The gut microbiota modulates glycaemic control and serum metabolite profiles in non-obese diabetic mice

Thomas U. Greiner, Tuulia Hyötyläinen, Mikael Knip, Fredrik Bäckhead (Corresponding Author), Matej Oresic (Corresponding Author)

Research output: Contribution to journalArticleScientificpeer-review

24 Citations (Scopus)

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.
Original languageEnglish
Article numbere110359
JournalPLoS ONE
Volume9
Issue number11
DOIs
Publication statusPublished - 2014
MoE publication typeA1 Journal article-refereed

Fingerprint

glycemic control
Inbred NOD Mouse
Medical problems
Metabolites
intestinal microorganisms
insulin-dependent diabetes mellitus
metabolites
Type 1 Diabetes Mellitus
mice
Serum
autoimmunity
Metabolome
Autoimmunity
Metabolism
diabetes
metabolism
Microbiota
interleukin-12
Immune System Diseases
Interleukin-12

Keywords

  • type 1 diabetes
  • diabetes mellitus
  • glucose metabolism
  • insulin
  • blood sugar
  • metabolites
  • autoimmunity
  • gut bacteria

Cite this

Greiner, Thomas U. ; Hyötyläinen, Tuulia ; Knip, Mikael ; Bäckhead, Fredrik ; Oresic, Matej. / The gut microbiota modulates glycaemic control and serum metabolite profiles in non-obese diabetic mice. In: PLoS ONE. 2014 ; Vol. 9, No. 11.
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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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The gut microbiota modulates glycaemic control and serum metabolite profiles in non-obese diabetic mice. / Greiner, Thomas U.; Hyötyläinen, Tuulia; Knip, Mikael; Bäckhead, Fredrik (Corresponding Author); Oresic, Matej (Corresponding Author).

In: PLoS ONE, Vol. 9, No. 11, e110359, 2014.

Research output: Contribution to journalArticleScientificpeer-review

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