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

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

Author information

1
Department of Medicine, New York University Langone Medical Center, New York, United States.
2
Human Microbiome Program, New York University Langone Medical Center, New York, United States.
3
Department of Biomolecular Chemistry, Wisconsin Institute for Discovery, University of Wisconsin School of Medicine and Public Health, Madison, United States.
4
Center for Data Science, New York University, New York, United States.
5
Department of Population Health, New York University Langone Medical Center, New York, United States.
6
Nutrition Research Institute, University of North Carolina at Chapel Hill School of Public Health, Kannapolis, United States.
7
Computer Science and Engineering, BioTechnology Institute, University of Minnesota, St. Paul, United States.
8
Janssen Prevention Center London, Janssen Pharmaceutical Companies of Johnson and Johnson, London, United Kingdom.
9
Department of Biomedical Sciences, Cummings School of Veterinary Medicine, Tufts University, North Grafton, United States.
10
Department of Microbiology, New York Uniersity Langone Medical Center, New York, United States.

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

PMID:
30039798
PMCID:
PMC6085123
DOI:
10.7554/eLife.37816
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

XZ, JL, KK, MB, TB, TB, HK, SN, RS, YL, WP, SJ, RS, BH, GA, VR, AL, Av, NN, AR, SS, DK, JD, HL, KR, RB, RW, MR, MB No competing interests declared

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