Effects of Gut Microbiota Manipulation by Antibiotics on Host Metabolism in Obese Humans: A Randomized Double-Blind Placebo-Controlled Trial

Cell Metab. 2016 Jul 12;24(1):63-74. doi: 10.1016/j.cmet.2016.06.016.

Abstract

The gut microbiota has been implicated in obesity and cardiometabolic diseases, although evidence in humans is scarce. We investigated how gut microbiota manipulation by antibiotics (7-day administration of amoxicillin, vancomycin, or placebo) affects host metabolism in 57 obese, prediabetic men. Vancomycin, but not amoxicillin, decreased bacterial diversity and reduced Firmicutes involved in short-chain fatty acid and bile acid metabolism, concomitant with altered plasma and/or fecal metabolite concentrations. Adipose tissue gene expression of oxidative pathways was upregulated by antibiotics, whereas immune-related pathways were downregulated by vancomycin. Antibiotics did not affect tissue-specific insulin sensitivity, energy/substrate metabolism, postprandial hormones and metabolites, systemic inflammation, gut permeability, and adipocyte size. Importantly, energy harvest, adipocyte size, and whole-body insulin sensitivity were not altered at 8-week follow-up, despite a still considerably altered microbial composition, indicating that interference with adult microbiota by 7-day antibiotic treatment has no clinically relevant impact on metabolic health in obese humans.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipocytes / drug effects
  • Adipocytes / metabolism
  • Adipocytes / pathology
  • Adult
  • Aged
  • Amoxicillin / pharmacology
  • Anti-Bacterial Agents / pharmacology*
  • Biomarkers / metabolism
  • Butyric Acid / blood
  • Cell Shape / drug effects
  • Double-Blind Method
  • Energy Metabolism / drug effects
  • Feces / chemistry
  • Gastrointestinal Microbiome / drug effects*
  • Gene Expression Regulation / drug effects
  • Humans
  • Inflammation / pathology
  • Insulin / pharmacology
  • Male
  • Middle Aged
  • Obesity / genetics
  • Obesity / metabolism*
  • Obesity / microbiology*
  • Organ Specificity / drug effects
  • Permeability
  • Placebos
  • Substrate Specificity / drug effects
  • Vancomycin / pharmacology

Substances

  • Anti-Bacterial Agents
  • Biomarkers
  • Insulin
  • Placebos
  • Butyric Acid
  • Vancomycin
  • Amoxicillin