Maternal cecal microbiota transfer rescues early-life antibiotic-induced enhancement of type 1 diabetes in mice-the long term restoration

ABSTRACT: Early-life antibiotic exposure perturbs the intestinal microbiota, alters innate intestinal immunity, and accelerates type 1 diabetes development in the NOD mouse model. Here we found that maternal cecal microbiota transfer (CMT) to NOD mice with early-life antibiotic perturbation partially rescued the induced T1D acceleration. The restoration effects on the intestinal microbiome were substantial and persistent, remediating the antibiotic-depleted diversity, relative abundance of particular taxa, and metabolic pathways. CMT also protected against perturbed cecal and serum metabolites and normalized innate and adaptive immune effectors. CMT restored patterns of ileal microRNA and histone regulation of gene expression and exon-splicing. Based on the analyses of experimental data, we propose an innate intestinal immune network involving CD44, TLR2, and Reg3g, as well as their multiple microRNA and epigenetic regulators that sense intestinal signaling by the gut microbiota. This regulation affects downstream immunological tone, leading to protection against the tissue-specific T1D injury.

INSTRUMENT(S): Illumina HiSeq 2500

ORGANISM(S): Mus musculus

SUBMITTER: Xue-Song Zhang 

PROVIDER: E-MTAB-9982 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress