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Nat Commun. 2016 Nov 14;7:13329. doi: 10.1038/ncomms13329.

Akkermansia muciniphila mediates negative effects of IFNγ on glucose metabolism.

Author information

1
College of Veterinary Medicine, Oregon State University, 105 Dryden Hall, 450 SW 30th Street, Corvallis, Oregon 97331, USA.
2
College of Pharmacy, Oregon State University, 1601 SW Jefferson Way, Corvallis, Oregon 97331, USA.
3
Department of Epidemiology, School of Public Health, University of São Paulo, Av. Dr Arnaldo, 715, São Paulo, SP 01246-904, Brazil.
4
Oswaldo Cruz Foundation, René Rachou Research Center, Av. Augusto de Lima, 1715, Belo Horizonte, MG 30190-002, Brazil.
5
Division of Pediatric Gastroenterology, University of North Carolina at Chapel Hill, 260 MacNider Building, CB# 7220, Chapel Hill, North Carolina 27599, USA.
6
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.
7
Mucosal Immunity Section, Laboratory of Immune Defenses, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892, USA.
8
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.

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.

PMID:
27841267
PMCID:
PMC5114536
DOI:
10.1038/ncomms13329
[Indexed for MEDLINE]
Free PMC Article

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