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mice, appswepsδe, pubmed, article, abxtreated, google, scholar, doi, male, cas, vehicle, levels, fig, gut, nature, disease, microbial, control, analysis, alzheimers, plaque, microglial, central, data, gene, rrna, altered, abx, brain, treatment, amyloid, microglia, number, plaquelocalized, fecal, month, microbiome, cecal, revealed, dna, controls, function, microbiota, mouse, supp, compared, fold, journal, neuroinflammation, innate,

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5′-gga-cta-cca-ggg-tat-cta-atc-ctg-tt-3′ 5′-tcc-tac-ggg-agg-cag-cag-t-3′ nature portfolio microglia/macrophage-specific calcium-binding protein privacy policy open-reference otu picking abx-treated appswe/ps1δe9 mice x60 z-stack images mini-beadbeater-8k cell disrupter long-term abx treatment author information authors advertising disease research center aging research unit plaque-localized gfap-positive astrocytes male appswe/ps1δe9 mice appswe/ps1δe9 mice treated female appswe/ps1δe9 mice regional variation psychiatry research 203 appswe/ps1δe9 mice leads microbiome-derived pro-inflammatory factors plaque-localized neuro-inflammation tlr2-mediated cd39 signalling z-stack images 0/ reprints gfap+ve positive somas nature communications 6 nature communications 5 nature genetics 41 nature genetics 43 nature methods 7 genome-wide association study nature medicine 18 aβ plaque-localized microglia nature neuroscience 18 16s rrna gene 16s rrna gene antibiotic-perturbed-microbiome shabana antibiotic treatment regime mouse monoclonal anti-aβ microglial-based innate immunity sterile micro-isolator cages display pro-inflammatory influenced neuro-inflammatory responses beneficial neuro-inflammation state cns neuro-inflammatory responses ice-cold heparinized pbs anti-inflammatory il-10 leads anti-aβ mab 3d6

Questions {❓}

• Was it through the loss of microbiome-derived pro-inflammatory factors, or through the gain of disease-preventing factors from a new steady state community development of gut microbiota?

Schema {🗺️}

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         description:Severe amyloidosis and plaque-localized neuro-inflammation are key pathological features of Alzheimer’s disease (AD). In addition to astrocyte and microglial reactivity, emerging evidence suggests a role of gut microbiota in regulating innate immunity and influencing brain function. Here, we examine the role of the host microbiome in regulating amyloidosis in the APPSWE/PS1ΔE9 mouse model of AD. We show that prolonged shifts in gut microbial composition and diversity induced by long-term broad-spectrum combinatorial antibiotic treatment regime decreases Aβ plaque deposition. We also show that levels of soluble Aβ are elevated and that levels of circulating cytokine and chemokine signatures are altered in this setting. Finally, we observe attenuated plaque-localised glial reactivity in these mice and significantly altered microglial morphology. These findings suggest the gut microbiota community diversity can regulate host innate immunity mechanisms that impact Aβ amyloidosis.
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            name:Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Diseases, Massachusetts General Hospital
            address:
               name:Department of Neurology, Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Diseases, Massachusetts General Hospital, Charlestown, USA
               type:PostalAddress
            type:Organization
      name:David M. Holtzman
      affiliation:
            name:Hope Center for Neurological Disorders, Charles F. and Joanne Knight Alzheimer’s Disease Research Center, Washington University School of Medicine
            address:
               name:Department of Neurology, Hope Center for Neurological Disorders, Charles F. and Joanne Knight Alzheimer’s Disease Research Center, Washington University School of Medicine, St. Louis, USA
               type:PostalAddress
            type:Organization
      name:Eugene B. Chang
      affiliation:
            name:The Microbiome Center, The University of Chicago
            address:
               name:The Microbiome Center, The University of Chicago, Chicago, USA
               type:PostalAddress
            type:Organization
            name:The University of Chicago
            address:
               name:Department of Medicine, The University of Chicago, Chicago, USA
               type:PostalAddress
            type:Organization
      name:Rudolph E. Tanzi
      affiliation:
            name:Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Diseases, Massachusetts General Hospital
            address:
               name:Department of Neurology, Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Diseases, Massachusetts General Hospital, Charlestown, USA
               type:PostalAddress
            type:Organization
      name:Sangram S. Sisodia
      affiliation:
            name:The University of Chicago
            address:
               name:Department of Neurobiology, The University of Chicago, Chicago, USA
               type:PostalAddress
            type:Organization
            name:The Microbiome Center, The University of Chicago
            address:
               name:The Microbiome Center, The University of Chicago, Chicago, USA
               type:PostalAddress
            type:Organization
PostalAddress:
      name:Department of Neurobiology, The University of Chicago, Chicago, USA
      name:The Microbiome Center, The University of Chicago, Chicago, USA
      name:Department of Neurology, Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Diseases, Massachusetts General Hospital, Charlestown, USA
      name:The Microbiome Center, The University of Chicago, Chicago, USA
      name:Department of Medicine, The University of Chicago, Chicago, USA
      name:The Microbiome Center, The University of Chicago, Chicago, USA
      name:Department of Medicine, The University of Chicago, Chicago, USA
      name:Department of Neurobiology, The University of Chicago, Chicago, USA
      name:Department of Neurobiology, The University of Chicago, Chicago, USA
      name:The Microbiome Center, The University of Chicago, Chicago, USA
      name:Department of Medicine, The University of Chicago, Chicago, USA
      name:Department of Neurology, Hope Center for Neurological Disorders, Charles F. and Joanne Knight Alzheimer’s Disease Research Center, Washington University School of Medicine, St. Louis, USA
      name:Department of Neurology, Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Diseases, Massachusetts General Hospital, Charlestown, USA
      name:Department of Neurology, Hope Center for Neurological Disorders, Charles F. and Joanne Knight Alzheimer’s Disease Research Center, Washington University School of Medicine, St. Louis, USA
      name:The Microbiome Center, The University of Chicago, Chicago, USA
      name:Department of Medicine, The University of Chicago, Chicago, USA
      name:Department of Neurology, Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Diseases, Massachusetts General Hospital, Charlestown, USA
      name:Department of Neurobiology, The University of Chicago, Chicago, USA
      name:The Microbiome Center, The University of Chicago, Chicago, USA

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