title: Maraviroc modifies gut microbiota composition in a mouse model of obesity: a plausible therapeutic option to prevent metabolic disorders in HIV-infected patients.
abstract: BACKGROUND
  The proportion of HIV-infected patients with overweight/obesity has increased in recent years. These patients have an increased metabolic/cardiovascular risk compared with non-obese patients. Modulation of gut microbiota composition arises as a promising tool to prevent the development of obesity and associated disorders. The aim of this study was to investigate the impacts of maraviroc (MVC), a CCR5 antagonist approved for clinical use in HIV-infected patients, on gut microbiota composition in a mouse model of obesity.
  
  
  METHODS
  Thirty two male C57BL/6 mice were assigned to:a) Control (chow diet), b) MVC (chow diet plus 300 mg/L MVC), c) High-fat diet (HFD) or d) HFD/MVC (HFD plus 300 mg/L MVC) groups. Body weight and food intake was recorded every 2-3 days. Mice were euthanized after 16 weeks of treatment and cecal contents were removed to analyse by real-time PCR four bacterial orders from the most dominant phyla in gut.
  
  
  RESULTS
  Mice fed with a HFD showed a significant increase in Enterobacteriales (p<0.001 vs. control). MVC treatment induced a significant decrease in control (p<0.05) and HFD fed mice (p<0.001). Interestingly, this order was positively associated with body weight gain, insulin resistance and fatty liver. HFD induced a significant decrease in Bacteroidales and Clostridiales levels (p<0.05 and p<0.01, respectively). MVC decreased the presence of Bacteroidales (p<0.05 vs. control) while an increase was observed in HFD/MVC mice (p=0.01 vs. HFD). No direct effects of MVC were observed on Clostridiales and Lactobacillales.
  
  
  CONCLUSIONS
  MVC may constitute a new therapeutic option to prevent obesity and related disorders in HIV-infected patients.
authors.affiliation: Patricia Pérez-Matute, HIV and Associated Metabolic Alterations Unit Infectious Diseases Department Center for Biomedical Research of La Rioja (CIBIR), Piqueras 98, 3rd floor, 26006 Logroño, Spain. cpperez@riojasalud.es.
authors.forename: Patricia
authors.initials: P
authors.lastname: Pérez-Matute
authors.forename: Laura
authors.initials: L
authors.lastname: Pérez-Martínez
authors.forename: Javier
authors.initials: J
authors.lastname: Aguilera-Lizarraga
authors.forename: José R
authors.initials: JR
authors.lastname: Blanco
authors.forename: José A
authors.initials: JA
authors.lastname: Oteo
mesh_terms: D000818:Animals; D018988:Bacterial Translocation / Q000187:drug effects; D041963:Bacteroidetes / Q000187:drug effects / Q000302:isolation & purification; D065100:CCR5 Receptor Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D002432:Cecum / Q000382:microbiology*; D003510:Cyclohexanes / Q000494:pharmacology* / Q000627:therapeutic use; D059305:Diet, High-Fat; D004353:Drug Evaluation, Preclinical; D000068536:Bacillota / Q000187:drug effects / Q000302:isolation & purification; D023581:HIV Fusion Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D000077592:Maraviroc; D008659:Metabolic Diseases / Q000209:etiology / Q000517:prevention & control*; D051379:Mice; D008810:Mice, Inbred C57BL; D064307:Microbiota / Q000187:drug effects*; D065626:Non-alcoholic Fatty Liver Disease / Q000209:etiology / Q000382:microbiology; D009765:Obesity / Q000150:complications / Q000517:prevention & control; D020560:Proteobacteria / Q000187:drug effects / Q000302:isolation & purification; D011897:Random Allocation; D013045:Species Specificity; D014230:Triazoles / Q000494:pharmacology* / Q000627:therapeutic use; D015430:Weight Gain
chemical_list: D065100:CCR5 Receptor Antagonists; D003510:Cyclohexanes; D023581:HIV Fusion Inhibitors; D014230:Triazoles; D000077592:Maraviroc