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ResearchIn-Press PreviewAutoimmunityMicrobiology Open Access | 10.1172/JCI163239

Epsilon toxin-producing Clostridium perfringens colonize the MS gut and epsilon toxin overcomes immune privilege

Yinghua Ma,1 David Sannino,1 Jennifer R. Linden,1 Sylvia Haigh,1 Baohua Zhao,1 John B. Grigg,2 Paul Zumbo,3 Friederike Dündar,4 Daniel J. Butler,5 Caterina P. Profaci,6 Kiel M. Telesford,1 Paige N. Winokur,7 Kareem R. Rumah,8 Susan A. Gauthier,9 Vincent A. Fischetti,8 Bruce A. McClane,10 Francisco A. Uzal,11 Lily Zexter,12 Michael Mazzucco,1 Richard Rudick,13 David Danko,14 Evan Balmuth,1 Nancy Nealon,12 Jai Perumal,12 Ulrike W. Kaunzner,12 Ilana L. Brito,15 Zhengming Chen,16 Jenny Z. Xiang,17 Doron Betel,4 Richard Daneman,18 Gregory F. Sonnenberg,17 Christopher E. Mason,20 and Timothy Vartanian1

1Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York, United States of America

2Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medical College, New York, United States of America

3Applied Bioinformatics Core, Weill Cornell Medical College, New York, United States of America

4Department of Medicine, Weill Cornell Medical College, New York, United States of America

5Department of Physiology and Biophysics, Institute for Computational Biomed, Weill Cornell Medical College, New York, United States of America

6Department of Pharmacology and Neurosciences, UCSD, San Diego, United States of America

7Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, Rockefeller University, New York, United States of America

8Laboratory of Bacterial Pathogenesis and Immunology, Rockefeller University, New York, United States of America

9Department of Neurology, Weill Cornell Medicine, New York, United States of America

10School of Medicine, University of Pittsburgh, Pittsburgh, United States of America

11California Animal Health and Food Safety Laboratory, UCD, Davis, United States of America

12Department of Neurology, Weill Cornell Medical College, New York, United States of America

13Astoria Biologica Inc., Stamford, United States of America

14Physiology and Biophysics, Institute for Computational Biomedicine, Weill Cornell Medical College, New York, United States of America

15Meinig School of Biomedical Engineering, Cornell University, Ithaca, United States of America

16Department of Population Health Sciences, Weill Cornell Medical College, New york, United States of America

17Department of Microbiology and Immunology, Weill Cornell Medical College, New York, United States of America

18Departments of Pharmacology and Neurosciences, UCSD, United States of America

19Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10065, United States of America

20Department of Physiology and Biophysics, Weill Cornell Medical College, New York City, United States of America

21Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York City, United States of America

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1Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York, United States of America

2Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medical College, New York, United States of America

3Applied Bioinformatics Core, Weill Cornell Medical College, New York, United States of America

4Department of Medicine, Weill Cornell Medical College, New York, United States of America

5Department of Physiology and Biophysics, Institute for Computational Biomed, Weill Cornell Medical College, New York, United States of America

6Department of Pharmacology and Neurosciences, UCSD, San Diego, United States of America

7Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, Rockefeller University, New York, United States of America

8Laboratory of Bacterial Pathogenesis and Immunology, Rockefeller University, New York, United States of America

9Department of Neurology, Weill Cornell Medicine, New York, United States of America

10School of Medicine, University of Pittsburgh, Pittsburgh, United States of America

11California Animal Health and Food Safety Laboratory, UCD, Davis, United States of America

12Department of Neurology, Weill Cornell Medical College, New York, United States of America

13Astoria Biologica Inc., Stamford, United States of America

14Physiology and Biophysics, Institute for Computational Biomedicine, Weill Cornell Medical College, New York, United States of America

15Meinig School of Biomedical Engineering, Cornell University, Ithaca, United States of America

16Department of Population Health Sciences, Weill Cornell Medical College, New york, United States of America

17Department of Microbiology and Immunology, Weill Cornell Medical College, New York, United States of America

18Departments of Pharmacology and Neurosciences, UCSD, United States of America

19Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10065, United States of America

20Department of Physiology and Biophysics, Weill Cornell Medical College, New York City, United States of America

21Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York City, United States of America

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1Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York, United States of America

2Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medical College, New York, United States of America

3Applied Bioinformatics Core, Weill Cornell Medical College, New York, United States of America

4Department of Medicine, Weill Cornell Medical College, New York, United States of America

5Department of Physiology and Biophysics, Institute for Computational Biomed, Weill Cornell Medical College, New York, United States of America

6Department of Pharmacology and Neurosciences, UCSD, San Diego, United States of America

7Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, Rockefeller University, New York, United States of America

8Laboratory of Bacterial Pathogenesis and Immunology, Rockefeller University, New York, United States of America

9Department of Neurology, Weill Cornell Medicine, New York, United States of America

10School of Medicine, University of Pittsburgh, Pittsburgh, United States of America

11California Animal Health and Food Safety Laboratory, UCD, Davis, United States of America

12Department of Neurology, Weill Cornell Medical College, New York, United States of America

13Astoria Biologica Inc., Stamford, United States of America

14Physiology and Biophysics, Institute for Computational Biomedicine, Weill Cornell Medical College, New York, United States of America

15Meinig School of Biomedical Engineering, Cornell University, Ithaca, United States of America

16Department of Population Health Sciences, Weill Cornell Medical College, New york, United States of America

17Department of Microbiology and Immunology, Weill Cornell Medical College, New York, United States of America

18Departments of Pharmacology and Neurosciences, UCSD, United States of America

19Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10065, United States of America

20Department of Physiology and Biophysics, Weill Cornell Medical College, New York City, United States of America

21Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York City, United States of America

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1Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York, United States of America

2Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medical College, New York, United States of America

3Applied Bioinformatics Core, Weill Cornell Medical College, New York, United States of America

4Department of Medicine, Weill Cornell Medical College, New York, United States of America

5Department of Physiology and Biophysics, Institute for Computational Biomed, Weill Cornell Medical College, New York, United States of America

6Department of Pharmacology and Neurosciences, UCSD, San Diego, United States of America

7Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, Rockefeller University, New York, United States of America

8Laboratory of Bacterial Pathogenesis and Immunology, Rockefeller University, New York, United States of America

9Department of Neurology, Weill Cornell Medicine, New York, United States of America

10School of Medicine, University of Pittsburgh, Pittsburgh, United States of America

11California Animal Health and Food Safety Laboratory, UCD, Davis, United States of America

12Department of Neurology, Weill Cornell Medical College, New York, United States of America

