Researchers Uncover Potential Cause Of Parkinson’s Disease

nurse helping old lady with Parkinson's disease

In a groundbreaking study published in Frontiers, researchers have found that certain strains of DSV (Desulfovibrio) bacteria, commonly found in the gut, may play a significant role in developing and progressing Parkinson’s disease (PD). The study, conducted using a model organism, C. elegans, demonstrated that DSV bacteria can induce alpha-synuclein aggregation, a protein closely associated with PD pathology.  

Previous research has already indicated a connection between alpha-synuclein aggregation and DSV bacteria. Alpha-synuclein accumulation had been observed in nematodes’ head region and the gut and brain of aged rats after exposure to curli-producing E. coli. Moreover, administering curli-producing E. coli to mice with alpha-synuclein overexpression led to motor impairment and increased alpha-synuclein aggregation in the gut and brain.  

In the current study, the researchers demonstrated that DSV strains, particularly those derived from PD patients, were more potent than curli-producing E. coli in promoting the accumulation of larger and more abundant alpha-synuclein aggregates. Additionally, worms fed DSV bacteria, exceptionally patient strains, experienced increased fatality rates, likely due to the overwhelming amount of accumulated alpha-synuclein totals and varying bacterial toxicity.  

A critical observation made during the study was that all tested DSV bacteria-induced alpha-synuclein aggregation in the head region of C. elegans worms. Furthermore, DSV bacteria isolated from the fecal samples of PD patients were more effective at inducing alpha-synuclein aggregation than those obtained from healthy individuals.

Additionally, patient-derived DSV strains significantly increased the mortality rate of the nematodes. These findings suggest that while all DSV strains possess standard features, DSV strains from PD patients exhibit greater virulence, leading to more muscular toxicity and increased alpha-synuclein aggregation.  

The study proposed several potential mechanisms for DSV bacteria to induce alpha-synuclein aggregation and exert their pathogenic effects. One hypothesis relates to the production of hydrogen sulfide (H2S) by DSV bacteria. H2S has been shown to facilitate cytochrome c release from mitochondria to the cytoplasm, potentially triggering alpha-synuclein aggregation in the presence of reactive oxygen species.

Thus, increased amounts of H2S-producing bacteria like DSV bacteria could contribute to the pathogenesis of PD. Variations in the hydrogenase systems of different DSV strains may affect their effectiveness in H2S production.  

The researchers also noted that the ability of DSV bacteria to interact with gastrointestinal cells might influence the process of alpha-synuclein aggregation. Previous studies have demonstrated that DSV bacteria, including those from the sulfate-reducing bacteria (SRB) group, can adhere to and invade epithelial cells, leading to damage and dysfunction of the intestinal barrier.

This impairment may allow DSV bacteria to interact with surrounding cells, increasing alpha-synuclein aggregation. Additionally, intestinal inflammation, triggered by DSV colonization and impaired barrier function, is believed to contribute to PD pathogenesis by promoting alpha-synuclein pathology.  

Lipopolysaccharides in the outer membrane of Gram-negative bacteria like DSV bacteria were identified as another potential virulence factor. Lipopolysaccharides have been shown to modulate alpha-synuclein aggregation and increase plasma H2S concentration. Since lipopolysaccharides can vary in structure among different DSV strains, this diversity may contribute to varied endotoxicity and the ability to induce alpha-synuclein aggregation.

Further research must fully elucidate the complex relationship between DSV bacteria and PD. By unraveling the underlying mechanisms and identifying specific virulence factors, scientists hope to advance our understanding of PD pathogenesis and develop novel therapeutic strategies. 

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