title: Divergent metabolic outcomes arising from targeted manipulation of the gut microbiota in diet-induced obesity.
abstract: OBJECTIVE
  The gut microbiota is an environmental regulator of fat storage and adiposity. Whether the microbiota represents a realistic therapeutic target for improving metabolic health is unclear. This study explored two antimicrobial strategies for their impact on metabolic abnormalities in murine diet-induced obesity: oral vancomycin and a bacteriocin-producing probiotic (Lactobacillus salivarius UCC118 Bac(+)).
  
  
  METHODS
  Male (7-week-old) C57BL/J6 mice (9-10/group) were fed a low-fat (lean) or a high-fat diet for 20 weeks with/without vancomycin by gavage at 2 mg/day, or with L. salivarius UCC118Bac(+) or the bacteriocin-negative derivative L. salivarius UCC118Bac(-) (each at a dose of 1×10(9) cfu/day by gavage). Compositional analysis of the microbiota was by 16S rDNA amplicon pyrosequencing.
  
  
  RESULTS
  Analysis of the gut microbiota showed that vancomycin treatment led to significant reductions in the proportions of Firmicutes and Bacteroidetes and a dramatic increase in Proteobacteria, with no change in Actinobacteria. Vancomycin-treated high-fat-fed mice gained less weight over the intervention period despite similar caloric intake, and had lower fasting blood glucose, plasma TNFα and triglyceride levels compared with diet-induced obese controls. The bacteriocin-producing probiotic had no significant impact on the proportions of Firmicutes but resulted in a relative increase in Bacteroidetes and Proteobacteria and a decrease in Actinobacteria compared with the non-bacteriocin-producing control. No improvement in metabolic profiles was observed in probiotic-fed diet-induced obese mice.
  
  
  CONCLUSIONS
  Both vancomycin and the bacteriocin-producing probiotic altered the gut microbiota in diet-induced obese mice, but in distinct ways. Only vancomycin treatment resulted in an improvement in the metabolic abnormalities associated with obesity thereby establishing that while the gut microbiota is a realistic therapeutic target, the specificity of the antimicrobial agent employed is critical.
authors.affiliation: Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland.
authors.forename: Eileen F
authors.initials: EF
authors.lastname: Murphy
authors.forename: Paul D
authors.initials: PD
authors.lastname: Cotter
authors.forename: Aileen
authors.initials: A
authors.lastname: Hogan
authors.forename: Orla
authors.initials: O
authors.lastname: O'Sullivan
authors.forename: Andy
authors.initials: A
authors.lastname: Joyce
authors.forename: Fiona
authors.initials: F
authors.lastname: Fouhy
authors.forename: Siobhan F
authors.initials: SF
authors.lastname: Clarke
authors.forename: Tatiana M
authors.initials: TM
authors.lastname: Marques
authors.forename: Paul W
authors.initials: PW
authors.lastname: O'Toole
authors.forename: Catherine
authors.initials: C
authors.lastname: Stanton
authors.forename: Eamonn M M
authors.initials: EM
authors.lastname: Quigley
authors.forename: Charlie
authors.initials: C
authors.lastname: Daly
authors.forename: Paul R
authors.initials: PR
authors.lastname: Ross
authors.forename: Robert M
authors.initials: RM
authors.lastname: O'Doherty
authors.forename: Fergus
authors.initials: F
authors.lastname: Shanahan
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects; D001430:Bacteriocins / Q000008:administration & dosage / Q000494:pharmacology; D001786:Blood Glucose / Q000187:drug effects; D059305:Diet, High-Fat / Q000009:adverse effects; D016503:Drug Delivery Systems; D015870:Gene Expression; D007249:Inflammation / Q000097:blood; D007413:Intestinal Mucosa / Q000187:drug effects / Q000382:microbiology; D007422:Intestines / Q000187:drug effects* / Q000382:microbiology; D007778:Lactobacillus / Q000502:physiology; D008297:Male; D054892:Metagenome / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism / Q000382:microbiology; D019936:Probiotics / Q000008:administration & dosage / Q000494:pharmacology*; D014280:Triglycerides / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000187:drug effects / Q000235:genetics; D014640:Vancomycin / Q000008:administration & dosage / Q000494:pharmacology*; D015430:Weight Gain / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D001430:Bacteriocins; D001786:Blood Glucose; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha; D014640:Vancomycin