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Cecal Microbiota Transfer Rescues Antibiotic-Induced Acceleration of Type 1 Diabetes  and Alteration of Intestinal Gene Expression

77 Pages Posted: 5 Jan 2021 Publication Status: Published

See all articles by Xue-Song Zhang

Xue-Song Zhang

Rutgers, The State University of New Jersey - Center for Advanced Biotechnology and Medicine

Yue Sandra Yin

Rutgers, The State University of New Jersey - Center for Advanced Biotechnology and Medicine

Jincheng Wang

Rutgers University, New Brunswick - Department of Biochemistry and Microbiology

Thomas Battaglia

New York University (NYU) - Human Microbiome Program

Kimberly Krautkramer

University of Gothenburg - The Wallenberg Laboratory

Wei Vivian Li

Rutgers University, Piscataway - Department of Biostatistics and Epidemiology

Jackie Li

New York University (NYU) - Human Microbiome Program

Mark Brown

Cleveland Clinic - Cardiovascular & Metabolic Sciences

Meifan Zhang

Rutgers, The State University of New Jersey - Center for Advanced Biotechnology and Medicine

Michelle Badri

New York University (NYU) - Human Microbiome Program

Abigail Armstrong

Rutgers, The State University of New Jersey - Center for Advanced Biotechnology and Medicine

Christopher M. Strauch

Cleveland Clinic - Cardiovascular & Metabolic Sciences

Zeneng Wang

Cleveland Clinic - Cardiovascular & Metabolic Sciences

Ina Nemet

Cleveland Clinic - Cardiovascular & Metabolic Sciences

Nicole Altomare

Rutgers, The State University of New Jersey - Center for Advanced Biotechnology and Medicine; Rutgers University, Piscataway - Robert Wood Johnson Medical School

Joseph C. Devlin

New York University (NYU) - Human Microbiome Program

Linchen He

New York University (NYU) - Department of Population Health

Jamie Morton

New York University (NYU) - Human Microbiome Program

John Alex Chalk

Rutgers, The State University of New Jersey - Center for Advanced Biotechnology and Medicine

Kelly Needles

Rutgers, The State University of New Jersey - Center for Advanced Biotechnology and Medicine

Viviane Liao

Rutgers, The State University of New Jersey - Center for Advanced Biotechnology and Medicine

Julia Mount

New York University (NYU) - Human Microbiome Program

Huilin Li

New York University (NYU) - Department of Population Health

Kelly V. Ruggles

New York University (NYU) - Human Microbiome Program

Richard A. Bonneau

New York University (NYU) - Human Microbiome Program

Maria Gloria Dominguez Bello

Rutgers, The State University of New Jersey - Department of Biochemistry and Microbiology

Fredrick Backhed

University of Gothenburg - Department of Molecular and Clinical Medicine; University of Gothenburg - Wallenberg Laboratory

Stanley L. Hazen

Lerner Research Institute - Department of Cardiovascular and Metabolic Sciences

Martin J. Blaser

Rutgers, The State University of New Jersey - Center for Advanced Biotechnology and Medicine

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Abstract

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

Suggested Citation

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.

Xue-Song Zhang (Contact Author)

Rutgers, The State University of New Jersey - Center for Advanced Biotechnology and Medicine ( email )

United States

Yue Sandra Yin

Rutgers, The State University of New Jersey - Center for Advanced Biotechnology and Medicine ( email )

United States

Jincheng Wang

Rutgers University, New Brunswick - Department of Biochemistry and Microbiology

New Brunswick, NJ
United States

Thomas Battaglia

New York University (NYU) - Human Microbiome Program ( email )

Bobst Library, E-resource Acquisitions
20 Cooper Square 3rd Floor
New York, NY 10003-711
United States

Kimberly Krautkramer

University of Gothenburg - The Wallenberg Laboratory ( email )

Viktoriagatan 30
Göteborg, 405 30
Sweden

Wei Vivian Li

Rutgers University, Piscataway - Department of Biostatistics and Epidemiology ( email )

