Lactobacillus rhamnosus GG culture supernatant ameliorates acute alcohol-induced intestinal permeability and liver injury
Lactobacillus rhamnosus GG culture supernatant ameliorates acute alcohol-induced intestinal permeability and liver injury
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DOI：
10.1152/ajpgi.00024.2012
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发表时间：
2012-07-01
影响因子：
4.5
通讯作者：
Feng, Wenke
中科院分区：
文献类型：
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作者：
Wang, Yuhua;Liu, Yanlong;Feng, Wenke
王毅，刘毅，马忠，马俊，冯伟.鼠李糖乳杆菌GG培养上清液改善急性酒精诱导的肠通透性和肝损伤。美国生理学胃肠和肝脏生理学杂志303：G32-G41，2012年。首次发表于2012年4月26日; doi：10.1152/ajpgi.00024.2012.-内毒素血症是酒精性肝病（ALD）的辅助因子，酒精诱导的肠道通透性增加是内毒素吸收的机制之一。益生菌已被证明可以促进肠上皮完整性，并保护炎症性肠病（IBD）和ALD中的屏障功能。虽然益生菌分泌的一些常见分子很可能有助于IBD中的这种作用，但益生菌培养物上清液在ALD中的作用尚未研究。我们研究了鼠李糖乳杆菌GG培养上清液（LGG-s）对急性酒精诱导的小鼠肠完整性和肝损伤模型的影响。对标准食物饮食的小鼠补充LGG培养物上清液（10（9）集落形成单位/小鼠）5天，并通过管饲法给予一剂6 g/kg体重的酒精。通过FITC-FD-4离体测量肠渗透性。通过测定血浆中丙氨酸氨基转移酶（ALT）的活性来检测酒精诱导的肝损伤，并通过肝切片的甘油三酯含量和油红O染色来评价肝脂肪变性。LGG-s预处理恢复了酒精诱导的回肠中claudin-1、肠三叶因子（ITF）、P-糖蛋白（P-gp）和cathelin相关抗菌肽（CRAMP）mRNA水平的降低，这些蛋白在肠屏障完整性中起重要作用。结果表明，LGG-s预处理显著抑制了酒精诱导的肠通透性、内毒素血症和随后的肝损伤。有趣的是，LGG-s预处理增加了回肠缺氧诱导因子（HIF）-2 α的mRNA表达，HIF-2 α是ITF、P-gp和CRAMP的重要转录因子。这些结果表明，LGG-s通过促进HIF信号传导，导致抑制酒精诱导的肠通透性增加和内毒素血症，从而改善急性酒精诱导的肝损伤。使用无菌LGG培养上清液为预防急性酒精性肝损伤提供了一种新的策略。
Wang Y, Liu Y, Sidhu A, Ma Z, McClain C, Feng W. Lactobacillus rhamnosus GG culture supernatant ameliorates acute alcohol-induced intestinal permeability and liver injury. Am J Physiol Gastrointest Liver Physiol 303: G32-G41, 2012. First published April 26, 2012; doi:10.1152/ajpgi.00024.2012.-Endotoxemia is a contributing cofactor to alcoholic liver disease (ALD), and alcohol-induced increased intestinal permeability is one of the mechanisms of endotoxin absorption. Probiotic bacteria have been shown to promote intestinal epithelial integrity and protect barrier function in inflammatory bowel disease (IBD) and in ALD. Although it is highly possible that some common molecules secreted by probiotics contribute to this action in IBD, the effect of probiotic culture supernatant has not yet been studied in ALD. We examined the effects of Lactobacillus rhamnosus GG culture supernatant (LGG-s) on the acute alcohol-induced intestinal integrity and liver injury in a mouse model. Mice on standard chow diet were supplemented with supernatant from LGG culture (10(9) colony-forming unit/mouse) for 5 days, and one dose of alcohol at 6 g/kg body wt was administered via gavage. Intestinal permeability was measured by FITC-FD-4 ex vivo. Alcohol-induced liver injury was examined by measuring the activity of alanine aminotransferase (ALT) in plasma, and liver steatosis was evaluated by triglyceride content and Oil Red O staining of the liver sections. LGG-s pretreatment restored alcohol-induced reduction in ileum mRNA levels of claudin-1, intestine trefoil factor (ITF), P-glycoprotein (P-gp), and cathelin-related antimicrobial peptide (CRAMP), which play important roles on intestinal barrier integrity. As a result, LGG-s pretreatment significantly inhibited the alcohol-induced intestinal permeability, endotoxemia and subsequently liver injury. Interestingly, LGG-s pretreatment increased ileum mRNA expression of hypoxia-inducible factor (HIF)-2 alpha, an important transcription factor of ITF, P-gp, and CRAMP. These results suggest that LGG-s ameliorates the acute alcohol-induced liver injury by promoting HIF signaling, leading to the suppression of alcohol-induced increased intestinal permeability and endotoxemia. The use of bacteria-free LGG culture supernatant provides a novel strategy for prevention of acute alcohol-induced liver injury.