慢性噪声暴露对衰老加速敏感小鼠微生物群-肠-脑轴的影响：对阿尔茨海默病的启示。

BACKGROUND: Chronic noise exposure is associated with neuroinflammation and gut microbiota dysregulation and increases the risk of Alzheimer's disease (AD). Environmental hazards are also thought to be associated with genetic susceptibility factors that increase AD pathogenesis. However, there is limited experimental evidence regarding the link between chronic noise stress and microbiome-gut-brain axis alterations, which may be closely related to AD development. METHODS: The aim of the present study was to systematically investigate the effects of chronic noise exposure on the microbiome-gut-brain axis in the senescence-accelerated mouse prone 8 (SAMP8) strain. We established SAMP8 mouse models to examine the consequences of noise exposure on the microbiome-gut-brain axis. Hippocampal amyloid-β (Aβ) assessment and the Morris water maze were used to evaluate AD-like changes, 16S ribosomal RNA sequencing analyses were used for intestinal flora measurements, and assessment of endothelial tight junctions and serum neurotransmitter and inflammatory mediator levels, as well as fecal microbiota transplant, was conducted to explore the underlying pathological mechanisms. RESULTS: Chronic noise exposure led to cognitive impairment and Aβ accumulation in young SAMP8 mice, similar to that observed in aging SAMP8 mice. Noise exposure was also associated with decreased gut microbiota diversity and compositional alterations. Axis-series studies showed that endothelial tight junction proteins were decreased in both the intestine and brain, whereas serum neurotransmitter and inflammatory mediator levels were elevated in young SAMP8 mice exposed to chronic noise, similar to the observations made in the aging group. The importance of intestinal bacteria in noise exposure-induced epithelial integrity impairment and Aβ accumulation was further confirmed through microbiota transplantation experiments. Moreover, the effects of chronic noise were generally intensity-dependent. CONCLUSION: Chronic noise exposure altered the gut microbiota, accelerated age-related neurochemical and inflammatory dysregulation, and facilitated AD-like changes in the brain of SAMP8 mice.

背景：慢性噪声暴露与神经炎症和肠道微生物失调有关，并增加阿尔茨海默病（AD）的风险。环境危害也被认为与增加 AD 发病机制的遗传易感性因素有关。然而，关于慢性噪声应激与微生物群-肠道-大脑轴改变之间的联系，目前实验证据有限，这可能与 AD 的发展密切相关。

方法：本研究旨在系统研究慢性噪声暴露对衰老加速小鼠易感 8 型（SAMP8）品系微生物群-肠道-大脑轴的影响。我们建立了 SAMP8 小鼠模型，以研究噪声暴露对微生物群-肠道-大脑轴的影响。海马淀粉样β（Aβ）评估和 Morris 水迷宫用于评估 AD 样变化，16S 核糖体 RNA 测序分析用于肠道菌群测量，评估内皮紧密连接和血清神经递质和炎症介质水平，以及粪便微生物群移植，用于探索潜在的病理机制。

结果：慢性噪声暴露导致年轻 SAMP8 小鼠认知障碍和 Aβ 积累，类似于衰老 SAMP8 小鼠。噪声暴露还与肠道微生物多样性降低和组成改变有关。轴系研究表明，肠道和大脑中的内皮紧密连接蛋白减少，而年轻 SAMP8 小鼠暴露于慢性噪声时血清神经递质和炎症介质水平升高，与衰老组的观察结果相似。通过微生物群移植实验进一步证实了肠道细菌在噪声暴露诱导的上皮完整性损伤和 Aβ 积累中的重要性。此外，慢性噪声的影响通常与强度有关。

结论：慢性噪声暴露改变了肠道微生物群，加速了与年龄相关的神经化学和炎症失调，并促进了 SAMP8 小鼠大脑中 AD 样变化。