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The Gut Microbiota Modulates Glycaemic Control and Serum Metabolite Profiles in Non-Obese Diabetic Mice

Journal article
Authors Thomas U. Greiner
T. Hyotylainen
M. Knip
Fredrik Bäckhed
M. Oresic
Published in Plos One
Volume 9
Issue 11
ISSN 1932-6203
Publication year 2014
Published at Wallenberg Laboratory
Institute of Medicine, Department of Molecular and Clinical Medicine
Language en
Links dx.doi.org/10.1371/journal.pone.011...
Keywords MASS-SPECTROMETRY, NOD MOUSE, AUTOIMMUNE, DYSREGULATION, SUPPRESSION, METAGENOME, CHILDREN, MELLITUS, OUTCOMES, DISEASE, Multidisciplinary Sciences
Subject categories Clinical Medicine, Basic Medicine

Abstract

Islet autoimmunity in children who later progress to type 1 diabetes is preceded by dysregulated serum metabolite profiles, but the origin of these metabolic changes is unknown. The gut microbiota affects host metabolism and changes in its composition contribute to several immune-mediated diseases; however, it is not known whether the gut microbiota is involved in the early metabolic disturbances in progression to type 1 diabetes. We rederived non-obese diabetic ( NOD) mice as germ free to explore the potential role of the gut microbiota in the development of diabetic autoimmunity and to directly investigate whether the metabolic profiles associated with the development of type 1 diabetes can be modulated by the gut microbiota. The absence of a gut microbiota in NOD mice did not affect the overall diabetes incidence but resulted in increased insulitis and levels of interferon gamma and interleukin 12; these changes were counterbalanced by improved peripheral glucose metabolism. Furthermore, we observed a markedly increased variation in blood glucose levels in the absence of a microbiota in NOD mice that did not progress to diabetes. Additionally, germ-free NOD mice had a metabolite profile similar to that of pre-diabetic children. Our data suggest that germ-free NOD mice have reduced glycaemic control and dysregulated immunologic and metabolic responses.

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