작성일 : 17-10-12 19:46
조회 : 4,248
| https://www.nature.com/articles/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
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.