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Sci Rep. 2017 Sep 5;7(1):10411. doi: 10.1038/s41598-017-11047-w.

Antibiotic-induced perturbations in microbial diversity during post-natal development alters amyloid pathology in an aged APPSWE/PS1ΔE9 murine model of Alzheimer's disease.

Author information

1
Department of Neurobiology, The University of Chicago, Chicago, IL, 60637, USA.
2
The Microbiome Center, The University of Chicago, Chicago, IL, 60637, USA.
3
Department of Medicine, The University of Chicago, Chicago, IL, 60637, USA.
4
Committee on Immunology, The University of Chicago, Chicago, IL, 60637, USA.
5
Department of Neurology, Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Diseases, Massachusetts General Hospital, Charlestown, MA, 02114, USA.
6
Department of Neurobiology, The University of Chicago, Chicago, IL, 60637, USA. ssisodia@bsd.uchicago.edu.
7
The Microbiome Center, The University of Chicago, Chicago, IL, 60637, USA. ssisodia@bsd.uchicago.edu.

Abstract

Recent evidence suggests the commensal microbiome regulates host immunity and influences brain function; findings that have ramifications for neurodegenerative diseases. In the context of Alzheimer's disease (AD), we previously reported that perturbations in microbial diversity induced by life-long combinatorial antibiotic (ABX) selection pressure in the APPSWE/PS1ΔE9 mouse model of amyloidosis is commensurate with reductions in amyloid-β (Aβ) plaque pathology and plaque-localised gliosis. Considering microbiota-host interactions, specifically during early post-natal development, are critical for immune- and neuro-development we now examine the impact of microbial community perturbations induced by acute ABX exposure exclusively during this period in APPSWE/PS1ΔE9 mice. We show that early post-natal (P) ABX treatment (P14-P21) results in long-term alterations of gut microbial genera (predominantly Lachnospiraceae and S24-7) and reduction in brain Aβ deposition in aged APPSWE/PS1ΔE9 mice. These mice exhibit elevated levels of blood- and brain-resident Foxp3+ T-regulatory cells and display an alteration in the inflammatory milieu of the serum and cerebrospinal fluid. Finally, we confirm that plaque-localised microglia and astrocytes are reduced in ABX-exposed mice. These findings suggest that ABX-induced microbial diversity perturbations during post-natal stages of development coincide with altered host immunity mechanisms and amyloidosis in a murine model of AD.

PMID:
28874832
PMCID:
PMC5585265
DOI:
10.1038/s41598-017-11047-w
[Indexed for MEDLINE]
Free PMC Article

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