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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Main Authors: Laura Bonfili, Valentina Cecarini, Sara Berardi, Silvia Scarpona, Jan S. Suchodolski, Cinzia Nasuti, Dennis Fiorini, Maria Chiara Boarelli, Giacomo Rossi, Anna Maria Eleuteri
Format: Article
Language:English
Published: Nature Publishing Group 2017-05-01
Series:Scientific Reports
Online Access:https://doi.org/10.1038/s41598-017-02587-2
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spelling 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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