Volume 30, Issue 3 p. 350-358
Research Article

Gut microbiota are related to Parkinson's disease and clinical phenotype

Filip Scheperjans MD, PhD

Corresponding Author

Filip Scheperjans MD, PhD

Department of Neurology, Helsinki University Central Hospital, and Department of Neurological Sciences, University of Helsinki, Helsinki, Finland

Correspondence to: Filip Scheperjans, Department of Neurology, Helsinki University Central Hospital, Haartmaninkatu 4, 00290 Helsinki, E-Mail: [email protected]Search for more papers by this author
Velma Aho MSc, BA

Velma Aho MSc, BA

Institute of Biotechnology, DNA Sequencing and Genomics Laboratory, University of Helsinki, Helsinki, Finland

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Pedro A. B. Pereira MSc

Pedro A. B. Pereira MSc

Institute of Biotechnology, DNA Sequencing and Genomics Laboratory, University of Helsinki, Helsinki, Finland

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Kaisa Koskinen PhD

Kaisa Koskinen PhD

Institute of Biotechnology, DNA Sequencing and Genomics Laboratory, University of Helsinki, Helsinki, Finland

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Lars Paulin MSc

Lars Paulin MSc

Institute of Biotechnology, DNA Sequencing and Genomics Laboratory, University of Helsinki, Helsinki, Finland

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Eero Pekkonen MD, PhD

Eero Pekkonen MD, PhD

Department of Neurology, Helsinki University Central Hospital, and Department of Neurological Sciences, University of Helsinki, Helsinki, Finland

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Elena Haapaniemi MD, PhD

Elena Haapaniemi MD, PhD

Department of Neurology, Helsinki University Central Hospital, and Department of Neurological Sciences, University of Helsinki, Helsinki, Finland

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Seppo Kaakkola MD, PhD

Seppo Kaakkola MD, PhD

Department of Neurology, Helsinki University Central Hospital, and Department of Neurological Sciences, University of Helsinki, Helsinki, Finland

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Johanna Eerola-Rautio MD, PhD

Johanna Eerola-Rautio MD, PhD

Department of Neurology, Helsinki University Central Hospital, and Department of Neurological Sciences, University of Helsinki, Helsinki, Finland

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Marjatta Pohja MD, PhD

Marjatta Pohja MD, PhD

Department of Neurology, Helsinki University Central Hospital, and Department of Neurological Sciences, University of Helsinki, Helsinki, Finland

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Esko Kinnunen MD, PhD

Esko Kinnunen MD, PhD

Department of Neurology, Hyvinkää Hospital, Hyvinkää, Finland

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Kari Murros MD, PhD

Kari Murros MD, PhD

Department of Neurology, Helsinki University Central Hospital, and Department of Neurological Sciences, University of Helsinki, Helsinki, Finland

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Petri Auvinen PhD

Petri Auvinen PhD

Institute of Biotechnology, DNA Sequencing and Genomics Laboratory, University of Helsinki, Helsinki, Finland

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First published: 05 December 2014
Citations: 1,274

Funding agencies: This study was funded by The Michael J. Fox Foundation for Parkinson's Research, The Finnish Parkinson Foundation, Helsinki University Central Hospital (T1010NL101), and Hyvinkää Hospital (M6095PEV12).

Relevant conflicts of interest/financial disclosures: F.S., V.A., P.A.B.P., K.K., L.P., and P.A. are listed as inventors on Finnish patent application 20145492. The authors report no other conflicts of interest relative to the research covered in this manuscript.

Full financial disclosures and author roles may be found in the online version of this article.

The study was approved by the ethics committee of the Hospital District of Helsinki and Uusimaa, and all participants gave informed consent. The study was registered at clinicaltrials.gov (NCT01536769).

Abstract

In the course of Parkinson's disease (PD), the enteric nervous system (ENS) and parasympathetic nerves are amongst the structures earliest and most frequently affected by alpha-synuclein pathology. Accordingly, gastrointestinal dysfunction, in particular constipation, is an important non-motor symptom in PD and often precedes the onset of motor symptoms by years. Recent research has shown that intestinal microbiota interact with the autonomic and central nervous system via diverse pathways including the ENS and vagal nerve. The gut microbiome in PD has not been previously investigated. We compared the fecal microbiomes of 72 PD patients and 72 control subjects by pyrosequencing the V1–V3 regions of the bacterial 16S ribosomal RNA gene. Associations between clinical parameters and microbiota were analyzed using generalized linear models, taking into account potential confounders. On average, the abundance of Prevotellaceae in feces of PD patients was reduced by 77.6% as compared with controls. Relative abundance of Prevotellaceae of 6.5% or less had 86.1% sensitivity and 38.9% specificity for PD. A logistic regression classifier based on the abundance of four bacterial families and the severity of constipation identified PD patients with 66.7% sensitivity and 90.3% specificity. The relative abundance of Enterobacteriaceae was positively associated with the severity of postural instability and gait difficulty. These findings suggest that the intestinal microbiome is altered in PD and is related to motor phenotype. Further studies are warranted to elucidate the temporal and causal relationships between gut microbiota and PD and the suitability of the microbiome as a biomarker. © 2014 International Parkinson and Movement Disorder Society