Title | Akkermansia muciniphila mediates negative effects of IFNγ on glucose metabolism. |
Publication Type | Journal Article |
Year of Publication | 2016 |
Authors | Greer, RL, Dong, X, Moraes, ACarolina F, Zielke, RA, Fernandes, GR, Peremyslova, E, Vasquez-Perez, S, Schoenborn, AA, Gomes, EP, Pereira, AC, Ferreira, SRG, Yao, M, Fuss, IJ, Strober, W, Sikora, AE, Taylor, GA, Gulati, AS, Morgun, A, Shulzhenko, N |
Journal | Nat Commun |
Volume | 7 |
Pagination | 13329 |
Date Published | 2016 11 14 |
ISSN | 2041-1723 |
Keywords | Animals, Carbohydrate Metabolism, Gastrointestinal Microbiome, Gene Expression, Glucose, GTP-Binding Proteins, Humans, Ileum, Interferon-gamma, Mice, Inbred C57BL, Mice, Knockout, Verrucomicrobia |
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.
|
DOI | 10.1038/ncomms13329 |
Alternate Journal | Nat Commun |
PubMed ID | 27841267 |
PubMed Central ID | PMC5114536 |
Grant List | I01 BX002369 / BX / BLRD VA / United States R01 DK103761 / DK / NIDDK NIH HHS / United States R03 DK104005 / DK / NIDDK NIH HHS / United States U01 AI109695 / AI / NIAID NIH HHS / United States |