| Literature DB >> 34289377 |
Xue-Song Zhang1, Yue Sandra Yin2, Jincheng Wang3, Thomas Battaglia4, Kimberly Krautkramer5, Wei Vivian Li6, Jackie Li4, Mark Brown7, Meifan Zhang2, Michelle H Badri8, Abigail J S Armstrong9, Christopher M Strauch10, Zeneng Wang10, Ina Nemet10, Nicole Altomare9, Joseph C Devlin4, Linchen He11, Jamie T Morton12, John Alex Chalk9, Kelly Needles9, Viviane Liao9, Julia Mount4, Huilin Li11, Kelly V Ruggles4, Richard A Bonneau13, Maria Gloria Dominguez-Bello14, Fredrik Bäckhed15, Stanley L Hazen16, Martin J Blaser17.
Abstract
Early-life antibiotic exposure perturbs the intestinal microbiota and accelerates type 1 diabetes (T1D) development in the NOD mouse model. Here, we found that maternal cecal microbiota transfer (CMT) to NOD mice after early-life antibiotic perturbation largely rescued the induced T1D enhancement. Restoration of the intestinal microbiome was significant and persistent, remediating the antibiotic-depleted diversity, relative abundance of particular taxa, and metabolic pathways. CMT also protected against perturbed metabolites and normalized innate and adaptive immune effectors. CMT restored major patterns of ileal microRNA and histone regulation of gene expression. Further experiments suggest a gut-microbiota-regulated T1D protection mechanism centered on Reg3γ, in an innate intestinal immune network involving CD44, TLR2, and Reg3γ. This regulation affects downstream immunological tone, which may lead to protection against tissue-specific T1D injury.Entities:
Keywords: NOD mice; animal models; autoimmune; cecal material transfer; gene expression; histone modification; innate immune; microRNA; microbiome; type 1 diabetes
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Year: 2021 PMID： 34289377 PMCID： PMC8370265 DOI： 10.1016/j.chom.2021.06.014
Source DB: PubMed Journal: Cell Host Microbe ISSN： 1931-3128 Impact factor: 31.316