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J Parkinsons Dis. 2019 Sep 20. doi: 10.3233/JPD-191693. [Epub ahead of print]

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.

Author information

1
Texas Tech University Health Sciences Center El Paso, Center of Emphasis in Neurosciences, Department of Molecular and Translational Medicine, Graduate School of Biomedical Sciences, El Paso, TX, USA.
2
Department of Internal Medicine, Division of Gastroenterology, Paul L Foster School of Medicine, El Paso, TX, USA.

Abstract

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 taxa Rikenellaceae and Ruminococcus.

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 beneficial 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.

KEYWORDS:

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

PMID:
31561385
DOI:
10.3233/JPD-191693

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