Antibiotic-mediated Gut Microbiome Perturbation Accelerates Development of Type 1 Diabetes in Mice

Nat Microbiol. 2016 Aug 22;1(11):16140. doi: 10.1038/nmicrobiol.2016.140.

Abstract

The early life microbiome plays important roles in host immunological and metabolic development. Because the incidence of type 1 diabetes (T1D) has been increasing substantially in recent decades, we hypothesized that early-life antibiotic use alters gut microbiota, which predisposes to disease. Using non-obese diabetic mice that are genetically susceptible to T1D, we examined the effects of exposure to either continuous low-dose antibiotics or pulsed therapeutic antibiotics (PAT) early in life, mimicking childhood exposures. We found that in mice receiving PAT, T1D incidence was significantly higher, and microbial community composition and structure differed compared with controls. In pre-diabetic male PAT mice, the intestinal lamina propria had lower Th17 and Treg proportions and intestinal SAA expression than in controls, suggesting key roles in transducing the altered microbiota signals. PAT affected microbial lipid metabolism and host cholesterol biosynthetic gene expression. These findings show that early-life antibiotic treatments alter the gut microbiota and its metabolic capacities, intestinal gene expression and T-cell populations, accelerating T1D onset in non-obese diabetic mice.

MeSH terms

  • Animals
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / adverse effects*
  • Cholesterol / biosynthesis
  • Diabetes Mellitus, Type 1 / etiology*
  • Drug Administration Schedule
  • Feces / microbiology
  • Gastrointestinal Microbiome / drug effects*
  • Gastrointestinal Microbiome / genetics
  • Gastrointestinal Microbiome / physiology
  • Gene Expression / drug effects
  • Genetic Predisposition to Disease
  • Lipid Metabolism / drug effects
  • Metabolome / drug effects
  • Mice
  • Mice, Inbred NOD
  • Mucous Membrane / drug effects
  • Mucous Membrane / immunology
  • Obesity
  • Penicillin V / administration & dosage
  • Penicillin V / adverse effects*
  • RNA, Ribosomal, 16S
  • T-Lymphocytes, Regulatory
  • Th17 Cells

Substances

  • Anti-Bacterial Agents
  • RNA, Ribosomal, 16S
  • Cholesterol
  • Penicillin V