Journal
TOXICOLOGY LETTERS
Volume 241, Issue -, Pages 103-110Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.toxlet.2015.11.019
Keywords
Lactobacillus rhamnosus GG supernatant; T regulatory cells; T helper 17 cells; Alcohol; Hepatic injury; Intestinal permeability
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Funding
- Natural Science Foundation of Zhejiang Province, China [LY15H030017]
- National Five-year Science and Technology Major Projects [2013ZX10005002-001]
- National Natural Science Foundation [81370481]
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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.
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