多组学揭示了微生物群-肠-大脑轴和迷走神经刺激的抗抑郁作用之间的关联
Dan Pan1, Mingchen Jiang2, Ying Wang1
1School of Nursing, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
Neurobiology of stress
|January 6, 2026
概括
通过皮肤耳道迷走神经刺激 (taVNS) 通过调节肠道微生物群和海马体信号通路来缓解抑郁症. 这种非侵入性方法增强了突触功能并重塑了微生物群落,为严重抑郁症提供了一种新的治疗途径.
科学领域:
- 神经科学是一个神经科学.
- 微生物学 微生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 大型抑郁症 (MDD) 存在重大挑战,原因是目前治疗方法的有效性和副作用有限.
- 通过皮肤进行耳膜迷走神经刺激 (taVNS) 为MDD提供了一种安全的,非侵入性的神经调节方法,但其机制需要阐明.
- 人们越来越认识到微生物群-肠-大脑轴对心理健康的作用,但其与抑郁症中的taVNS的相互作用尚未完全理解.
研究的目的:
- 研究taVNS的抗抑郁机制,特别是它对微生物群-肠-大脑轴的影响.
- 探索海马蛋白表达和taVNS引起的肠道微生物变化之间的关系.
- 确定参与taVNS介导抗抑郁药效应的关键分子通路.
主要方法:
- 建立了一个慢性不可预测的轻度压力 (CUMS) 鼠标模型来模拟抑郁症.
- 服用taVNS14天,然后进行海马体蛋白质基因分析和便基因基因测序.
- 使用西斑,qRT-PCR和显微镜验证关键信号通路 (例如,GluN1/MAPK/BDNF) 和微生物变化.
主要成果:
- 在CUMS大鼠中,taVNS治疗显著改善了类似抑郁症的行为.
- 河马蛋白质组分析显示高调的谷氨酸离子体受体N-甲基-D-酸盐类型子单元1 (GluN1) 和来自大脑的神经营养因子 (BDNF),与恢复的基激活蛋白激酶 (MAPK) 信号.
- 转基因组测序显示taVNS增加了Akkermansia muciniphila和Ligilactobacillus murinus,同时降低了Limosilactobacillus reuteri和Lactobacillus johnsonii.
结论:
- 通过GluN1/MAPK/BDNF通路,taVNS通过恢复Glutamatergic神经元中的突触功能来表现出抗抑郁的特性.
- taVNS重新塑造了肠道微生物群的组成,这表明微生物群-肠道-大脑轴在其治疗作用中发挥了作用.
- 海马突突蛋白-1 (Syngr1) 和 *Ligilactobacillus* 丰度之间的正相关性突出显示了微生物群-肠-大脑轴作为taVNS抗抑郁作用的潜在调解者.
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