Divergent metabolic outcomes arising from targeted manipulation of the gut microbiota in diet-induced obesity

作者：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^*

来源：Gut, 2013, 62(2): 220-226.

DOI：10.1136/gutjnl-2011-300705

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(+)). %26lt;br%26gt;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 1x10(9) cfu/day by gavage). Compositional analysis of the microbiota was by 16S rDNA amplicon pyrosequencing. %26lt;br%26gt;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 TNF alpha 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. %26lt;br%26gt;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.

• 出版日期2013-2