Zhang Yamei, Liu Junying, Liu Xinyu, Zhou Yan, Geng Jia, Shi Zheng, Ma Li
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.
Mol Neurobiol. 2024 Feb;61(2):919-934. doi: 10.1007/s12035-023-03595-2. Epub 2023 Sep 5.
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.
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。