Li Xiaofang, Fu Bo, Zhao Chunli, Hu Junjie, Zhang Xinyao, Fu Yiming, She Xiaojun, Gu Cui, Cheng Mengzhu, Wang Fenghan, Song Xiaoqiong, Dai Jie, Yin Jiayi, Fu Yu, Zheng Pengfang, Wu Fangshan, Zhu Yingwen, Ma Kefeng, Gao Xiujie, Wang Miao, Zeng Qiang, Cui Bo
Tianjin Institute of Environmental and Operational Medicine, Tianjin 300050, China; School of Public Health and Management, Binzhou Medical University, Yantai 264003, China.
Tianjin Institute of Environmental and Operational Medicine, Tianjin 300050, China.
Brain Behav Immun. 2023 Nov;114:221-239. doi: 10.1016/j.bbi.2023.08.021. Epub 2023 Aug 28.
Epidemiological investigations show that noise exposure in early life is associated with health and cognitive impairment. The gut microbiome established in early life plays a crucial role in modulating developmental processes that subsequently affect brain function and behavior. Here, we examined the impact of early-life exposure to noise on cognitive function in adolescent rats by analyzing the gut microbiome and metabolome to elucidate the underlying mechanisms. Chronic noise exposure during early life led to cognitive deficits, hippocampal injury, and neuroinflammation. Early-life noise exposure showed significant difference on the composition and function of the gut microbiome throughout adolescence, subsequently causing axis-series changes in fecal short-chain fatty acid (SCFA) metabolism and serum metabolome profiles, as well as dysregulation of endothelial tight junction proteins, in both intestine and brain. We also observed sex-dependent effects of microbiota depletion on SCFA-related beneficial bacteria in adolescence. Experiments on microbiota transplantation and SCFA supplementation further confirmed the role of intestinal bacteria and related SCFAs in early-life noise-exposure-induced impairments in cognition, epithelial integrity, and neuroinflammation. Overall, these results highlight the homeostatic imbalance of microbiota-gut-brain axis as an important physiological response toward environmental noise during early life and reveals subtle differences in molecular signaling processes between male and female rats.
流行病学调查表明，早年接触噪音与健康和认知障碍有关。早年建立的肠道微生物群在调节随后影响脑功能和行为的发育过程中起着关键作用。在此，我们通过分析肠道微生物群和代谢组来阐明潜在机制，研究早年接触噪音对青春期大鼠认知功能的影响。早年长期接触噪音会导致认知缺陷、海马损伤和神经炎症。早年噪音暴露在整个青春期对肠道微生物群的组成和功能有显著影响，随后导致粪便短链脂肪酸（SCFA）代谢和血清代谢组谱的一系列变化，以及肠道和大脑中内皮紧密连接蛋白的失调。我们还观察到微生物群耗竭对青春期SCFA相关有益细菌的性别依赖性影响。微生物群移植和补充SCFA的实验进一步证实了肠道细菌和相关SCFAs在早年噪音暴露引起的认知、上皮完整性和神经炎症损伤中的作用。总体而言，这些结果突出了微生物群-肠道-脑轴的稳态失衡是早年对环境噪音的重要生理反应，并揭示了雄性和雌性大鼠之间分子信号传导过程中的细微差异。
