PMID- 28350851 OWN - NLM STAT- MEDLINE DCOM- 20170831 LR - 20230801 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 12 IP - 3 DP - 2017 TI - Alcohol-related changes in the intestinal microbiome influence neutrophil infiltration, inflammation and steatosis in early alcoholic hepatitis in mice. PG - e0174544 LID - 10.1371/journal.pone.0174544 [doi] LID - e0174544 AB - BACKGROUND: Alcohol-induced intestinal dysbiosis disrupts homeostatic gut-liver axis function and is essential in the development of alcoholic liver disease. Here, we investigate changes in enteric microbiome composition in a model of early alcoholic steatohepatitis and dissect the pathogenic role of intestinal microbes in alcohol-induced liver pathology. MATERIALS AND METHODS: Wild type mice received a 10-day diet that was either 5% alcohol-containing or an isocaloric control diet plus a single binge. 16S rDNA sequencing defined the bacterial communities in the cecum of alcohol- and pair-fed animals. Some mice were treated with an antibiotic cocktail prior to and throughout alcohol feeding. Liver neutrophils, cytokines and steatosis were evaluated. RESULTS: Acute-on-chronic alcohol administration induced shifts in various bacterial phyla in the cecum, including increased Actinobacteria and a reduction in Verrucomicrobia driven entirely by a reduction in the genus Akkermansia. Antibiotic treatment reduced the gut bacterial load and circulating bacterial wall component lipopolysaccharide (LPS). We found that bacterial load suppression prevented alcohol-related increases in the number of myeloperoxidase- (MPO) positive infiltrating neutrophils in the liver. Expression of liver mRNA tumor necrosis factor alpha (Tnfalpha), C-X-C motif chemokine ligand 1 (Cxcl1) and circulating protein monocyte chemoattractant protein-1 (MCP-1) were also reduced in antibiotic-treated alcohol-fed mice. Alcohol-induced hepatic steatosis measured by Oil-Red O staining was significantly reduced in antibiotic treated mice. Genes regulating lipid production and storage were also altered by alcohol and antibiotic treatment. Interestingly, antibiotic treatment did not protect from alcohol-induced increases in serum aminotransferases (ALT/AST). CONCLUSIONS: Our data indicate that acute-on-chronic alcohol feeding alters the microflora at multiple taxonomic levels and identifies loss of Akkermansia as an early marker of alcohol-induced gut dysbiosis. We conclude that gut microbes influence liver inflammation, neutrophil infiltration and liver steatosis following alcohol consumption and these data further emphasize the role of the gut-liver axis in early alcoholic liver disease. FAU - Lowe, Patrick P AU - Lowe PP AD - Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America. FAU - Gyongyosi, Benedek AU - Gyongyosi B AD - Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America. FAU - Satishchandran, Abhishek AU - Satishchandran A AD - Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America. FAU - Iracheta-Vellve, Arvin AU - Iracheta-Vellve A AD - Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America. FAU - Ambade, Aditya AU - Ambade A AD - Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America. FAU - Kodys, Karen AU - Kodys K AD - Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America. FAU - Catalano, Donna AU - Catalano D AD - Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America. FAU - Ward, Doyle V AU - Ward DV AD - Center for Microbiome Research, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America. AD - Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America. FAU - Szabo, Gyongyi AU - Szabo G AD - Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, United States of America. LA - eng GR - F30 AA024680/AA/NIAAA NIH HHS/United States GR - R01 AA017729/AA/NIAAA NIH HHS/United States GR - U01 AA021893/AA/NIAAA NIH HHS/United States GR - U01 AA021907/AA/NIAAA NIH HHS/United States PT - Journal Article DEP - 20170328 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Anti-Bacterial Agents) RN - 0 (Central Nervous System Depressants) RN - 0 (RNA, Ribosomal, 16S) RN - 3K9958V90M (Ethanol) SB - IM EIN - PLoS One. 2017 May 31;12 (5):e0179070. PMID: 28562651 MH - Animals MH - Anti-Bacterial Agents/administration & dosage/pharmacology MH - Bacteria/classification/drug effects/genetics MH - Central Nervous System Depressants/administration & dosage/toxicity MH - Ethanol/administration & dosage/toxicity MH - Fatty Liver/chemically induced/*genetics MH - Fatty Liver, Alcoholic/etiology/genetics MH - Female MH - Gastrointestinal Microbiome/drug effects/*genetics MH - Gene Expression/drug effects MH - Hepatitis, Alcoholic/etiology/*genetics MH - Inflammation/chemically induced/*genetics MH - Liver/drug effects/metabolism/pathology MH - Mice, Inbred C57BL MH - Neutrophil Infiltration/drug effects/*genetics MH - RNA, Ribosomal, 16S/genetics MH - Reverse Transcriptase Polymerase Chain Reaction PMC - PMC5370121 COIS- Competing Interests: The authors have declared that no competing interests exist. EDAT- 2017/03/30 06:00 MHDA- 2017/09/01 06:00 PMCR- 2017/03/28 CRDT- 2017/03/29 06:00 PHST- 2016/11/11 00:00 [received] PHST- 2017/03/10 00:00 [accepted] PHST- 2017/03/29 06:00 [entrez] PHST- 2017/03/30 06:00 [pubmed] PHST- 2017/09/01 06:00 [medline] PHST- 2017/03/28 00:00 [pmc-release] AID - PONE-D-16-44278 [pii] AID - 10.1371/journal.pone.0174544 [doi] PST - epublish SO - PLoS One. 2017 Mar 28;12(3):e0174544. doi: 10.1371/journal.pone.0174544. eCollection 2017.