title: Lactobacillus rhamnosus GG culture supernatant ameliorates acute alcohol-induced intestinal permeability and liver injury.
abstract: 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)-2α, 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.
authors.affiliation: Department of Medicine, School of Medicine, University of Louisville, 505 S. Hancock St., Louisville, KY 40202, USA.
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Wang
authors.forename: Yanlong
authors.initials: Y
authors.lastname: Liu
authors.forename: Anju
authors.initials: A
authors.lastname: Sidhu
authors.forename: Zhenhua
authors.initials: Z
authors.lastname: Ma
authors.forename: Craig
authors.initials: C
authors.lastname: McClain
authors.forename: Wenke
authors.initials: W
authors.lastname: Feng
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D002492:Central Nervous System Depressants / Q000037:antagonists & inhibitors* / Q000097:blood / Q000633:toxicity; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D003470:Culture Media / Q000737:chemistry; D000431:Ethanol / Q000037:antagonists & inhibitors* / Q000097:blood / Q000633:toxicity; D051793:Hypoxia-Inducible Factor 1 / Q000378:metabolism; D007082:Ileum / Q000187:drug effects / Q000378:metabolism; D007413:Intestinal Mucosa / Q000187:drug effects*; D052201:Lacticaseibacillus rhamnosus / Q000378:metabolism*; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008108:Liver Diseases, Alcoholic / Q000473:pathology / Q000517:prevention & control*; D008111:Liver Function Tests; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010539:Permeability / Q000187:drug effects*; D009195:Peroxidase / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D019108:Tight Junctions / Q000187:drug effects; D014280:Triglycerides / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D002492:Central Nervous System Depressants; D003470:Culture Media; D000431:Ethanol; D051793:Hypoxia-Inducible Factor 1; D009195:Peroxidase; D017382:Reactive Oxygen Species; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D000099162:Endothelial PAS Domain-Containing Protein 1