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https://www.arca.fiocruz.br/handle/icict/18353
AKKERMANSIA MUCINIPHILA MEDIATES NEGATIVE EFFECTS OF IFN GAMMA ON GLUCOSE METABOLISM.
Author
Greer, Renee L.
Dong, Xiaoxi
Moraes, Ana Carolina F.
Zielke, Ryszard A.
Rernandes, Gabriel R
Peremyslova, Ekaterina
Vasquez-Perez, Stephany
Schoenborn, Alexi A.
Gomes, Everton P.
Pereira, Alexandre C.
Ferreira, Sandra R. G.
Yao, Michael
Fuss, Ivan J.
Strober, Warren
Sikora, Aleksandra E.
Taylor, Gregory A.
Gulati, Ajay S.
Morgun, Andrey
Shulzhenko, Natalia
Dong, Xiaoxi
Moraes, Ana Carolina F.
Zielke, Ryszard A.
Rernandes, Gabriel R
Peremyslova, Ekaterina
Vasquez-Perez, Stephany
Schoenborn, Alexi A.
Gomes, Everton P.
Pereira, Alexandre C.
Ferreira, Sandra R. G.
Yao, Michael
Fuss, Ivan J.
Strober, Warren
Sikora, Aleksandra E.
Taylor, Gregory A.
Gulati, Ajay S.
Morgun, Andrey
Shulzhenko, Natalia
Affilliation
Oregon State University. College of Veterinary Medicine. Corvallis, Oregon, USA
Oregon State University. College of Veterinary Medicine. Corvallis, Oregon, USA
Universidade de São Paulo. Escola de Saúde Pública. Departamento de Epidemiologia. São Paulo, SP, Brazil
Oswaldo Cruz Foundation. René Rachou Research Center. Belo Horizonte, MG, Brasil
Oregon State University. college of Pharmacy. Corvallis, Oregon, USA
Oregon State University. College of Veterinary Medicine. Corvallis, Oregon, USA
University of North Carolina at Chapel Hill. Division of Pediatric Gastroenterology. Chapel Hill, North Carolina, USA
University of São Paulo Medical School. Laboratory of Genetics and Molecular Cardiology. Heart Institute. São Paulo, SP, Brazil
University of São Paulo Medical School. Laboratory of Genetics and Molecular Cardiology. Heart Institute. São Paulo, SP, Brazil
Universidade de São Paulo. Escola de Saúde Pública. Departamento de Epidemiologia. São Paulo, SP, Brazil
National Institute of Allergy and Infectious Diseases. Laboratory of Immune Defenses. Mucosal Immunity Section. Bethesda, Maryland , USA
National Institute of Allergy and Infectious Diseases. Laboratory of Immune Defenses. Mucosal Immunity Section. Bethesda, Maryland , USA
National Institute of Allergy and Infectious Diseases. Laboratory of Immune Defenses. Mucosal Immunity Section. Bethesda, Maryland , USA
Oregon State University. College of Pharmacy. Corvallis, Oregon, USA
Duke University Medical Center. Division of Geriatrics and Center for the Study of Aging and Human Development. Departments of Medicine, Molecular Genetics and Microbiology and Immunology. VA Medical Center. Education and Clinical Center. Geriatric Research. Durham, North Carolina, USA
University of North Carolina at Chapel Hill. Division of Pediatric Gastroenterology. Chapel Hill, North Carolina, USA
Oregon State University. College of Pharmacy. Corvallis, Oregon, USA
Oregon State University. College of Veterinary Medicine. Corvallis, Oregon, USA
Oregon State University. College of Veterinary Medicine. Corvallis, Oregon, USA
Universidade de São Paulo. Escola de Saúde Pública. Departamento de Epidemiologia. São Paulo, SP, Brazil
Oswaldo Cruz Foundation. René Rachou Research Center. Belo Horizonte, MG, Brasil
Oregon State University. college of Pharmacy. Corvallis, Oregon, USA
Oregon State University. College of Veterinary Medicine. Corvallis, Oregon, USA
University of North Carolina at Chapel Hill. Division of Pediatric Gastroenterology. Chapel Hill, North Carolina, USA
University of São Paulo Medical School. Laboratory of Genetics and Molecular Cardiology. Heart Institute. São Paulo, SP, Brazil
University of São Paulo Medical School. Laboratory of Genetics and Molecular Cardiology. Heart Institute. São Paulo, SP, Brazil
Universidade de São Paulo. Escola de Saúde Pública. Departamento de Epidemiologia. São Paulo, SP, Brazil
National Institute of Allergy and Infectious Diseases. Laboratory of Immune Defenses. Mucosal Immunity Section. Bethesda, Maryland , USA
National Institute of Allergy and Infectious Diseases. Laboratory of Immune Defenses. Mucosal Immunity Section. Bethesda, Maryland , USA
National Institute of Allergy and Infectious Diseases. Laboratory of Immune Defenses. Mucosal Immunity Section. Bethesda, Maryland , USA
Oregon State University. College of Pharmacy. Corvallis, Oregon, USA
Duke University Medical Center. Division of Geriatrics and Center for the Study of Aging and Human Development. Departments of Medicine, Molecular Genetics and Microbiology and Immunology. VA Medical Center. Education and Clinical Center. Geriatric Research. Durham, North Carolina, USA
University of North Carolina at Chapel Hill. Division of Pediatric Gastroenterology. Chapel Hill, North Carolina, USA
Oregon State University. College of Pharmacy. Corvallis, Oregon, USA
Oregon State University. College of Veterinary Medicine. Corvallis, Oregon, USA
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 IFN gamma on glucose tolerance. In IFN gamma-deficient mice, A. muciniphila is significantly increased and restoration of IFN gamma levels reduces A. muciniphila abundance. We further show that IFN gamma-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 IFN gamma-regulated gene in the mouse ileum that controls gut A. muciniphila levels. A. muciniphila is also linked to IFN gamma-regulated gene expression in the intestine and glucose parameters in humans, suggesting that this trialogue between IFN gamma, A. muciniphila and glucose tolerance might be an evolutionally conserved mechanism regulating metabolic health in mice and humans
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