Faecalibacterium prausnitzii, depleted in the Parkinson’s disease microbiome, improves motor deficits in α-synuclein overexpressing mice
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Description
Gut microbiome composition is altered in Parkinson's disease (PD), a neurodegenerative disorder characterized by motor dysfunction and frequently accompanied by gastrointestinal (GI) symptoms. Notably, microbial taxa with anti-inflammatory properties are consistently depleted in PD patients compared to controls. To explore whether specific gut bacteria may be disease-protective, we assembled a microbial consortium of 8 human-associated taxa that are reduced in individuals with PD across multiple cohorts and geographies. Treatment of α-synuclein overexpressing (Thy1-ASO) mice, an animal model of PD, with this consortium improved motor and GI deficits. A single bacterial species from this consortium, *Faecalibacterium prausnitzii*, was sufficient to correct gut microbiome deviations in Thy1-ASO mice, induce anti-inflammatory immune responses, and promote protective colonic gene expression profiles. Accordingly, oral treatment with *F. prausnitzii* robustly ameliorated motor and GI symptoms and reduced α-synuclein aggregates in the brain. These findings support the emerging hypothesis of functional contributions by the microbiome to PD and embolden development of potential probiotic therapies.
Identifier (DOI)
10.1101/2025.09.18.677192