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Divergent metabolic outcomes arising from targeted manipulation of the gut microbiota in diet-induced obesity.
Gut. 2013 Feb; 62(2):220-6.Gut

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.

Authors+Show Affiliations

Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22345653

Citation

Murphy, Eileen F., et al. "Divergent Metabolic Outcomes Arising From Targeted Manipulation of the Gut Microbiota in Diet-induced Obesity." Gut, vol. 62, no. 2, 2013, pp. 220-6.
Murphy EF, Cotter PD, Hogan A, et al. Divergent metabolic outcomes arising from targeted manipulation of the gut microbiota in diet-induced obesity. Gut. 2013;62(2):220-6.
Murphy, E. F., Cotter, P. D., Hogan, A., O'Sullivan, O., Joyce, A., Fouhy, F., Clarke, S. F., Marques, T. M., O'Toole, P. W., Stanton, C., Quigley, E. M., Daly, C., Ross, P. R., O'Doherty, R. M., & Shanahan, F. (2013). Divergent metabolic outcomes arising from targeted manipulation of the gut microbiota in diet-induced obesity. Gut, 62(2), 220-6. https://doi.org/10.1136/gutjnl-2011-300705
Murphy EF, et al. Divergent Metabolic Outcomes Arising From Targeted Manipulation of the Gut Microbiota in Diet-induced Obesity. Gut. 2013;62(2):220-6. PubMed PMID: 22345653.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Divergent metabolic outcomes arising from targeted manipulation of the gut microbiota in diet-induced obesity. AU - Murphy,Eileen F, AU - Cotter,Paul D, AU - Hogan,Aileen, AU - O'Sullivan,Orla, AU - Joyce,Andy, AU - Fouhy,Fiona, AU - Clarke,Siobhan F, AU - Marques,Tatiana M, AU - O'Toole,Paul W, AU - Stanton,Catherine, AU - Quigley,Eamonn M M, AU - Daly,Charlie, AU - Ross,Paul R, AU - O'Doherty,Robert M, AU - Shanahan,Fergus, Y1 - 2012/02/16/ PY - 2012/2/21/entrez PY - 2012/2/22/pubmed PY - 2013/3/6/medline SP - 220 EP - 6 JF - Gut JO - Gut VL - 62 IS - 2 N2 - 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. SN - 1468-3288 UR - https://www.unboundmedicine.com/medline/citation/22345653/Divergent_metabolic_outcomes_arising_from_targeted_manipulation_of_the_gut_microbiota_in_diet_induced_obesity_ DB - PRIME DP - Unbound Medicine ER -