TY - JOUR
T1 - Antibiotic-induced acceleration of type 1 diabetes alters maturation of innate intestinal immunity
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.
N1 - Publisher Copyright:
© Zhang et al.
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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U2 - 10.7554/eLife.37816
DO - 10.7554/eLife.37816
M3 - Article
C2 - 30039798
AN - SCOPUS:85052150412
SN - 2050-084X
VL - 7
JO - eLife
JF - eLife
M1 - e37816
ER -