Weissella cibaria SGW054 alleviates neurodegenerative progression in Proteus mirabilis- and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-in-duced Parkinson's disease mice by regulating gut microbiota dysbiosis

초록

Emerging evidence suggests that gut microbiota dysbiosis contributes to the initial stages of neuroinflammation and dopaminergic neurodegeneration in Parkinson's disease (PD). Probiotics are receiving attention as a treatment for PD because they restore gut microbiota balance and brain homeostasis. In this study, we demonstrated that Weissella cibaria SGW054 (SGW054), a probiotic strain, exhibited antibacterial activity against Proteus mirabilis (PM), which induces PD pathology. We evaluated the therapeutic effects of SGW054 on PD pathology in PM-induced PD model mice. Subsequently, we assessed the effects of SGW054 in mice exposed to 1-methyl-4phenyl-1,2,3,6-tetrahydropyridine (MPTP), a toxin commonly used to induce PD, and explored its influence on gut microbiota composition. SGW054 improved motor dysfunction and neurodegeneration in PM-treated PD model mice. Additionally, SGW054 reduced microgliosis, colonic inflammatory cytokine release, gut barrier disruption, and the translocation of alpha-synuclein aggregates from the gut to the brain by controlling fecal PM levels. In an MPTP-induced PD mouse model, SGW054 mitigated glial hyperactivation and lowered the release of proinflammatory cytokines, such as tumor necrosis factor-alpha, in both the brain and colon, thereby relieving dopaminergic neuronal damage and behavioral complications. Fecal microbiota analysis demonstrated that SGW054 administration alleviated MPTP-induced microbiota dysbiosis, decreasing PM and Lachnospiraceae abundance while increasing probiotic bacteria levels (Bacteroidaceae, Bacteroides, and Faecalibacterium), which strongly correlated with the anti-inflammatory and neuroprotective effects of SGW054. Collectively, our findings indicate that SGW054 may serve as a novel therapeutic supplement for PD by protecting against dopaminergic neuronal loss, restoring inflammatory homeostasis, and correcting gut microbiota dysbiosis in both gut-initiated and brain-initiated PD subtypes.

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