Oral administration of Proteus mirabilis damages dopaminergic neurons and motor functions in mice
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Recently, studies on the relationship between gut dysbiosis and Parkinson’s disease (PD) have increased, but whether a specific gut bacterium may cause PD remains unexplored. Here, we report, for the first time, that a specific gut bacterium directly induces PD symptoms and dopaminergic neuronal damage in the mouse brain. We found that the number of Enterobacteriaceae, particularly Proteus mirabilis, markedly and commonly increased in PD mouse models. Administration of P. mirabilis isolated from PD mice significantly induced motor deficits, selectively caused dopaminergic neuronal damage and inflammation in substantia nigra and striatum, and stimulated α-synuclein aggregation in the brain as well as in the colon. We found that lipopolysaccharides, a virulence factor of P. mirabilis, may be associated in these pathological changes via gut leakage and inflammatory actions. Our results suggest a role of P. mirabilis on PD pathogenesis in the brain.
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Proteus mirabilis can cause motor dyskinesia, produce neuroinflammation and cause dopaminergic neuronal damage by producing LPS.
“Proteus mirabilis can cause motor dyskinesia, produce neuroinflammation and cause dopaminergic neuronal damage by producing LPS (Choi et al. 2018).”
From Therapeutic effect of GLP-1 engineered strain on mice model of Alzheimer’s disease and Parkinson’s disease (2020) · cites this paper as Choi et al. 2018
Proteus mirabilis may trigger neuroinflammation and lead to pathological changes related to PD by its metabolites (such as lipopolysaccharide).
“that may trigger neuroinflammation and lead to pathological changes related to PD by its metabolites (such as lipopolysaccharide) [39]”
From Neuroprotective Effect of Ceftriaxone on MPTP‐Induced Parkinson’s Disease Mouse Model by Regulating Inflammation and Intestinal Microbiota (2021) · cites this paper as [39]
Mice exposed to MPTP or 6-hydroxydopamine presented increased amount of Proteus mirabilis in their feces.
“Mice exposed to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) or 6-hydroxydopamine presented increased amount of Proteus mirabilis in their feces.”
From The Role of Microbiota-Gut-Brain Axis in Neuropsychiatric and Neurological Disorders (2021) · cites this paper as [408]
After repeated oral administration of Proteus mirabilis isolated from MPTP/6-hydroxydopamine models to wild-type mice, the treated animals displayed Parkinson's disease-like symptoms, including impaired motor function, elevated α-synuclein aggregation in the brain and colon, and dopaminergic neuronal loss.
“After repeated oral administration of these bacteria isolated from the above-mentioned models to WT mice, the treated animals displayed Parkinson's disease-like symptoms, including impaired motor function, elevated α-synuclein aggregation in the brain and colon as well as dopaminergic neuronal loss [408].”
From The Role of Microbiota-Gut-Brain Axis in Neuropsychiatric and Neurological Disorders (2021) · cites this paper as [408]
Repeated oral administration of Proteus mirabilis or its derived LPS to MPTP-treated or young mice was sufficient to induce a PD-like phenotype with motor deficit, loss of dopaminergic neurons in the nigra, brain and gut inflammation with disruption of the intestinal epithelial barrier, and formation of α-syn inclusions in the brain and in the colon.
“In the end, in a differently induced model of PD, the repeated oral administration of Proteus mirabilis or its derived LPS to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated or young mice was sufficient to induce a PD-like phenotype with motor deficit, loss of dopaminergic neurons in the nigra, brain and gut inflammation with disruption of the intestinal epithelial barrier, and formation of α”
From The gut-brain axis: how microbiota and host inflammasome influence brain physiology and pathology (2020) · cites this paper as [185]
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Inflammation, Infectious Triggers, and Parkinson's Disease
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- Authors
- Choi, J. G., Kim, N., Ju, I. G., Eo, H., Lim, S.-M., Jang, S.-E., Kim, D.-H., & Oh, M. S.
- Affiliations
- Kyung Hee University (KR)
- Corresponding author
- Kim, Dong-Hyun
- Oh, Myung Sook
- ORCID
- Venue
- Scientific Reports
- Published
- 2018-01-19
- Volume
- 8
- Issue
- 1
- Pages
- 1275-1275
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC5775305
- OpenAlex
- W2782946155
- Cited by
- 170
- References
- 65
- Citations by year
- 2026: 12 · 2025: 19 · 2024: 23 · 2023: 32 · 2022: 23 · 2021: 25 · 2020: 19 · 2019: 14 · 2018: 3
- FWCI
- 10.36
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- Funders
- National Research Foundation (2015R1A2A2A01004341)
- National Research Foundation of Korea (NRF-2017R1A5A2014768, 2017R1A5A2014768, NRF-2015R1A2A2A01004341)
- Ministry of Science and ICT, South Korea (NRF-2017R1A5A2014768, 2017R1A5A2014768)
- Topics
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Proteus mirabilis, Parkinson's disease, dopaminergic neurons, motor impairment, gut dysbiosis, Enterobacteriaceae, lipopolysaccharide, leaky gut, neuroinflammation, substantia nigra, striatum, alpha-synuclein aggregation, gut-brain axis, oral administration
- MeSH terms
- Gastrointestinal Microbiome, Animals, Colon, Corpus Striatum, Lipopolysaccharides, Male, Mice, Inbred C57BL, Movement, Proteus mirabilis, Substantia Nigra, MPTP Poisoning, Mice, Dopaminergic Neurons
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