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

Xue Song Zhang; Yue Sandra Yin; Jincheng Wang; Thomas Battaglia; Kimberly Krautkramer; Wei Vivian Li; Jackie Li; Mark Brown; Meifan Zhang; Michelle H. Badri; Abigail J.S. Armstrong; Christopher M. Strauch; Zeneng Wang; Ina Nemet; Nicole Altomare; Joseph C. Devlin; Linchen He; Jamie T. Morton; John Alex Chalk; Kelly Needles; Viviane Liao; Julia Mount; Huilin Li; Kelly V. Ruggles; Richard A. Bonneau; Maria Gloria Dominguez-Bello; Fredrik Bäckhed; Stanley L. Hazen; Martin J. Blaser

doi:10.1016/j.chom.2021.06.014

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

Xue Song Zhang, Yue Sandra Yin, Jincheng Wang, Thomas Battaglia, Kimberly Krautkramer, Wei Vivian Li, Jackie Li, Mark Brown, Meifan Zhang, Michelle H. Badri, Abigail J.S. Armstrong, Christopher M. Strauch, Zeneng Wang, Ina Nemet, Nicole Altomare, Joseph C. Devlin, Linchen He, Jamie T. Morton, John Alex Chalk, Kelly NeedlesViviane Liao, Julia Mount, Huilin Li, Kelly V. Ruggles, Richard A. Bonneau, Maria Gloria Dominguez-Bello, Fredrik Bäckhed, Stanley L. Hazen, Martin J. Blaser

Research output: Contribution to journal › Article › peer-review

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.

Original language	English (US)
Pages (from-to)	1249-1265.e9
Journal	Cell Host and Microbe
Volume	29
Issue number	8
DOIs	https://doi.org/10.1016/j.chom.2021.06.014
State	Published - Aug 11 2021

Keywords

NOD mice
animal models
autoimmune
cecal material transfer
gene expression
histone modification
innate immune
microRNA
microbiome
type 1 diabetes

ASJC Scopus subject areas

Parasitology
Microbiology
Virology

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10.1016/j.chom.2021.06.014

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Zhang, X. S., Yin, Y. S., Wang, J., Battaglia, T., Krautkramer, K., Li, W. V., Li, J., Brown, M., Zhang, M., Badri, M. H., Armstrong, A. J. S., Strauch, C. M., Wang, Z., Nemet, I., Altomare, N., Devlin, J. C., He, L., Morton, J. T., Chalk, J. A., ... Blaser, M. J. (2021). Maternal cecal microbiota transfer rescues early-life antibiotic-induced enhancement of type 1 diabetes in mice. Cell Host and Microbe, 29(8), 1249-1265.e9. https://doi.org/10.1016/j.chom.2021.06.014

Zhang, XS, Yin, YS, Wang, J, Battaglia, T, Krautkramer, K, Li, WV, Li, J, Brown, M, Zhang, M, Badri, MH, Armstrong, AJS, Strauch, CM, Wang, Z, Nemet, I, Altomare, N, Devlin, JC, He, L, Morton, JT, Chalk, JA, Needles, K, Liao, V, Mount, J, Li, H, Ruggles, KV, Bonneau, RA, Dominguez-Bello, MG, Bäckhed, F, Hazen, SL & Blaser, MJ 2021, 'Maternal cecal microbiota transfer rescues early-life antibiotic-induced enhancement of type 1 diabetes in mice', Cell Host and Microbe, vol. 29, no. 8, pp. 1249-1265.e9. https://doi.org/10.1016/j.chom.2021.06.014

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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.}",

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year = "2021",

month = aug,

day = "11",

doi = "10.1016/j.chom.2021.06.014",

language = "English (US)",

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AU - Zhang, Xue Song

AU - Yin, Yue Sandra

AU - Wang, Jincheng

AU - Battaglia, Thomas

AU - Krautkramer, Kimberly

AU - Li, Wei Vivian

AU - Li, Jackie

AU - Brown, Mark

AU - Zhang, Meifan

AU - Badri, Michelle H.

AU - Armstrong, Abigail J.S.

AU - Strauch, Christopher M.

AU - Wang, Zeneng

AU - Nemet, Ina

AU - Altomare, Nicole

AU - Devlin, Joseph C.

AU - He, Linchen

AU - Morton, Jamie T.

AU - Chalk, John Alex

AU - Needles, Kelly

AU - Liao, Viviane

AU - Mount, Julia

AU - Li, Huilin

AU - Ruggles, Kelly V.

AU - Bonneau, Richard A.

AU - Dominguez-Bello, Maria Gloria

AU - Bäckhed, Fredrik

AU - Hazen, Stanley L.

AU - Blaser, Martin J.

PY - 2021/8/11

Y1 - 2021/8/11

N2 - 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.

AB - 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.

KW - NOD mice

KW - animal models

KW - autoimmune

KW - cecal material transfer

KW - gene expression

KW - histone modification

KW - innate immune

KW - microRNA

KW - microbiome

KW - type 1 diabetes

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SN - 1931-3128

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SP - 1249-1265.e9

JO - Cell Host and Microbe

JF - Cell Host and Microbe

IS - 8

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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