@article{67494e6576f045e8838bfb1cac695383,
title = "Maternal cecal microbiota transfer rescues early-life antibiotic-induced enhancement of type 1 diabetes in mice",
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.",
keywords = "NOD mice, animal models, autoimmune, cecal material transfer, gene expression, histone modification, innate immune, microRNA, microbiome, type 1 diabetes",
author = "Zhang, {Xue Song} and Yin, {Yue Sandra} and Jincheng Wang and Thomas Battaglia and Kimberly Krautkramer and Li, {Wei Vivian} and Jackie Li and Mark Brown and Meifan Zhang and Badri, {Michelle H.} and Armstrong, {Abigail J.S.} and Strauch, {Christopher M.} and Zeneng Wang and Ina Nemet and Nicole Altomare and Devlin, {Joseph C.} and Linchen He and Morton, {Jamie T.} and Chalk, {John Alex} and Kelly Needles and Viviane Liao and Julia Mount and Huilin Li and Ruggles, {Kelly V.} and Bonneau, {Richard A.} and Dominguez-Bello, {Maria Gloria} and Fredrik B{\"a}ckhed and Hazen, {Stanley L.} and Blaser, {Martin J.}",
note = "Funding Information: We thank Tadasu Lizumi, Menghan Liu, Kun Qian, and Drew Jones of New York University Medical Center; Anthony R. Williamson & Marcus Rauch of Janssen Prevention Center London; Gang Fang of Mount Sinai Medical Center; Carolina Tropini laboratory of the University of British Columbia; NYU Langone Health Genome Technology Center & metabolomics Core Resource; Rutgers Cancer Institute histopathology core facility & Comprehensive Genomics Shared Resource; and Rutgers University Ernest Mario School of Pharmacy Cytometry & Cell Sorting Laboratory assistance with these studies. These studies were supported by Janssen Labs London ( 15-A0-00-00-0039-29-01 ), NIH grants ( R01GM128955-01 , P01HL14783 , 5R01DK110014 , R01DK120679 ), the TransAtlantic Networks of Excellence Program ( 33.17CVD01 ) from the Fondation Leducq , the C&D Research Fund , the Emch Fund for Microbial Diversity , and an anonymous donor. Funding Information: We thank Tadasu Lizumi, Menghan Liu, Kun Qian, and Drew Jones of New York University Medical Center; Anthony R. Williamson & Marcus Rauch of Janssen Prevention Center London; Gang Fang of Mount Sinai Medical Center; Carolina Tropini laboratory of the University of British Columbia; NYU Langone Health Genome Technology Center & metabolomics Core Resource; Rutgers Cancer Institute histopathology core facility & Comprehensive Genomics Shared Resource; and Rutgers University Ernest Mario School of Pharmacy Cytometry & Cell Sorting Laboratory assistance with these studies. These studies were supported by Janssen Labs London (15-A0-00-00-0039-29-01), NIH grants (R01GM128955-01, P01HL14783, 5R01DK110014, R01DK120679), the TransAtlantic Networks of Excellence Program (33.17CVD01) from the Fondation Leducq, the C&D Research Fund, the Emch Fund for Microbial Diversity, and an anonymous donor. Conceptualization and study design, M.J.B. and X.-S.Z.; performing experiments, X.-S.Z. Y.S.Y. K.K. J.L. M.B. M.Z. C.M.S. Z.W. N.A. J.A.C. K.N. L.M. and V.L.; animal work and sampling, J.L. and X.-S.Z.; data analysis, X.-S.Z. Y.S.Y. J.W. T.B. K.K. W.V.L. M.H.B. A.J.S.A. J.C.D. L.H. J.T.M. and K.V.R.; visualization, X.-S.Z. Y.S.Y. J.W. T.B. K.K. W.V.L. M.H.B. J.C.D. and J.T.M.; writing–original draft, X.-S.Z. and M.J.B.; writing–review and editing, X.-S.Z. M.J.B. M.G.D.-B. F.B. S.L.H. K.K. M.B. I.N. H.L. W.V.L. J.W. and I.N.; supervision, M.J.B. S.L.H. F.B. M.G.D.-B. R.A.B. M.B. K.V.R. and H.L. Z.W. and S.L.H. report being named as co-inventors on pending and issued patents held by the Cleveland Clinic relating to cardiovascular diagnostics and therapeutics and being eligible to receive royalty payments for inventions or discoveries related to cardiovascular diagnostics or therapeutics from Cleveland HeartLab, Quest Diagnostics, and Procter & Gamble. S.L.H. also reports being a paid consultant for Procter & Gamble, having received research funds from Procter & Gamble and Roche Diagnostics, and being eligible to receive royalty payments for inventions or discoveries related to cardiovascular diagnostics or therapeutics from Cleveland HeartLab, Quest Diagnostics, and Procter & Gamble. The other authors report that they have no relationships relevant to the contents of this paper to disclose. One or more of the authors of this paper self-identifies as a member of the LGBTQ+ community. One or more of the authors of this paper self-identifies as living with a disability. Publisher Copyright: {\textcopyright} 2021 Elsevier Inc.",
year = "2021",
month = aug,
day = "11",
doi = "10.1016/j.chom.2021.06.014",
language = "English (US)",
volume = "29",
pages = "1249--1265.e9",
journal = "Cell Host and Microbe",
issn = "1931-3128",
publisher = "Cell Press",
number = "8",
}