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Akkermansia muciniphila mediates negative effects of IFN? 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 IFN? on glucose tolerance. In IFN?-deficient mice, A. muciniphila is significantly increased and restoration of IFN? levels reduces A. muciniphila abundance. We further show that IFN?-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?-regulated gene in the mouse ileum that controls gut A. muciniphila levels. A. muciniphila is also linked to IFN?-regulated gene expression in the intestine and glucose parameters in humans, suggesting that this trialogue between IFN?, A. muciniphila and glucose tolerance might be an evolutionally conserved mechanism regulating metabolic health in mice and humans.

SUBMITTER: Greer RL

PROVIDER: S-EPMC5114536 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature

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Akkermansia muciniphila mediates negative effects of IFNγ on glucose metabolism.

Greer Renee L RL Dong Xiaoxi X Moraes Ana Carolina F AC Zielke Ryszard A RA Fernandes Gabriel R GR Peremyslova Ekaterina E Vasquez-Perez Stephany S Schoenborn Alexi A AA Gomes Everton P EP Pereira Alexandre C AC Ferreira Sandra R G SR Yao Michael M Fuss Ivan J IJ Strober Warren W Sikora Aleksandra E AE Taylor Gregory A GA Gulati Ajay S AS Morgun Andrey A Shulzhenko Natalia N

Nature communications 20161114

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 improve ...[more]

PMID: 27841267

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Project description:Recently, Akkermansia muciniphila an anaerobic member of the gut microbiota, has been proposed as a next-generation probiotic. The aim of this study was evaluation of the effect of alive and pasteurized A. muciniphila on health status, intestinal integrity, immune response, lipid metabolism, and gut microbial composition in normal-diet fed mice as well as direct effects of the bacterium on Caco-2 cell line. A total of 30 mice were distributed into three different groups, control, alive, and pasteurized A. muciniphila-treated group. After acclimation, control and treatment groups were administrated with PBS and 109 CFU/200µL of bacterial suspension for 5 weeks, respectively. Besides, Caco-2 separately exposed to alive, pasteurized A. muciniphila and PBS for 24 h. The results showed that administration of A. muciniphila leads to reduction in body, liver, and white adipose weight. Histology data revealed both treatments had no adverse effects in colon, liver, and adipose tissues as well as induced better gut structure. Moreover, biochemical parameters and inflammatory biomarkers in plasma demonstrated that pasteurized A. muciniphila had more pronounce effect. Furthermore, alive A. muciniphia had better effects on the modulation of gene expression related to fatty acid synthesis, energy homeostasis, and immune response in the liver; meanwhile, these effects in the adipose was more in the pasteurized A. muciniphila administration. More importantly, the improvement of gut health by enhancing strengthen intestinal integrity and maintaining immune homeostasis was seen in both treatments; notably, pasteurized A. muciniphila had more effective. Similarly, treatment with the pasteurized form more effectively upregulated tight junction and regulated immune response-related genes in Caco-2 cell line. Both treatments triggered the improvement of microbiota communities, particularly the alive form. Therefore, both forms of A. muciniphila could modulate lipid and immune homeostasis, improved some gut microbiota, and promoted the overall health, while all these effects were dominantly observed in pasteurized form. In conclusion, pasteurized A. muciniphila can be considered as new medical supplement to maintain health state and prevent diseases in normal mice through different mechanisms.

Dataset Information

Akkermansia muciniphila mediates negative effects of IFN? on glucose metabolism.

Publications

Akkermansia muciniphila mediates negative effects of IFNγ on glucose metabolism.

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