Intestinal ELF4 Deletion Exacerbates Alcoholic Liver Disease by Disrupting Gut Homeostasis.
Intestinal ELF4 Deletion Exacerbates Alcoholic Liver Disease by Disrupting Gut Homeostasis.
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肠道 ELF4 缺失会破坏肠道稳态，从而加剧酒精性肝病
DOI：
10.3390/ijms23094825
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发表时间：
2022-04-27
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
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作者：
酒精性肝病(ALD)以肠道屏障破坏和肠道生物失调为特征。E74样ETS转录因子4(ELF4)功能障碍导致结肠炎。我们的目的是在ALD小鼠模型中验证肠道ELF4在维持肠道屏障和肠道内稳态的正常功能中起关键作用的假说。肠道ELF4缺乏导致肠屏障功能障碍。ELF4−/−小鼠表现出肠道微生物区系(GM)失调，表现为变形杆菌所占比例较大。ELF4−/−小鼠体内内毒素水平升高，是ELF4−/−小鼠与WT小鼠最重要的差异代谢物。酒精暴露增加了WT小鼠的肝脏与体重的比率，以及肝脏的炎症反应和脂肪变性。这些有害影响在Elf4−/−小鼠身上被夸大了。酒精暴露显著增加ELF4−/−小鼠的血清甘油三酯、丙氨酸氨基转移酶和天冬氨酸氨基转移酶水平，但对WT小鼠没有影响。此外，酒精暴露导致ELF4−/−小鼠肝脏中与胆固醇代谢和脂肪代谢相关的基因表达丰富。16SRRNA测序显示ELF4−/−小鼠体内阿克曼原虫和毕洛菲拉病毒的丰度降低。综上所述，肠道ELF4在维持肠道内稳态和减轻酒精暴露所致的肝脏脂肪变性和损伤方面是一个重要的宿主保护因子。
Alcohol liver disease (ALD) is characterized by intestinal barrier disruption and gut dysbiosis. Dysfunction of E74-like ETS transcription factor 4 (ELF4) leads to colitis. We aimed to test the hypothesis that intestinal ELF4 plays a critical role in maintaining the normal function of intestinal barrier and gut homeostasis in a mouse model of ALD. Intestinal ELF4 deficiency resulted in dysfunction of the intestinal barrier. Elf4−/− mice exhibited gut microbiota (GM) dysbiosis with the characteristic of a larger proportion of Proteobacteria. The LPS increased in Elf4−/− mice and was the most important differential metabolite between Elf4−/− mice and WT mice. Alcohol exposure increased liver-to-body weight ratio, and hepatic inflammation response and steatosis in WT mice. These deleterious effects were exaggerated in Elf4−/− mice. Alcohol exposure significantly increased serum levels of TG, ALT, and AST in Elf4−/− mice but not in WT mice. In addition, alcohol exposure resulted in enriched expression of genes associated with cholesterol metabolism and lipid metabolism in livers from Elf4−/− mice. 16S rRNA sequencing showed a decrease abundance of Akkermansia and Bilophila in Elf4−/− mice. In conclusion, intestinal ELF4 is an important host protective factor in maintaining gut homeostasis and alleviating alcohol exposure-induced hepatic steatosis and injury.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
17.1
作者：
Arrieta, Marie-Claire;Stiemsma, Leah T.;Finlay, B. Brett
通讯作者：
Finlay, B. Brett
影响因子：
24.5
作者：
Camilleri, Michael
通讯作者：
Camilleri, Michael
影响因子：
24.5
作者：
Grander, Christoph;Adolph, Timon E.;Tilg, Herbert
通讯作者：
Tilg, Herbert
影响因子：
5.8
作者：
Du H;Xia H;Liu T;Li Y;Liu J;Xie B;Chen J;Liu T;Cao L;Liu S;Li S;Wang P;Wang D;Zhang Z;Li Y;Guo X;Wu A;Li M;You F
通讯作者：
You F