Published in:
01-10-2014 | Article
Fermentable fibres condition colon microbiota and promote diabetogenesis in NOD mice
Authors:
Raine K. Toivonen, Rohini Emani, Eveliina Munukka, Anniina Rintala, Asta Laiho, Sami Pietilä, Juha-Pekka Pursiheimo, Pasi Soidinsalo, Mari Linhala, Erkki Eerola, Pentti Huovinen, Arno Hänninen
Published in:
Diabetologia
|
Issue 10/2014
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Abstract
Aims/hypothesis
Gut microbiota (GM) and diet both appear to be important in the pathogenesis of type 1 diabetes. Fermentable fibres (FFs), of which there is an ample supply in natural, diabetes-promoting diets, are used by GM as a source of energy. Our aim was to determine whether FFs modify GM and diabetes incidence in the NOD mouse.
Methods
Female NOD mice were weaned to a semisynthetic diet and the effects of FF supplementation on diabetes incidence and insulitis were evaluated. Real-time quantitative PCR was employed to determine the effects imposed to gene transcripts in the colon and lymph nodes. Changes to GM were analysed by next-generation sequencing.
Results
NOD mice fed semisynthetic diets free from FFs were largely protected from diabetes while semisynthetic diets supplemented with the FFs pectin and xylan (PX) resulted in higher diabetes incidence. Semisynthetic diet free from FFs altered GM composition significantly; addition of PX changed the composition of the GM towards that found in natural-diet-fed mice and increased production of FF-derived short-chain fatty acid metabolites in the colon. The highly diabetogenic natural diet was associated with expression of proinflammatory and stress-related genes in the colon, while the semisynthetic diet free from FFs promoted Il4, Il22, Tgfβ and Foxp3 transcripts in the colon and/or pancreatic lymph node. PX in the same diet counteracted these effects and promoted stress-related IL-18 activation in gut epithelial cells. 16S RNA sequencing revealed each diet to give rise to its particular GM composition, with different Firmicutes to Bacteroidetes ratios, and enrichment of mucin-degrading Ruminococcaceae following diabetes-protective FF-free diet.
Conclusions/interpretation
FFs condition microbiota, affect colon homeostasis and are important components of natural, diabetes-promoting diets in NOD mice.