13Astoria Biologica Inc., Stamford, United States of America

14Physiology and Biophysics, Institute for Computational Biomedicine, Weill Cornell Medical College, New York, United States of America

15Meinig School of Biomedical Engineering, Cornell University, Ithaca, United States of America

16Department of Population Health Sciences, Weill Cornell Medical College, New york, United States of America

17Department of Microbiology and Immunology, Weill Cornell Medical College, New York, United States of America

18Departments of Pharmacology and Neurosciences, UCSD, United States of America

19Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10065, United States of America

20Department of Physiology and Biophysics, Weill Cornell Medical College, New York City, United States of America

21Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York City, United States of America

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1Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York, United States of America

2Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medical College, New York, United States of America

3Applied Bioinformatics Core, Weill Cornell Medical College, New York, United States of America

4Department of Medicine, Weill Cornell Medical College, New York, United States of America

5Department of Physiology and Biophysics, Institute for Computational Biomed, Weill Cornell Medical College, New York, United States of America

6Department of Pharmacology and Neurosciences, UCSD, San Diego, United States of America

7Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, Rockefeller University, New York, United States of America

8Laboratory of Bacterial Pathogenesis and Immunology, Rockefeller University, New York, United States of America

9Department of Neurology, Weill Cornell Medicine, New York, United States of America

10School of Medicine, University of Pittsburgh, Pittsburgh, United States of America

11California Animal Health and Food Safety Laboratory, UCD, Davis, United States of America

12Department of Neurology, Weill Cornell Medical College, New York, United States of America

13Astoria Biologica Inc., Stamford, United States of America

14Physiology and Biophysics, Institute for Computational Biomedicine, Weill Cornell Medical College, New York, United States of America

15Meinig School of Biomedical Engineering, Cornell University, Ithaca, United States of America

16Department of Population Health Sciences, Weill Cornell Medical College, New york, United States of America

17Department of Microbiology and Immunology, Weill Cornell Medical College, New York, United States of America

18Departments of Pharmacology and Neurosciences, UCSD, United States of America

19Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10065, United States of America

20Department of Physiology and Biophysics, Weill Cornell Medical College, New York City, United States of America

21Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York City, United States of America

Find articles by Zhao, B. in: JCI | PubMed | Google Scholar

1Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York, United States of America

2Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medical College, New York, United States of America

3Applied Bioinformatics Core, Weill Cornell Medical College, New York, United States of America

4Department of Medicine, Weill Cornell Medical College, New York, United States of America

5Department of Physiology and Biophysics, Institute for Computational Biomed, Weill Cornell Medical College, New York, United States of America

6Department of Pharmacology and Neurosciences, UCSD, San Diego, United States of America

7Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, Rockefeller University, New York, United States of America

8Laboratory of Bacterial Pathogenesis and Immunology, Rockefeller University, New York, United States of America

9Department of Neurology, Weill Cornell Medicine, New York, United States of America

10School of Medicine, University of Pittsburgh, Pittsburgh, United States of America

11California Animal Health and Food Safety Laboratory, UCD, Davis, United States of America

12Department of Neurology, Weill Cornell Medical College, New York, United States of America

13Astoria Biologica Inc., Stamford, United States of America

14Physiology and Biophysics, Institute for Computational Biomedicine, Weill Cornell Medical College, New York, United States of America

15Meinig School of Biomedical Engineering, Cornell University, Ithaca, United States of America

16Department of Population Health Sciences, Weill Cornell Medical College, New york, United States of America

17Department of Microbiology and Immunology, Weill Cornell Medical College, New York, United States of America

18Departments of Pharmacology and Neurosciences, UCSD, United States of America

19Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10065, United States of America

20Department of Physiology and Biophysics, Weill Cornell Medical College, New York City, United States of America

21Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York City, United States of America

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1Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York, United States of America

2Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medical College, New York, United States of America

3Applied Bioinformatics Core, Weill Cornell Medical College, New York, United States of America

4Department of Medicine, Weill Cornell Medical College, New York, United States of America

5Department of Physiology and Biophysics, Institute for Computational Biomed, Weill Cornell Medical College, New York, United States of America

6Department of Pharmacology and Neurosciences, UCSD, San Diego, United States of America

7Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, Rockefeller University, New York, United States of America

8Laboratory of Bacterial Pathogenesis and Immunology, Rockefeller University, New York, United States of America

9Department of Neurology, Weill Cornell Medicine, New York, United States of America

10School of Medicine, University of Pittsburgh, Pittsburgh, United States of America

11California Animal Health and Food Safety Laboratory, UCD, Davis, United States of America

12Department of Neurology, Weill Cornell Medical College, New York, United States of America

13Astoria Biologica Inc., Stamford, United States of America

14Physiology and Biophysics, Institute for Computational Biomedicine, Weill Cornell Medical College, New York, United States of America

15Meinig School of Biomedical Engineering, Cornell University, Ithaca, United States of America

16Department of Population Health Sciences, Weill Cornell Medical College, New york, United States of America

17Department of Microbiology and Immunology, Weill Cornell Medical College, New York, United States of America

18Departments of Pharmacology and Neurosciences, UCSD, United States of America

19Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10065, United States of America

20Department of Physiology and Biophysics, Weill Cornell Medical College, New York City, United States of America

21Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York City, United States of America

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1Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York, United States of America

2Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medical College, New York, United States of America

3Applied Bioinformatics Core, Weill Cornell Medical College, New York, United States of America

4Department of Medicine, Weill Cornell Medical College, New York, United States of America

5Department of Physiology and Biophysics, Institute for Computational Biomed, Weill Cornell Medical College, New York, United States of America

6Department of Pharmacology and Neurosciences, UCSD, San Diego, United States of America

7Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, Rockefeller University, New York, United States of America

8Laboratory of Bacterial Pathogenesis and Immunology, Rockefeller University, New York, United States of America

9Department of Neurology, Weill Cornell Medicine, New York, United States of America

10School of Medicine, University of Pittsburgh, Pittsburgh, United States of America

11California Animal Health and Food Safety Laboratory, UCD, Davis, United States of America

12Department of Neurology, Weill Cornell Medical College, New York, United States of America

13Astoria Biologica Inc., Stamford, United States of America

14Physiology and Biophysics, Institute for Computational Biomedicine, Weill Cornell Medical College, New York, United States of America

15Meinig School of Biomedical Engineering, Cornell University, Ithaca, United States of America

16Department of Population Health Sciences, Weill Cornell Medical College, New york, United States of America

17Department of Microbiology and Immunology, Weill Cornell Medical College, New York, United States of America

18Departments of Pharmacology and Neurosciences, UCSD, United States of America

19Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10065, United States of America

