军事医学科学院：环境噪音扰乱菌群
[IF:5.793]
在EOAD小鼠模型中，环境噪声应激干扰共生菌群稳态，通过破坏上皮屏障诱导氧化-炎症和AD样神经病理
10.1186/s12974-020-02053-3
01-06, Article
Abstract & Authors:展开
Abstract:收起
Background: Both genetic factors and environmental hazards, including environmental noise stress, have been associated with gut microbiome that exacerbates Alzheimer’s disease (AD) pathology. However, the role and mechanism of environmental risk factors in early-onset AD (EOAD) pathogenesis remain unclear.
Methods: The molecular pathways underlying EOAD pathophysiology following environmental noise exposure were evaluated using C57BL/6 wild-type (WT) and APP/PS1 Tg mouse models. The composition differences in intestinal microbiota were analyzed by 16S rRNA sequencing and Tax4Fun to predict the metagenome content from sequencing results. An assessment of the flora dysbiosis-triggered dyshomeostasis of oxi-inflamm-barrier and the effects of the CNS end of the gut–brain axis was conducted to explore the underlying pathological mechanisms.
Results: Both WT and APP/PS1 mice showed a statistically significant relationship between environmental noise and the taxonomic composition of the corresponding gut microbiome. Bacterial-encoded functional categories in noise-exposed WT and APP/PS1 mice included phospholipid and galactose metabolism, oxidative stress, and cell senescence. These alterations corresponded with imbalanced intestinal oxidation and anti-oxidation systems and low-grade systemic inflammation following noise exposure. Mechanistically, axis-series experiments demonstrated that following noise exposure, intestinal and hippocampal tight junction protein levels reduced, whereas serum levels of inflammatory mediator were elevated. Regarding APP/PS1 overexpression, noise-induced abnormalities in the gut–brain axis may contribute to aggravation of neuropathology in the presymptomatic stage of EOAD mice model.
Conclusion: Our results demonstrate that noise exposure has deleterious effects on the homeostasis of oxi-inflamm-barrier in the microbiome–gut–brain axis. Therefore, at least in a genetic context, chronic noise may aggravate the progression of EOAD.
First Authors:
Huimin Chi,Wa Cao,Ming Zhang
Correspondence Authors:
Bo Cui
All Authors:
Huimin Chi,Wa Cao,Ming Zhang,Donghong Su,Honglian Yang,Zhe Li,Chao Li,Xiaojun She,Kun Wang,Xiujie Gao,Kefeng Ma,Pengfang Zheng,Xiaofang Li,Bo Cui