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      Gut Microbiota and Dysbiosis in Alzheimer’s Disease: Implications for Pathogenesis and Treatment

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          Abstract

          Understanding how gut flora influences gut-brain communications has been the subject of significant research over the past decade. The broadening of the term “microbiota-gut-brain axis” from “gut-brain axis” underscores a bidirectional communication system between the gut and the brain. The microbiota-gut-brain axis involves metabolic, endocrine, neural, and immune pathways which are crucial for the maintenance of brain homeostasis. Alterations in the composition of gut microbiota are associated with multiple neuropsychiatric disorders. Although a causal relationship between gut dysbiosis and neural dysfunction remains elusive, emerging evidence indicates that gut dysbiosis may promote amyloid-beta aggregation, neuroinflammation, oxidative stress, and insulin resistance in the pathogenesis of Alzheimer’s disease (AD). Illustration of the mechanisms underlying the regulation by gut microbiota may pave the way for developing novel therapeutic strategies for AD. In this narrative review, we provide an overview of gut microbiota and their dysregulation in the pathogenesis of AD. Novel insights into the modification of gut microbiota composition as a preventive or therapeutic approach for AD are highlighted.

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          Most cited references144

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          Neuroinflammation in Alzheimer's disease.

          Increasing evidence suggests that Alzheimer's disease pathogenesis is not restricted to the neuronal compartment, but includes strong interactions with immunological mechanisms in the brain. Misfolded and aggregated proteins bind to pattern recognition receptors on microglia and astroglia, and trigger an innate immune response characterised by release of inflammatory mediators, which contribute to disease progression and severity. Genome-wide analysis suggests that several genes that increase the risk for sporadic Alzheimer's disease encode factors that regulate glial clearance of misfolded proteins and the inflammatory reaction. External factors, including systemic inflammation and obesity, are likely to interfere with immunological processes of the brain and further promote disease progression. Modulation of risk factors and targeting of these immune mechanisms could lead to future therapeutic or preventive strategies for Alzheimer's disease. Copyright © 2015 Elsevier Ltd. All rights reserved.
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            Expert consensus document: The International Scientific Association for Probiotics and Prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics

            With the continued interest in the role of the gut microbiota in health, attention has now turned to how to harness the microbiota for the benefit of the host. This Consensus Statement outlines the definition and scope of the term 'prebiotic' as determined by an expert panel convened by the International Scientific Association for Probiotics and Prebiotics in December 2016.
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              Host-gut microbiota metabolic interactions.

              The composition and activity of the gut microbiota codevelop with the host from birth and is subject to a complex interplay that depends on the host genome, nutrition, and life-style. The gut microbiota is involved in the regulation of multiple host metabolic pathways, giving rise to interactive host-microbiota metabolic, signaling, and immune-inflammatory axes that physiologically connect the gut, liver, muscle, and brain. A deeper understanding of these axes is a prerequisite for optimizing therapeutic strategies to manipulate the gut microbiota to combat disease and improve health.
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                Author and article information

                Contributors
                kangdingliu@163.com
                drzhl@hotmail.com , zhanghl@nsfc.gov.cn
                Journal
                Mol Neurobiol
                Mol Neurobiol
                Molecular Neurobiology
                Springer US (New York )
                0893-7648
                1559-1182
                23 August 2020
                23 August 2020
                2020
                : 57
                : 12
                : 5026-5043
                Affiliations
                [1 ]GRID grid.64924.3d, ISNI 0000 0004 1760 5735, Department of Neurology, First Hospital of Jilin University, , Jilin University, ; Xinmin Street 71, Changchun, 130021 China
                [2 ]GRID grid.66875.3a, ISNI 0000 0004 0459 167X, Departments of Laboratory Medicine and Pathology, Neurology and Immunology, , Mayo Clinic, ; Rochester, MN USA
                [3 ]GRID grid.419696.5, ISNI 0000 0001 0841 8282, Department of Life Sciences, , National Natural Science Foundation of China, ; Shuangqing Road 83, Beijing, 100085 China
                Author information
                http://orcid.org/0000-0001-9205-5559
                Article
                2073
                10.1007/s12035-020-02073-3
                7541367
                32829453
                fbcbf467-24f3-4180-9255-0f183a76fd92
                © The Author(s) 2020

                Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

                History
                : 18 May 2020
                : 11 August 2020
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: 81771299
                Award Recipient :
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                © Springer Science+Business Media, LLC, part of Springer Nature 2020

                Neurosciences
                alzheimer’s disease,gut microbiota,microbiota-gut-brain axis,gut dysbiosis
                Neurosciences
                alzheimer’s disease, gut microbiota, microbiota-gut-brain axis, gut dysbiosis

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