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J Exp Med. 2019 Jul 1;216(7):1542-1560. doi: 10.1084/jem.20182386. Epub 2019 May 16.

Sex-specific effects of microbiome perturbations on cerebral Aβ amyloidosis and microglia phenotypes.

Author information

1
Department of Neurobiology, The University of Chicago, Chicago, IL.
2
Ann Romney Center for Neurological Diseases, Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.
3
Department of Pediatrics and Scripps Institution of Oceanography, University of California, San Diego, La Jolla, CA.
4
Department of Neurobiology, The University of Chicago, Chicago, IL ssisodia@bsd.uchicago.edu.

Abstract

We demonstrated that an antibiotic cocktail (ABX)-perturbed gut microbiome is associated with reduced amyloid-β (Aβ) plaque pathology and astrogliosis in the male amyloid precursor protein (APP)SWE /presenilin 1 (PS1)ΔE9 transgenic model of Aβ amyloidosis. We now show that in an independent, aggressive APPSWE/PS1L166P (APPPS1-21) mouse model of Aβ amyloidosis, an ABX-perturbed gut microbiome is associated with a reduction in Aβ pathology and alterations in microglial morphology, thus establishing the generality of the phenomenon. Most importantly, these latter alterations occur only in brains of male mice, not in the brains of female mice. Furthermore, ABX treatment lead to alterations in levels of selected microglial expressed transcripts indicative of the "M0" homeostatic state in male but not in female mice. Finally, we found that transplants of fecal microbiota from age-matched APPPS1-21 male mice into ABX-treated APPPS1-21 male restores the gut microbiome and partially restores Aβ pathology and microglial morphology, thus demonstrating a causal role of the microbiome in the modulation of Aβ amyloidosis and microglial physiology in mouse models of Aβ amyloidosis.

PMID:
31097468
PMCID:
PMC6605759
[Available on 2020-01-01]
DOI:
10.1084/jem.20182386

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