Lactobacillus rhamnosus GG supernatant promotes intestinal barrier function, balances Treg and TH17 cells and ameliorates hepatic injury in a mouse model of chronic-binge alcohol feeding
Lactobacillus rhamnosus GG supernatant promotes intestinal barrier function, balances Treg and TH17 cells and ameliorates hepatic injury in a mouse model of chronic-binge alcohol feeding
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DOI：
10.1016/j.toxlet.2015.11.019
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发表时间：
2016-01-22
影响因子：
3.5
通讯作者：
Chen, Yong-Ping
中科院分区：
文献类型：
--
作者：
Chen, Rui-Cong;Xu, Lan-Man;Chen, Yong-Ping
肠道屏障功能受损在酒精性肝损伤中起关键作用，随后过量吸收内毒素和细菌易位激活免疫反应，加重肝损伤。鼠李糖乳杆菌GG上清液（LGG-s）被认为具有改善肠道屏障功能和减轻慢性和狂饮酒精所致肝损伤的作用，但其机制尚不清楚。本研究采用慢性狂饮酒精喂养模型，研究LGG-s对C57BL/6小鼠酒精性肝病的预防作用，并探讨其机制。小鼠饲喂含5%酒精的Lieber-DeCarli日粮10 d，第11天灌胃1剂酒精。在一组中，与酒精一起补充LGG-s。对照组小鼠喂食等热量饮食。9小时后，处死小鼠进行分析。长期酗酒会导致肝酶升高、脂肪变性和形态改变，而补充LGG-s则会减弱这些变化。LGG-s显著改善了肠道屏障功能，其表现为回肠紧密连接蛋白mRNA表达和绒毛隐窝组织学表达增加，肝脏大肠杆菌蛋白水平降低。重要的是，流式细胞术分析显示，酒精减少T-reg细胞群，增加T(H)17细胞群和IL-17分泌，这被LGG-s逆转。总之，我们的研究结果表明，LGG-s在预防慢性酗酒暴露引起的肝损伤方面是有效的，并揭示了T-reg和T(H)17细胞平衡在LGG-s应用中的重要性。2015爱思唯尔爱尔兰有限公司版权所有。
Impaired intestinal barrier function plays a critical role in alcohol-induced hepatic injury, and the subsequent excessive absorbed endotoxin and bacterial translocation activate the immune response that aggravates the liver injury. Lactobacillus rhamnosus GG supernatant (LGG-s) has been suggested to improve intestinal barrier function and alleviate the liver injury induced by chronic and binge alcohol consumption, but the underlying mechanisms are still not clear. In this study, chronic-binge alcohol fed model was used to determine the effects of LGG-s on the prevention of alcoholic liver disease in C57BL/6 mice and investigate underlying mechanisms. Mice were fed Lieber-DeCarli diet containing 5% alcohol for 10 days, and one dose of alcohol was gavaged on Day 11. In one group, LGG-s was supplemented along with alcohol. Control mice were fed isocaloric diet. Nine hours later the mice were sacrificed for analysis. Chronic-binge alcohol exposure induced an elevation in liver enzymes, steatosis and morphology changes, while LGG-s supplementation attenuated these changes. Treatment with LGG-s significantly improved intestinal barrier function reflected by increased mRNA expression of tight junction (TJ) proteins and villus-crypt histology in ileum, and decreased Escherichia coli (E. coli) protein level in liver. Importantly, flow cytometry analysis showed that alcohol reduced T-reg cell population while increased T(H)17 cell population as well as IL-17 secretion, which was reversed by LGG-s administration. In conclusion, our findings indicate that LGG-s is effective in preventing chronic-binge alcohol exposure-induced liver injury and shed a light on the importance of the balance of T-reg and T(H)17 cells in the role of LGG-s application. (C) 2015 Elsevier Ireland Ltd. All rights reserved.