 sample size Number of subjects in the case (exposed) group: 5

Antibiotics exclusion Number of days without antibiotics usage (if applicable) and other antibiotics-related criteria used to exclude participants (if any): Not specified