Journal Article

Akkermansia muciniphila mediates negative effects of IFNγ on glucose metabolism

Dong, Xiaoxi, Zielke, Ryszard A., Taylor, Gregory A., Gomes, Everton P., Strober, Warren, Ferreira, Sandra R. G., Sikora, Aleksandra E., Moraes, Ana Carolina F., Schoenborn, Alexi A., Greer, Renee L., Gulati, Ajay S., Morgun, Andrey, Fuss, Ivan J., Pereira, Alexandre C., Yao, Michael, Shulzhenko, Natalia, Fernandes, Gabriel R., Vasquez-Perez, Stephany, Peremyslova, Ekaterina

2016

Overview

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. Mice deficient in the pro-inflammatory cytokine IFNγ have improved glucose tolerance. Here, the authors show that this effect depends on the gut microbe Akkermansia muciniphila , whose abundance increases in the absence IFNγ, and which is known to have beneficial effects on host metabolism.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 38/91 / 631/250/127/1212 / 631/250/347 / 631/443/319 / 692/4020/2741/2135 / Animals / Carbohydrate Metabolism / Gastrointestinal Microbiome - genetics / Gastrointestinal Microbiome - physiology / Gene Expression / Glucose - metabolism / GTP-Binding Proteins - genetics / GTP-Binding Proteins - metabolism / Humanities and Social Sciences / Humans / Ileum - metabolism / Ileum - microbiology / Interferon-gamma - genetics / Interferon-gamma - metabolism / Mice, Inbred C57BL / Mice, Knockout / multidisciplinary / Science / Science (multidisciplinary) / Verrucomicrobia - genetics / Verrucomicrobia - physiology