title: Gut microbiota dysbiosis is associated with inflammation and bacterial translocation in mice with CCl4-induced fibrosis.
abstract: BACKGROUND
  Gut is the major source of endogenous bacteria causing infections in advanced cirrhosis. Intestinal barrier dysfunction has been described in cirrhosis and account for an increased bacterial translocation rate.
  
  
  OBJECTIVE
  We hypothesize that microbiota composition may be affected and change along with the induction of experimental cirrhosis, affecting the inflammatory response.
  
  
  METHODS
  Progressive liver damage was induced in Balb/c mice by weight-controlled oral administration of carbon tetrachloride. Laparotomies were performed at weeks 6, 10, 13 and 16 in a subgroup of treated mice (n = 6/week) and control animals (n = 4/week). Liver tissue specimens, mesenteric lymph nodes, intestinal content and blood were collected at laparotomies. Fibrosis grade, pro-fibrogenic genes expression, gut bacterial composition, bacterial translocation, host's specific butyrate-receptor GPR-43 and serum cytokine levels were measured.
  
  
  RESULTS
  Expression of pro-fibrogenic markers was significantly increased compared with control animals and correlated with the accumulated dose of carbon tetrachloride. Bacterial translocation episodes were less frequent in control mice than in treated animals. Gram-positive anaerobic Clostridia spp count was decreased in treated mice compared with control animals and with other gut common bacterial species, altering the aerobic/anaerobic ratio. This fact was associated with a decreased gene expression of GPR43 in neutrophils of treated mice and inversely correlated with TNF-alpha and IL-6 up-regulation in serum of treated mice along the study protocol. This pro-inflammatory scenario favoured blood bacterial translocation in treated animals, showing the highest bacterial translocation rate and aerobic/anaerobic ratio at the same weeks.
  
  
  CONCLUSIONS
  Gut microbiota alterations are associated with the development of an inflammatory environment, fibrosis progression and bacterial translocation in carbon tetrachloride-treated mice.
authors.affiliation: Unidad Hepática, Hospital General Universitario, Alicante, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Gómez-Hurtado
authors.forename: Arlette
authors.initials: A
authors.lastname: Santacruz
authors.forename: Gloria
authors.initials: G
authors.lastname: Peiró
authors.forename: Pedro
authors.initials: P
authors.lastname: Zapater
authors.forename: Ana
authors.initials: A
authors.lastname: Gutiérrez
authors.forename: Miguel
authors.initials: M
authors.lastname: Pérez-Mateo
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Sanz
authors.forename: Rubén
authors.initials: R
authors.lastname: Francés
mesh_terms: D000818:Animals; D001419:Bacteria / Q000145:classification / Q000235:genetics* / Q000378:metabolism; D018988:Bacterial Translocation; D044822:Biodiversity; D015415:Biomarkers / Q000378:metabolism; D002252:Carbon Tetrachloride Poisoning; D004269:DNA, Bacterial / Q000235:genetics; D005243:Feces / Q000382:microbiology; D005260:Female; D041981:Gastrointestinal Tract / Q000382:microbiology* / Q000473:pathology*; D020869:Gene Expression Profiling; D007249:Inflammation / Q000150:complications / Q000473:pathology*; D007813:Laparotomy; D008103:Liver Cirrhosis / Q000139:chemically induced / Q000150:complications / Q000473:pathology* / Q000601:surgery; D054892:Metagenome / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D015415:Biomarkers; D004269:DNA, Bacterial