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

Antibiotic-mediated gut microbiome perturbation accelerates development of type 1 diabetes in mice.

Author information

  • 1Departments of Medicine and Microbiology, Human Microbiome Program, New York University Langone Medical Center, Medical Service, New York, New York 10016, USA.
  • 2Department of Molecular and Clinical Medicine, University of Gothenburg, 40530 Gothenburg, Sweden.
  • 3Biomedical Informatics and Computational Biology Program, University of Minnesota, Minneapolis, Minneapolis 55455, USA.
  • 4Systems and Translational Sciences, RTI International, Research Triangle Park, North Carolina 27709, USA.
  • 5Departments of Population Health, New York University Langone Medical Center, New York, New York 10016, USA.
  • 6Department of Biomedical Sciences, Cummings School of Veterinary Medicine, Tufts University, North Grafton, Massachusetts 01536, USA.
  • 7Department of Microbiology, New York University Langone Medical Center, New York, New York 10016, USA.
  • 8Skirball Institute, New York University Langone Medical Center, New York, New York 10016, USA.
  • 9Computer Science and Engineering, University of Minnesota, Minneapolis, Minneapolis 55455, USA.
  • 10Biotechnology Institute, University of Minnesota, Saint Paul, Minneapolis 55108, USA.
  • 11CHIBI, New York University Langone Medical Center, New York, New York 10016, USA.
  • 12Novo Nordisk Foundation Center for Basic Metabolic Research, Section for Metabolic Receptology and Enteroendocrinology, Faculty of Health Sciences, University of Copenhagen, Copenhagen DK-2200, Denmark.
  • 13New York Harbor Veterans Affairs Medical Center, New York, New York 10010, USA.

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.

PMID:
27782139
DOI:
10.1038/nmicrobiol.2016.140
[PubMed - in process]
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