title: 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.
abstract: 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 Treg cell population while increased TH17 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 Treg and TH17 cells in the role of LGG-s application.
authors.affiliation: Department of Infectious Diseases, the First Affiliated Hospital of Wenzhou Medical University; Hepatology Institute of Wenzhou Medical University; Wenzhou Key Laboratory of Hepatology, Wenzhou, Zhejiang, China.
authors.forename: Rui-Cong
authors.initials: RC
authors.lastname: Chen
authors.affiliation: Department of Infectious Diseases, the First Affiliated Hospital of Wenzhou Medical University; Hepatology Institute of Wenzhou Medical University; Wenzhou Key Laboratory of Hepatology, Wenzhou, Zhejiang, China.
authors.forename: Lan-Man
authors.initials: LM
authors.lastname: Xu
authors.affiliation: Department of Infectious Diseases, the First Affiliated Hospital of Wenzhou Medical University; Hepatology Institute of Wenzhou Medical University; Wenzhou Key Laboratory of Hepatology, Wenzhou, Zhejiang, China.
authors.forename: Shan-Jie
authors.initials: SJ
authors.lastname: Du
authors.affiliation: Department of Infectious Diseases, the First Affiliated Hospital of Wenzhou Medical University; Hepatology Institute of Wenzhou Medical University; Wenzhou Key Laboratory of Hepatology, Wenzhou, Zhejiang, China.
authors.forename: Si-Si
authors.initials: SS
authors.lastname: Huang
authors.affiliation: Department of Infectious Diseases, the First Affiliated Hospital of Wenzhou Medical University; Hepatology Institute of Wenzhou Medical University; Wenzhou Key Laboratory of Hepatology, Wenzhou, Zhejiang, China.
authors.forename: He
authors.initials: H
authors.lastname: Wu
authors.affiliation: Department of Infectious Diseases, the First Affiliated Hospital of Wenzhou Medical University; Hepatology Institute of Wenzhou Medical University; Wenzhou Key Laboratory of Hepatology, Wenzhou, Zhejiang, China.
authors.forename: Jia-Jia
authors.initials: JJ
authors.lastname: Dong
authors.affiliation: Department of Infectious Diseases, the First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Jian-Rong
authors.initials: JR
authors.lastname: Huang
authors.affiliation: Department of Infectious Diseases, the First Affiliated Hospital of Wenzhou Medical University; Hepatology Institute of Wenzhou Medical University; Wenzhou Key Laboratory of Hepatology, Wenzhou, Zhejiang, China.
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Wang
authors.affiliation: Department of Infectious Diseases, the First Affiliated Hospital of Wenzhou Medical University; Hepatology Institute of Wenzhou Medical University; Wenzhou Key Laboratory of Hepatology, Wenzhou, Zhejiang, China; Department of Medicine, Alcohol Research Center, University of Louisville School of Medicine, Louisville, KY, United States. Electronic address: wenke.feng@louisville.edu.
authors.forename: Wen-Ke
authors.initials: WK
authors.lastname: Feng
authors.affiliation: Department of Infectious Diseases, the First Affiliated Hospital of Wenzhou Medical University; Hepatology Institute of Wenzhou Medical University; Wenzhou Key Laboratory of Hepatology, Wenzhou, Zhejiang, China. Electronic address: 13505777281@163.com.
authors.forename: Yong-Ping
authors.initials: YP
authors.lastname: Chen
mesh_terms: D000818:Animals; D063425:Binge Drinking / Q000150:complications / Q000473:pathology*; D002908:Chronic Disease; D004032:Diet; D029968:Escherichia coli Proteins / Q000378:metabolism; D005235:Fatty Liver, Alcoholic / Q000473:pathology; D020381:Interleukin-17 / Q000096:biosynthesis; D007408:Intestinal Absorption / Q000187:drug effects; D007422:Intestines / Q000166:cytology / Q000187:drug effects*; D052201:Lacticaseibacillus rhamnosus / Q000737:chemistry*; D008099:Liver / Q000201:enzymology / Q000473:pathology; D008108:Liver Diseases, Alcoholic / Q000201:enzymology / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects*; D058504:Th17 Cells / Q000187:drug effects*; D062725:Tight Junction Proteins / Q000096:biosynthesis
chemical_list: D029968:Escherichia coli Proteins; D020381:Interleukin-17; D062725:Tight Junction Proteins
keywords: Alcohol; Hepatic injury; Intestinal permeability; Lactobacillus rhamnosus GG supernatant; T helper 17 cells; T regulatory cells