Rutgers University, Piscataway - Robert Wood Johnson Medical School; Rutgers, The State University of New Jersey - Center for Advanced Biotechnology and Medicine
Early-life antibiotic exposure perturbs the intestinal microbiota, alters innate intestinal immunity, and accelerates type 1 diabetes (T1D) 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 analyses of experimental data, we propose an innate intestinal immune network involving CD44, TLR2, and Reg3γ, 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.
Keywords: microbiome, cecal material transfer, NOD mice, animal models, innate immune, gene expression, microRNA, histone modification, autoimmune, type 1 diabetes
Zhang, Xue-Song and Yin, Yue Sandra and Wang, Jincheng and Battaglia, Thomas and Krautkramer, Kimberly and Li, Wei Vivian and Li, Jackie and Brown, Mark and Zhang, Meifan and Badri, Michelle and Armstrong, Abigail and Strauch, Christopher M. and Wang, Zeneng and Nemet, Ina and Altomare, Nicole and Devlin, Joseph C. and He, Linchen and Morton, Jamie and Chalk, John Alex and Needles, Kelly and Liao, Viviane and Mount, Julia and Li, Huilin and Ruggles, Kelly V. and Bonneau, Richard A. and Dominguez Bello, Maria Gloria and Backhed, Fredrick and Hazen, Stanley L. and Blaser, Martin J., Cecal Microbiota Transfer Rescues Antibiotic-Induced Acceleration of Type 1 Diabetes and Alteration of Intestinal Gene Expression. Available at SSRN: https://ssrn.com/abstract=3760758 or http://dx.doi.org/10.2139/ssrn.3760758
This version of the paper has not been formally peer reviewed.
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