title: Antibiotic-induced perturbations in gut microbial diversity influences neuro-inflammation and amyloidosis in a murine model of Alzheimer's disease.
abstract: 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.
authors.affiliation: Department of Neurobiology, The University of Chicago, Chicago, IL, 60637, USA.|The Microbiome Center, The University of Chicago, Chicago, IL, 60637, USA.
authors.forename: Myles R
authors.initials: MR
authors.lastname: Minter
authors.affiliation: Department of Neurology, Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Diseases, Massachusetts General Hospital, Charlestown, MA 02114, USA.
authors.forename: Can
authors.initials: C
authors.lastname: Zhang
authors.affiliation: The Microbiome Center, The University of Chicago, Chicago, IL, 60637, USA.|Department of Medicine, The University of Chicago, Chicago, IL, 60637, USA.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Leone
authors.affiliation: The Microbiome Center, The University of Chicago, Chicago, IL, 60637, USA.|Department of Medicine, The University of Chicago, Chicago, IL, 60637, USA.
authors.forename: Daina L
authors.initials: DL
authors.lastname: Ringus
authors.affiliation: Department of Neurobiology, The University of Chicago, Chicago, IL, 60637, USA.
authors.forename: Xiaoqiong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Neurobiology, The University of Chicago, Chicago, IL, 60637, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Oyler-Castrillo
authors.affiliation: The Microbiome Center, The University of Chicago, Chicago, IL, 60637, USA.|Department of Medicine, The University of Chicago, Chicago, IL, 60637, USA.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Musch
authors.affiliation: 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, MO, 63110, USA.
authors.forename: Fan
authors.initials: F
authors.lastname: Liao
authors.affiliation: Department of Neurology, Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Diseases, Massachusetts General Hospital, Charlestown, MA 02114, USA.
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Ward
authors.affiliation: 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, MO, 63110, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Holtzman
authors.affiliation: The Microbiome Center, The University of Chicago, Chicago, IL, 60637, USA.|Department of Medicine, The University of Chicago, Chicago, IL, 60637, USA.
authors.forename: Eugene B
authors.initials: EB
authors.lastname: Chang
authors.affiliation: Department of Neurology, Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Diseases, Massachusetts General Hospital, Charlestown, MA 02114, USA.
authors.forename: Rudolph E
authors.initials: RE
authors.lastname: Tanzi
authors.affiliation: Department of Neurobiology, The University of Chicago, Chicago, IL, 60637, USA.|The Microbiome Center, The University of Chicago, Chicago, IL, 60637, USA.
authors.forename: Sangram S
authors.initials: SS
authors.lastname: Sisodia
mesh_terms: D000544:Alzheimer Disease / Q000503:physiopathology*; D000686:Amyloidosis / Q000503:physiopathology*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage; D004195:Disease Models, Animal; D064806:Dysbiosis / Q000139:chemically induced; D000069196:Gastrointestinal Microbiome / Q000276:immunology*; D007113:Immunity, Innate; D007249:Inflammation / Q000503:physiopathology*; D051379:Mice
chemical_list: D000900:Anti-Bacterial Agents