Piscataway, NJ
United States

Jackie Li

New York University (NYU) - Human Microbiome Program

Bobst Library, E-resource Acquisitions
20 Cooper Square 3rd Floor
New York, NY 10003-711
United States

Mark Brown

Cleveland Clinic - Cardiovascular & Metabolic Sciences

9500 Euclid Ave.
Cleveland, OH 44195
United States

Meifan Zhang

Rutgers, The State University of New Jersey - Center for Advanced Biotechnology and Medicine ( email )

United States

Michelle Badri

New York University (NYU) - Human Microbiome Program ( email )

Bobst Library, E-resource Acquisitions
20 Cooper Square 3rd Floor
New York, NY 10003-711
United States

Abigail Armstrong

Rutgers, The State University of New Jersey - Center for Advanced Biotechnology and Medicine

United States

Christopher M. Strauch

Cleveland Clinic - Cardiovascular & Metabolic Sciences ( email )

9500 Euclid Ave.
Cleveland, OH 44195
United States

Zeneng Wang

Cleveland Clinic - Cardiovascular & Metabolic Sciences ( email )

9500 Euclid Ave.
Cleveland, OH 44195
United States

Ina Nemet

Cleveland Clinic - Cardiovascular & Metabolic Sciences ( email )

9500 Euclid Ave.
Cleveland, OH 44195
United States

Nicole Altomare

Rutgers, The State University of New Jersey - Center for Advanced Biotechnology and Medicine ( email )

United States

Rutgers University, Piscataway - Robert Wood Johnson Medical School ( email )

Joseph C. Devlin

New York University (NYU) - Human Microbiome Program

Bobst Library, E-resource Acquisitions
20 Cooper Square 3rd Floor
New York, NY 10003-711
United States

Linchen He

New York University (NYU) - Department of Population Health ( email )

Bobst Library, E-resource Acquisitions
20 Cooper Square 3rd Floor
New York, NY 10003-711
United States

Jamie Morton

New York University (NYU) - Human Microbiome Program

Bobst Library, E-resource Acquisitions
20 Cooper Square 3rd Floor
New York, NY 10003-711
United States

John Alex Chalk

Rutgers, The State University of New Jersey - Center for Advanced Biotechnology and Medicine ( email )

United States

Kelly Needles

Rutgers, The State University of New Jersey - Center for Advanced Biotechnology and Medicine ( email )

United States

Viviane Liao

Rutgers, The State University of New Jersey - Center for Advanced Biotechnology and Medicine ( email )

United States

Julia Mount

New York University (NYU) - Human Microbiome Program ( email )

Bobst Library, E-resource Acquisitions
20 Cooper Square 3rd Floor
New York, NY 10003-711
United States

Huilin Li

New York University (NYU) - Department of Population Health ( email )

Bobst Library, E-resource Acquisitions
20 Cooper Square 3rd Floor
New York, NY 10003-711
United States

Kelly V. Ruggles

New York University (NYU) - Human Microbiome Program ( email )

Bobst Library, E-resource Acquisitions
20 Cooper Square 3rd Floor
New York, NY 10003-711
United States

Richard A. Bonneau

New York University (NYU) - Human Microbiome Program

Bobst Library, E-resource Acquisitions
20 Cooper Square 3rd Floor
New York, NY 10003-711
United States

Maria Gloria Dominguez Bello

Rutgers, The State University of New Jersey - Department of Biochemistry and Microbiology ( email )

311 North 5th Street
New Brunswick, NJ 08854
United States

Fredrick Backhed

University of Gothenburg - Department of Molecular and Clinical Medicine ( email )

University of Gothenburg - Wallenberg Laboratory ( email )

Viktoriagatan 30
Göteborg, 405 30
Sweden

Stanley L. Hazen

Lerner Research Institute - Department of Cardiovascular and Metabolic Sciences

United States

Martin J. Blaser

Rutgers, The State University of New Jersey - Center for Advanced Biotechnology and Medicine ( email )

United States

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