Alpha synuclein overexpression can drive microbiome dysbiosis in mice
Abstract Growing evidence indicates that persons with Parkinson disease (PD), have a unique composition of indigenous gut microbes. Given the long prodromal or pre-diagnosed period, longitudinal studies of the human and rodent gut microbiome before symptomatic onset and for the duration of the disea...
Saved in:
| Main Authors: | , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-02-01
|
| Series: | Scientific Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/s41598-024-82139-7 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1832571786561060864 |
|---|---|
| author | Timothy R. Sampson Zachary D Wallen Woong-Jai Won David G. Standaert Haydeh Payami Ashley S. Harms |
| author_facet | Timothy R. Sampson Zachary D Wallen Woong-Jai Won David G. Standaert Haydeh Payami Ashley S. Harms |
| author_sort | Timothy R. Sampson |
| collection | DOAJ |
| description | Abstract Growing evidence indicates that persons with Parkinson disease (PD), have a unique composition of indigenous gut microbes. Given the long prodromal or pre-diagnosed period, longitudinal studies of the human and rodent gut microbiome before symptomatic onset and for the duration of the disease are currently lacking. PD is partially characterized by the accumulation of the protein α-synuclein (α-syn) into insoluble aggregates, in both the central and enteric nervous systems. As such, several experimental rodent and non-human primate models of α-syn overexpression recapitulate some of the hallmark pathophysiologies of PD. These animal models provide an opportunity to assess how the gut microbiome changes with age under disease-relevant conditions. Here, we used a transgenic mouse strain, which overexpress wild-type human α-syn to test how the gut microbiome composition responds in this model of PD pathology during aging. Using shotgun metagenomics, we find significant, age and genotype-dependent bacterial taxa whose abundance becomes altered with age. We reveal that α-syn overexpression can drive alterations to the gut microbiome composition and suggest that it limits diversity through age. Taxa that were most affected by genotype-age interaction were Lactobacillus and Bifidobacteria. In a mouse model, we showed direct link between alpha synuclein geneotype (hallmark of PD), a dysbiotic and low-diversity gut microbiome, and dysbiotic levels of Bifidobacteria and Lactobacillus (most robust features of PD microbiome). Given emerging data on the potential contributions of the gut microbiome to PD pathologies, our data provide an experimental foundation to understand how the PD-associated microbiome may arise as a trigger or co-pathology to disease. |
| format | Article |
| id | doaj-art-52433602ff114ce9917e45e0d812f784 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-52433602ff114ce9917e45e0d812f7842025-02-02T12:17:44ZengNature PortfolioScientific Reports2045-23222025-02-0115111210.1038/s41598-024-82139-7Alpha synuclein overexpression can drive microbiome dysbiosis in miceTimothy R. Sampson0Zachary D Wallen1Woong-Jai Won2David G. Standaert3Haydeh Payami4Ashley S. Harms5Aligning Science Across Parkinson’s (ASAP) Collaborative Research NetworkDepartment of Neurology, University of Alabama at BirminghamDepartment of Neurology, University of Alabama at BirminghamDepartment of Neurology, University of Alabama at BirminghamDepartment of Neurology, University of Alabama at BirminghamDepartment of Neurology, University of Alabama at BirminghamAbstract Growing evidence indicates that persons with Parkinson disease (PD), have a unique composition of indigenous gut microbes. Given the long prodromal or pre-diagnosed period, longitudinal studies of the human and rodent gut microbiome before symptomatic onset and for the duration of the disease are currently lacking. PD is partially characterized by the accumulation of the protein α-synuclein (α-syn) into insoluble aggregates, in both the central and enteric nervous systems. As such, several experimental rodent and non-human primate models of α-syn overexpression recapitulate some of the hallmark pathophysiologies of PD. These animal models provide an opportunity to assess how the gut microbiome changes with age under disease-relevant conditions. Here, we used a transgenic mouse strain, which overexpress wild-type human α-syn to test how the gut microbiome composition responds in this model of PD pathology during aging. Using shotgun metagenomics, we find significant, age and genotype-dependent bacterial taxa whose abundance becomes altered with age. We reveal that α-syn overexpression can drive alterations to the gut microbiome composition and suggest that it limits diversity through age. Taxa that were most affected by genotype-age interaction were Lactobacillus and Bifidobacteria. In a mouse model, we showed direct link between alpha synuclein geneotype (hallmark of PD), a dysbiotic and low-diversity gut microbiome, and dysbiotic levels of Bifidobacteria and Lactobacillus (most robust features of PD microbiome). Given emerging data on the potential contributions of the gut microbiome to PD pathologies, our data provide an experimental foundation to understand how the PD-associated microbiome may arise as a trigger or co-pathology to disease.https://doi.org/10.1038/s41598-024-82139-7MetagenomicsAlpha-synucleinTransgeneParkinson’s diseaseGut microbiomeAge-related dysbiosis |
| spellingShingle | Timothy R. Sampson Zachary D Wallen Woong-Jai Won David G. Standaert Haydeh Payami Ashley S. Harms Alpha synuclein overexpression can drive microbiome dysbiosis in mice Scientific Reports Metagenomics Alpha-synuclein Transgene Parkinson’s disease Gut microbiome Age-related dysbiosis |
| title | Alpha synuclein overexpression can drive microbiome dysbiosis in mice |
| title_full | Alpha synuclein overexpression can drive microbiome dysbiosis in mice |
| title_fullStr | Alpha synuclein overexpression can drive microbiome dysbiosis in mice |
| title_full_unstemmed | Alpha synuclein overexpression can drive microbiome dysbiosis in mice |
| title_short | Alpha synuclein overexpression can drive microbiome dysbiosis in mice |
| title_sort | alpha synuclein overexpression can drive microbiome dysbiosis in mice |
| topic | Metagenomics Alpha-synuclein Transgene Parkinson’s disease Gut microbiome Age-related dysbiosis |
| url | https://doi.org/10.1038/s41598-024-82139-7 |
| work_keys_str_mv | AT timothyrsampson alphasynucleinoverexpressioncandrivemicrobiomedysbiosisinmice AT zacharydwallen alphasynucleinoverexpressioncandrivemicrobiomedysbiosisinmice AT woongjaiwon alphasynucleinoverexpressioncandrivemicrobiomedysbiosisinmice AT davidgstandaert alphasynucleinoverexpressioncandrivemicrobiomedysbiosisinmice AT haydehpayami alphasynucleinoverexpressioncandrivemicrobiomedysbiosisinmice AT ashleysharms alphasynucleinoverexpressioncandrivemicrobiomedysbiosisinmice |