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Divergent metabolic outcomes arising from targeted manipulation of the gut microbiota in diet-induced obesity
  1. Eileen F Murphy1,2,
  2. Paul D Cotter1,3,
  3. Aileen Hogan1,
  4. Orla O'Sullivan3,
  5. Andy Joyce2,
  6. Fiona Fouhy3,4,
  7. Siobhan F Clarke3,4,
  8. Tatiana M Marques1,3,
  9. Paul W O'Toole1,4,
  10. Catherine Stanton1,3,
  11. Eamonn M M Quigley1,5,
  12. Charlie Daly1,
  13. Paul R Ross1,3,
  14. Robert M O'Doherty1,6,7,
  15. Fergus Shanahan1,5
  1. 1Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland
  2. 2Alimentary Health Ltd., Cork, Ireland
  3. 3Teagasc Food Research Centre, Moorepark Fermoy, County Cork, Ireland
  4. 4Department of Microbiology, University College Cork, Cork, Ireland
  5. 5Department of Medicine, University College Cork, Cork, Ireland
  6. 6Department of Medicine, Division of Endocrinology and Metabolism, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
  7. 7Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
  1. Correspondence to Professor Fergus Shanahan, Department of Medicine and Alimentary Pharmabiotic Centre, University College Cork, National University of Ireland, Cork, Ireland; f.shanahan{at}ucc.ie Professor Robert O'Doherty, Department of Medicine, Division of Endocrinology and Metabolism and Department of Microbiology and Molecular Genetics, University of Pittsburgh, Pittsburgh, PA 15261, USA; rmo1{at}pitt.edu

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+).

Design 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 1×109 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.

Conclusion 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.

  • Antimicrobials
  • diet-induced obesity
  • gut microbiota
  • mouse models

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Footnotes

  • Funding The authors are supported in part by Teagasc (an agency of the Irish government Department of Agriculture, Fisheries and Food), by Science Foundation Ireland (in the form of a research centre grant to the Alimentary Pharmabiotic Centre and a PI award to PWOT and PC), by grant NIH RO1 DK058855 (to ROD) and by Alimentary Health Ltd.

  • Correction notice This article has been corrected since it was published Online First. An additional corresponding author, Professor Robert O'Doherty, has been added.

  • Competing interests None.

  • Ethics approval All experiments were approved by the University College Cork Animal Ethics Committee.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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