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. RogersSusan Jenkins Sumner, Dan Knights, John M. Denu, Huilin Li, Kelly V. Ruggles, Richard Bonneau, R. Anthony Williamson, Marcus Rauch, Martin J. Blaser

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


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.

Original languageEnglish (US)
Article numbere37816
StatePublished - Jul 24 2018

Bibliographical note

Funding Information:
For assistance with these studies, we thank Savannah Costa, Yunzhu Li, Menghan Liu, Xuhui Zheng, James Zhou, Chad Trent, Matthew Farkouh, and Zhan Gao of New York University Medical Center, Shijia Zhu and Gang Fang of Mount Sinai Medical Center, NYU Langone Health Genome Technology Center, and NYU Metabolomics Core Resource Laboratory. These studies were supported by Jans-sen Labs London (15-A0-00-00-0039-29-01), NIH Grants [5T35DK007421, R37GM059785, F30 DK108494, T32GM008692, R01DK110014], −33.17CVD01 (TransAtlantic Networks of Excellence Program) from the Fondation Leducq, and the C and D fund.

Publisher Copyright:
© Zhang et al.

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