Impact of alcohol-induced intestinal microbiota dysbiosis in a rodent model of Alzheimer’s disease

Introduction: Alzheimer’s disease (AD) is a devastating neurodegenerative disorder. While genetics are important in the development of AD, environment and lifestyle are also important factors influencing AD. One such lifestyle factor is alcohol consumption. Unhealthy and excessive chronic alcohol co...

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Main Authors: Dulce M. Frausto, Phillip A. Engen, Ankur Naqib, Aeja Jackson, Laura Tran, Stefan J. Green, Maliha Shaikh, Christopher B. Forsyth, Ali Keshavarzian, Robin M. Voigt
Format: Article
Language:English
Published: Frontiers Media S.A. 2022-08-01
Series:Frontiers in Aging
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fragi.2022.916336/full
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author Dulce M. Frausto
Phillip A. Engen
Ankur Naqib
Aeja Jackson
Laura Tran
Stefan J. Green
Stefan J. Green
Maliha Shaikh
Christopher B. Forsyth
Christopher B. Forsyth
Christopher B. Forsyth
Ali Keshavarzian
Ali Keshavarzian
Ali Keshavarzian
Ali Keshavarzian
Robin M. Voigt
Robin M. Voigt
Robin M. Voigt
author_facet Dulce M. Frausto
Phillip A. Engen
Ankur Naqib
Aeja Jackson
Laura Tran
Stefan J. Green
Stefan J. Green
Maliha Shaikh
Christopher B. Forsyth
Christopher B. Forsyth
Christopher B. Forsyth
Ali Keshavarzian
Ali Keshavarzian
Ali Keshavarzian
Ali Keshavarzian
Robin M. Voigt
Robin M. Voigt
Robin M. Voigt
author_sort Dulce M. Frausto
collection DOAJ
description Introduction: Alzheimer’s disease (AD) is a devastating neurodegenerative disorder. While genetics are important in the development of AD, environment and lifestyle are also important factors influencing AD. One such lifestyle factor is alcohol consumption. Unhealthy and excessive chronic alcohol consumption is associated with a greater risk of all types of dementia, especially AD. Alcohol consumption has numerous effects on the body, including alterations to the intestinal microbiota (dysbiosis) and intestinal barrier dysfunction (leakiness and intestinal hyperpermeability), with evidence indicating that inflammation resulting from dysbiosis and barrier dysfunction can promote neuroinflammation impacting brain structure and function.Objective: This study sought to determine the impact of alcohol-induced dysbiosis and barrier dysfunction on AD-like behavior and brain pathology using a transgenic rodent model of AD (3xTg-AD).Methods: Alcohol (20%) was administered to 3xTg-AD mice in the drinking water for 20 weeks. Intestinal (stool) microbiota, intestinal barrier permeability, systemic inflammation (IL-6), behavior, and AD pathology (phosphorylated tau and β-amyloid), and microglia were examined.Results: Alcohol consumption changed the intestinal microbiota community (dysbiosis) and increased intestinal barrier permeability in both control and 3xTg-AD mice (oral/urine sugar test and lipopolysaccharide-binding protein (LBP)). However, alcohol consumption did not influence serum IL-6, behavior, or β-amyloid, phosphorylated tau, or microglia in 3xTg-AD mice. Important differences in genotype and sex were noted.Conclusion: Alcohol-induced microbiota dysbiosis and intestinal barrier dysfunction did not exacerbate behavior or AD-like brain pathology in the 3xTg-AD mouse model of AD which could, in part, be the result of a lack of systemic inflammation.
