title: Parkinson's disease and Parkinson's disease medications have distinct signatures of the gut microbiome.
abstract: There is mounting evidence for a connection between the gut and Parkinson's disease (PD). Dysbiosis of gut microbiota could explain several features of PD.
  
  
  
  The objective of this study was to determine if PD involves dysbiosis of gut microbiome, disentangle effects of confounders, and identify candidate taxa and functional pathways to guide research.
  
  
  
  A total of 197 PD cases and 130 controls were studied. Microbial composition was determined by 16S rRNA gene sequencing of DNA extracted from stool. Metadata were collected on 39 potential confounders including medications, diet, gastrointestinal symptoms, and demographics. Statistical analyses were conducted while controlling for potential confounders and correcting for multiple testing. We tested differences in the overall microbial composition, taxa abundance, and functional pathways.
  
  
  
  Independent microbial signatures were detected for PD (P = 4E-5), participants' region of residence within the United States (P = 3E-3), age (P = 0.03), sex (P = 1E-3), and dietary fruits/vegetables (P = 0.01). Among patients, independent signals were detected for catechol-O-methyltransferase-inhibitors (P = 4E-4), anticholinergics (P = 5E-3), and possibly carbidopa/levodopa (P = 0.05). We found significantly altered abundances of the Bifidobacteriaceae, Christensenellaceae, [Tissierellaceae], Lachnospiraceae, Lactobacillaceae, Pasteurellaceae, and Verrucomicrobiaceae families. Functional predictions revealed changes in numerous pathways, including the metabolism of plant-derived compounds and xenobiotics degradation.
  
  
  
  PD is accompanied by dysbiosis of gut microbiome. Results coalesce divergent findings of prior studies, reveal altered abundance of several taxa, nominate functional pathways, and demonstrate independent effects of PD medications on the microbiome. The findings provide new leads and testable hypotheses on the pathophysiology and treatment of PD. © 2017 International Parkinson and Movement Disorder Society.
authors.affiliation: Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Erin M
authors.initials: EM
authors.lastname: Hill-Burns
authors.affiliation: Department of Pediatrics, University of California San Diego, La Jolla, California, USA.
authors.forename: Justine W
authors.initials: JW
authors.lastname: Debelius
authors.affiliation: Department of Computer Science and Engineering, University of California San Diego, La Jolla, California, USA.
authors.forename: James T
authors.initials: JT
authors.lastname: Morton
authors.affiliation: Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: William T
authors.initials: WT
authors.lastname: Wissemann
authors.affiliation: Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Matthew R
authors.initials: MR
authors.lastname: Lewis
authors.affiliation: Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
authors.forename: Zachary D
authors.initials: ZD
authors.lastname: Wallen
authors.affiliation: Biostatistics and Computational Biology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, USA.
authors.forename: Shyamal D
authors.initials: SD
authors.lastname: Peddada
authors.affiliation: Department of Neurology, Emory University School of Medicine, Atlanta, Georgia, USA.
authors.forename: Stewart A
authors.initials: SA
authors.lastname: Factor
authors.affiliation: Department of Neurology, Albany Medical College, Albany, New York, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Molho
authors.affiliation: Veterans Affairs Puget Sound Health Care System and Department of Neurology, University of Washington, Seattle, Washington, USA.
authors.forename: Cyrus P
authors.identifier: 0000-0002-7739-4306
authors.initials: CP
authors.lastname: Zabetian
authors.affiliation: Department of Pediatrics, University of California San Diego, La Jolla, California, USA.|Department of Computer Science and Engineering, University of California San Diego, La Jolla, California, USA.|Center for Microbiome Innovation, University of California San Diego, La Jolla, California, USA.
authors.forename: Rob
authors.initials: R
authors.lastname: Knight
authors.affiliation: Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama, USA.|Center for Genomic Medicine, HudsonAlpha Institute for Biotechnology, Huntsville, Alabama, USA.
authors.forename: Haydeh
authors.initials: H
authors.lastname: Payami
mesh_terms: D000367:Age Factors; D000978:Antiparkinson Agents / Q000627:therapeutic use*; D001644:Bifidobacterium / Q000235:genetics; D002230:Carbidopa / Q000627:therapeutic use; D016022:Case-Control Studies; D065098:Catechol O-Methyltransferase Inhibitors / Q000627:therapeutic use*; D018680:Cholinergic Antagonists / Q000627:therapeutic use*; D015986:Confounding Factors, Epidemiologic; D004032:Diet; D004338:Drug Combinations; D064806:Dysbiosis / Q000453:epidemiology* / Q000382:microbiology; D005260:Female; D005638:Fruit; D000069196:Gastrointestinal Microbiome / Q000235:genetics*; D006801:Humans; D007777:Lactobacillaceae / Q000235:genetics; D007980:Levodopa / Q000627:therapeutic use; D008297:Male; D010300:Parkinson Disease / Q000188:drug therapy / Q000453:epidemiology* / Q000382:microbiology; D015661:Pasteurellaceae / Q000235:genetics; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D012307:Risk Factors; D012737:Sex Factors; D014481:United States / Q000453:epidemiology; D014675:Vegetables; D061327:Verrucomicrobia / Q000235:genetics
chemical_list: D000978:Antiparkinson Agents; D065098:Catechol O-Methyltransferase Inhibitors; D018680:Cholinergic Antagonists; D004338:Drug Combinations; D012336:RNA, Ribosomal, 16S; C009265:carbidopa, levodopa drug combination; D007980:Levodopa; D002230:Carbidopa
keywords: Parkinson's disease; confounding; functional pathways; gut microbiome; medications