20Department of Physiology and Biophysics, Weill Cornell Medical College, New York City, United States of America

21Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York City, United States of America

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1Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York, United States of America

2Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medical College, New York, United States of America

3Applied Bioinformatics Core, Weill Cornell Medical College, New York, United States of America

4Department of Medicine, Weill Cornell Medical College, New York, United States of America

5Department of Physiology and Biophysics, Institute for Computational Biomed, Weill Cornell Medical College, New York, United States of America

6Department of Pharmacology and Neurosciences, UCSD, San Diego, United States of America

7Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, Rockefeller University, New York, United States of America

8Laboratory of Bacterial Pathogenesis and Immunology, Rockefeller University, New York, United States of America

9Department of Neurology, Weill Cornell Medicine, New York, United States of America

10School of Medicine, University of Pittsburgh, Pittsburgh, United States of America

11California Animal Health and Food Safety Laboratory, UCD, Davis, United States of America

12Department of Neurology, Weill Cornell Medical College, New York, United States of America

13Astoria Biologica Inc., Stamford, United States of America

14Physiology and Biophysics, Institute for Computational Biomedicine, Weill Cornell Medical College, New York, United States of America

15Meinig School of Biomedical Engineering, Cornell University, Ithaca, United States of America

16Department of Population Health Sciences, Weill Cornell Medical College, New york, United States of America

17Department of Microbiology and Immunology, Weill Cornell Medical College, New York, United States of America

18Departments of Pharmacology and Neurosciences, UCSD, United States of America

19Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10065, United States of America

20Department of Physiology and Biophysics, Weill Cornell Medical College, New York City, United States of America

21Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York City, United States of America

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1Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York, United States of America

2Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medical College, New York, United States of America

3Applied Bioinformatics Core, Weill Cornell Medical College, New York, United States of America

4Department of Medicine, Weill Cornell Medical College, New York, United States of America

5Department of Physiology and Biophysics, Institute for Computational Biomed, Weill Cornell Medical College, New York, United States of America

6Department of Pharmacology and Neurosciences, UCSD, San Diego, United States of America

7Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, Rockefeller University, New York, United States of America

8Laboratory of Bacterial Pathogenesis and Immunology, Rockefeller University, New York, United States of America

9Department of Neurology, Weill Cornell Medicine, New York, United States of America

10School of Medicine, University of Pittsburgh, Pittsburgh, United States of America

11California Animal Health and Food Safety Laboratory, UCD, Davis, United States of America

12Department of Neurology, Weill Cornell Medical College, New York, United States of America

13Astoria Biologica Inc., Stamford, United States of America

14Physiology and Biophysics, Institute for Computational Biomedicine, Weill Cornell Medical College, New York, United States of America

15Meinig School of Biomedical Engineering, Cornell University, Ithaca, United States of America

16Department of Population Health Sciences, Weill Cornell Medical College, New york, United States of America

17Department of Microbiology and Immunology, Weill Cornell Medical College, New York, United States of America

18Departments of Pharmacology and Neurosciences, UCSD, United States of America

19Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10065, United States of America

20Department of Physiology and Biophysics, Weill Cornell Medical College, New York City, United States of America

21Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York City, United States of America

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1Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York, United States of America

2Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medical College, New York, United States of America

3Applied Bioinformatics Core, Weill Cornell Medical College, New York, United States of America

4Department of Medicine, Weill Cornell Medical College, New York, United States of America

5Department of Physiology and Biophysics, Institute for Computational Biomed, Weill Cornell Medical College, New York, United States of America

6Department of Pharmacology and Neurosciences, UCSD, San Diego, United States of America

7Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, Rockefeller University, New York, United States of America

8Laboratory of Bacterial Pathogenesis and Immunology, Rockefeller University, New York, United States of America

9Department of Neurology, Weill Cornell Medicine, New York, United States of America

10School of Medicine, University of Pittsburgh, Pittsburgh, United States of America

11California Animal Health and Food Safety Laboratory, UCD, Davis, United States of America

12Department of Neurology, Weill Cornell Medical College, New York, United States of America

13Astoria Biologica Inc., Stamford, United States of America

14Physiology and Biophysics, Institute for Computational Biomedicine, Weill Cornell Medical College, New York, United States of America

15Meinig School of Biomedical Engineering, Cornell University, Ithaca, United States of America

16Department of Population Health Sciences, Weill Cornell Medical College, New york, United States of America

17Department of Microbiology and Immunology, Weill Cornell Medical College, New York, United States of America

18Departments of Pharmacology and Neurosciences, UCSD, United States of America

19Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10065, United States of America

20Department of Physiology and Biophysics, Weill Cornell Medical College, New York City, United States of America

21Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York City, United States of America

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1Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York, United States of America

2Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medical College, New York, United States of America

3Applied Bioinformatics Core, Weill Cornell Medical College, New York, United States of America

4Department of Medicine, Weill Cornell Medical College, New York, United States of America

5Department of Physiology and Biophysics, Institute for Computational Biomed, Weill Cornell Medical College, New York, United States of America

6Department of Pharmacology and Neurosciences, UCSD, San Diego, United States of America

7Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, Rockefeller University, New York, United States of America

8Laboratory of Bacterial Pathogenesis and Immunology, Rockefeller University, New York, United States of America

9Department of Neurology, Weill Cornell Medicine, New York, United States of America

10School of Medicine, University of Pittsburgh, Pittsburgh, United States of America

11California Animal Health and Food Safety Laboratory, UCD, Davis, United States of America

12Department of Neurology, Weill Cornell Medical College, New York, United States of America

13Astoria Biologica Inc., Stamford, United States of America

14Physiology and Biophysics, Institute for Computational Biomedicine, Weill Cornell Medical College, New York, United States of America

15Meinig School of Biomedical Engineering, Cornell University, Ithaca, United States of America

16Department of Population Health Sciences, Weill Cornell Medical College, New york, United States of America

17Department of Microbiology and Immunology, Weill Cornell Medical College, New York, United States of America

18Departments of Pharmacology and Neurosciences, UCSD, United States of America

19Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10065, United States of America

20Department of Physiology and Biophysics, Weill Cornell Medical College, New York City, United States of America

21Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York City, United States of America

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1Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York, United States of America

2Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medical College, New York, United States of America

3Applied Bioinformatics Core, Weill Cornell Medical College, New York, United States of America

4Department of Medicine, Weill Cornell Medical College, New York, United States of America

5Department of Physiology and Biophysics, Institute for Computational Biomed, Weill Cornell Medical College, New York, United States of America

6Department of Pharmacology and Neurosciences, UCSD, San Diego, United States of America

7Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, Rockefeller University, New York, United States of America

