Intestinal Epithelial Inactivity of Dual Oxidase 2 Results in Microbiome-Mediated Metabolic Syndrome.
Intestinal Epithelial Inactivity of Dual Oxidase 2 Results in Microbiome-Mediated Metabolic Syndrome.
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DOI：
10.1016/j.jcmgh.2023.06.009
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发表时间：
2023
影响因子：
7.2
通讯作者：
Abreu, Maria T.
中科院分区：
文献类型：
--
作者：
Hazime, Hajar;Ducasa, G. Michelle;Santander, Ana M.;Brito, Nivis;Gonzalez, Eddy E.;Ban, Yuguang;Kaunitz, Jonathan;Akiba, Yasutada;Fernandez, Irina;Burgueno, Juan F.;Abreu, Maria T.
代谢综合征（MetS）的特征在于肥胖、葡萄糖耐受不良和肝脂肪变性。肠道微生物组的改变在MetS的发展中起着重要作用。然而，这种情况发生的机制知之甚少。双氧化酶2（DUOX 2）是在肠上皮中表达的抗微生物还原型烟酰胺腺嘌呤二核苷酸磷酸氧化酶。在这里，我们认为上皮DUOX 2活性提供了肠道微生物组和MetS发展之间的机制联系。携带肠上皮特异性缺失双氧化酶成熟因子1/2（DA IEC-KO）的小鼠和野生型同窝小鼠喂食标准饮食，并在24周时处死。通过葡萄糖耐量、血脂试验以及体重和器官重量测量来确定代谢变化。通过Amplex Red测定DUOX 2活性。通过异硫氰酸荧光素-葡聚糖、微生物移位评估和门静脉脂多糖测量确定肠通透性。对粪便微生物组进行宏基因组分析。微生物组的作用是在驱虫处理的小鼠中评估的。DA IEC-KO雄性动物显示体重和器官重量增加，伴有葡萄糖耐受不良，血浆脂质和肝酶水平升高，肝脏和脂肪组织肥胖增加。DA IEC-KO雄性动物肝脏和脂肪组织中F4/80、CD 68、解偶联蛋白1、碳水化合物反应元件结合蛋白、瘦素和脂联素的表达发生改变。DA IEC-KO雄性产生较少的上皮H2 O2，改变了粪便中阿克曼氏菌科和毛螺菌科的相对丰度，并显示门静脉脂多糖和肠道渗透性增加。保护女性屏障缺陷和代谢综合征，尽管产生较少的H2 O2。抗生素消耗消除了观察到的所有MetS表型。DUOX 2的肠上皮不活动以微生物组依赖性方式促进MetS。
Metabolic syndrome (MetS) is characterized by obesity, glucose intolerance, and hepatic steatosis. Alterations in the gut microbiome play important roles in the development of MetS. However, the mechanisms by which this occurs are poorly understood. Dual oxidase 2 (DUOX2) is an antimicrobial reduced nicotinamide adenine dinucleotide phosphate oxidase expressed in the gut epithelium. Here, we posit that epithelial DUOX2 activity provides a mechanistic link between the gut microbiome and the development of MetS. Mice carrying an intestinal epithelial-specific deletion of dual oxidase maturation factor 1/2 (DA IEC-KO), and wild-type littermates were fed a standard diet and killed at 24 weeks. Metabolic alterations were determined by glucose tolerance, lipid tests, and body and organ weight measurements. DUOX2 activity was determined by Amplex Red. Intestinal permeability was determined by fluorescein isothiocyanate–dextran, microbial translocation assessments, and portal vein lipopolysaccharide measurements. Metagenomic analysis of the stool microbiome was performed. The role of the microbiome was assessed in antibiotic-treated mice. DA IEC-KO males showed increased body and organ weights accompanied by glucose intolerance and increased plasma lipid and liver enzyme levels, and increased adiposity in the liver and adipose tissue. Expression of F4/80, CD68, uncoupling protein 1, carbohydrate response element binding protein, leptin, and adiponectin was altered in the liver and adipose tissue of DA IEC-KO males. DA IEC-KO males produced less epithelial H2O2, had altered relative abundance of Akkermansiaceae and Lachnospiraceae in stool, and showed increased portal vein lipopolysaccharides and intestinal permeability. Females were protected from barrier defects and MetS, despite producing less H2O2. Antibiotic depletion abrogated all MetS phenotypes observed. Intestinal epithelial inactivity of DUOX2 promotes MetS in a microbiome-dependent manner.
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影响因子：
82.9
作者：
Depommier, Clara;Everard, Amandine;Cani, Patrice D.
通讯作者：
Cani, Patrice D.
影响因子：
2.9
作者：
CHOMCZYNSKI, P;SACCHI, N
通讯作者：
SACCHI, N
影响因子：
29.4
作者：
Chassaing B;Ley RE;Gewirtz AT
通讯作者：
Gewirtz AT
DOI：
10.1016/j.jcmgh.2021.02.007
发表时间：
2021
影响因子：
7.2
作者：
Ghosh S;Whitley CS;Haribabu B;Jala VR
通讯作者：
Jala VR
DOI：
10.1073/pnas.1605443113
发表时间：
2016-09-13
影响因子：
11.1
作者：
Alvarez, Luis A.;Kovacic, Lidija;Knaus, Ulla G.
通讯作者：
Knaus, Ulla G.