Alteration of gut microbiota by vancomycin and bacitracin improves insulin resistance via glucagon-like peptide 1 in diet-induced obesity

FASEB J. 2015 Jun;29(6):2397-411. doi: 10.1096/fj.14-265983. Epub 2015 Feb 20.

Abstract

Firmicutes and Bacteroidetes, 2 major phyla of gut microbiota, are involved in lipid and bile acid metabolism to maintain systemic energy homeostasis in host. Recently, accumulating evidence has suggested that dietary changes promptly induce the alteration of abundance of both Firmicutes and Bacteroidetes in obesity and its related metabolic diseases. Nevertheless, the metabolic roles of Firmicutes and Bacteroidetes on such disease states remain unclear. The aim of this study was to determine the effects of antibiotic-induced depletion of Firmicutes and Bacteroidetes on dysregulation of energy homeostasis in obesity. Treatment of C57BL/6J mice with the antibiotics (vancomycin [V] and bacitracin [B]), in the drinking water, before diet-induced obesity (DIO) greatly decreased both Firmicutes and Bacteroidetes in the gut as revealed by pyrosequencing of the microbial 16S rRNA gene. Concomitantly, systemic glucose intolerance, hyperinsulinemia, and insulin resistance in DIO were ameliorated via augmentation of GLP-1 secretion (active form; 2.03-fold, total form; 5.09-fold) independently of obesity as compared with untreated DIO controls. Furthermore, there were increases in metabolically beneficial metabolites derived from the gut. Together, our data suggest that Firmicutes and Bacteroidetes potentially mediate insulin resistance through modulation of GLP-1 secretion in obesity.

Keywords: gut hormone; insulin sensitivity; metabolites.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • Bacitracin / pharmacology
  • Bacteroidetes / classification
  • Bacteroidetes / drug effects
  • Bacteroidetes / genetics
  • Blood Glucose / metabolism
  • Blotting, Western
  • Cell Line, Tumor
  • Diet, High-Fat / adverse effects
  • Gastrointestinal Tract / metabolism
  • Gastrointestinal Tract / microbiology*
  • Glucagon-Like Peptide 1 / blood
  • Glucagon-Like Peptide 1 / metabolism*
  • Gram-Positive Bacteria / classification
  • Gram-Positive Bacteria / drug effects
  • Gram-Positive Bacteria / genetics
  • Humans
  • Insulin / blood
  • Insulin Resistance*
  • Metabolomics / methods
  • Mice, Inbred C57BL
  • Microbiota / drug effects*
  • Microbiota / genetics
  • Obesity / blood
  • Obesity / etiology
  • Obesity / metabolism*
  • RNA, Ribosomal, 16S / genetics
  • Sequence Analysis, DNA
  • Vancomycin / pharmacology

Substances

  • Anti-Bacterial Agents
  • Blood Glucose
  • Insulin
  • RNA, Ribosomal, 16S
  • Bacitracin
  • Vancomycin
  • Glucagon-Like Peptide 1