Antibiotic-induced acceleration of type 1 diabetes alters maturation of innate intestinal immunity

Elife. 2018 Jul 25;7:e37816. doi: 10.7554/eLife.37816.

Abstract

The early-life intestinal microbiota plays a key role in shaping host immune system development. We found that a single early-life antibiotic course (1PAT) accelerated type 1 diabetes (T1D) development in male NOD mice. The single course had deep and persistent effects on the intestinal microbiome, leading to altered cecal, hepatic, and serum metabolites. The exposure elicited sex-specific effects on chromatin states in the ileum and liver and perturbed ileal gene expression, altering normal maturational patterns. The global signature changes included specific genes controlling both innate and adaptive immunity. Microbiome analysis revealed four taxa each that potentially protect against or accelerate T1D onset, that were linked in a network model to specific differences in ileal gene expression. This simplified animal model reveals multiple potential pathways to understand pathogenesis by which early-life gut microbiome perturbations alter a global suite of intestinal responses, contributing to the accelerated and enhanced T1D development.

Keywords: NOD mice; animal models; autoimmune; gene expression; immune maturation; immunology; infectious disease; inflammation; microbiology; microbiome; mouse.

Publication types

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

MeSH terms

  • Adaptive Immunity / drug effects
  • Animals
  • Anti-Bacterial Agents / adverse effects*
  • Anti-Bacterial Agents / immunology
  • Diabetes Mellitus, Type 1 / immunology*
  • Diabetes Mellitus, Type 1 / microbiology
  • Diabetes Mellitus, Type 1 / pathology
  • Female
  • Gastrointestinal Microbiome / drug effects
  • Gastrointestinal Microbiome / immunology*
  • Ileum / immunology
  • Ileum / microbiology
  • Immunity, Innate / drug effects*
  • Immunity, Innate / immunology
  • Intestines / microbiology
  • Mice
  • Mice, Inbred NOD
  • Microbiota / drug effects
  • Microbiota / immunology

Substances

  • Anti-Bacterial Agents