Human Defensin-5 Blocks Ethanol and Colitis-Induced Dysbiosis, Tight Junction Disruption and Inflammation in Mouse Intestine.
Human Defensin-5 Blocks Ethanol and Colitis-Induced Dysbiosis, Tight Junction Disruption and Inflammation in Mouse Intestine.
复制标题
DOI：
10.1038/s41598-018-34263-4
复制
发表时间：
2018-11-02
影响因子：
4.6
通讯作者：
Rao R
中科院分区：
文献类型：
--
作者：
Shukla PK;Meena AS;Rao V;Rao RG;Balazs L;Rao R
饮酒已被证明会导致生物失调，但其中涉及的机制尚不清楚。众所周知，复发性结肠炎会诱导结肠中α-防御素的表达，但饮酒对其影响尚不清楚。我们研究了乙醇对小鼠小肠α-防御素表达和结肠炎诱导的结肠表达的影响。此外，我们评估了人类防御素-5(HD5)对酒精和结肠炎诱导的肠屏障功能障碍和粘膜损伤的影响。采用葡聚糖硫酸钠(DSS)诱导大鼠复发性结肠炎模型，共3个周期，每次5d，间隔15d，30d后缓解。在间歇期和恢复期，在添加或不添加HD5的液体饮食中喂饲乙醇。分析α-防御素的表达、紧密连接(TJ)完整性和细胞因子/趋化因子的表达。慢性乙醇喂养减少了小肠中α-防御素的表达，并减少了结肠炎诱导的结肠中防御素的表达。HD5对产肠毒素脆弱类杆菌和大肠杆菌的生长有抑制作用，对非产毒脆弱类杆菌和益生菌乳杆菌无影响。乙醇和结肠炎可提高结肠粘膜中肠杆菌科细菌、细菌和细菌的比例。喂养HD5可减轻酒精和结肠炎引起的生物失调、肠上皮TJ破坏、粘膜炎症、促炎细胞因子和趋化因子在小肠和结肠的表达，以及内毒素血症。这些结果表明，乙醇抑制肠道α-防御素的表达，导致生物失调、屏障功能障碍、炎症和内毒素血症。HD5可减轻乙醇和结肠炎引起的肠道损伤，提示防御素的表达是治疗酒精性组织损伤和结肠炎的潜在靶点。
Alcohol consumption has been shown to cause dysbiosis, but the mechanism involved in it is unknown. Recurrent colitis is known to induce expression of α-defensins in the colon, but the effect of alcohol consumption on it is not known. We investigated the effect of ethanol on α-defensin expression in the small intestine and colitis-induced expression in colon in mice. Furthermore, we evaluated the effect of human defensin-5 (HD5) on ethanol and colitis-induced gut barrier dysfunction and mucosal damage. Recurrent colitis was induced by feeding dextran sulfate sodium (DSS), 3 cycles of 5-days each with 15 days intervals, followed by 30-days remission. Ethanol was fed during the intervals and recovery in a liquid diet with or without HD5. Expression of α-defensins, tight junction (TJ) integrity and cytokine/chemokine expression were analyzed. Chronic ethanol feeding reduced α-defensin expression in the small intestine and colitis-induced defensin expression in the colon. HD5 attenuated the growth of enterotoxigenic Bacteriodes fragilis and E. coli, but had no effect on non-toxigenic Bacteriodes fragilis or probiotics, the Lactobacilli. Ethanol and colitis elevated Enterobacteriaceae, Firmicutes and Firmicutes to Bacteriodetes ratio in colonic mucosa. HD5 feeding attenuated ethanol and colitis-induced dysbiosis, disruption of intestinal epithelial TJ, mucosal inflammation, expression of pro-inflammatory cytokines and chemokines in the small intestine and colon, and endotoxemia. These results demonstrate that ethanol suppresses intestinal α-defensin expression, leading to dysbiosis, barrier dysfunction, inflammation and endotoxemia. HD5 feeding attenuates intestinal injury caused by ethanol and colitis, indicating that defensin expression is a potential target for treatment of alcoholic tissue injury and colitis.
登录
查看更多内容
DOI：
10.1002/hep.23009
发表时间：
2009-08
期刊：
Hepatology (Baltimore, Md.)
影响因子：
--
作者：
Rao R
通讯作者：
Rao R
影响因子：
7.3
作者：
Armbruster NS;Stange EF;Wehkamp J
通讯作者：
Wehkamp J
影响因子：
2.3
作者：
Bevins, Charles L.
通讯作者：
Bevins, Charles L.
影响因子：
5.2
作者：
Preet, Simran;Verma, Indu;Rishi, Praveen
通讯作者：
Rishi, Praveen
影响因子：
15.3
作者：
Menard, Sandrine;Foerster, Valentina;Lotz, Michael;Guetle, Dominique;Duerr, Claudia U.;Gallo, Richard L.;Henriques-Normark, Birgitta;Puetsep, Katrin;Andersson, Mats;Glocker, Erik O.;Hornef, Mathias W.
通讯作者：
Hornef, Mathias W.