8Laboratory of Bacterial Pathogenesis and Immunology, Rockefeller University, New York, United States of America

9Department of Neurology, Weill Cornell Medicine, New York, United States of America

10School of Medicine, University of Pittsburgh, Pittsburgh, United States of America

11California Animal Health and Food Safety Laboratory, UCD, Davis, United States of America

12Department of Neurology, Weill Cornell Medical College, New York, United States of America

13Astoria Biologica Inc., Stamford, United States of America

14Physiology and Biophysics, Institute for Computational Biomedicine, Weill Cornell Medical College, New York, United States of America

15Meinig School of Biomedical Engineering, Cornell University, Ithaca, United States of America

16Department of Population Health Sciences, Weill Cornell Medical College, New york, United States of America

17Department of Microbiology and Immunology, Weill Cornell Medical College, New York, United States of America

18Departments of Pharmacology and Neurosciences, UCSD, United States of America

19Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10065, United States of America

20Department of Physiology and Biophysics, Weill Cornell Medical College, New York City, United States of America

21Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York City, United States of America

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1Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York, United States of America

2Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medical College, New York, United States of America

3Applied Bioinformatics Core, Weill Cornell Medical College, New York, United States of America

4Department of Medicine, Weill Cornell Medical College, New York, United States of America

5Department of Physiology and Biophysics, Institute for Computational Biomed, Weill Cornell Medical College, New York, United States of America

6Department of Pharmacology and Neurosciences, UCSD, San Diego, United States of America

7Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, Rockefeller University, New York, United States of America

8Laboratory of Bacterial Pathogenesis and Immunology, Rockefeller University, New York, United States of America

9Department of Neurology, Weill Cornell Medicine, New York, United States of America

10School of Medicine, University of Pittsburgh, Pittsburgh, United States of America

11California Animal Health and Food Safety Laboratory, UCD, Davis, United States of America

12Department of Neurology, Weill Cornell Medical College, New York, United States of America

13Astoria Biologica Inc., Stamford, United States of America

14Physiology and Biophysics, Institute for Computational Biomedicine, Weill Cornell Medical College, New York, United States of America

15Meinig School of Biomedical Engineering, Cornell University, Ithaca, United States of America

16Department of Population Health Sciences, Weill Cornell Medical College, New york, United States of America

17Department of Microbiology and Immunology, Weill Cornell Medical College, New York, United States of America

18Departments of Pharmacology and Neurosciences, UCSD, United States of America

19Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10065, United States of America

20Department of Physiology and Biophysics, Weill Cornell Medical College, New York City, United States of America

21Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York City, United States of America

Find articles by Gauthier, S. in: JCI | PubMed | Google Scholar |

1Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York, United States of America

2Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medical College, New York, United States of America

3Applied Bioinformatics Core, Weill Cornell Medical College, New York, United States of America

4Department of Medicine, Weill Cornell Medical College, New York, United States of America

5Department of Physiology and Biophysics, Institute for Computational Biomed, Weill Cornell Medical College, New York, United States of America

6Department of Pharmacology and Neurosciences, UCSD, San Diego, United States of America

7Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, Rockefeller University, New York, United States of America

8Laboratory of Bacterial Pathogenesis and Immunology, Rockefeller University, New York, United States of America

9Department of Neurology, Weill Cornell Medicine, New York, United States of America

10School of Medicine, University of Pittsburgh, Pittsburgh, United States of America

11California Animal Health and Food Safety Laboratory, UCD, Davis, United States of America

12Department of Neurology, Weill Cornell Medical College, New York, United States of America

13Astoria Biologica Inc., Stamford, United States of America

14Physiology and Biophysics, Institute for Computational Biomedicine, Weill Cornell Medical College, New York, United States of America

15Meinig School of Biomedical Engineering, Cornell University, Ithaca, United States of America

16Department of Population Health Sciences, Weill Cornell Medical College, New york, United States of America

17Department of Microbiology and Immunology, Weill Cornell Medical College, New York, United States of America

18Departments of Pharmacology and Neurosciences, UCSD, United States of America

19Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10065, United States of America

20Department of Physiology and Biophysics, Weill Cornell Medical College, New York City, United States of America

21Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York City, United States of America

Find articles by Fischetti, V. in: JCI | PubMed | Google Scholar

1Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York, United States of America

2Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medical College, New York, United States of America

3Applied Bioinformatics Core, Weill Cornell Medical College, New York, United States of America

4Department of Medicine, Weill Cornell Medical College, New York, United States of America

5Department of Physiology and Biophysics, Institute for Computational Biomed, Weill Cornell Medical College, New York, United States of America

6Department of Pharmacology and Neurosciences, UCSD, San Diego, United States of America

7Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, Rockefeller University, New York, United States of America

8Laboratory of Bacterial Pathogenesis and Immunology, Rockefeller University, New York, United States of America

9Department of Neurology, Weill Cornell Medicine, New York, United States of America

10School of Medicine, University of Pittsburgh, Pittsburgh, United States of America

11California Animal Health and Food Safety Laboratory, UCD, Davis, United States of America

12Department of Neurology, Weill Cornell Medical College, New York, United States of America

13Astoria Biologica Inc., Stamford, United States of America

14Physiology and Biophysics, Institute for Computational Biomedicine, Weill Cornell Medical College, New York, United States of America

15Meinig School of Biomedical Engineering, Cornell University, Ithaca, United States of America

16Department of Population Health Sciences, Weill Cornell Medical College, New york, United States of America

17Department of Microbiology and Immunology, Weill Cornell Medical College, New York, United States of America

18Departments of Pharmacology and Neurosciences, UCSD, United States of America

19Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10065, United States of America

20Department of Physiology and Biophysics, Weill Cornell Medical College, New York City, United States of America

21Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York City, United States of America

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1Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York, United States of America

2Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medical College, New York, United States of America

3Applied Bioinformatics Core, Weill Cornell Medical College, New York, United States of America

4Department of Medicine, Weill Cornell Medical College, New York, United States of America

5Department of Physiology and Biophysics, Institute for Computational Biomed, Weill Cornell Medical College, New York, United States of America

6Department of Pharmacology and Neurosciences, UCSD, San Diego, United States of America

7Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, Rockefeller University, New York, United States of America

8Laboratory of Bacterial Pathogenesis and Immunology, Rockefeller University, New York, United States of America

9Department of Neurology, Weill Cornell Medicine, New York, United States of America

10School of Medicine, University of Pittsburgh, Pittsburgh, United States of America

11California Animal Health and Food Safety Laboratory, UCD, Davis, United States of America

12Department of Neurology, Weill Cornell Medical College, New York, United States of America

