Journal article
Altered gut microbiome in Parkinson’s disease and the influence of lipopolysaccharide in a human α-Synuclein over-expressing mouse model
Frontiers in Neuroscience, Vol.13, Article number 839
2019
Abstract
The interaction between the gut microbiota and alpha-synuclein (αSyn) aggregation in Parkinson's disease (PD) is receiving increasing attention. The objective of this study was to investigate gut microbiota, and effects of an inflammatory lipopolysaccharide (LPS) trigger in a human αSyn over-expressing mouse model of PD (Thy1-αSyn). Stool samples from patients with confirmed PD and Thy1-αSyn mice were analyzed using 16S ribosomal RNA sequencing. Compared to healthy controls, the relative abundance of mucin-degrading Verrucomicrobiae and LPS-producing Gammaproteobacteria were greater in PD patients. In mice, the abundance of Gammaproteobacteria was negligible in both Thy1-αSyn and wild-type (WT) animals, while Verrucomicrobiae were reduced in Thy1-αSyn mice. The effect of LPS on intestinal barrier function was investigated in vitro using intestinal epithelial (IEC-6) cells, and in vivo via administration of LPS in drinking water to Thy1-αSyn mice. Acute exposure to LPS in vitro resulted in a reduction and altered distribution of the tight junction markers ZO-1 and e-Cadherin around the cell membrane in IEC-6 cells, as shown by immunohistochemistry. LPS administration in Thy1-αSyn mice resulted in the emergence of early motor manifestations at 10 weeks, compared to untreated mice who were still asymptomatic at this age. This study reaffirms that an altered microbiome exists in patients with PD, and supports the notion of a proinflammatory gut microbiome environment as a trigger for PD pathogenesis. Copyright
Details
- Title
- Altered gut microbiome in Parkinson’s disease and the influence of lipopolysaccharide in a human α-Synuclein over-expressing mouse model
- Authors/Creators
- A.M. Gorecki (Author/Creator) - The University of Western AustraliaL. Preskey (Author/Creator) - The University of Notre Dame AustraliaM.C. Bakeberg (Author/Creator) - The University of Western AustraliaJ.E. Kenna (Author/Creator) - The University of Western AustraliaC. Gildenhuys (Author/Creator) - The University of Notre Dame AustraliaG. MacDougall (Author/Creator) - The University of Notre Dame AustraliaS.A. Dunlop (Author/Creator) - The University of Western AustraliaF.L. Mastaglia (Author/Creator) - The University of Western AustraliaP.A. Akkari (Author/Creator) - The University of Western AustraliaF. Koengten (Author/Creator) - The University of Notre Dame AustraliaR.S. Anderton (Author/Creator) - The University of Western Australia
- Publication Details
- Frontiers in Neuroscience, Vol.13, Article number 839
- Publisher
- Frontiers Media S.A.
- Identifiers
- 991005540367107891
- Copyright
- © 2019 Gorecki, Preskey, Bakeberg, Kenna, Gildenhuys, MacDougall, Dunlop, Mastaglia, Akkari, Koengten and Anderton.
- Murdoch Affiliation
- Centre for Molecular Medicine and Innovative Therapeutics
- Language
- English
- Resource Type
- Journal article
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- Collaboration types
- Domestic collaboration
- Citation topics
- 1 Clinical & Life Sciences
- 1.120 Inflammatory Bowel Diseases & Infections
- 1.120.384 Gut Microbiota
- Web Of Science research areas
- Neurosciences
- ESI research areas
- Neuroscience & Behavior