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

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. [Display omitted] •CMT rescued antibiotic-induced T1D enhancement in NOD mice•CMT restored potential T1D-protective bacterial taxa•CMT restored global patterns of gene expression and modifications in the ileum•The study reveals a regulatory network of the innate immunity-sensing intestinal signals Using a mouse model in which early-life antibiotics enhance T1D, Zhang et al. show that subsequent maternal cecal microbiota transfer reduces illness. The restorative effects on the intestinal microbiome and metabolism, ileal wall gene expression and regulation, and innate and adaptive immune effectors suggest a gut-microbiota-regulated T1D protective mechanism.