13Astoria Biologica Inc., Stamford, United States of America

14Physiology and Biophysics, Institute for Computational Biomedicine, Weill Cornell Medical College, New York, United States of America

15Meinig School of Biomedical Engineering, Cornell University, Ithaca, United States of America

16Department of Population Health Sciences, Weill Cornell Medical College, New york, United States of America

17Department of Microbiology and Immunology, Weill Cornell Medical College, New York, United States of America

18Departments of Pharmacology and Neurosciences, UCSD, United States of America

19Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10065, United States of America

20Department of Physiology and Biophysics, Weill Cornell Medical College, New York City, United States of America

21Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York City, United States of America

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1Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York, United States of America

2Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medical College, New York, United States of America

3Applied Bioinformatics Core, Weill Cornell Medical College, New York, United States of America

4Department of Medicine, Weill Cornell Medical College, New York, United States of America

5Department of Physiology and Biophysics, Institute for Computational Biomed, Weill Cornell Medical College, New York, United States of America

6Department of Pharmacology and Neurosciences, UCSD, San Diego, United States of America

7Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, Rockefeller University, New York, United States of America

8Laboratory of Bacterial Pathogenesis and Immunology, Rockefeller University, New York, United States of America

9Department of Neurology, Weill Cornell Medicine, New York, United States of America

10School of Medicine, University of Pittsburgh, Pittsburgh, United States of America

11California Animal Health and Food Safety Laboratory, UCD, Davis, United States of America

12Department of Neurology, Weill Cornell Medical College, New York, United States of America

13Astoria Biologica Inc., Stamford, United States of America

14Physiology and Biophysics, Institute for Computational Biomedicine, Weill Cornell Medical College, New York, United States of America

15Meinig School of Biomedical Engineering, Cornell University, Ithaca, United States of America

16Department of Population Health Sciences, Weill Cornell Medical College, New york, United States of America

17Department of Microbiology and Immunology, Weill Cornell Medical College, New York, United States of America

18Departments of Pharmacology and Neurosciences, UCSD, United States of America

19Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10065, United States of America

20Department of Physiology and Biophysics, Weill Cornell Medical College, New York City, United States of America

21Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York City, United States of America

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1Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York, United States of America

2Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medical College, New York, United States of America

3Applied Bioinformatics Core, Weill Cornell Medical College, New York, United States of America

4Department of Medicine, Weill Cornell Medical College, New York, United States of America

5Department of Physiology and Biophysics, Institute for Computational Biomed, Weill Cornell Medical College, New York, United States of America

6Department of Pharmacology and Neurosciences, UCSD, San Diego, United States of America

7Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, Rockefeller University, New York, United States of America

8Laboratory of Bacterial Pathogenesis and Immunology, Rockefeller University, New York, United States of America

9Department of Neurology, Weill Cornell Medicine, New York, United States of America

10School of Medicine, University of Pittsburgh, Pittsburgh, United States of America

11California Animal Health and Food Safety Laboratory, UCD, Davis, United States of America

12Department of Neurology, Weill Cornell Medical College, New York, United States of America

13Astoria Biologica Inc., Stamford, United States of America

14Physiology and Biophysics, Institute for Computational Biomedicine, Weill Cornell Medical College, New York, United States of America

15Meinig School of Biomedical Engineering, Cornell University, Ithaca, United States of America

16Department of Population Health Sciences, Weill Cornell Medical College, New york, United States of America

17Department of Microbiology and Immunology, Weill Cornell Medical College, New York, United States of America

18Departments of Pharmacology and Neurosciences, UCSD, United States of America

19Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10065, United States of America

20Department of Physiology and Biophysics, Weill Cornell Medical College, New York City, United States of America

21Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York City, United States of America

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1Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York, United States of America

2Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medical College, New York, United States of America

3Applied Bioinformatics Core, Weill Cornell Medical College, New York, United States of America

4Department of Medicine, Weill Cornell Medical College, New York, United States of America

5Department of Physiology and Biophysics, Institute for Computational Biomed, Weill Cornell Medical College, New York, United States of America

6Department of Pharmacology and Neurosciences, UCSD, San Diego, United States of America

7Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, Rockefeller University, New York, United States of America

8Laboratory of Bacterial Pathogenesis and Immunology, Rockefeller University, New York, United States of America

9Department of Neurology, Weill Cornell Medicine, New York, United States of America

10School of Medicine, University of Pittsburgh, Pittsburgh, United States of America

11California Animal Health and Food Safety Laboratory, UCD, Davis, United States of America

12Department of Neurology, Weill Cornell Medical College, New York, United States of America

13Astoria Biologica Inc., Stamford, United States of America

14Physiology and Biophysics, Institute for Computational Biomedicine, Weill Cornell Medical College, New York, United States of America

15Meinig School of Biomedical Engineering, Cornell University, Ithaca, United States of America

16Department of Population Health Sciences, Weill Cornell Medical College, New york, United States of America

17Department of Microbiology and Immunology, Weill Cornell Medical College, New York, United States of America

18Departments of Pharmacology and Neurosciences, UCSD, United States of America

19Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10065, United States of America

20Department of Physiology and Biophysics, Weill Cornell Medical College, New York City, United States of America

21Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York City, United States of America

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1Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York, United States of America

2Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medical College, New York, United States of America

3Applied Bioinformatics Core, Weill Cornell Medical College, New York, United States of America

4Department of Medicine, Weill Cornell Medical College, New York, United States of America

5Department of Physiology and Biophysics, Institute for Computational Biomed, Weill Cornell Medical College, New York, United States of America

6Department of Pharmacology and Neurosciences, UCSD, San Diego, United States of America

7Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, Rockefeller University, New York, United States of America

8Laboratory of Bacterial Pathogenesis and Immunology, Rockefeller University, New York, United States of America

9Department of Neurology, Weill Cornell Medicine, New York, United States of America

10School of Medicine, University of Pittsburgh, Pittsburgh, United States of America

11California Animal Health and Food Safety Laboratory, UCD, Davis, United States of America

12Department of Neurology, Weill Cornell Medical College, New York, United States of America

13Astoria Biologica Inc., Stamford, United States of America

14Physiology and Biophysics, Institute for Computational Biomedicine, Weill Cornell Medical College, New York, United States of America

15Meinig School of Biomedical Engineering, Cornell University, Ithaca, United States of America

16Department of Population Health Sciences, Weill Cornell Medical College, New york, United States of America

17Department of Microbiology and Immunology, Weill Cornell Medical College, New York, United States of America

18Departments of Pharmacology and Neurosciences, UCSD, United States of America

19Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10065, United States of America

