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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Frontiers Media S.A.
2022-08-01
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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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