title: Dietary nucleotides protect against alcoholic liver injury by attenuating inflammation and regulating gut microbiota in rats.
abstract: Nucleotides have been reported to be effective in attenuating liver damage and regulating gut microbiota. However, the protective effect of nucleotides against alcoholic liver injury remains unknown. The present study aims to investigate whether nucleotides ameliorate alcoholic liver injury and explores the possible mechanism. Male Wistar rats were given alcohol, equivalent distilled water or an isocaloric amount of dextrose intragastrically twice daily for up to 6 weeks respectively. Two subgroups of alcohol-treated rats were fed with a nucleotide-supplemented AIN-93G rodent diet. Serum enzymes, inflammatory cytokines and microbiota composition of the caecum content were evaluated. We found that nucleotides could significantly decrease serum alanine aminotransferase and aspartate aminotransferase, plasma lipopolysaccharide and inflammatory cytokine levels. Sequencing of 16S rRNA genes revealed that nucleotide-treated rats showed a higher abundance of Firmicutes and a lower abundance of Bacteroidetes than alcohol-treated rats. Moreover, nucleotide treatment inhibited the protein expression of toll-like receptor 4, CD14 and repressed the phosphorylation of inhibitor kappa Bα and nuclear factor-κB p65 in the liver. These results suggested that nucleotides suppressed the inflammatory response and regulated gut microbiota in alcoholic liver injury. The partial inhibition of lipopolysaccharide - toll-like receptor 4-nuclear factor-κB p65 signaling in the liver may be attributed to this mechanism.
authors.affiliation: Department of Nutrition and Food Hygiene, School of Public Health, Peking University, Beijing, P. R. China. liyongbmu@163.com.
authors.forename: Xiaxia
authors.initials: X
authors.lastname: Cai
authors.forename: Lei
authors.initials: L
authors.lastname: Bao
authors.forename: Nan
authors.initials: N
authors.lastname: Wang
authors.forename: Jinwei
authors.initials: J
authors.lastname: Ren
authors.forename: Qihe
authors.initials: Q
authors.lastname: Chen
authors.forename: Meihong
authors.initials: M
authors.lastname: Xu
authors.forename: Di
authors.initials: D
authors.lastname: Li
authors.forename: Ruixue
authors.initials: R
authors.lastname: Mao
authors.forename: Yong
authors.initials: Y
authors.lastname: Li
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D001219:Aspartate Aminotransferases / Q000097:blood; D002432:Cecum / Q000187:drug effects / Q000382:microbiology; D016207:Cytokines / Q000097:blood; D004032:Diet; D019587:Dietary Supplements; D005235:Fatty Liver, Alcoholic / Q000188:drug therapy*; D000069196:Gastrointestinal Microbiome / Q000187:drug effects*; D059014:High-Throughput Nucleotide Sequencing; D007249:Inflammation / Q000188:drug therapy*; D008070:Lipopolysaccharides / Q000097:blood; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D009711:Nucleotides / Q000494:pharmacology*; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D017422:Sequence Analysis, DNA; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D016207:Cytokines; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009711:Nucleotides; D012336:RNA, Ribosomal, 16S; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase