Faecalibacterium prausnitzii , depleted in the Parkinson’s disease microbiome, improves motor deficits in α-synuclein overexpressing mice

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.