Antibiotics-induced perturbations in gut microbial diversity influence metabolic phenotypes in a murine model of high-fat diet-induced obesity

Appl Microbiol Biotechnol. 2019 Jul;103(13):5269-5283. doi: 10.1007/s00253-019-09764-5. Epub 2019 Apr 24.

Abstract

Gut microbiota play a key role in the regulation of obesity and associated metabolic disorders. To study the relationship between them, antibiotics have been widely used to generate pseudo-germ-free rodents as control models. However, it is not clear whether antibiotics impact an animal's metabolic phenotype. Therefore, the effect of antibiotics-induced gut microbial perturbations on metabolic phenotypes in high-fat diet (HFD) fed mice was investigated. The results showed that antibiotics perturbed gut microbial composition and structure. Community diversity and richness were reduced, and the phyla Firmicutes/Bacteroidetes (F/B) ratio was decreased by antibiotics. Visualization of Unifrac distance data using principal component analysis (PCA) and unweighted pair-group method with arithmetic mean (UPGAM) demonstrated that fecal samples of HFD-fed mice separated from those of chow diet (CD) fed mice. Fecal samples from antibiotics-treated and non-treated mice were clustered into two different microbial populations. Moreover, antibiotics suppressed HFD-induced metabolic features, including body weight gain (BWG), liver weight (LW), epididymal fat weight (EFW), and serum levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), alanine aminotransferase (ALT), fasting blood glucose (FBG), and insulin (INS) significantly (P < 0.05). Lachnospiraceae, Ruminiclostridium and Helicobacter, biomarkers of mouse gut microbiota before treatment by antibiotics, were positively correlated with obesity phenotypes significantly (P < 0.05) and were decreased by (92.95 ± 5.09) %, (97.73 ± 2.09) % and (99.48 ± 0.21) % respectively after 30 days of treatment by antibiotics. However, Bacteroidia were enriched in HFD-fed antibiotics-treated mice and were negatively correlated with obesity phenotypes significantly (P < 0.05). We suggested that the antibiotics-induced depletion of Lachnospiraceae, Ruminiclostridium, and Helicobacter, and the decrease in F/B ratio in gut microbiota played a role in the prevention of HFD-induced obesity in mice.

Keywords: Antibiotics; Gut microbiota; HFD (high fat diet); Metabolic phenotype; Obesity.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / administration & dosage*
  • Bacteroidetes / classification*
  • Bacteroidetes / drug effects
  • Diet, High-Fat
  • Disease Models, Animal
  • Feces / microbiology
  • Firmicutes / classification*
  • Firmicutes / drug effects
  • Gastrointestinal Microbiome / drug effects*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Obesity / microbiology*
  • Phenotype

Substances

  • Anti-Bacterial Agents