title: Akkermansia muciniphila mediates negative effects of IFNγ on glucose metabolism.
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.
authors.affiliation: College of Veterinary Medicine, Oregon State University, 105 Dryden Hall, 450 SW 30th Street, Corvallis, Oregon 97331, USA.
authors.forename: Renee L
authors.initials: RL
authors.lastname: Greer
authors.affiliation: College of Pharmacy, Oregon State University, 1601 SW Jefferson Way, Corvallis, Oregon 97331, USA.
authors.forename: Xiaoxi
authors.initials: X
authors.lastname: Dong
authors.affiliation: Department of Epidemiology, School of Public Health, University of São Paulo, Av. Dr Arnaldo, 715, São Paulo, SP 01246-904, Brazil.
authors.forename: Ana Carolina F
authors.initials: AC
authors.lastname: Moraes
authors.affiliation: College of Pharmacy, Oregon State University, 1601 SW Jefferson Way, Corvallis, Oregon 97331, USA.
authors.forename: Ryszard A
authors.initials: RA
authors.lastname: Zielke
authors.affiliation: Oswaldo Cruz Foundation, René Rachou Research Center, Av. Augusto de Lima, 1715, Belo Horizonte, MG 30190-002, Brazil.
authors.forename: Gabriel R
authors.identifier: 0000-0002-4897-8521
authors.initials: GR
authors.lastname: Fernandes
authors.affiliation: College of Pharmacy, Oregon State University, 1601 SW Jefferson Way, Corvallis, Oregon 97331, USA.
authors.forename: Ekaterina
authors.initials: E
authors.lastname: Peremyslova
authors.affiliation: College of Veterinary Medicine, Oregon State University, 105 Dryden Hall, 450 SW 30th Street, Corvallis, Oregon 97331, USA.
authors.forename: Stephany
authors.initials: S
authors.lastname: Vasquez-Perez
authors.affiliation: Division of Pediatric Gastroenterology, University of North Carolina at Chapel Hill, 260 MacNider Building, CB# 7220, Chapel Hill, North Carolina 27599, USA.
authors.forename: Alexi A
authors.initials: AA
authors.lastname: Schoenborn
authors.affiliation: Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of São Paulo Medical School, Av. Dr Eneas de Carvalho Aguiar, 44, São Paulo, SP 05403-000, Brazil.
authors.forename: Everton P
authors.initials: EP
authors.lastname: Gomes
authors.affiliation: Laboratory of Genetics and Molecular Cardiology, Heart Institute (InCor), University of São Paulo Medical School, Av. Dr Eneas de Carvalho Aguiar, 44, São Paulo, SP 05403-000, Brazil.
authors.forename: Alexandre C
authors.initials: AC
authors.lastname: Pereira
authors.affiliation: Department of Epidemiology, School of Public Health, University of São Paulo, Av. Dr Arnaldo, 715, São Paulo, SP 01246-904, Brazil.
authors.forename: Sandra R G
authors.initials: SR
authors.lastname: Ferreira
authors.affiliation: Mucosal Immunity Section, Laboratory of Immune Defenses, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Yao
authors.affiliation: Mucosal Immunity Section, Laboratory of Immune Defenses, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892, USA.
authors.forename: Ivan J
authors.initials: IJ
authors.lastname: Fuss
authors.affiliation: Mucosal Immunity Section, Laboratory of Immune Defenses, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892, USA.
authors.forename: Warren
authors.initials: W
authors.lastname: Strober
authors.affiliation: College of Pharmacy, Oregon State University, 1601 SW Jefferson Way, Corvallis, Oregon 97331, USA.
authors.forename: Aleksandra E
authors.initials: AE
authors.lastname: Sikora
authors.affiliation: Geriatric Research, Education and Clinical Center, VA Medical Center, Departments of Medicine, Molecular Genetics and Microbiology and Immunology, Division of Geriatrics and Center for the Study of Aging and Human Development, Duke Box 3003, Duke University Medical Center, Durham, North Carolina 27710, USA.
authors.forename: Gregory A
authors.initials: GA
authors.lastname: Taylor
authors.affiliation: Division of Pediatric Gastroenterology, University of North Carolina at Chapel Hill, 260 MacNider Building, CB# 7220, Chapel Hill, North Carolina 27599, USA.
authors.forename: Ajay S
authors.initials: AS
authors.lastname: Gulati
authors.affiliation: College of Pharmacy, Oregon State University, 1601 SW Jefferson Way, Corvallis, Oregon 97331, USA.
authors.forename: Andrey
authors.initials: A
authors.lastname: Morgun
authors.affiliation: College of Veterinary Medicine, Oregon State University, 105 Dryden Hall, 450 SW 30th Street, Corvallis, Oregon 97331, USA.
authors.forename: Natalia
authors.initials: N
authors.lastname: Shulzhenko
mesh_terms: D000818:Animals; D050260:Carbohydrate Metabolism; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D000069196:Gastrointestinal Microbiome / Q000235:genetics / Q000502:physiology*; D015870:Gene Expression; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007082:Ileum / Q000378:metabolism / Q000382:microbiology; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D061327:Verrucomicrobia / Q000235:genetics / Q000502:physiology*
chemical_list: C096000:Ifi1 protein, mouse; D007371:Interferon-gamma; D019204:GTP-Binding Proteins; D005947:Glucose