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 & 9 others Susan 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 journalArticle

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.

Original languageEnglish (US)
Article numbere37816
JournaleLife
Volume7
DOIs
StatePublished - Jul 24 2018

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Medical problems
Type 1 Diabetes Mellitus
Innate Immunity
Anti-Bacterial Agents
Gene expression
Gene Expression
Inbred NOD Mouse
Immune system
Liver
Microbiota
Adaptive Immunity
Metabolites
Ileum
Chromatin
Immune System
Animals
Animal Models
Genes
Serum
Gastrointestinal Microbiome

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Zhang, X. S., Li, J., Krautkramer, K. A., Badri, M., Battaglia, T., Borbet, T. C., ... Blaser, M. J. (2018). Antibiotic-induced acceleration of type 1 diabetes alters maturation of innate intestinal immunity. eLife, 7, [e37816]. https://doi.org/10.7554/eLife.37816

Antibiotic-induced acceleration of type 1 diabetes alters maturation of innate intestinal immunity. / Zhang, Xue Song; Li, Jackie; Krautkramer, Kimberly A.; Badri, Michelle; Battaglia, Thomas; Borbet, Timothy C.; Koh, Hyunwook; Ng, Sandy; Sibley, Rachel A.; Li, Yuanyuan; Pathmasiri, Wimal; Jindal, Shawn; Shields-Cutler, Robin R.; Hillmann, Ben; Al-Ghalith, Gabriel A.; Ruiz, Victoria E.; Livanos, Alexandra; Van‘t Wout, Angélique B.; Nagalingam, Nabeetha; Rogers, Arlin B.; Sumner, Susan Jenkins; Knights, Dan; Denu, John M.; Li, Huilin; Ruggles, Kelly V.; Bonneau, Richard; Williamson, R. Anthony; Rauch, Marcus; Blaser, Martin J.

In: eLife, Vol. 7, e37816, 24.07.2018.

Research output: Contribution to journalArticle

Zhang, XS, Li, J, Krautkramer, KA, Badri, M, Battaglia, T, Borbet, TC, Koh, H, Ng, S, Sibley, RA, Li, Y, Pathmasiri, W, Jindal, S, Shields-Cutler, RR, Hillmann, B, Al-Ghalith, GA, Ruiz, VE, Livanos, A, Van‘t Wout, AB, Nagalingam, N, Rogers, AB, Sumner, SJ, Knights, D, Denu, JM, Li, H, Ruggles, KV, Bonneau, R, Williamson, RA, Rauch, M & Blaser, MJ 2018, 'Antibiotic-induced acceleration of type 1 diabetes alters maturation of innate intestinal immunity', eLife, vol. 7, e37816. https://doi.org/10.7554/eLife.37816
Zhang XS, Li J, Krautkramer KA, Badri M, Battaglia T, Borbet TC et al. Antibiotic-induced acceleration of type 1 diabetes alters maturation of innate intestinal immunity. eLife. 2018 Jul 24;7. e37816. https://doi.org/10.7554/eLife.37816
Zhang, Xue Song ; Li, Jackie ; Krautkramer, Kimberly A. ; Badri, Michelle ; Battaglia, Thomas ; Borbet, Timothy C. ; Koh, Hyunwook ; Ng, Sandy ; Sibley, Rachel A. ; Li, Yuanyuan ; Pathmasiri, Wimal ; Jindal, Shawn ; Shields-Cutler, Robin R. ; Hillmann, Ben ; Al-Ghalith, Gabriel A. ; Ruiz, Victoria E. ; Livanos, Alexandra ; Van‘t Wout, Angélique B. ; Nagalingam, Nabeetha ; Rogers, Arlin B. ; Sumner, Susan Jenkins ; Knights, Dan ; Denu, John M. ; Li, Huilin ; Ruggles, Kelly V. ; Bonneau, Richard ; Williamson, R. Anthony ; Rauch, Marcus ; Blaser, Martin J. / Antibiotic-induced acceleration of type 1 diabetes alters maturation of innate intestinal immunity. In: eLife. 2018 ; Vol. 7.
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AU - Rogers, Arlin B.

AU - Sumner, Susan Jenkins

AU - Knights, Dan

AU - Denu, John M.

AU - Li, Huilin

AU - Ruggles, Kelly V.

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AU - Williamson, R. Anthony

AU - Rauch, Marcus

AU - Blaser, Martin J.

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