Activated Drp1-mediated mitochondrial ROS influence the gut microbiome and intestinal barrier after hemorrhagic shock
Activated Drp1-mediated mitochondrial ROS influence the gut microbiome and intestinal barrier after hemorrhagic shock
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失血性休克后激活的 Drp1 介导的线粒体 ROS 影响肠道微生物组和肠道屏障
DOI：
10.18632/aging.102690
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发表时间：
2020-01-31
期刊：
影响因子：
5.2
通讯作者：
Li, Tao
中科院分区：
文献类型：
--
作者：
Duan, Chenyang;Kuang, Lei;Li, Tao
线粒体动力蛋白相关蛋白(Drp1)在失血性休克后肠道微生物群组成和肠道屏障功能中的作用尚未得到证实，因此本研究对此进行了研究。在这里，我们在WT和Drp1 KO小鼠模型中使用了16S rRNA基因测序和基于质谱学的代谢组学分析相结合的方法，以检测失血性休克后激活的Drp1对肠道微生物组的功能影响以及线粒体的代谢调节。我们的数据表明，失血性休克后线粒体Drp1活性的变化参与了肠屏障功能的调节。激活的Drp1显著扰乱拟杆菌门中的肠道微生物组组成。休克后小鼠体内短链脂肪酸(SCFA)产生菌如类杆菌、丁酸单胞菌和臭杆菌的数量明显减少，且与紧密连接蛋白ZO1的分布和肠道通透性呈负相关。综上所述，这些数据表明，Drp1的激活以ROS特异性的方式扰乱肠道微生物群落和SCFA的产生，从而实质上扰乱失血性休克后的紧密连接和肠道屏障功能。我们的发现为靶向Drp1介导的线粒体功能以及微生物群治疗休克后肠屏障功能障碍提供了新的见解。
A role of the mitochondrial dynamin-related protein (Drp1) on gut microbiome composition and intestinal barrier function after hemorrhagic shock has not been identified previously and thus addressed in this study. Here, we used a combination of 16S rRNA gene sequencing and mass spectrometry-based metabolomics profiling in WT and Drp1 KO mouse models to examine the functional impact of activated Drp1 on the gut microbiome as well as mitochondrial metabolic regulation after hemorrhagic shock. Our data showed that changes in mitochondrial Drp1 activity participated in the regulation of intestinal barrier function after hemorrhagic shock. Activated Drp1 significantly perturbed gut microbiome composition in the Bacteroidetes phylum. The abundance of short-chain fatty acid (SCFA) producing microbes, such as Bacteroides, Butyricimonas and Odoribacter, was markedly decreased in mice after shock, and was inversely correlated with both the distribution of the tight junction protein ZO1 and intestinal permeability. Together, these data suggest that Drp1 activation perturbs the gut microbiome community and SCFA production in a ROS-specific manner and thereby substantially disturbs tight junctions and intestinal barrier function after hemorrhagic shock. Our findings provide novel insights for targeting Drp1-mediated mitochondrial function as well as the microbiome in the treatment of intestinal barrier dysfunction after shock.