IgA-Biome Profiles Correlate with Clinical Parkinson’s Disease Subtypes

Author:

Brown Eric L.1,Essigmann Heather T.1,Hoffman Kristi L.2,Alexander Ashley S.3,Newmark Michael3,Jiang Zhi-Dong1,Suescun Jessika4,Schiess Mya C.4,Hanis Craig L.5,DuPont Herbert L.136

Affiliation:

1. Center for Infectious Diseases, Division of Epidemiology, Human Genetics and Environmental Sciences, University of Texas School of Public Health, Houston, TX, USA

2. Alkek Center for Metagenomics and Microbiome Research, Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, TX, USA

3. Kelsey Research Foundation, Houston, TX, USA

4. Department of Neurology/UTMOVE University of Texas McGovern Medical School, Houston, TX, USA

5. Human Genetics Center, Division of Epidemiology, Human Genetics and Environmental Sciences, University of Texas School of Public Health, Houston, TX, USA

6. Department of Internal Medicine, University of Texas McGovern Medical School, Houston, TX, USA

Abstract

Background: Parkinson’s disease is a heterogeneous neurodegenerative disorder with distinctive gut microbiome patterns suggesting that interventions targeting the gut microbiota may prevent, slow, or reverse disease progression and severity. Objective: Because secretory IgA (SIgA) plays a key role in shaping the gut microbiota, characterization of the IgA-Biome of individuals classified into either the akinetic rigid (AR) or tremor dominant (TD) Parkinson’s disease clinical subtypes was used to further define taxa unique to these distinct clinical phenotypes. Methods: Flow cytometry was used to separate IgA-coated and -uncoated bacteria from stool samples obtained from AR and TD patients followed by amplification and sequencing of the V4 region of the 16 S rDNA gene on the MiSeq platform (Illumina). Results: IgA-Biome analyses identified significant alpha and beta diversity differences between the Parkinson’s disease phenotypes and the Firmicutes/Bacteroides ratio was significantly higher in those with TD compared to those with AR. In addition, discriminant taxa analyses identified a more pro-inflammatory bacterial profile in the IgA+ fraction of those with the AR clinical subclass compared to IgA-Biome analyses of those with the TD subclass and with the taxa identified in the unsorted control samples. Conclusion: IgA-Biome analyses underscores the importance of the host immune response in shaping the gut microbiome potentially affecting disease progression and presentation. In the present study, IgA-Biome analyses identified a unique proinflammatory microbial signature in the IgA+ fraction of those with AR that would have otherwise been undetected using conventional microbiome analysis approaches.

Publisher

IOS Press

Subject

Cellular and Molecular Neuroscience,Neurology (clinical)

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