20Department of Physiology and Biophysics, Weill Cornell Medical College, New York City, United States of America

21Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York City, United States of America

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1Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York, United States of America

2Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medical College, New York, United States of America

3Applied Bioinformatics Core, Weill Cornell Medical College, New York, United States of America

4Department of Medicine, Weill Cornell Medical College, New York, United States of America

5Department of Physiology and Biophysics, Institute for Computational Biomed, Weill Cornell Medical College, New York, United States of America

6Department of Pharmacology and Neurosciences, UCSD, San Diego, United States of America

7Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, Rockefeller University, New York, United States of America

8Laboratory of Bacterial Pathogenesis and Immunology, Rockefeller University, New York, United States of America

9Department of Neurology, Weill Cornell Medicine, New York, United States of America

10School of Medicine, University of Pittsburgh, Pittsburgh, United States of America

11California Animal Health and Food Safety Laboratory, UCD, Davis, United States of America

12Department of Neurology, Weill Cornell Medical College, New York, United States of America

13Astoria Biologica Inc., Stamford, United States of America

14Physiology and Biophysics, Institute for Computational Biomedicine, Weill Cornell Medical College, New York, United States of America

15Meinig School of Biomedical Engineering, Cornell University, Ithaca, United States of America

16Department of Population Health Sciences, Weill Cornell Medical College, New york, United States of America

17Department of Microbiology and Immunology, Weill Cornell Medical College, New York, United States of America

18Departments of Pharmacology and Neurosciences, UCSD, United States of America

19Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10065, United States of America

20Department of Physiology and Biophysics, Weill Cornell Medical College, New York City, United States of America

21Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York City, United States of America

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1Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York, United States of America

2Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medical College, New York, United States of America

3Applied Bioinformatics Core, Weill Cornell Medical College, New York, United States of America

4Department of Medicine, Weill Cornell Medical College, New York, United States of America

5Department of Physiology and Biophysics, Institute for Computational Biomed, Weill Cornell Medical College, New York, United States of America

6Department of Pharmacology and Neurosciences, UCSD, San Diego, United States of America

7Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, Rockefeller University, New York, United States of America

8Laboratory of Bacterial Pathogenesis and Immunology, Rockefeller University, New York, United States of America

9Department of Neurology, Weill Cornell Medicine, New York, United States of America

10School of Medicine, University of Pittsburgh, Pittsburgh, United States of America

11California Animal Health and Food Safety Laboratory, UCD, Davis, United States of America

12Department of Neurology, Weill Cornell Medical College, New York, United States of America

13Astoria Biologica Inc., Stamford, United States of America

14Physiology and Biophysics, Institute for Computational Biomedicine, Weill Cornell Medical College, New York, United States of America

15Meinig School of Biomedical Engineering, Cornell University, Ithaca, United States of America

16Department of Population Health Sciences, Weill Cornell Medical College, New york, United States of America

17Department of Microbiology and Immunology, Weill Cornell Medical College, New York, United States of America

18Departments of Pharmacology and Neurosciences, UCSD, United States of America

19Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10065, United States of America

20Department of Physiology and Biophysics, Weill Cornell Medical College, New York City, United States of America

21Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York City, United States of America

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1Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York, United States of America

2Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medical College, New York, United States of America

3Applied Bioinformatics Core, Weill Cornell Medical College, New York, United States of America

4Department of Medicine, Weill Cornell Medical College, New York, United States of America

5Department of Physiology and Biophysics, Institute for Computational Biomed, Weill Cornell Medical College, New York, United States of America

6Department of Pharmacology and Neurosciences, UCSD, San Diego, United States of America

7Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, Rockefeller University, New York, United States of America

8Laboratory of Bacterial Pathogenesis and Immunology, Rockefeller University, New York, United States of America

9Department of Neurology, Weill Cornell Medicine, New York, United States of America

10School of Medicine, University of Pittsburgh, Pittsburgh, United States of America

11California Animal Health and Food Safety Laboratory, UCD, Davis, United States of America

12Department of Neurology, Weill Cornell Medical College, New York, United States of America

13Astoria Biologica Inc., Stamford, United States of America

14Physiology and Biophysics, Institute for Computational Biomedicine, Weill Cornell Medical College, New York, United States of America

15Meinig School of Biomedical Engineering, Cornell University, Ithaca, United States of America

16Department of Population Health Sciences, Weill Cornell Medical College, New york, United States of America

17Department of Microbiology and Immunology, Weill Cornell Medical College, New York, United States of America

18Departments of Pharmacology and Neurosciences, UCSD, United States of America

19Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10065, United States of America

20Department of Physiology and Biophysics, Weill Cornell Medical College, New York City, United States of America

21Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York City, United States of America

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1Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York, United States of America

2Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medical College, New York, United States of America

3Applied Bioinformatics Core, Weill Cornell Medical College, New York, United States of America

4Department of Medicine, Weill Cornell Medical College, New York, United States of America

5Department of Physiology and Biophysics, Institute for Computational Biomed, Weill Cornell Medical College, New York, United States of America

6Department of Pharmacology and Neurosciences, UCSD, San Diego, United States of America

7Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, Rockefeller University, New York, United States of America

8Laboratory of Bacterial Pathogenesis and Immunology, Rockefeller University, New York, United States of America

9Department of Neurology, Weill Cornell Medicine, New York, United States of America

10School of Medicine, University of Pittsburgh, Pittsburgh, United States of America

11California Animal Health and Food Safety Laboratory, UCD, Davis, United States of America

12Department of Neurology, Weill Cornell Medical College, New York, United States of America

13Astoria Biologica Inc., Stamford, United States of America

14Physiology and Biophysics, Institute for Computational Biomedicine, Weill Cornell Medical College, New York, United States of America

15Meinig School of Biomedical Engineering, Cornell University, Ithaca, United States of America

16Department of Population Health Sciences, Weill Cornell Medical College, New york, United States of America

17Department of Microbiology and Immunology, Weill Cornell Medical College, New York, United States of America

18Departments of Pharmacology and Neurosciences, UCSD, United States of America

19Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10065, United States of America

20Department of Physiology and Biophysics, Weill Cornell Medical College, New York City, United States of America

21Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York City, United States of America

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1Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York, United States of America

2Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medical College, New York, United States of America

3Applied Bioinformatics Core, Weill Cornell Medical College, New York, United States of America

4Department of Medicine, Weill Cornell Medical College, New York, United States of America

5Department of Physiology and Biophysics, Institute for Computational Biomed, Weill Cornell Medical College, New York, United States of America

6Department of Pharmacology and Neurosciences, UCSD, San Diego, United States of America

7Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, Rockefeller University, New York, United States of America

