Gut Commensal Parabacteroides goldsteinii mitigates LRRK2 Parkinsonism through reducing neuroinflammation and multifaceted effects on gut homeostasis [ST]

Our study confirms that gut microbiota is essential for motor dysfunction and neuropathology in LRRK2 G2019S mice. Monoculturing Parabacteroides goldsteinii mitigates age-related motor dysfunction, alpha-synuclein expression, neuroinflammation, and dopaminergic degeneration. Its effects on the gut microenvironment include suppressing the toll-like receptor 4 signaling pathway, facilitating the differentiation of intestinal dendritic cells and macrophages, and promoting anti-inflammatory intraepithelial CD4+ CD8aa+ T cells. It also upregulates tissue repair and immune differentiation pathways, enhances intestinal epithelial junction and mitochondrial function genes, and reduces colonic alpha-synuclein levels. Overall design: Transcriptomics and spatial transcriptomics analyses to investigate the effects of Parabacterioides goldsteinii on the brain and gut in LRRK2 G2019S mice.