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.

Guadalupe Vidal-Martinez,Brandon Chin,Barbara Yang,Cynthia Camarillo,Irene Sarosiek,Gloria V Herrera,Ruth G Perez

doi:10.3233/jpd-191693

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 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.

Highlights

The gut microbiome plays an important role in regulating metabolism [1,2,3], immunity [4], and neurological function [5,6,7]
The Parkinson’s disease (PD) group had a mean Bristol Stool Form Scale (BSFS) score of 3.0 and frequency of 5–10, which is consistent with constipation
Analysis of microbiota revealed that ␣- and ␤diversity were not significantly different; though significant differences were seen in % relative abundance (RA) by Mann-Whitney U tests

Summary

Introduction

The gut microbiome plays an important role in regulating metabolism [1,2,3], immunity [4], and neurological function [5,6,7]. Gut microbiome changes in PD and MSA often parallel associated gastrointestinal (GI) hyperpermeability, constipation, and dysmotility. Such GI changes can begin years before gait/motor symptoms, suggesting that specific microbial signatures may yield predictive biomarkers for early PD or MSA diagnosis [18]. Parkinson’s disease (PD) and multiple system atrophy (MSA) patients often suffer from gastrointestinal (GI) dysfunction and GI dysbiosis (microbial imbalance). 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. Families Bacteroidaceae and Lachnospiraceae and genera Prevotella and Bacteroides were detected in both humans and PD mice, suggesting potential shared biomarkers. It remains to be determined if mouse microbiota have predictive power for human subjects

Objectives

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Conclusion