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粪菌移植介导的胃饥饿素恢复改善创伤性脑损伤后的神经功能:来自16S rRNA测序和体内研究的证据

Fecal Microbiota Transplantation-Mediated Ghrelin Restoration Improves Neurological Functions After Traumatic Brain Injury: Evidence from 16S rRNA Sequencing and In Vivo Studies.

作者信息

Zhang Yamei, Liu Junying, Liu Xinyu, Zhou Yan, Geng Jia, Shi Zheng, Ma Li

机构信息

Key Laboratory of Clinical Genetics, Affiliated Hospital of Chengdu University, No. 82, North Section 2, 2nd Ring Road, Chengdu, 610081, People's Republic of China.

State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, People's Republic of China.

出版信息

Mol Neurobiol. 2024 Feb;61(2):919-934. doi: 10.1007/s12035-023-03595-2. Epub 2023 Sep 5.

DOI:10.1007/s12035-023-03595-2
PMID:37668964
Abstract

This study aimed to investigate how gut microbiota dysbiosis impacts the repair of the blood-brain barrier and neurological deficits following traumatic brain injury (TBI). Through 16S rRNA sequencing analysis, we compared the gut microbiota of TBI rats and normal controls, discovering significant differences in abundance, species composition, and ecological function, potentially linked to Ghrelin-mediated brain-gut axis functionality. Further, in vivo experiments showed that fecal microbiota transplantation or Ghrelin injection could block the intracerebral TNF signaling pathway, enhance GLP-1 expression, significantly reduce brain edema post-TBI, promote the repair of the blood-brain barrier, and improve neurological deficits. However, the TNF signaling pathway activation could reverse these beneficial effects. In summary, our research suggests that by restoring the balance of gut microbiota, the levels of Ghrelin can be elevated, leading to the blockade of intracerebral TNF signaling pathway and enhanced GLP-1 expression, thereby mitigating post-TBI blood-brain barrier disruption and neurological injuries.

摘要

本研究旨在探讨肠道微生物群失调如何影响创伤性脑损伤(TBI)后血脑屏障的修复和神经功能缺损。通过16S rRNA测序分析,我们比较了TBI大鼠和正常对照的肠道微生物群,发现其丰度、物种组成和生态功能存在显著差异,这可能与胃饥饿素介导的脑-肠轴功能有关。此外,体内实验表明,粪便微生物群移植或注射胃饥饿素可阻断脑内TNF信号通路,增强GLP-1表达,显著减轻TBI后脑水肿,促进血脑屏障的修复,并改善神经功能缺损。然而,TNF信号通路的激活可逆转这些有益作用。总之,我们的研究表明,通过恢复肠道微生物群的平衡,可以提高胃饥饿素水平,导致脑内TNF信号通路的阻断和GLP-1表达的增强,从而减轻TBI后血脑屏障的破坏和神经损伤。

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本文引用的文献

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Enrofloxacin exposure induces anxiety-like behavioral responses in zebrafish by affecting the microbiota-gut-brain axis.恩诺沙星暴露通过影响微生物群-肠-脑轴诱导斑马鱼出现焦虑样行为反应。
Sci Total Environ. 2023 Feb 1;858(Pt 3):160094. doi: 10.1016/j.scitotenv.2022.160094. Epub 2022 Nov 11.
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Pathogenesis and management of traumatic brain injury (TBI): role of neuroinflammation and anti-inflammatory drugs.外伤性脑损伤(TBI)的发病机制和治疗:神经炎症及抗炎药物的作用。
Inflammopharmacology. 2022 Aug;30(4):1153-1166. doi: 10.1007/s10787-022-01017-8. Epub 2022 Jul 8.
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Fecal Microbiota Transfer Attenuates Gut Dysbiosis and Functional Deficits After Traumatic Brain Injury.
乳酸壳聚糖通过影响微生物群-肠-脑轴改善小鼠重复性闭合性颅脑损伤所致的运动和神经功能障碍。
Metab Brain Dis. 2025 Jan 3;40(1):81. doi: 10.1007/s11011-024-01517-2.
粪便微生物群移植可减轻创伤性脑损伤后的肠道菌群失调和功能障碍。
Shock. 2022 Jun 1;57(6):251-259. doi: 10.1097/SHK.0000000000001934.
4
Fecal Microbiota Transplantation Exerts Neuroprotective Effects in a Mouse Spinal Cord Injury Model by Modulating the Microenvironment at the Lesion Site.粪便微生物群移植通过调节损伤部位的微环境在小鼠脊髓损伤模型中发挥神经保护作用。
Microbiol Spectr. 2022 Jun 29;10(3):e0017722. doi: 10.1128/spectrum.00177-22. Epub 2022 Apr 25.
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Characteristics of Gut Microbiome After Traumatic Brain Injury.创伤性脑损伤后肠道微生物群的特征
J Neurosurg Anesthesiol. 2023 Jan 1;35(1):86-90. doi: 10.1097/ANA.0000000000000789. Epub 2021 Jul 8.
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Acta Neuropathol Commun. 2021 Mar 10;9(1):40. doi: 10.1186/s40478-021-01137-2.
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Brain Res. 2021 Feb 15;1753:147225. doi: 10.1016/j.brainres.2020.147225. Epub 2020 Dec 24.