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对肠道微生物组细胞外囊泡与宿主相互作用的多层次分析揭示了与肠-大脑轴信号传递的联系

Walid Mottawea^1,2, Basit Yousuf¹, Salma Sultan¹

¹NuGut Research Platform, School of Nutrition Sciences, Faculty of Health Sciences, University of Ottawa, Ottawa, Canada.

Microbiology spectrum

|December 19, 2024

概括

微生物体释放的细胞外囊泡 (MEV) 携带神经活性化合物和蛋白质. 这些囊泡可以穿越肠道和血脑屏障,可能会影响肠-脑轴通信.

科学领域:

微生物学微生物学
神经科学是一个神经科学.
细胞生物学细胞生物学

背景情况:

微生物释放的细胞外囊泡 (MEVs) 对于细胞间信号传递至关重要.
它们在肠-大脑轴中的作用在很大程度上仍未被探索.
MEVs可能会将生物活性化合物通过宿主屏障运送到大脑.

研究的目的:

调查MEVs对生物活性代谢物的载荷能力.
评估MEVs与宿主细胞屏障相互作用和穿越细胞屏障的能力.
探索MEVs在肠-大脑轴上的影响.

主要方法:

从体外和便样本中对MEVs进行多omics (代谢学,代谢蛋白学) 分析.
在特定的 Bacteroides 菌株中隔离和描述GABA 生产.
在实验室中评估MEVs的障碍穿越 (半细胞运输,内细胞分裂) 和细胞效应 (RNA-seq).
在小鼠体内生物分布研究.

主要成果:

MEV含有神经活性代谢物 (例如,阿拉基多尼尔多巴胺, gabapentin,谷氨酸,N-乙乙醇胺) 和GABA.
确定了参与谷氨酸/谷氨酸/GABA通路的丰富蛋白质,与Bacteroides spp.相关.
MEVs证明了剂量依赖的对细胞运输和肠道和大脑内皮细胞的内细胞化.
在体内研究证实了MEVs的生物分布到多个器官,包括大脑.
MEVs调节了肠道细胞中的免疫通路和细胞亡.

结论:

MEV 拥有大量的神经活性化合物和蛋白质.
MEVs可以有效地穿越肠道和血脑屏障.
这些发现凸显了MEVs作为肠-大脑轴中介者的潜力.
MEV可能会通过其运输的货物影响大脑功能和行为.

关键词:

细菌菌菌类的存在细胞外囊泡中的细胞外囊泡.我们的肠道微生物组.肠-大脑轴肠-大脑轴神经活性代谢物是神经活性代谢物.γ-氨基黄油酸 (GABA) 是一种

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