Microbiota modulation counteracts Alzheimer’s disease progression influencing neuronal proteolysis and gut hormones plasma levels
Abstract Gut microbiota has a proven role in regulating multiple neuro-chemical pathways through the highly interconnected gut-brain axis. Oral bacteriotherapy thus has potential in the treatment of central nervous system-related pathologies, such as Alzheimer’s disease (AD). Current AD treatments a...
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doaj-5c43f4eb347f46d58ef7a5f70dd9776e2020-12-08T01:19:27ZengNature Publishing GroupScientific Reports2045-23222017-05-017112110.1038/s41598-017-02587-2Microbiota modulation counteracts Alzheimer’s disease progression influencing neuronal proteolysis and gut hormones plasma levelsLaura Bonfili0Valentina Cecarini1Sara Berardi2Silvia Scarpona3Jan S. Suchodolski4Cinzia Nasuti5Dennis Fiorini6Maria Chiara Boarelli7Giacomo Rossi8Anna Maria Eleuteri9School of Biosciences and Veterinary Medicine, University of Camerino, via Gentile III da VaranoSchool of Biosciences and Veterinary Medicine, University of Camerino, via Gentile III da VaranoSchool of Biosciences and Veterinary Medicine, University of Camerino, via Gentile III da VaranoSchool of Biosciences and Veterinary Medicine, University of Camerino, via Gentile III da VaranoGastrointestinal Laboratory, Department of Small Animal Clinical Sciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M UniversitySchool of Pharmacy, Pharmacology Unit, University of Camerino, via Madonna delle CarceriDivision of Chemistry, School of Science and Technology, University of CamerinoDivision of Chemistry, School of Science and Technology, University of CamerinoSchool of Biosciences and Veterinary Medicine, University of Camerino, via Gentile III da VaranoSchool of Biosciences and Veterinary Medicine, University of Camerino, via Gentile III da VaranoAbstract Gut microbiota has a proven role in regulating multiple neuro-chemical pathways through the highly interconnected gut-brain axis. Oral bacteriotherapy thus has potential in the treatment of central nervous system-related pathologies, such as Alzheimer’s disease (AD). Current AD treatments aim to prevent onset, delay progression and ameliorate symptoms. In this work, 3xTg-AD mice in the early stage of AD were treated with SLAB51 probiotic formulation, thereby affecting the composition of gut microbiota and its metabolites. This influenced plasma concentration of inflammatory cytokines and key metabolic hormones considered therapeutic targets in neurodegeneration. Treated mice showed partial restoration of two impaired neuronal proteolytic pathways (the ubiquitin proteasome system and autophagy). Their cognitive decline was decreased compared with controls, due to a reduction in brain damage and reduced accumulation of amyloid beta aggregates. Collectively, our results clearly prove that modulation of the microbiota induces positive effects on neuronal pathways that are able to slow down the progression of Alzheimer’s disease.https://doi.org/10.1038/s41598-017-02587-2 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Laura Bonfili Valentina Cecarini Sara Berardi Silvia Scarpona Jan S. Suchodolski Cinzia Nasuti Dennis Fiorini Maria Chiara Boarelli Giacomo Rossi Anna Maria Eleuteri |
spellingShingle |
Laura Bonfili Valentina Cecarini Sara Berardi Silvia Scarpona Jan S. Suchodolski Cinzia Nasuti Dennis Fiorini Maria Chiara Boarelli Giacomo Rossi Anna Maria Eleuteri Microbiota modulation counteracts Alzheimer’s disease progression influencing neuronal proteolysis and gut hormones plasma levels Scientific Reports |
author_facet |
Laura Bonfili Valentina Cecarini Sara Berardi Silvia Scarpona Jan S. Suchodolski Cinzia Nasuti Dennis Fiorini Maria Chiara Boarelli Giacomo Rossi Anna Maria Eleuteri |
author_sort |
Laura Bonfili |
title |
Microbiota modulation counteracts Alzheimer’s disease progression influencing neuronal proteolysis and gut hormones plasma levels |
title_short |
Microbiota modulation counteracts Alzheimer’s disease progression influencing neuronal proteolysis and gut hormones plasma levels |
title_full |
Microbiota modulation counteracts Alzheimer’s disease progression influencing neuronal proteolysis and gut hormones plasma levels |
title_fullStr |
Microbiota modulation counteracts Alzheimer’s disease progression influencing neuronal proteolysis and gut hormones plasma levels |
title_full_unstemmed |
Microbiota modulation counteracts Alzheimer’s disease progression influencing neuronal proteolysis and gut hormones plasma levels |
title_sort |
microbiota modulation counteracts alzheimer’s disease progression influencing neuronal proteolysis and gut hormones plasma levels |
publisher |
Nature Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2017-05-01 |
description |
Abstract Gut microbiota has a proven role in regulating multiple neuro-chemical pathways through the highly interconnected gut-brain axis. Oral bacteriotherapy thus has potential in the treatment of central nervous system-related pathologies, such as Alzheimer’s disease (AD). Current AD treatments aim to prevent onset, delay progression and ameliorate symptoms. In this work, 3xTg-AD mice in the early stage of AD were treated with SLAB51 probiotic formulation, thereby affecting the composition of gut microbiota and its metabolites. This influenced plasma concentration of inflammatory cytokines and key metabolic hormones considered therapeutic targets in neurodegeneration. Treated mice showed partial restoration of two impaired neuronal proteolytic pathways (the ubiquitin proteasome system and autophagy). Their cognitive decline was decreased compared with controls, due to a reduction in brain damage and reduced accumulation of amyloid beta aggregates. Collectively, our results clearly prove that modulation of the microbiota induces positive effects on neuronal pathways that are able to slow down the progression of Alzheimer’s disease. |
url |
https://doi.org/10.1038/s41598-017-02587-2 |
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