尹恝+周宏伟+何彦:脑卒中与肠道菌群失调的双向互作
创作:mildbreeze 审核:mildbreeze 03月01日
  • 在缺血性脑卒中患者中存在动态的肠道菌群失调和恢复,肠杆菌科的富集可预测患者的不良预后;
  • 小鼠试验显示,脑缺血会迅速引起肠道的缺血-再灌注损伤,通过自由基反应产生过量的硝酸盐,导致菌群失调、肠杆菌科扩张;
  • 肠杆菌科的过度增殖,通过LPS-TLR4途径加重全身炎症,恶化脑梗死;
  • 用氨基胍或超氧化物歧化酶减少硝酸盐生成,或用钨酸盐抑制细菌的硝酸盐呼吸,均可抑制肠杆菌科细菌生长,减轻小鼠系统性炎症,减轻脑梗死。
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mildbreeze
中风(脑卒中)是导致死亡和残疾的一个重要原因,目前仍缺乏有效的神经保护防治手段。中风的许多风险因素都与肠道菌群有关,然而,中风和肠道菌群之间的作用关系仍待深入研究。Gut最新发表了来自南方医科大学珠江医院尹恝、周宏伟和何彦与团队的一项研究,揭示了中风与肠道菌群失调之间的双向互作关系:缺血性脑卒中会迅速引发肠道菌群失调、肠杆菌科细菌过度生长,而这种菌群失调反过来会加重脑梗死。该研究进一步阐明了这一现象背后的生物学机制,为临床预后预测和防治干预,提供了具有转化价值的新思路。
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Gut [IF:19.819]

Rapid gut dysbiosis induced by stroke exacerbates brain infarction in turn

中风引起迅速的肠道菌群失调,反过来加剧脑梗死

10.1136/gutjnl-2020-323263

02-09, Article

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Objective : Stroke is a leading cause of death and disability worldwide. Neuroprotective approaches have failed in clinical trials, thus warranting therapeutic innovations with alternative targets. The gut microbiota is an important contributor to many risk factors for stroke. However, the bidirectional interactions between stroke and gut microbiota remain largely unknown.
Design : We performed two clinical cohort studies to capture the gut dysbiosis dynamics after stroke and their relationship with stroke prognosis. Then, we used a middle cerebral artery occlusion model to explore gut dysbiosis post-stroke in mice and address the causative relationship between acute ischaemic stroke and gut dysbiosis. Finally, we tested whether aminoguanidine, superoxide dismutase and tungstate can alleviate post-stroke brain infarction by restoring gut dysbiosis.
Results : Brain ischaemia rapidly induced intestinal ischaemia and produced excessive nitrate through free radical reactions, resulting in gut dysbiosis with Enterobacteriaceae expansion. Enterobacteriaceae enrichment exacerbated brain infarction by enhancing systemic inflammation and is an independent risk factor for the primary poor outcome of patients with stroke. Administering aminoguanidine or superoxide dismutase to diminish nitrate generation or administering tungstate to inhibit nitrate respiration all resulted in suppressed Enterobacteriaceae overgrowth, reduced systemic inflammation and alleviated brain infarction. These effects were gut microbiome dependent and indicated the translational value of the brain–gut axis in stroke treatment.
Conclusions : This study reveals a reciprocal relationship between stroke and gut dysbiosis. Ischaemic stroke rapidly triggers gut microbiome dysbiosis with Enterobacteriaceae overgrowth that in turn exacerbates brain infarction.

First Authors:
Kaiyu Xu

Correspondence Authors:
Yan He,Hongwei Zhou,Jia Yin

All Authors:
Kaiyu Xu,Xuxuan Gao,Genghong Xia,Muxuan Chen,Nianyi Zeng,Shan Wang,Chao You,Xiaolin Tian,Huiling Di,Wenli Tang,Pan Li,Huidi Wang,Xiuli Zeng,Chuhong Tan,Fanguo Meng,Hailong Li,Yan He,Hongwei Zhou,Jia Yin

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