8Laboratory of Bacterial Pathogenesis and Immunology, Rockefeller University, New York, United States of America

9Department of Neurology, Weill Cornell Medicine, New York, United States of America

10School of Medicine, University of Pittsburgh, Pittsburgh, United States of America

11California Animal Health and Food Safety Laboratory, UCD, Davis, United States of America

12Department of Neurology, Weill Cornell Medical College, New York, United States of America

13Astoria Biologica Inc., Stamford, United States of America

14Physiology and Biophysics, Institute for Computational Biomedicine, Weill Cornell Medical College, New York, United States of America

15Meinig School of Biomedical Engineering, Cornell University, Ithaca, United States of America

16Department of Population Health Sciences, Weill Cornell Medical College, New york, United States of America

17Department of Microbiology and Immunology, Weill Cornell Medical College, New York, United States of America

18Departments of Pharmacology and Neurosciences, UCSD, United States of America

19Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10065, United States of America

20Department of Physiology and Biophysics, Weill Cornell Medical College, New York City, United States of America

21Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York City, United States of America

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1Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York, United States of America

2Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medical College, New York, United States of America

3Applied Bioinformatics Core, Weill Cornell Medical College, New York, United States of America

4Department of Medicine, Weill Cornell Medical College, New York, United States of America

5Department of Physiology and Biophysics, Institute for Computational Biomed, Weill Cornell Medical College, New York, United States of America

6Department of Pharmacology and Neurosciences, UCSD, San Diego, United States of America

7Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, Rockefeller University, New York, United States of America

8Laboratory of Bacterial Pathogenesis and Immunology, Rockefeller University, New York, United States of America

9Department of Neurology, Weill Cornell Medicine, New York, United States of America

10School of Medicine, University of Pittsburgh, Pittsburgh, United States of America

11California Animal Health and Food Safety Laboratory, UCD, Davis, United States of America

12Department of Neurology, Weill Cornell Medical College, New York, United States of America

13Astoria Biologica Inc., Stamford, United States of America

14Physiology and Biophysics, Institute for Computational Biomedicine, Weill Cornell Medical College, New York, United States of America

15Meinig School of Biomedical Engineering, Cornell University, Ithaca, United States of America

16Department of Population Health Sciences, Weill Cornell Medical College, New york, United States of America

17Department of Microbiology and Immunology, Weill Cornell Medical College, New York, United States of America

18Departments of Pharmacology and Neurosciences, UCSD, United States of America

19Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10065, United States of America

20Department of Physiology and Biophysics, Weill Cornell Medical College, New York City, United States of America

21Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York City, United States of America

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1Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York, United States of America

2Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medical College, New York, United States of America

3Applied Bioinformatics Core, Weill Cornell Medical College, New York, United States of America

4Department of Medicine, Weill Cornell Medical College, New York, United States of America

5Department of Physiology and Biophysics, Institute for Computational Biomed, Weill Cornell Medical College, New York, United States of America

6Department of Pharmacology and Neurosciences, UCSD, San Diego, United States of America

7Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, Rockefeller University, New York, United States of America

8Laboratory of Bacterial Pathogenesis and Immunology, Rockefeller University, New York, United States of America

9Department of Neurology, Weill Cornell Medicine, New York, United States of America

10School of Medicine, University of Pittsburgh, Pittsburgh, United States of America

11California Animal Health and Food Safety Laboratory, UCD, Davis, United States of America

12Department of Neurology, Weill Cornell Medical College, New York, United States of America

13Astoria Biologica Inc., Stamford, United States of America

14Physiology and Biophysics, Institute for Computational Biomedicine, Weill Cornell Medical College, New York, United States of America

15Meinig School of Biomedical Engineering, Cornell University, Ithaca, United States of America

16Department of Population Health Sciences, Weill Cornell Medical College, New york, United States of America

17Department of Microbiology and Immunology, Weill Cornell Medical College, New York, United States of America

18Departments of Pharmacology and Neurosciences, UCSD, United States of America

19Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10065, United States of America

20Department of Physiology and Biophysics, Weill Cornell Medical College, New York City, United States of America

21Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York City, United States of America

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1Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York, United States of America

2Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medical College, New York, United States of America

3Applied Bioinformatics Core, Weill Cornell Medical College, New York, United States of America

4Department of Medicine, Weill Cornell Medical College, New York, United States of America

5Department of Physiology and Biophysics, Institute for Computational Biomed, Weill Cornell Medical College, New York, United States of America

6Department of Pharmacology and Neurosciences, UCSD, San Diego, United States of America

7Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, Rockefeller University, New York, United States of America

8Laboratory of Bacterial Pathogenesis and Immunology, Rockefeller University, New York, United States of America

9Department of Neurology, Weill Cornell Medicine, New York, United States of America

10School of Medicine, University of Pittsburgh, Pittsburgh, United States of America

11California Animal Health and Food Safety Laboratory, UCD, Davis, United States of America

12Department of Neurology, Weill Cornell Medical College, New York, United States of America

13Astoria Biologica Inc., Stamford, United States of America

14Physiology and Biophysics, Institute for Computational Biomedicine, Weill Cornell Medical College, New York, United States of America

15Meinig School of Biomedical Engineering, Cornell University, Ithaca, United States of America

16Department of Population Health Sciences, Weill Cornell Medical College, New york, United States of America

17Department of Microbiology and Immunology, Weill Cornell Medical College, New York, United States of America

18Departments of Pharmacology and Neurosciences, UCSD, United States of America

19Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10065, United States of America

20Department of Physiology and Biophysics, Weill Cornell Medical College, New York City, United States of America

21Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York City, United States of America

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1Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York, United States of America

2Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medical College, New York, United States of America

3Applied Bioinformatics Core, Weill Cornell Medical College, New York, United States of America

4Department of Medicine, Weill Cornell Medical College, New York, United States of America

5Department of Physiology and Biophysics, Institute for Computational Biomed, Weill Cornell Medical College, New York, United States of America

6Department of Pharmacology and Neurosciences, UCSD, San Diego, United States of America

7Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, Rockefeller University, New York, United States of America

8Laboratory of Bacterial Pathogenesis and Immunology, Rockefeller University, New York, United States of America

9Department of Neurology, Weill Cornell Medicine, New York, United States of America

10School of Medicine, University of Pittsburgh, Pittsburgh, United States of America

11California Animal Health and Food Safety Laboratory, UCD, Davis, United States of America

12Department of Neurology, Weill Cornell Medical College, New York, United States of America

13Astoria Biologica Inc., Stamford, United States of America

14Physiology and Biophysics, Institute for Computational Biomedicine, Weill Cornell Medical College, New York, United States of America

