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

Xue-Song Zhang; Jackie Li; Kimberly A Krautkramer; Michelle Badri; Thomas Battaglia; Timothy C Borbet; Hyunwook Koh; Sandy Ng; Rachel A Sibley; Yuanyuan Li; Wimal Pathmasiri; Shawn Jindal; Robin R Shields-Cutler; Ben Hillmann; Gabriel A Al-Ghalith; Victoria E Ruiz; Alexandra Livanos; Angélique B van 't Wout; Nabeetha Nagalingam; Arlin B Rogers; Susan Jenkins Sumner; Dan Knights; John M Denu; Huilin Li; Kelly V Ruggles; Richard Bonneau; R Anthony Williamson; Marcus Rauch; Martin J Blaser

doi:10.7554/eLife.37816

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

Journal article

Open access

Peer reviewed

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

Xue-Song Zhang, Jackie Li, Kimberly A Krautkramer, Michelle Badri, Thomas Battaglia, Timothy C Borbet, Hyunwook Koh, Sandy Ng, Rachel A Sibley, Yuanyuan Li, …

eLife, Vol.7

07/25/2018

DOI: https://doi.org/10.7554/eLife.37816

PMCID: PMC6085123

PMID: 30039798

Abstract

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

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.

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Title: Antibiotic-induced acceleration of type 1 diabetes alters maturation of innate intestinal immunity
Creators: Xue-Song Zhang - Human Microbiome Program, New York University Langone Medical Center, New York, United States
Jackie Li - Human Microbiome Program, New York University Langone Medical Center, New York, United States
Kimberly A Krautkramer - Department of Biomolecular Chemistry, Wisconsin Institute for Discovery, University of Wisconsin School of Medicine and Public Health, Madison, United States
Michelle Badri - Center for Data Science, New York University, New York, United States
Thomas Battaglia - Human Microbiome Program, New York University Langone Medical Center, New York, United States
Timothy C Borbet - Human Microbiome Program, New York University Langone Medical Center, New York, United States
Hyunwook Koh - Department of Population Health, New York University Langone Medical Center, New York, United States
Sandy Ng - Human Microbiome Program, New York University Langone Medical Center, New York, United States
Rachel A Sibley - Human Microbiome Program, New York University Langone Medical Center, New York, United States
Yuanyuan Li - Nutrition Research Institute, University of North Carolina at Chapel Hill School of Public Health, Kannapolis, United States
Wimal Pathmasiri - Nutrition Research Institute, University of North Carolina at Chapel Hill School of Public Health, Kannapolis, United States
Shawn Jindal - Human Microbiome Program, New York University Langone Medical Center, New York, United States
Robin R Shields-Cutler - Computer Science and Engineering, BioTechnology Institute, University of Minnesota, St. Paul, United States
Ben Hillmann - Computer Science and Engineering, BioTechnology Institute, University of Minnesota, St. Paul, United States
Gabriel A Al-Ghalith - Computer Science and Engineering, BioTechnology Institute, University of Minnesota, St. Paul, United States
Victoria E Ruiz - Human Microbiome Program, New York University Langone Medical Center, New York, United States
Alexandra Livanos - Human Microbiome Program, New York University Langone Medical Center, New York, United States
Angélique B van 't Wout - Janssen Prevention Center London, Janssen Pharmaceutical Companies of Johnson and Johnson, London, United Kingdom
Nabeetha Nagalingam - Janssen Prevention Center London, Janssen Pharmaceutical Companies of Johnson and Johnson, London, United Kingdom
Arlin B Rogers - Department of Biomedical Sciences, Cummings School of Veterinary Medicine, Tufts University, North Grafton, United States
Susan Jenkins Sumner - Nutrition Research Institute, University of North Carolina at Chapel Hill School of Public Health, Kannapolis, United States
Dan Knights - Computer Science and Engineering, BioTechnology Institute, University of Minnesota, St. Paul, United States
John M Denu - Department of Biomolecular Chemistry, Wisconsin Institute for Discovery, University of Wisconsin School of Medicine and Public Health, Madison, United States
Huilin Li - Department of Population Health, New York University Langone Medical Center, New York, United States
Kelly V Ruggles - Human Microbiome Program, New York University Langone Medical Center, New York, United States
Richard Bonneau - Center for Data Science, New York University, New York, United States
R Anthony Williamson - Janssen Prevention Center London, Janssen Pharmaceutical Companies of Johnson and Johnson, London, United Kingdom
Marcus Rauch - Janssen Prevention Center London, Janssen Pharmaceutical Companies of Johnson and Johnson, London, United Kingdom
Martin J Blaser - Department of Microbiology, New York Uniersity Langone Medical Center, New York, United States
Publication Details: eLife, Vol.7
Date published: 07/25/2018
Grant note: R01 DK110014 / NIDDK NIH HHS T32 DK007665 / NIDDK NIH HHS T35 DK007421 / NIDDK NIH HHS 5T35DK007421 / NIH HHS 15-A0-00-00-0039-29-01 / Janssen Labs London -33.17CVD01 / Fondation Leducq T32 GM008692 / NIGMS NIH HHS F30 DK108494 / NIDDK NIH HHS R37GM059785 / NIH HHS T32 GM007308 / NIGMS NIH HHS 15-A0-00-00-0039-29-01 / Janssen Research and Development R01DK110014 / NIH HHS R37 GM059785 / NIGMS NIH HHS F30DK108494 / NIH HHS
Academic Unit: Center for Advanced Biotechnology and Medicine; Center for Advanced Biotechnology and Medicine
Language: English
Resource Type: Journal article
Identifiers: 991031666084504646