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从肠道到大脑：γ-氨基丁酸（GABA）治疗焦虑和失眠的机制及临床应用

From the gut to the brain, mechanisms and clinical applications of γ-aminobutyric acid (GABA) on the treatment of anxiety and insomnia.

作者信息

Jiang Chengji, Chen You, Sun Tao

机构信息

Center for Precision Medicine, School of Medicine and Biomedical Sciences, Huaqiao University, Xiamen, China.

GeneYoung Biopharmaceuticals, Shenzhen, China.

出版信息

Front Neurosci. 2025 May 7;19:1570173. doi: 10.3389/fnins.2025.1570173. eCollection 2025.

DOI:10.3389/fnins.2025.1570173
PMID:40400620
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12093412/
Abstract

Anxiety and insomnia are prevalent global mood disorders, and affect approximately 4 and 10 out of every 100 individuals, respectively. Common abnormal brain activity and altered neural circuitries are detected in patients with anxiety disorders and insomnia, suggesting overlapping pathogenesis in these two disorders. Promisingly, GABA from dietary supplements and GABA produced by gut microbiota have shown significant treatment effects in anxiety and insomnia. This review summarizes neurological mechanisms causing anxiety and insomnia, reveals cellular pathways transferring GABA from the gut to the brain, and delivers the therapeutic potential of gut derived GABA for anxiety and insomnia. Moreover, this review proposes emerging therapeutic strategies utilizing engineered GABA-producing bacteria to target anxiety and insomnia, and highlights the potential of live biotherapeutics as novel interventions for mood disorders.

摘要

焦虑症和失眠症是全球普遍存在的情绪障碍，分别影响约每100人中的4人和10人。在焦虑症和失眠症患者中检测到常见的大脑活动异常和神经回路改变，这表明这两种疾病的发病机制存在重叠。有前景的是，膳食补充剂中的γ-氨基丁酸（GABA）和肠道微生物群产生的GABA已在焦虑症和失眠症治疗中显示出显著效果。本综述总结了导致焦虑症和失眠症的神经机制，揭示了GABA从肠道转移到大脑的细胞途径，并阐述了肠道来源的GABA对焦虑症和失眠症的治疗潜力。此外，本综述提出了利用工程化产GABA细菌治疗焦虑症和失眠症的新兴治疗策略，并强调了活体生物治疗剂作为情绪障碍新型干预措施的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b43/12093412/97d8c0eb332c/fnins-19-1570173-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b43/12093412/bd5b6fe21223/fnins-19-1570173-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b43/12093412/6702f068cf08/fnins-19-1570173-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b43/12093412/0520dbafdbc8/fnins-19-1570173-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b43/12093412/97d8c0eb332c/fnins-19-1570173-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b43/12093412/bd5b6fe21223/fnins-19-1570173-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b43/12093412/6702f068cf08/fnins-19-1570173-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b43/12093412/0520dbafdbc8/fnins-19-1570173-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5b43/12093412/97d8c0eb332c/fnins-19-1570173-g004.jpg

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本文引用的文献

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Multi-Omics Reveal the Improvements of Nutrient Digestion, Absorption, and Metabolism and Intestinal Function via GABA Supplementation in Weanling Piglets.多组学揭示了通过补充GABA对断奶仔猪营养物质消化、吸收、代谢及肠道功能的改善作用。
Animals (Basel). 2024 Nov 6;14(22):3177. doi: 10.3390/ani14223177.
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Gut microbiota modulates neurotransmitter and gut-brain signaling.
肠道微生物群调节神经递质和肠道-大脑信号传递。
Microbiol Res. 2024 Oct;287:127858. doi: 10.1016/j.micres.2024.127858. Epub 2024 Jul 26.
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The effect of physical exercise interventions on insomnia: A systematic review and meta-analysis.运动干预对失眠的影响：系统评价和荟萃分析。
Sleep Med Rev. 2024 Aug;76:101948. doi: 10.1016/j.smrv.2024.101948. Epub 2024 May 9.
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Genetic Circuits for Feedback Control of Gamma-Aminobutyric Acid Biosynthesis in Probiotic Nissle 1917.用于益生菌Nissle 1917中γ-氨基丁酸生物合成反馈控制的遗传电路
Metabolites. 2024 Jan 11;14(1):44. doi: 10.3390/metabo14010044.
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