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Intracerebroventricular Injection of Amyloid-β Peptides in Normal Mice to Acutely Induce Alzheimer-like Cognitive Deficits
Published on: March 16, 2016
Impact of Acute and Chronic Amyloid-β Peptide Exposure on Gut Microbial Commensals in the Mouse
Malena Dos Santos Guilherme1, Hristo Todorov2,3,4, Carina Osterhof5
1Department of Psychiatry and Psychotherapy, University Medical Center, Johannes Gutenberg University Mainz, Mainz, Germany.
Abstract:
Alzheimer's disease (AD) is the most common form of dementia. Besides its cognitive phenotype, AD leads to crucial changes in gut microbiome composition in model mice and in patients, but the reported data are still highly inconsistent. Therefore, we investigated chronic effects of AD-characteristic neurotoxic amyloid-β (Aβ) peptides as provided by transgenic overexpression (5xFAD mouse model) and acute effects due to oral application of Aβ on gut microbes. Astonishingly, one-time feeding of wild type mice with Aβ42 provoked immediate changes in gut microbiome composition (β diversity) as compared to controls. Such obvious changes were not observed when comparing 5xFAD mice with wild type littermates. However, acute as well as chronic exposure to Aβ significantly affected the abundance of numerous individual operational taxonomic units. This provides first evidence that acute in vivo exposure to Aβ results in a shift in the enteric microbiome. Furthermore, we suggest that chronic exposure to Aβ might trigger an adaptive response of gut microbiota which could thereby result in dysbiosis in model mice but also in human patients.
Insights
Alzheimer's disease (AD) neurotoxins, amyloid-beta (Aβ), rapidly alter gut microbiome composition. Chronic Aβ exposure may also induce adaptive gut microbiota responses, potentially leading to dysbiosis in AD models and patients.
Area of Science:
- Neuroscience
- Microbiology
- Gastroenterology
Background:
- Alzheimer's disease (AD) is a common dementia characterized by cognitive decline.
- AD is associated with gut microbiome alterations, but findings are inconsistent.
- Amyloid-beta (Aβ) peptides are implicated in AD pathogenesis.
Purpose of the Study:
- To investigate the chronic effects of Aβ in a transgenic AD mouse model (5xFAD).
- To examine the acute effects of oral Aβ administration on gut microbiota.
- To clarify the relationship between Aβ exposure and gut microbiome changes.
Main Methods:
- Oral administration of Aβ42 to wild-type mice.
- Comparison of gut microbiome composition between 5xFAD mice and wild-type littermates.
- Analysis of operational taxonomic units (OTUs) abundance after Aβ exposure.
Main Results:
- A single oral Aβ42 dose induced immediate changes in gut microbiome diversity (β diversity) in wild-type mice.
- No significant microbiome changes were observed between 5xFAD mice and controls.
- Both acute and chronic Aβ exposure altered the abundance of specific OTUs.
Conclusions:
- Acute in vivo Aβ exposure can shift the enteric microbiome composition.
- Chronic Aβ exposure may trigger adaptive gut microbiota responses, potentially causing dysbiosis.
- These findings suggest a link between Aβ and gut dysbiosis in AD models and patients.
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