title: Fermentable fibres condition colon microbiota and promote diabetogenesis in NOD mice.
abstract: OBJECTIVE
  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
  FFs condition microbiota, affect colon homeostasis and are important components of natural, diabetes-promoting diets in NOD mice.
authors.affiliation: Department of Medical Microbiology and Immunology, University of Turku, Kiinamyllynkatu 13, 20520, Turku, Finland, raine.toivonen@utu.fi.
authors.forename: Raine K
authors.initials: RK
authors.lastname: Toivonen
authors.forename: Rohini
authors.initials: R
authors.lastname: Emani
authors.forename: Eveliina
authors.initials: E
authors.lastname: Munukka
authors.forename: Anniina
authors.initials: A
authors.lastname: Rintala
authors.forename: Asta
authors.initials: A
authors.lastname: Laiho
authors.forename: Sami
authors.initials: S
authors.lastname: Pietilä
authors.forename: Juha-Pekka
authors.initials: JP
authors.lastname: Pursiheimo
authors.forename: Pasi
authors.initials: P
authors.lastname: Soidinsalo
authors.forename: Mari
authors.initials: M
authors.lastname: Linhala
authors.forename: Erkki
authors.initials: E
authors.lastname: Eerola
authors.forename: Pentti
authors.initials: P
authors.lastname: Huovinen
authors.forename: Arno
authors.initials: A
authors.lastname: Hänninen
mesh_terms: D000818:Animals; D003106:Colon / Q000382:microbiology*; D003922:Diabetes Mellitus, Type 1 / Q000139:chemically induced / Q000378:metabolism* / Q000382:microbiology*; D005260:Female; D041981:Gastrointestinal Tract / Q000382:microbiology; D051543:Hepatocyte Nuclear Factor 3-gamma / Q000378:metabolism; D020382:Interleukin-18 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D007378:Interleukins / Q000378:metabolism; D008198:Lymph Nodes / Q000382:microbiology; D051379:Mice; D016688:Mice, Inbred NOD; D064307:Microbiota / Q000187:drug effects*; D010368:Pectins / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014990:Xylans / Q000494:pharmacology*; D000097043:Interleukin-22
chemical_list: D051543:Hepatocyte Nuclear Factor 3-gamma; D020382:Interleukin-18; D015847:Interleukin-4; D007378:Interleukins; D010368:Pectins; D016212:Transforming Growth Factor beta; D014990:Xylans; D000097043:Interleukin-22; C496506:Foxa3 protein, mouse