15Meinig School of Biomedical Engineering, Cornell University, Ithaca, United States of America

16Department of Population Health Sciences, Weill Cornell Medical College, New york, United States of America

17Department of Microbiology and Immunology, Weill Cornell Medical College, New York, United States of America

18Departments of Pharmacology and Neurosciences, UCSD, United States of America

19Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10065, United States of America

20Department of Physiology and Biophysics, Weill Cornell Medical College, New York City, United States of America

21Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York City, United States of America

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1Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York, United States of America

2Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medical College, New York, United States of America

3Applied Bioinformatics Core, Weill Cornell Medical College, New York, United States of America

4Department of Medicine, Weill Cornell Medical College, New York, United States of America

5Department of Physiology and Biophysics, Institute for Computational Biomed, Weill Cornell Medical College, New York, United States of America

6Department of Pharmacology and Neurosciences, UCSD, San Diego, United States of America

7Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, Rockefeller University, New York, United States of America

8Laboratory of Bacterial Pathogenesis and Immunology, Rockefeller University, New York, United States of America

9Department of Neurology, Weill Cornell Medicine, New York, United States of America

10School of Medicine, University of Pittsburgh, Pittsburgh, United States of America

11California Animal Health and Food Safety Laboratory, UCD, Davis, United States of America

12Department of Neurology, Weill Cornell Medical College, New York, United States of America

13Astoria Biologica Inc., Stamford, United States of America

14Physiology and Biophysics, Institute for Computational Biomedicine, Weill Cornell Medical College, New York, United States of America

15Meinig School of Biomedical Engineering, Cornell University, Ithaca, United States of America

16Department of Population Health Sciences, Weill Cornell Medical College, New york, United States of America

17Department of Microbiology and Immunology, Weill Cornell Medical College, New York, United States of America

18Departments of Pharmacology and Neurosciences, UCSD, United States of America

19Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10065, United States of America

20Department of Physiology and Biophysics, Weill Cornell Medical College, New York City, United States of America

21Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York City, United States of America

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1Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York, United States of America

2Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medical College, New York, United States of America

3Applied Bioinformatics Core, Weill Cornell Medical College, New York, United States of America

4Department of Medicine, Weill Cornell Medical College, New York, United States of America

5Department of Physiology and Biophysics, Institute for Computational Biomed, Weill Cornell Medical College, New York, United States of America

6Department of Pharmacology and Neurosciences, UCSD, San Diego, United States of America

7Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, Rockefeller University, New York, United States of America

8Laboratory of Bacterial Pathogenesis and Immunology, Rockefeller University, New York, United States of America

9Department of Neurology, Weill Cornell Medicine, New York, United States of America

10School of Medicine, University of Pittsburgh, Pittsburgh, United States of America

11California Animal Health and Food Safety Laboratory, UCD, Davis, United States of America

12Department of Neurology, Weill Cornell Medical College, New York, United States of America

13Astoria Biologica Inc., Stamford, United States of America

14Physiology and Biophysics, Institute for Computational Biomedicine, Weill Cornell Medical College, New York, United States of America

15Meinig School of Biomedical Engineering, Cornell University, Ithaca, United States of America

16Department of Population Health Sciences, Weill Cornell Medical College, New york, United States of America

17Department of Microbiology and Immunology, Weill Cornell Medical College, New York, United States of America

18Departments of Pharmacology and Neurosciences, UCSD, United States of America

19Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10065, United States of America

20Department of Physiology and Biophysics, Weill Cornell Medical College, New York City, United States of America

21Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York City, United States of America

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1Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York, United States of America

2Jill Roberts Institute for Research in Inflammatory Bowel Disease, Weill Cornell Medical College, New York, United States of America

3Applied Bioinformatics Core, Weill Cornell Medical College, New York, United States of America

4Department of Medicine, Weill Cornell Medical College, New York, United States of America

5Department of Physiology and Biophysics, Institute for Computational Biomed, Weill Cornell Medical College, New York, United States of America

6Department of Pharmacology and Neurosciences, UCSD, San Diego, United States of America

7Harold and Margaret Milliken Hatch Laboratory of Neuroendocrinology, Rockefeller University, New York, United States of America

8Laboratory of Bacterial Pathogenesis and Immunology, Rockefeller University, New York, United States of America

9Department of Neurology, Weill Cornell Medicine, New York, United States of America

10School of Medicine, University of Pittsburgh, Pittsburgh, United States of America

11California Animal Health and Food Safety Laboratory, UCD, Davis, United States of America

12Department of Neurology, Weill Cornell Medical College, New York, United States of America

13Astoria Biologica Inc., Stamford, United States of America

14Physiology and Biophysics, Institute for Computational Biomedicine, Weill Cornell Medical College, New York, United States of America

15Meinig School of Biomedical Engineering, Cornell University, Ithaca, United States of America

16Department of Population Health Sciences, Weill Cornell Medical College, New york, United States of America

17Department of Microbiology and Immunology, Weill Cornell Medical College, New York, United States of America

18Departments of Pharmacology and Neurosciences, UCSD, United States of America

19Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY 10065, United States of America

20Department of Physiology and Biophysics, Weill Cornell Medical College, New York City, United States of America

21Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York City, United States of America

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Published February 28, 2023 - More info

J Clin Invest. https://doi.org/10.1172/JCI163239.
Copyright © 2023, Ma et al. This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
Published February 28, 2023 - Version history
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Abstract

Multiple Sclerosis (MS) is a complex disease of the CNS thought to require an environmental trigger. Gut dysbiosis is common in MS, but specifically causative species are unknown. To address this knowledge gap, we used sensitive and quantitative PCR detection to show that people with MS were more likely to harbor and show a greater abundance of epsilon toxin (ETX)-producing strains of C. perfringens within their gut microbiomes compared to healthy controls (HC). MS patient-derived isolates produced functional ETX and had a genetic architecture typical of highly conjugative plasmids. In the active immunization model of experimental autoimmune encephalomyelitis (EAE), where pertussis toxin (PTX) is used to overcome CNS immune privilege, ETX can substitute for PTX. In contrast to PTX-induced EAE, where inflammatory demyelination is largely restricted to the spinal cord, ETX-induced EAE caused demyelination in the corpus callosum, thalamus, cerebellum, brainstem, and spinal cord, more akin to the neuroanatomical lesion distribution in MS. CNS endothelial cell transcriptional profiles revealed ETX-induced genes that are known to play a role in overcoming CNS immune privilege. Together, these findings suggest that ETX-producing C. perfringens strains are biologically plausible pathogens in MS that trigger inflammatory demyelination in the context of circulating myelin autoreactive lymphocytes.

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