Parkinson's Disease and Parkinson's Disease Medications Have Distinct Signatures of the Gut Microbiome

被引:676
作者
Hill-Burns, Erin M. [1 ]
Debelius, Justine W. [2 ]
Morton, James T. [3 ]
Wissemann, William T. [1 ]
Lewis, Matthew R. [1 ]
Wallen, Zachary D. [1 ]
Peddada, Shyamal D. [4 ]
Factor, Stewart A. [5 ]
Molho, Eric [6 ]
Zabetian, Cyrus P. [7 ,8 ]
Knight, Rob [2 ,3 ,9 ]
Payami, Haydeh [1 ,10 ]
机构
[1] Univ Alabama Birmingham, Dept Neurol, UAB Stn, Birmingham, AL 35294 USA
[2] Univ Calif San Diego, Dept Pediat, La Jolla, CA 92093 USA
[3] Univ Calif San Diego, Dept Comp Sci & Engn, La Jolla, CA 92093 USA
[4] NIEHS, Biostat & Computat Biol Branch, POB 12233, Res Triangle Pk, NC 27709 USA
[5] Emory Univ, Sch Med, Dept Neurol, Atlanta, GA 30322 USA
[6] Albany Med Coll, Dept Neurol, Albany, NY 12208 USA
[7] Univ Washington, Vet Affairs Puget Sound Hlth Care Syst, Seattle, WA 98195 USA
[8] Univ Washington, Dept Neurol, Seattle, WA 98195 USA
[9] Univ Calif San Diego, Ctr Microbiome Innovat, La Jolla, CA 92093 USA
[10] HudsonAlpha Inst Biotechnol, Ctr Genom Med, Huntsville, AL USA
关键词
Parkinson's disease; medications; confounding; gut microbiome; functional pathways; RIBOSOMAL-RNA SEQUENCES; CHAIN FATTY-ACIDS; SODIUM-BUTYRATE; MANIFESTATIONS; ASSIGNMENT; MICROGLIA; BACTERIA; MODEL;
D O I
10.1002/mds.26942
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Background: 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. Objective: 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. Methods: 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. Meta-data 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. Results: 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. Conclusion: 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. (C) 2017 International Parkinson and Movement Disorder Society
引用
收藏
页码:739 / 749
页数:11
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