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

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...

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Vydáno v:Movement disorders Ročník 30; číslo 3; s. 350 - 358
Hlavní autoři: Scheperjans, Filip, Aho, Velma, Pereira, Pedro A. B., Koskinen, Kaisa, Paulin, Lars, Pekkonen, Eero, Haapaniemi, Elena, Kaakkola, Seppo, Eerola-Rautio, Johanna, Pohja, Marjatta, Kinnunen, Esko, Murros, Kari, Auvinen, Petri
Médium: Journal Article
Jazyk:angličtina
Vydáno: United States Blackwell Publishing Ltd 01.03.2015
Wiley Subscription Services, Inc
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ISSN:0885-3185, 1531-8257, 1531-8257
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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
AbstractList 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. copyright 2014 International Parkinson and Movement Disorder Society
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.
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
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.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.
Author Murros, Kari
Eerola-Rautio, Johanna
Kinnunen, Esko
Scheperjans, Filip
Koskinen, Kaisa
Auvinen, Petri
Paulin, Lars
Haapaniemi, Elena
Kaakkola, Seppo
Aho, Velma
Pereira, Pedro A. B.
Pekkonen, Eero
Pohja, Marjatta
Author_xml – sequence: 1
  givenname: Filip
  surname: Scheperjans
  fullname: Scheperjans, Filip
  email: filip.scheperjans@hus.fi
  organization: Department of Neurology, Helsinki University Central Hospital, and Department of Neurological Sciences, University of Helsinki, Helsinki, Finland
– sequence: 2
  givenname: Velma
  surname: Aho
  fullname: Aho, Velma
  organization: Institute of Biotechnology, DNA Sequencing and Genomics Laboratory, University of Helsinki, Helsinki, Finland
– sequence: 3
  givenname: Pedro A. B.
  surname: Pereira
  fullname: Pereira, Pedro A. B.
  organization: Institute of Biotechnology, DNA Sequencing and Genomics Laboratory, University of Helsinki, Helsinki, Finland
– sequence: 4
  givenname: Kaisa
  surname: Koskinen
  fullname: Koskinen, Kaisa
  organization: Institute of Biotechnology, DNA Sequencing and Genomics Laboratory, University of Helsinki, Helsinki, Finland
– sequence: 5
  givenname: Lars
  surname: Paulin
  fullname: Paulin, Lars
  organization: Institute of Biotechnology, DNA Sequencing and Genomics Laboratory, University of Helsinki, Helsinki, Finland
– sequence: 6
  givenname: Eero
  surname: Pekkonen
  fullname: Pekkonen, Eero
  organization: Department of Neurology, Helsinki University Central Hospital, and Department of Neurological Sciences, University of Helsinki, Helsinki, Finland
– sequence: 7
  givenname: Elena
  surname: Haapaniemi
  fullname: Haapaniemi, Elena
  organization: Department of Neurology, Helsinki University Central Hospital, and Department of Neurological Sciences, University of Helsinki, Helsinki, Finland
– sequence: 8
  givenname: Seppo
  surname: Kaakkola
  fullname: Kaakkola, Seppo
  organization: Department of Neurology, Helsinki University Central Hospital, and Department of Neurological Sciences, University of Helsinki, Helsinki, Finland
– sequence: 9
  givenname: Johanna
  surname: Eerola-Rautio
  fullname: Eerola-Rautio, Johanna
  organization: Department of Neurology, Helsinki University Central Hospital, and Department of Neurological Sciences, University of Helsinki, Helsinki, Finland
– sequence: 10
  givenname: Marjatta
  surname: Pohja
  fullname: Pohja, Marjatta
  organization: Department of Neurology, Helsinki University Central Hospital, and Department of Neurological Sciences, University of Helsinki, Helsinki, Finland
– sequence: 11
  givenname: Esko
  surname: Kinnunen
  fullname: Kinnunen, Esko
  organization: Department of Neurology, Hyvinkää Hospital, Hyvinkää, Finland
– sequence: 12
  givenname: Kari
  surname: Murros
  fullname: Murros, Kari
  organization: Department of Neurology, Helsinki University Central Hospital, and Department of Neurological Sciences, University of Helsinki, Helsinki, Finland
– sequence: 13
  givenname: Petri
  surname: Auvinen
  fullname: Auvinen, Petri
  organization: Institute of Biotechnology, DNA Sequencing and Genomics Laboratory, University of Helsinki, Helsinki, Finland
BackLink https://www.ncbi.nlm.nih.gov/pubmed/25476529$$D View this record in MEDLINE/PubMed
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Keywords gut-brain-axis
biomarker
microbiome
non-motor symptoms
gastrointestinal dysfunction
Language English
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2014 International Parkinson and Movement Disorder Society.
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(NCT01536769).
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
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).
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.
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clinicaltrials.gov
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Snippet In the course of Parkinson's disease (PD), the enteric nervous system (ENS) and parasympathetic nerves are amongst the structures earliest and most frequently...
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SubjectTerms Aged
biomarker
Case-Control Studies
Enterobacteriaceae
Feces - chemistry
Feces - microbiology
Female
gastrointestinal dysfunction
Gastrointestinal Microbiome
gut-brain-axis
Humans
Male
microbiome
Middle Aged
Movement disorders
non-motor symptoms
Parkinson Disease - microbiology
ROC Curve
Severity of Illness Index
Title Gut microbiota are related to Parkinson's disease and clinical phenotype
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Volume 30
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