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

Moiseyenko, A.; Antonello, G.; Schonhoff, A. M.; Boktor, J. C.; Long, K.; Dirks, B.; Oguienko, A. D.; Winnett, A. V.; Simpson, P.; Daeizadeh, D.; Ismagilov, R. F.; Krajmalnik-Brown, R.; Segata, N.; Waldron, L. D.; Mazmanian, S. K.

doi:10.1101/2025.09.18.677192

bioRxiv · 10.1101/2025.09.18.677192

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

Moiseyenko, A.·Antonello, G.·Schonhoff, A. M.·Boktor, J. C.·Long, K.·Dirks, B.·Oguienko, A. D.·Winnett, A. V.·Simpson, P.·Daeizadeh, D.·Ismagilov, R. F.·Krajmalnik-Brown, R.·Segata, N.·Waldron, L. D.·Mazmanian, S. K.

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Abstract

Gut microbiome composition is altered in Parkinsons 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 -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 -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.

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Moiseyenko, A., Antonello, G., Schonhoff, A. M., Boktor, J. C., Long, K., Dirks, B., Oguienko, A. D., Winnett, A. V., Simpson, P., Daeizadeh, D., Ismagilov, R. F., Krajmalnik-Brown, R., Segata, N., Waldron, L. D., Mazmanian, S. K.. 2025-09-21. Faecalibacterium prausnitzii, depleted in the Parkinson's disease microbiome, improves motor deficits in α-synuclein overexpressing mice. https://doi.org/10.1101/2025.09.18.677192

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