Characterizing dysbiosis of gut microbiome in PD: evidence for overabundance of opportunistic pathogens

• Type of Material: Article
• Authors: Zachary D. Wallen, University of Alabama Birmingham; Mary Appah, University of Alabama Birmingham; Marissa N. Dean, University of Alabama Birmingham; Cheryl L. Sesler, University of Alabama Birmingham; Stewart Factor, Emory University; Eric Molho, Albany Medical College; Cyrus P. Zabetian, University of Washington; David G. Standaert, University of Alabama Birmingham; Haydeh Payami, University of Alabama Birmingham
• Language: English
• Date: 2020-06-12
• Publisher: Nature Publishing Group
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2020.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s41531-020-0112-6
• Title of Journal or Parent Work: NPJ Parkinsons Disease
• Volume: 6
• Issue: 1
• Start Page: 11
• End Page: 11
• Grant/Funding Information: This work was supported by the National Institute of Neurological Disorders and Stroke grant R01 NS036960 (to H.P.),; NIH Udall grant P50 NS062684 (to C.P.Z.) and P50 NS108675 (to D.G.S.), and NIH Training Grant T32NS095775 (to Z.D.W.).; The US Army Medical Research Materiel Command endorsed by the US Army through the Parkinson’s Research Program Investigator-Initiated Research Award under Award number W81XWH1810508 (to H.P.)
• Keywords: Life Sciences & Biomedicine; Science & Technology; Chain fatty acids; Metaanalysis; Alpha sinuclein; Neurosciences & Neurology; Wide association; Butyrate; Neurosciences; Expression; Risk; Parkinsons disease (PD); Vagotomy
• Research Categories: Health Sciences, Public Health; Health Sciences, Health Care Management; Biology, Neuroscience

Abstract

In Parkinson’s disease (PD), gastrointestinal features are common and often precede the motor signs. Braak and colleagues proposed that PD may start in the gut, triggered by a pathogen, and spread to the brain. Numerous studies have examined the gut microbiome in PD; all found it to be altered, but found inconsistent results on associated microorganisms. Studies to date have been small (N = 20 to 306) and are difficult to compare or combine due to varied methodology. We conducted a microbiome-wide association study (MWAS) with two large datasets for internal replication (N = 333 and 507). We used uniform methodology when possible, interrogated confounders, and applied two statistical tests for concordance, followed by correlation network analysis to infer interactions. Fifteen genera were associated with PD at a microbiome-wide significance level, in both datasets, with both methods, with or without covariate adjustment. The associations were not independent, rather they represented three clusters of co-occurring microorganisms. Cluster 1 was composed of opportunistic pathogens and all were elevated in PD. Cluster 2 was short-chain fatty acid (SCFA)-producing bacteria and all were reduced in PD. Cluster 3 was carbohydrate-metabolizing probiotics and were elevated in PD. Depletion of anti-inflammatory SCFA-producing bacteria and elevated levels of probiotics are confirmatory. Overabundance of opportunistic pathogens is an original finding and their identity provides a lead to experimentally test their role in PD.