Parkinson's disease and bacteriophages as its overlooked contributors

Abstract

Recent studies suggest that alterations in the gut phagobiota may contribute to pathophysiological processes in mammals; however, the association of bacteriophage community structure with Parkinson's disease (PD) has not been yet characterized. Towards this end, we used a published dataset to analyse bacteriophage composition and determine the phage/bacteria ratio in faecal samples from drug-naive PD patients and healthy participants. Our analyses revealed significant alterations in the representation of certain bacteriophages in the phagobiota of PD patients. We identified shifts of the phage/bacteria ratio in lactic acid bacteria known to produce dopamine and regulate intestinal permeability, which are major factors implicated in PD pathogenesis. Furthermore, we observed the depletion of Lactococcus spp. in the PD group, which was most likely due to the increase of lytic c2-like and 936-like lactococcal phages frequently present in dairy products. Our findings add bacteriophages to the list of possible factors associated with the development of PD, suggesting that gut phagobiota composition may serve as a diagnostic tool as well as a target for therapeutic intervention, which should be confirmed in further studies. Our results open a discussion on the role of environmental phages and phagobiota composition in health and disease.

Figure 1

Decreased bacterial richness in the microbiome of PD patients. (A) ACE, (B) Chao1 and α-diversity, (C) Shannon, (D) Simpson, and (E) inverse Simpson indexes; *p < 0.05 compared to control, (F) PCoA plots of β-diversity in PD and control samples based on Bray-Curtis dissimilarity analyses of relative OTU composition in the samples. Each dot represents a scaled measure of the composition of a given sample, colour- and shape-coded according to the group.

Figure 2

Comparison of relative abundance of predominant bacteria in PD patients and healthy participants. Faecal bacterial communities were analysed by high-throughput Illumina Hiseq4000 sequencing. Relative abundances of bacterial genera (A) and families (B) across control and PD groups.

Figure 3

Phagobiome richness in PD patients and healthy individuals. (A) ACE, (B) Chao1 and α-diversity, (C) Shannon, (D) Simpson, and (E) inverse Simpson indexes. Bacteriophage population diversity in PD patients and healthy individuals. (F) β-Diversity of phagobiota was measured using Spearman index. The X axis indicates samples and the Y axis shows Spearman index values: 0.5 means low difference and 1 means high difference (i.e., all species are different) in species diversity between samples. (G) PCoA plots of bacteriophage β-diversity based on Bray-Curtis dissimilarity analyses. Each dot represents a scaled measure of the composition of a given sample, colour- and shape-coded according to the group.

Figure 4

Comparison of relative abundance of predominant bacteriophage families. Faecal bacteriophage communities were analysed by high-throughput Illumina Hiseq4000 sequencing. Relative abundances of bacteriophage families in (A) control and (B) PD groups are shown.

Figure 5

Exploration of bacteriophage diversity in PD patients and healthy participants. The bar graph shows bacteriophage abundance at the genus level in the PD or control group (relative abundance ≥0.01% found in at least two samples per group).

Figure 6

The phage/bacteria ratio in PD patients and healthy individuals. The ratio was calculated as phage abundance normalized to that of the respective bacterial hosts in each sample of the PD and control groups.

Figure 7

Distribution of lytic and temperate Lactococcus bacteriophages in the PD and control groups. (A) The graph shows the abundance of lytic and temperate lactococcus phages. in each group. (B) The abundance of different lytic Lacotococcus phages in PD and control groups The scale on log for each row, indicates the negative values are down (Red) and positive values are up (Green) in comparison between PD and Control for each phage type.