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Akkermansia muciniphila mediates negative effects of IFNγ on glucose metabolism

Author

Listed:
  • Renee L. Greer

    (College of Veterinary Medicine, Oregon State University)

  • Xiaoxi Dong

    (College of Pharmacy, Oregon State University)

  • Ana Carolina F. Moraes

    (School of Public Health, University of São Paulo)

  • Ryszard A. Zielke

    (College of Pharmacy, Oregon State University)

  • Gabriel R. Fernandes

    (Oswaldo Cruz Foundation, René Rachou Research Center)

  • Ekaterina Peremyslova

    (College of Pharmacy, Oregon State University)

  • Stephany Vasquez-Perez

    (College of Veterinary Medicine, Oregon State University)

  • Alexi A. Schoenborn

    (University of North Carolina at Chapel Hill)

  • Everton P. Gomes

    (Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of São Paulo Medical School)

  • Alexandre C. Pereira

    (Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of São Paulo Medical School)

  • Sandra R. G. Ferreira

    (School of Public Health, University of São Paulo)

  • Michael Yao

    (Mucosal Immunity Section, Laboratory of Immune Defenses, National Institute of Allergy and Infectious Diseases)

  • Ivan J. Fuss

    (Mucosal Immunity Section, Laboratory of Immune Defenses, National Institute of Allergy and Infectious Diseases)

  • Warren Strober

    (Mucosal Immunity Section, Laboratory of Immune Defenses, National Institute of Allergy and Infectious Diseases)

  • Aleksandra E. Sikora

    (College of Pharmacy, Oregon State University)

  • Gregory A. Taylor

    (Geriatric Research, Education and Clinical Center, VA Medical Center, Molecular Genetics and Microbiology and Immunology)

  • Ajay S. Gulati

    (University of North Carolina at Chapel Hill)

  • Andrey Morgun

    (College of Pharmacy, Oregon State University)

  • Natalia Shulzhenko

    (College of Veterinary Medicine, Oregon State University)

Abstract

Cross-talk between the gut microbiota and the host immune system regulates host metabolism, and its dysregulation can cause metabolic disease. Here, we show that the gut microbe Akkermansia muciniphila can mediate negative effects of IFNγ on glucose tolerance. In IFNγ-deficient mice, A. muciniphila is significantly increased and restoration of IFNγ levels reduces A. muciniphila abundance. We further show that IFNγ-knockout mice whose microbiota does not contain A. muciniphila do not show improvement in glucose tolerance and adding back A. muciniphila promoted enhanced glucose tolerance. We go on to identify Irgm1 as an IFNγ-regulated gene in the mouse ileum that controls gut A. muciniphila levels. A. muciniphila is also linked to IFNγ-regulated gene expression in the intestine and glucose parameters in humans, suggesting that this trialogue between IFNγ, A. muciniphila and glucose tolerance might be an evolutionally conserved mechanism regulating metabolic health in mice and humans.

Suggested Citation

  • Renee L. Greer & Xiaoxi Dong & Ana Carolina F. Moraes & Ryszard A. Zielke & Gabriel R. Fernandes & Ekaterina Peremyslova & Stephany Vasquez-Perez & Alexi A. Schoenborn & Everton P. Gomes & Alexandre C, 2016. "Akkermansia muciniphila mediates negative effects of IFNγ on glucose metabolism," Nature Communications, Nature, vol. 7(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms13329
    DOI: 10.1038/ncomms13329
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