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spelling doaj.art-0673e0f38e28418eaacd21f0b7e10b512022-12-22T02:45:22ZengFrontiers Media S.A.Frontiers in Aging2673-62172022-08-01310.3389/fragi.2022.916336916336Impact of alcohol-induced intestinal microbiota dysbiosis in a rodent model of Alzheimer’s diseaseDulce M. Frausto0Phillip A. Engen1Ankur Naqib2Aeja Jackson3Laura Tran4Stefan J. Green5Stefan J. Green6Maliha Shaikh7Christopher B. Forsyth8Christopher B. Forsyth9Christopher B. Forsyth10Ali Keshavarzian11Ali Keshavarzian12Ali Keshavarzian13Ali Keshavarzian14Robin M. Voigt15Robin M. Voigt16Robin M. Voigt17Rush Center for Integrated Microbiome and Chronobiology Research, Rush University Medical Center, Chicago, IL, United StatesRush Center for Integrated Microbiome and Chronobiology Research, Rush University Medical Center, Chicago, IL, United StatesRush Center for Integrated Microbiome and Chronobiology Research, Rush University Medical Center, Chicago, IL, United StatesRush Center for Integrated Microbiome and Chronobiology Research, Rush University Medical Center, Chicago, IL, United StatesRush Center for Integrated Microbiome and Chronobiology Research, Rush University Medical Center, Chicago, IL, United StatesGenomics and Microbiome Core Facility, Rush University Medical Center, Chicago, IL, United StatesDepartment of Medicine, Rush University Medical Center, Chicago, IL, United StatesRush Center for Integrated Microbiome and Chronobiology Research, Rush University Medical Center, Chicago, IL, United StatesRush Center for Integrated Microbiome and Chronobiology Research, Rush University Medical Center, Chicago, IL, United StatesDepartment of Medicine, Rush University Medical Center, Chicago, IL, United StatesDepartment of Anatomy and Cell Biology, Rush University Medical Center, Chicago, IL, United StatesRush Center for Integrated Microbiome and Chronobiology Research, Rush University Medical Center, Chicago, IL, United StatesDepartment of Medicine, Rush University Medical Center, Chicago, IL, United StatesDepartment of Anatomy and Cell Biology, Rush University Medical Center, Chicago, IL, United StatesDepartment of Physiology, Rush University Medical Center, Chicago, IL, United StatesRush Center for Integrated Microbiome and Chronobiology Research, Rush University Medical Center, Chicago, IL, United StatesDepartment of Medicine, Rush University Medical Center, Chicago, IL, United StatesDepartment of Anatomy and Cell Biology, Rush University Medical Center, Chicago, IL, United StatesIntroduction: Alzheimer’s disease (AD) is a devastating neurodegenerative disorder. While genetics are important in the development of AD, environment and lifestyle are also important factors influencing AD. One such lifestyle factor is alcohol consumption. Unhealthy and excessive chronic alcohol consumption is associated with a greater risk of all types of dementia, especially AD. Alcohol consumption has numerous effects on the body, including alterations to the intestinal microbiota (dysbiosis) and intestinal barrier dysfunction (leakiness and intestinal hyperpermeability), with evidence indicating that inflammation resulting from dysbiosis and barrier dysfunction can promote neuroinflammation impacting brain structure and function.Objective: This study sought to determine the impact of alcohol-induced dysbiosis and barrier dysfunction on AD-like behavior and brain pathology using a transgenic rodent model of AD (3xTg-AD).Methods: Alcohol (20%) was administered to 3xTg-AD mice in the drinking water for 20 weeks. Intestinal (stool) microbiota, intestinal barrier permeability, systemic inflammation (IL-6), behavior, and AD pathology (phosphorylated tau and β-amyloid), and microglia were examined.Results: Alcohol consumption changed the intestinal microbiota community (dysbiosis) and increased intestinal barrier permeability in both control and 3xTg-AD mice (oral/urine sugar test and lipopolysaccharide-binding protein (LBP)). However, alcohol consumption did not influence serum IL-6, behavior, or β-amyloid, phosphorylated tau, or microglia in 3xTg-AD mice. Important differences in genotype and sex were noted.Conclusion: Alcohol-induced microbiota dysbiosis and intestinal barrier dysfunction did not exacerbate behavior or AD-like brain pathology in the 3xTg-AD mouse model of AD which could, in part, be the result of a lack of systemic inflammation.https://www.frontiersin.org/articles/10.3389/fragi.2022.916336/fullAlzheimer’s diseasemicrobiotaalcohol consumption3xTg-ADbehaviorbrain pathology
spellingShingle Dulce M. Frausto
Phillip A. Engen
Ankur Naqib
Aeja Jackson
Laura Tran
Stefan J. Green
Stefan J. Green
Maliha Shaikh
Christopher B. Forsyth
Christopher B. Forsyth
Christopher B. Forsyth
Ali Keshavarzian
Ali Keshavarzian
Ali Keshavarzian
Ali Keshavarzian
Robin M. Voigt
Robin M. Voigt
Robin M. Voigt
Impact of alcohol-induced intestinal microbiota dysbiosis in a rodent model of Alzheimer’s disease
Frontiers in Aging
Alzheimer’s disease
microbiota
alcohol consumption
3xTg-AD
behavior
brain pathology
title Impact of alcohol-induced intestinal microbiota dysbiosis in a rodent model of Alzheimer’s disease
title_full Impact of alcohol-induced intestinal microbiota dysbiosis in a rodent model of Alzheimer’s disease
title_fullStr Impact of alcohol-induced intestinal microbiota dysbiosis in a rodent model of Alzheimer’s disease
title_full_unstemmed Impact of alcohol-induced intestinal microbiota dysbiosis in a rodent model of Alzheimer’s disease
title_short Impact of alcohol-induced intestinal microbiota dysbiosis in a rodent model of Alzheimer’s disease
title_sort impact of alcohol induced intestinal microbiota dysbiosis in a rodent model of alzheimer s disease
topic Alzheimer’s disease
microbiota
alcohol consumption
3xTg-AD
behavior
brain pathology
url https://www.frontiersin.org/articles/10.3389/fragi.2022.916336/full
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