Akkermansia muciniphila mediates negative effects of IFNγ on glucose metabolism

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. Pereira, Sandra R. G. Ferreira, Michael Yao, Ivan J. Fuss, Warren Strober, Aleksandra E. Sikora, Gregory A. Taylor, Ajay S. Gulati, Andrey Morgun () and Natalia Shulzhenko ()
Additional contact information
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

Nature Communications, 2016, vol. 7, issue 1, 1-13

Abstract: 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.

Date: 2016
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DOI: 10.1038/ncomms13329

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