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

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 journal › Article › peer-review

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 language	English (US)
Article number	e37816
Journal	eLife
Volume	7
DOIs	https://doi.org/10.7554/eLife.37816
State	Published - Jul 24 2018

ASJC Scopus subject areas

General Neuroscience
General Biochemistry, Genetics and Molecular Biology
General Immunology and Microbiology

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10.7554/eLife.37816

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Zhang, X. S., Li, J., Krautkramer, K. A., Badri, M., Battaglia, T., Borbet, T. C., Koh, H., Ng, S., Sibley, R. A., Li, Y., Pathmasiri, W., Jindal, S., Shields-Cutler, R. R., Hillmann, B., Al-Ghalith, G. A., Ruiz, V. E., Livanos, A., Van‘t Wout, A. B., Nagalingam, N., ... Blaser, M. J. (2018). Antibiotic-induced acceleration of type 1 diabetes alters maturation of innate intestinal immunity. eLife, 7, Article e37816. https://doi.org/10.7554/eLife.37816

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

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title = "Antibiotic-induced acceleration of type 1 diabetes alters maturation of innate intestinal immunity",

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.",

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

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year = "2018",

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doi = "10.7554/eLife.37816",

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AU - Zhang, Xue Song

AU - Li, Jackie

AU - Krautkramer, Kimberly A.

AU - Badri, Michelle

AU - Battaglia, Thomas

AU - Borbet, Timothy C.

AU - Koh, Hyunwook

AU - Ng, Sandy

AU - Sibley, Rachel A.

AU - Li, Yuanyuan

AU - Pathmasiri, Wimal

AU - Jindal, Shawn

AU - Shields-Cutler, Robin R.

AU - Hillmann, Ben

AU - Al-Ghalith, Gabriel A.

AU - Ruiz, Victoria E.

AU - Livanos, Alexandra

AU - Van‘t Wout, Angélique B.

AU - Nagalingam, Nabeetha

AU - Rogers, Arlin B.

AU - Sumner, Susan Jenkins

AU - Knights, Dan

AU - Denu, John M.

AU - Li, Huilin

AU - Ruggles, Kelly V.

AU - Bonneau, Richard

AU - Williamson, R. Anthony

AU - Rauch, Marcus

AU - Blaser, Martin J.

PY - 2018/7/24

Y1 - 2018/7/24

N2 - 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.

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

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ASJC Scopus subject areas

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