Altered Gut Microbiome in Parkinson’s Disease and the Influence of Lipopolysaccharide in a Human α-Synuclein Over-Expressing Mouse Model
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-express...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-08-01
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| Series: | Frontiers in Neuroscience |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fnins.2019.00839/full |
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| author | Anastazja M. Gorecki Anastazja M. Gorecki Leah Preskey Leah Preskey Megan C. Bakeberg Megan C. Bakeberg Jade E. Kenna Jade E. Kenna Christi Gildenhuys Christi Gildenhuys Gabriella MacDougall Gabriella MacDougall Sarah A. Dunlop Sarah A. Dunlop Frank L. Mastaglia Frank L. Mastaglia P. Anthony Akkari P. Anthony Akkari P. Anthony Akkari Frank Koengten Frank Koengten Ryan S. Anderton Ryan S. Anderton Ryan S. Anderton |
| author_facet | Anastazja M. Gorecki Anastazja M. Gorecki Leah Preskey Leah Preskey Megan C. Bakeberg Megan C. Bakeberg Jade E. Kenna Jade E. Kenna Christi Gildenhuys Christi Gildenhuys Gabriella MacDougall Gabriella MacDougall Sarah A. Dunlop Sarah A. Dunlop Frank L. Mastaglia Frank L. Mastaglia P. Anthony Akkari P. Anthony Akkari P. Anthony Akkari Frank Koengten Frank Koengten Ryan S. Anderton Ryan S. Anderton Ryan S. Anderton |
| author_sort | Anastazja M. Gorecki |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-13T04:08:43Z |
| format | Article |
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| issn | 1662-453X |
| language | English |
| last_indexed | 2024-12-13T04:08:43Z |
| publishDate | 2019-08-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Neuroscience |
| spelling | doaj.art-04730994c78d43979c8cc8ce085422b82022-12-22T00:00:07ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2019-08-011310.3389/fnins.2019.00839473589Altered Gut Microbiome in Parkinson’s Disease and the Influence of Lipopolysaccharide in a Human α-Synuclein Over-Expressing Mouse ModelAnastazja M. Gorecki0Anastazja M. Gorecki1Leah Preskey2Leah Preskey3Megan C. Bakeberg4Megan C. Bakeberg5Jade E. Kenna6Jade E. Kenna7Christi Gildenhuys8Christi Gildenhuys9Gabriella MacDougall10Gabriella MacDougall11Sarah A. Dunlop12Sarah A. Dunlop13Frank L. Mastaglia14Frank L. Mastaglia15P. Anthony Akkari16P. Anthony Akkari17P. Anthony Akkari18Frank Koengten19Frank Koengten20Ryan S. Anderton21Ryan S. Anderton22Ryan S. Anderton23Perron Institute for Neurological and Translational Science, Nedlands, WA, AustraliaCentre for Neuromuscular & Neurological Disorders, The University of Western Australia, Crawley, WA, AustraliaOzgene Pty Ltd., Bentley, WA, AustraliaSchool of Medicine, The University of Notre Dame Australia, Fremantle, WA, AustraliaPerron Institute for Neurological and Translational Science, Nedlands, WA, AustraliaCentre for Neuromuscular & Neurological Disorders, The University of Western Australia, Crawley, WA, AustraliaPerron Institute for Neurological and Translational Science, Nedlands, WA, AustraliaCentre for Neuromuscular & Neurological Disorders, The University of Western Australia, Crawley, WA, AustraliaPerron Institute for Neurological and Translational Science, Nedlands, WA, AustraliaInstitute for Health Research and School of Health Sciences, The University of Notre Dame Australia, Fremantle, WA, AustraliaPerron Institute for Neurological and Translational Science, Nedlands, WA, AustraliaInstitute for Health Research and School of Health Sciences, The University of Notre Dame Australia, Fremantle, WA, AustraliaPerron Institute for Neurological and Translational Science, Nedlands, WA, AustraliaSchool of Biological Sciences, The University of Western Australia, Nedlands, WA, AustraliaPerron Institute for Neurological and Translational Science, Nedlands, WA, AustraliaCentre for Neuromuscular & Neurological Disorders, The University of Western Australia, Crawley, WA, AustraliaPerron Institute for Neurological and Translational Science, Nedlands, WA, AustraliaCentre for Neuromuscular & Neurological Disorders, The University of Western Australia, Crawley, WA, AustraliaThe Centre for Molecular Medicine and Innovative Therapeutics, Murdoch University, Murdoch, WA, AustraliaOzgene Pty Ltd., Bentley, WA, AustraliaSchool of Medicine, The University of Notre Dame Australia, Fremantle, WA, AustraliaPerron Institute for Neurological and Translational Science, Nedlands, WA, AustraliaCentre for Neuromuscular & Neurological Disorders, The University of Western Australia, Crawley, WA, AustraliaInstitute for Health Research and School of Health Sciences, The University of Notre Dame Australia, Fremantle, WA, AustraliaThe 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.https://www.frontiersin.org/article/10.3389/fnins.2019.00839/fullParkinson’s diseasemicrobiomelipopolysaccharideGammaproteobacteriaThy1-αSyngastrointestinal |
| spellingShingle | Anastazja M. Gorecki Anastazja M. Gorecki Leah Preskey Leah Preskey Megan C. Bakeberg Megan C. Bakeberg Jade E. Kenna Jade E. Kenna Christi Gildenhuys Christi Gildenhuys Gabriella MacDougall Gabriella MacDougall Sarah A. Dunlop Sarah A. Dunlop Frank L. Mastaglia Frank L. Mastaglia P. Anthony Akkari P. Anthony Akkari P. Anthony Akkari Frank Koengten Frank Koengten Ryan S. Anderton Ryan S. Anderton Ryan S. Anderton Altered Gut Microbiome in Parkinson’s Disease and the Influence of Lipopolysaccharide in a Human α-Synuclein Over-Expressing Mouse Model Frontiers in Neuroscience Parkinson’s disease microbiome lipopolysaccharide Gammaproteobacteria Thy1-αSyn gastrointestinal |
| title | Altered Gut Microbiome in Parkinson’s Disease and the Influence of Lipopolysaccharide in a Human α-Synuclein Over-Expressing Mouse Model |
| title_full | Altered Gut Microbiome in Parkinson’s Disease and the Influence of Lipopolysaccharide in a Human α-Synuclein Over-Expressing Mouse Model |
| title_fullStr | Altered Gut Microbiome in Parkinson’s Disease and the Influence of Lipopolysaccharide in a Human α-Synuclein Over-Expressing Mouse Model |
| title_full_unstemmed | Altered Gut Microbiome in Parkinson’s Disease and the Influence of Lipopolysaccharide in a Human α-Synuclein Over-Expressing Mouse Model |
| title_short | Altered Gut Microbiome in Parkinson’s Disease and the Influence of Lipopolysaccharide in a Human α-Synuclein Over-Expressing Mouse Model |
| title_sort | altered gut microbiome in parkinson s disease and the influence of lipopolysaccharide in a human α synuclein over expressing mouse model |
| topic | Parkinson’s disease microbiome lipopolysaccharide Gammaproteobacteria Thy1-αSyn gastrointestinal |
| url | https://www.frontiersin.org/article/10.3389/fnins.2019.00839/full |
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