Gut dysbiosis contributes to amyloid pathology, associated with C/EBPΒ/AEP signaling activation in Alzheimer's disease mouse model

Chun Chen, Eun Hee Ahn, Seong Su Kang, Xia Liu, Ashfaqul Alam, Keqiang Ye

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

Abstract

The gut-brain axis is bidirectional, and gut microbiota influence brain disorders including Alzheimer’s disease (AD). CCAAT/enhancer binding protein β/asparagine endopeptidase (C/EBPβ/AEP) signaling spatiotemporally mediates AD pathologies in the brain via cleaving both β-amyloid precursor protein and Tau. We show that gut dysbiosis occurs in 5xFAD mice, and is associated with escalation of the C/EBPβ/AEP pathway in the gut with age. Unlike that of aged wild-type mice, the microbiota of aged 3xTg mice accelerate AD pathology in young 3xTg mice, accompanied by active C/EBPβ/AEP signaling in the brain. Antibiotic treatment diminishes this signaling and attenuates amyloidogenic processes in 5xFAD, improving cognitive functions. The prebiotic R13 inhibits this pathway and suppresses amyloid aggregates in the gut. R13-induced Lactobacillus salivarius antagonizes the C/EBPβ/AEP axis, mitigating gut leakage and oxidative stress. Our findings support the hypothesis that C/EBPβ/AEP signaling is activated by gut dysbiosis, implicated in AD pathologies in the gut.

Original languageEnglish
Article numbereaba0466
JournalScience advances
Volume6
Issue number31
DOIs
StatePublished - Jul 2020

Bibliographical note

Funding Information:
This work is supported by a grant from the NIH (RF1, AG051538; RO1, NS105982) to K.Y. This study was supported in part by the Rodent Behavioral Core (RBC), which is subsidized by the Emory University School of Medicine and is one of the Emory Integrated Core Facilities. Additional support was provided by the Viral Vector Core of the Emory Neuroscience NINDS Core Facilities (P30NS055077). Further support was provided by the Georgia Clinical and Translational Science Alliance of the National Institutes of Health under award number UL1TR002378. Author contributions: K.Y. conceived the project designed the experiments

Publisher Copyright:
Copyright © 2020 The Authors, some rights reserved.

ASJC Scopus subject areas

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