Dataset Information

Impact of Acute and Chronic Amyloid-β Peptide Exposure on Gut Microbial Commensals in the Mouse.

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.

SUBMITTER: Dos Santos Guilherme M

PROVIDER: S-EPMC7251927 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Impact of Acute and Chronic Amyloid-β Peptide Exposure on Gut Microbial Commensals in the Mouse.

Dos Santos Guilherme Malena M Todorov Hristo H Osterhof Carina C Möllerke Anton A Cub Kristina K Hankeln Thomas T Gerber Susanne S Endres Kristina K

Frontiers in microbiology 20200520

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 wil ...[more]

PMID: 32508799

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Project description:BackgroundPesticide residues have contaminated our environment and nutrition over the last century. Although these compounds are present at very low concentrations, their long-term effects on human health is of concern. The link between pesticide residues and Alzheimer's disease is not clear and difficult to establish. To date, no in vivo experiments have yet modeled the impact of this chronic contamination on neurodegenerative disorders.ObjectivesWe investigated the impact of fungicide residues on the pathological markers of Alzheimer's disease in a transgenic mouse model.MethodsTransgenic (J20, hAPPSw/Ind) mice were chronically exposed to a cocktail of residues of cyprodinil, mepanipyrim, and pyrimethanil at 0.1μg/L in their drinking water for 9 months. We assessed the effects of fungicide residues on the pathological markers of the disease including Aβ aggregates, neuroinflammation, and neuronal loss. Then, we studied the dynamics of Aβ aggregation in vivo via a longitudinal study using two-photon microscopy. Finally, we investigated the molecular mechanisms involved in the production and clearance of Aβ peptides.ResultsWe found that a chronic exposure to three fungicide residues exacerbated aggregation, microgliosis, and neuronal loss. These fungicides also increased vascular amyloid aggregates reminiscent of cerebral amyloid angiopathy between 6 and 9 months of treatment. The mechanism of action revealed that fungicides promoted Aβ peptide fibril formation in vitro and involved an in vivo overexpression of the levels of the β-secretase-cleaving enzyme (BACE1) combined with impairment of Aβ clearance through neprylisin (NEP).ConclusionsChronic exposure of the J20 mouse model of Alzheimer's disease to a cocktail of fungicides, at the regulatory concentration allowed in tap water (0.1μg/L), strengthened the preexisting pathological markers: neuroinflammation, Aβ aggregation, and APP β-processing. We hypothesize prevention strategies toward pesticide long-term exposure may be an alternative to counterbalance the lack of treatment and to slow down the worldwide Alzheimer's epidemic. https://doi.org/10.1289/EHP5550.

Dataset Information

Impact of Acute and Chronic Amyloid-β Peptide Exposure on Gut Microbial Commensals in the Mouse.

Publications

Impact of Acute and Chronic Amyloid-β Peptide Exposure on Gut Microbial Commensals in the Mouse.

Similar Datasets

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