Oral administration of Proteus mirabilis damages dopaminergic neurons and motor functions in mice

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 neurona...

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Published inScientific reports Vol. 8; no. 1; pp. 1275 - 13
Main Authors Choi, Jin Gyu, Kim, Namkwon, Ju, In Gyoung, Eo, Hyeyoon, Lim, Su-Min, Jang, Se-Eun, Kim, Dong-Hyun, Oh, Myung Sook
Format Journal Article
LanguageEnglish
Published England Nature Publishing Group 19.01.2018
Nature Publishing Group UK
Subjects
Animal models
Animals
Brain injury
Colon
Colon - microbiology
Corpus Striatum - pathology
Dopamine receptors
Dopaminergic Neurons - pathology
Dopaminergic Neurons - physiology
Dysbacteriosis
Gastrointestinal Microbiome
Inflammation
Lipopolysaccharides
Lipopolysaccharides - toxicity
Male
Mice
Mice, Inbred C57BL
Movement
Movement disorders
MPTP Poisoning - microbiology
Neostriatum
Neurodegenerative diseases
Oral administration
Parkinson's disease
Proteus mirabilis
Proteus mirabilis - pathogenicity
Rodents
Substantia nigra
Substantia Nigra - pathology
Synuclein
Virulence factors
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Summary: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.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-018-19646-x