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The gut microbiota modulates glycaemic control and serum metabolite profiles in non-obese diabetic mice
Wallenberg Laboratory and Sahlgrenska Center for Cardiovascular and Metabolic Research, Department of Molecular and Clinical Medicine, Institute of Medicine, Gothenburg, Sweden.
Örebro University, School of Science and Technology. VTT Technical Research Centre of Finland, Espoo, Finland; Steno Diabetes Center, Gentofte, Denmark.
Children's Hospital, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland; Diabetes and Obesity Research Program, University of Helsinki, Helsinki, Finland; Folkhälsan Research Center, Helsinki, Finland; Department of Pediatrics, Tampere University Hospital, Tampere, Finland.
Wallenberg Laboratory and Sahlgrenska Center for Cardiovascular and Metabolic Research, Department of Molecular and Clinical Medicine, Institute of Medicine, Gothenburg, Sweden; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
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2014 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 11, article id e110359Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Oxford University Press, 2014. Vol. 9, no 11, article id e110359
National Category
Endocrinology and Diabetes
Identifiers
URN: urn:nbn:se:oru:diva-63699DOI: 10.1371/journal.pone.0110359ISI: 000349144400014PubMedID: 25390735Scopus ID: 2-s2.0-84911928672OAI: oai:DiVA.org:oru-63699DiVA, id: diva2:1169264
Funder
Swedish Research CouncilSwedish Foundation for Strategic Research Swedish Child Diabetes Foundation
Note

Funding agencies:

Human Frontier of Science Program RGY64/2008 

Juvenile Diabetes Research Foundation 36-2008-919

European Community HEALTH-2008-202013 HEALTH-2011-277713

Academy of Finland Centre of Excellence in Molecular Systems Immunology and Physiology Research (SyMMyS) 250114

LUA-ALF grant from Vastra Gotalandsregionen 

Available from: 2017-12-22 Created: 2017-12-22 Last updated: 2018-01-30Bibliographically approved

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Hyötyläinen, TuuliaOresic, Matej

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