Akkermansia muciniphila mediates negative effects of IFN gamma on glucose metabolism

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Greer, Renee L. ; Dong, Xiaoxi ; Moraes, Ana Carolina F. ; Zielke, Ryszard A. ; Fernandes, 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

• Document type: Journal article
• Source: NATURE COMMUNICATIONS; v. 7, NOV 14 2016.
• Web of Science Citations: 53

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. (AU)

• FAPESP's process: 12/03880-9 - Subclinical atherosclerosis analysis in a vegetarian population in the State of São Paulo, Brazil
• Grantee: Alexandre da Costa Pereira
• Support Opportunities: Regular Research Grants
• FAPESP's process: 12/12626-9 - Analysis of the intestinal microbiota in adults with different dietary patterns and possible associations with inflammatory status, insulin sensitivity and body adiposity
• Grantee: Sandra Roberta Gouvea Ferreira Vivolo
• Support Opportunities: Regular Research Grants