Desulfovibrio bacteria enhance alpha-synuclein aggregation in a Caenorhabditis elegans model of Parkinson's disease.

Introduction: The aggregation of the neuronal protein alpha-synuclein (alpha-syn) is a key feature in the pathology of Parkinson's disease (PD). Alpha-syn aggregation has been suggested to be induced in the gut cells by pathogenic gut microbes such as Desulfovibrio bacteria, which has been shown to be associated with PD. This study aimed to investigate whether Desulfovibrio bacteria induce alpha-syn aggregation. Methods: Fecal samples of ten PD patients and their healthy spouses were collected for molecular detection of Desulfovibrio species, followed by bacterial isolation. Isolated Desulfovibrio strains were used as diets to feed Caenorhabditis elegans nematodes which overexpress human alpha-syn fused with yellow fluorescence protein. Curli-producing Escherichia coli MC4100, which has been shown to facilitate alpha-syn aggregation in animal models, was used as a control bacterial strain, and E. coli LSR11, incapable of producing curli, was used as another control strain. The head sections of the worms were imaged using confocal microscopy. We also performed survival assay to determine the effect of Desulfovibrio bacteria on the survival of the nematodes. Results and Discussion: Statistical analysis revealed that worms fed Desulfovibrio bacteria from PD patients harbored significantly more (P<0.001, Kruskal-Wallis and Mann-Whitney U test) and larger alpha-syn aggregates (P<0.001) than worms fed Desulfovibrio bacteria from healthy individuals or worms fed E. coli strains. In addition, during similar follow-up time, worms fed Desulfovibrio strains from PD patients died in significantly higher quantities than worms fed E. coli LSR11 bacteria (P<0.01). These results suggest that Desulfovibrio bacteria contribute to PD development by inducing alpha-syn aggregation.

Desulfovibrio Bacteria Are Associated With Parkinson's Disease.

Parkinson's disease (PD) is the most prevalent movement disorder known and predominantly affects the elderly. It is a progressive neurodegenerative disease wherein α-synuclein, a neuronal protein, aggregates to form toxic structures in nerve cells. The cause of Parkinson's disease (PD) remains unknown. Intestinal dysfunction and changes in the gut microbiota, common symptoms of PD, are evidently linked to the pathogenesis of PD. Although a multitude of studies have investigated microbial etiologies of PD, the microbial role in disease progression remains unclear. Here, we show that Gram-negative sulfate-reducing bacteria of the genus Desulfovibrio may play a potential role in the development of PD. Conventional and quantitative real-time PCR analysis of feces from twenty PD patients and twenty healthy controls revealed that all PD patients harbored Desulfovibrio bacteria in their gut microbiota and these bacteria were present at higher levels in PD patients than in healthy controls. Additionally, the concentration of Desulfovibrio species correlated with the severity of PD. Desulfovibrio bacteria produce hydrogen sulfide and lipopolysaccharide, and several strains synthesize magnetite, all of which likely induce the oligomerization and aggregation of α-synuclein protein. The substances originating from Desulfovibrio bacteria likely take part in pathogenesis of PD. These findings may open new avenues for the treatment of PD and the identification of people at risk for developing PD.