AUTHOR=Huynh Vy A. , Takala Timo M. , Murros Kari E. , Diwedi Bidhi , Saris Per E. J. 

TITLE=Desulfovibrio bacteria enhance alpha-synuclein aggregation in a Caenorhabditis elegans model of Parkinson’s disease

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=13

YEAR=2023

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2023.1181315

DOI=10.3389/fcimb.2023.1181315

ISSN=2235-2988

ABSTRACT=<sec><title>Introduction</title><p>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 <italic>Desulfovibrio</italic> bacteria, which has been shown to be associated with PD. This study aimed to investigate whether <italic>Desulfovibrio</italic> bacteria induce alpha-syn aggregation.</p></sec><sec><title>Methods</title><p>Fecal samples of ten PD patients and their healthy spouses were collected for molecular detection of <italic>Desulfovibrio</italic> species, followed by bacterial isolation. Isolated <italic>Desulfovibrio</italic> strains were used as diets to feed <italic>Caenorhabditis elegans</italic> nematodes which overexpress human alpha-syn fused with yellow fluorescence protein. Curli-producing <italic>Escherichia coli</italic> MC4100, which has been shown to facilitate alpha-syn aggregation in animal models, was used as a control bacterial strain, and <italic>E. coli</italic> 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 <italic>Desulfovibrio</italic> bacteria on the survival of the nematodes.</p></sec><sec><title>Results and Discussion</title><p>Statistical analysis revealed that worms fed <italic>Desulfovibrio</italic> bacteria from PD patients harbored significantly more (<italic>P</italic>&lt;0.001, Kruskal-Wallis and Mann-Whitney U test) and larger alpha-syn aggregates (<italic>P</italic>&lt;0.001) than worms fed <italic>Desulfovibrio</italic> bacteria from healthy individuals or worms fed <italic>E. coli</italic> strains. In addition, during similar follow-up time, worms fed <italic>Desulfovibrio</italic> strains from PD patients died in significantly higher quantities than worms fed <italic>E. coli</italic> LSR11 bacteria (<italic>P</italic>&lt;0.01). These results suggest that <italic>Desulfovibrio</italic> bacteria contribute to PD development by inducing alpha-syn aggregation.</p></sec>