Institute of Environmental and Operational Medicine, Chinese Academy of Military Medical sciences, Tianjin, China.
School of Public Health and Management, Weifang Medical University, Weifang, China.
J Neuroinflammation. 2021 Jan 6;18(1):9. doi: 10.1186/s12974-020-02053-3.
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.
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.
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.
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.
遗传因素和环境危害，包括环境噪声应激，都与肠道微生物群有关，而肠道微生物群会加剧阿尔茨海默病（AD）的病理。然而，环境危险因素在早发性 AD（EOAD）发病机制中的作用和机制仍不清楚。
通过 C57BL/6 野生型（WT）和 APP/PS1 Tg 小鼠模型，评估了环境噪声暴露后 EOAD 发病机制的分子途径。通过 16S rRNA 测序和 Tax4Fun 分析肠道微生物群的组成差异，从测序结果预测宏基因组含量。评估了菌群失调引发的氧化-炎症-屏障失衡以及中枢神经系统末端的肠道-脑轴的作用，以探讨潜在的病理机制。
WT 和 APP/PS1 小鼠均显示环境噪声与相应肠道微生物群的分类组成之间存在统计学显著关系。在噪声暴露的 WT 和 APP/PS1 小鼠中，细菌编码的功能类别包括磷脂和半乳糖代谢、氧化应激和细胞衰老。这些改变与氧化和抗氧化系统失衡以及噪声暴露后低水平全身炎症相对应。在机制上，轴系实验表明，噪声暴露后，肠道和海马紧密连接蛋白水平降低，而炎症介质的血清水平升高。对于 APP/PS1 的过表达，噪声引起的肠道-脑轴异常可能导致 EOAD 小鼠模型在无症状前阶段神经病理学加重。
我们的结果表明，噪声暴露对微生物群-肠道-脑轴中氧化-炎症-屏障的内稳态有有害影响。因此，至少在遗传背景下，慢性噪声可能会加剧 EOAD 的进展。
