Ischemic Stroke Impacts the Gut Microbiome, Ileal Epithelial and Immune Homeostasis.
Ischemic Stroke Impacts the Gut Microbiome, Ileal Epithelial and Immune Homeostasis.
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DOI：
10.1016/j.isci.2022.105437
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发表时间：
2022-11-18
期刊：
影响因子：
5.8
通讯作者：
Mohamadzadeh, Mansour
中科院分区：
文献类型：
--
作者：
Ge, Yong;Zadeh, Mojgan;Yang, Changjun;Candelario-Jalil, Eduardo;Mohamadzadeh, Mansour
缺血性卒中严重影响神经血管稳态，可能导致神经系统疾病。然而，中风诱导的炎症改变分子和代谢回路的机制，特别是在回肠上皮细胞（iECs），目前仍然难以捉摸。使用多组学方法，我们说明了中风损害了回肠微生物组和相关代谢物，导致炎症信号增加和代谢物改变，可能会破坏iEC稳态。大量转录组学和代谢组学分析表明，中风后第一天内，中风增强了脂肪酸氧化，同时减少了iEC中的三羧酸（TCA）循环。有趣的是，单细胞RNA测序分析显示，中风使iEC内的细胞类型特异性基因反应失调，并降低了杯状细胞和簇状细胞的频率。此外，卒中增加了回肠中的白细胞介素-17 A + γδ T细胞，但减少了CD 4 + T细胞。总的来说，我们的研究结果提供了中风引起的肠道生态失调的全面概述，并揭示了IEC内的反应性基因编程对疾病发展的影响。中风损害肠道微生物组和相关代谢回路中风后小鼠iEC中线粒体FAO和TCA循环失调中风与回肠上皮细胞结构的改变相关生物科学;免疫学;代谢组学;转录组学
Ischemic stroke critically impacts neurovascular homeostasis, potentially resulting in neurological disorders. However, the mechanisms through which stroke-induced inflammation modifies the molecular and metabolic circuits, particularly in ileal epithelial cells (iECs), currently remain elusive. Using multiomic approaches, we illustrated that stroke impaired the ileal microbiome and associated metabolites, leading to increased inflammatory signals and altered metabolites, potentially deteriorating the iEC homeostasis. Bulk transcriptomic and metabolomic profiling demonstrated that stroke enhanced fatty acid oxidation while reducing the tricarboxylic acid (TCA) cycle in iECs within the first day after stroke. Intriguingly, single-cell RNA sequencing analysis revealed that stroke dysregulated cell-type-specific gene responses within iECs and reduced frequencies of goblet and tuft cells. Additionally, stroke augmented interleukin-17A+ γδ T cells but decreased CD4+ T cells in the ileum. Collectively, our findings provide a comprehensive overview of stroke-induced intestinal dysbiosis and unveil responsive gene programming within iECs with implications for disease development. Stroke impairs the gut microbiome and associated metabolic circuits Mitochondrial FAO and TCA cycle are dysregulated in iECs of poststroke mice Stroke is associated with alterations in the ileal epithelial cell structure Biological sciences; Immunology; Metabolomics; Transcriptomics
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影响因子：
82.9
作者：
Benakis C;Brea D;Caballero S;Faraco G;Moore J;Murphy M;Sita G;Racchumi G;Ling L;Pamer EG;Iadecola C;Anrather J
通讯作者：
Anrather J
DOI：
10.1016/j.jcmgh.2020.11.011
发表时间：
2021
影响因子：
7.2
作者：
Bilotta AJ;Ma C;Yang W;Yu Y;Yu Y;Zhao X;Zhou Z;Yao S;Dann SM;Cong Y
通讯作者：
Cong Y
影响因子：
5.9
作者：
通讯作者：
--
DOI：
10.1007/s00018-020-03543-6
发表时间：
2020-11
期刊：
Cellular and molecular life sciences : CMLS
影响因子：
--
作者：
Fung C;Vanden Berghe P
通讯作者：
Vanden Berghe P
影响因子：
7
作者：
Crooks, Benjamin;Stamataki, Nikoleta S.;McLaughlin, John T.
通讯作者：
McLaughlin, John T.