Divergent metabolic outcomes arising from targeted manipulation of the gut microbiota in diet-induced obesity. Issue 2 (16th February 2012)

• Record Type: Journal Article
• Authors: Murphy, Eileen F; Cotter, Paul D; Hogan, Aileen; O'Sullivan, Orla; Joyce, Andy; Fouhy, Fiona; Clarke, Siobhan F; Marques, Tatiana M; O'Toole, Paul W; Stanton, Catherine; Quigley, Eamonn M M; Daly, Charlie; Ross, Paul R; O'Doherty, Robert M; Shanahan, Fergus
• Is Part Of: Gut. Volume 62:Issue 2(2013)
• Page Start: 220
• Page End: 226
• Publication Date: 2012-02-16
• Subjects: Antimicrobials -- diet-induced obesity -- gut microbiota -- mouse models; Gastroenterology -- Periodicals; 616.33
• DOI: 10.1136/gutjnl-2011-300705
• Languages: English
• ISSNs: 0017-5749

Abstract

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 1×10 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. 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.