Prebiotic Inulin and Sodium Butyrate Attenuate Obesity-Induced Intestinal Barrier Dysfunction by Induction of Antimicrobial Peptides.
Prebiotic Inulin and Sodium Butyrate Attenuate Obesity-Induced Intestinal Barrier Dysfunction by Induction of Antimicrobial Peptides.
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DOI：
10.3389/fimmu.2021.678360
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发表时间：
2021
影响因子：
7.3
通讯作者：
Bischoff SC
中科院分区：
文献类型：
--
作者：
Beisner J;Filipe Rosa L;Kaden-Volynets V;Stolzer I;Günther C;Bischoff SC
粘膜屏障缺陷与代谢性疾病如肥胖和非酒精性脂肪性肝病（NAFLD）有关。喂食西式饮食（WSD）的小鼠会发生肥胖，其特征是饮食诱导的肠屏障功能障碍、细菌内毒素易位和随后的肝脏脂肪变性。为了研究菊粉和丁酸钠是否能改善肠道屏障功能障碍，本实验以C57BL/6小鼠为研究对象，分别饲喂在对照组饲粮中添加10%菊粉和5%丁酸钠的WSD±果糖12周。菊粉和丁酸钠通过降低体重增加、肝脏重量、血浆和肝脏甘油三酯水平来减轻wsd诱导的肥胖小鼠模型中的肝炎。此外，添加菊粉或丁酸钠可诱导Paneth细胞α-防御素和基质金属蛋白酶-7 （MMP7）的表达，并受到WSD的抑制，尤其是添加果糖的WSD。对回肠抗菌肽功能的影响伴随着结肠中β-防御素-1和紧密连接基因的诱导，导致肠道通透性和内毒素血症的改善。小肠隐窝类器官培养结果表明，菊粉发酵产物短链脂肪酸（SCFA）丁酸酯、丙酸酯和乙酸酯可诱导Paneth细胞α-防御素的体外表达，组蛋白去乙酰化和STAT3可能在丁酸介导的α-防御素诱导中起作用。综上所述，菊粉和丁酸钠可减轻饮食诱导的屏障功能障碍，并诱导Paneth细胞抗菌素的表达。益生元纤维或丁酸钠的管理可能是一个有趣的治疗方法，以改善饮食引起的肥胖。
Defects in the mucosal barrier have been associated with metabolic diseases such as obesity and non-alcoholic fatty liver disease (NAFLD). Mice fed a Western-style diet (WSD) develop obesity and are characterized by a diet-induced intestinal barrier dysfunction, bacterial endotoxin translocation and subsequent liver steatosis. To examine whether inulin or sodium butyrate could improve gut barrier dysfunction, C57BL/6 mice were fed a control diet or a WSD ± fructose supplemented with either 10% inulin or 5% sodium butyrate for 12 weeks respectively. Inulin and sodium butyrate attenuated hepatosteatitis in the WSD-induced obesity mouse model by reducing weight gain, liver weight, plasma and hepatic triglyceride level. Furthermore, supplementation with inulin or sodium butyrate induced expression of Paneth cell α-defensins and matrix metalloproteinase-7 (MMP7), which was impaired by the WSD and particularly the fructose-added WSD. Effects on antimicrobial peptide function in the ileum were accompanied by induction of β-defensin-1 and tight junction genes in the colon resulting in improved intestinal permeability and endotoxemia. Organoid culture of small intestinal crypts revealed that the short chain fatty acids (SCFA) butyrate, propionate and acetate, fermentation products of inulin, induce Paneth cell α-defensin expression in vitro, and that histone deacetylation and STAT3 might play a role in butyrate-mediated induction of α-defensins. In summary, inulin and sodium butyrate attenuate diet-induced barrier dysfunction and induce expression of Paneth cell antimicrobials. The administration of prebiotic fiber or sodium butyrate could be an interesting therapeutic approach to improve diet-induced obesity.
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影响因子：
6.1
作者：
Ferreira-Lazarte, Alvaro;Olano, Agustin;Javier Moreno, F.
通讯作者：
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影响因子：
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