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

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.

Keywords: 16S RNA gene sequencing; IgA-Biome; Parkinson’s disease; Parkinson’s disease clinical subtypes; microbiome; secretory IgA.

Fig. 1

Percent IgA-coated bacteria in stool according to Parkinson’s disease clinical subtype. Each dot represents a study participant. Horizontal bars represent the mean±standard error. Mann-Whitney t-test, p < 0.0002.

Fig. 2

IgA-Biome alpha diversity by PD clinical subtype. Box plots depict sample richness (Observed OTU) and evenness (Shannon Diversity Index) among (A) presort only and (B) presort and sorted samples according to IgA-bound status. *p = 0.01 and p = 0.0017 FDR adjusted Mann-Whitley and ***p = 0.00898 FDR adjusted Kruskal-Wallis.

Fig. 3

Beta diversity analyses of the stool IgA-Biomes of PD individuals classified by their clinical subtype. Beta diversity visualized by principal coordinate analysis measured by unweighted UniFrac. Statistical significance was measured using PERMANOVA.

Fig. 4

Box plots depict unweighted UniFrac dissimilarities by IgA-Biome profile according to Parkinson’s disease clinical subtype. UniFrac distances closer to 1 indicated higher community similarity. *p < 0.0385 (IgA⁺), *p < 0.0442 (IgA^–), and *p < 0.0133 (presort) Mann-Whitney t-test.

Fig. 5

Relative abundance of phyla from individuals classified as either AR (purple) or TD (blue). Depicted are the 9 phyla present in greatest abundance. The relative abundances Firmicutes (FDR *p < 0.00225) and Tenericutes (FDR *p < 0.0294) were significantly different between Parkinson’s disease individuals classified as either AR or TD. Mann-Whitney t-test.

Fig. 6

The Firmicutes/Bacteroidetes ratio by Parkinson’s disease clinical subtype and IgA coating profile. The Firmicutes/Bacteroides ratio for each individual was calculated for presort, IgA⁺, and IgA^– samples. Individuals classified as TD had significantly higher Firmicutes/Bacteroides ratios than the ratio of those classified as AR across all IgA-Biome compartments. *p < 0.025; Mann-Whitney t-test.

Fig. 7

LEfSe identifies bacterial biomarkers associated with IgA-coated and uncoated genera across the Parkinson’s disease clinical subtypes. Analyses were conducted using parameters α<0.10 and linear discriminant analysis (LDA) threshold≥2.0.

Fig. 8

LEfSe identifies bacterial biomarkers associated with Presort samples across the Parkinson’s disease clinical subtypes. Analyses were conducted using parameters α<0.10 and linear discriminant analysis (LDA) threshold≥2.0.