Strain-specific effects of Desulfovibrio on neurodegeneration and oxidative stress in a Caenorhabditis elegans PD model

Abstract

The gut microbiota is increasingly recognized as a key contributor to intestinal and brain pathologies, including Parkinson’s disease (PD). Sulfate-reducing Desulfovibrio (DSV) species have emerged as microbial drivers through hydrogen sulfide and other neurotoxic factors. Using the Caenorhabditis elegans PD model NL5901 expressing human α-synuclein, we examined the effects of six DSV strains from human, animal, and environmental sources on food preference, α-syn aggregation, ROS production, gene expression, and lifespan. C. elegans strongly preferred environmental strains, particularly D. vulgaris DSM 644 (94.7% vs. 5.3% over D. piger DSM 749). In contrast, the animal isolate D. desulfuricans DSM 6949 and PD isolate D. spp. MUU 26 induced the highest α-syn aggregation (49.05 and 40.15 aggregates), ROS (3.42-fold, 3.01-fold), and sod-3, daf-16, and hsp-16.1 repression. DSM 644-fed worms exhibited a protective transcriptional profile and the greatest lifespan extension (median 36 days). These results highlight strain-specific effects of DSV on neurodegeneration, oxidative stress, and aging, reinforcing the need for mechanistic validation in mammalian PD models.