title: Hepatic and fecal metabolomic analysis of the effects of Lactobacillus rhamnosus GG on alcoholic fatty liver disease in mice.
abstract: The interactions among the gut, liver, and immune system play an important role in liver disease. Probiotics have been used for the treatment and prevention of many pathological conditions, including liver diseases. Comprehensive two-dimensional gas chromatography time-of-flight mass spectrometry (GC×GC-TOF MS) was used herein, in conjunction with chemometric data analysis, to identify metabolites significantly affected by probiotics in mice fed with or without alcohol. The metabolomics analysis indicates that the levels of fatty acids increased in mouse liver and decreased in mouse feces when mice were chronically exposed to alcohol. Supplementing the alcohol-fed mice with culture supernatant from Lactobacillus rhamnosus GG (LGGs) normalized these alcohol-induced abnormalities and prevented alcoholic liver disease (ALD). These results agree well with previous studies. In addition to diet-derived long chain fatty acids (LCFAs), LGGs may positively modify the gut's bacterial population to stimulate LCFA synthesis, which has been shown to enhance intestinal barrier function, reduce endotoxemia, and prevent ALD. We also found that several amino acids, including l-isoleucine, a branched chain amino acid, were downregulated in the liver and fecal samples from animals exposed to alcohol and that the levels of these amino acids were corrected by LGGs. These results demonstrate that LGGs alleviates alcohol-induced fatty liver by mechanisms involving increasing intestinal and decreasing hepatic fatty acids and increasing amino acid concentration.
authors.affiliation: Departments of Chemistry, ‡Pharmacology & Toxicology, §Medicine, and ⊥Center for Regulatory and Environmental Analytical Metabolomics, University of Louisville , Louisville, Kentucky 40292, United States.
authors.forename: Xue
authors.initials: X
authors.lastname: Shi
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Wei
authors.forename: Xinmin
authors.initials: X
authors.lastname: Yin
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Wang
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.forename: Cuiqing
authors.initials: C
authors.lastname: Zhao
authors.forename: Haiyang
authors.initials: H
authors.lastname: Zhao
authors.forename: Craig J
authors.initials: CJ
authors.lastname: McClain
authors.forename: Wenke
authors.initials: W
authors.lastname: Feng
authors.forename: Xiang
authors.initials: X
authors.lastname: Zhang
mesh_terms: D000818:Animals; D005235:Fatty Liver, Alcoholic / Q000378:metabolism*; D005243:Feces; D008401:Gas Chromatography-Mass Spectrometry; D052201:Lacticaseibacillus rhamnosus / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D055432:Metabolomics; D051379:Mice
keywords: GC×GC-TOF MS; alcohol liver disease; liver; metabolomics; probiotics