title: Casein hydrolysate diet controls intestinal T cell activation, free radical production and microbial colonisation in NOD mice.
abstract: OBJECTIVE
  Dietary and microbial factors and the gut immune system are important in autoimmune diabetes. We evaluated inflammatory activity in the whole gut in prediabetic NOD mice using ex vivo imaging of reactive oxygen and nitrogen species (RONS), and correlated this with the above-mentioned factors.
  
  
  METHODS
  NOD mice were fed a normal diet or an anti-diabetogenic casein hydrolysate (CH) diet. RONS activity was detected by chemiluminescence imaging of the whole gut. Proinflammatory and T cell cytokines were studied in the gut and islets, and dietary effects on gut microbiota and short-chain fatty acids were determined.
  
  
  RESULTS
  Prediabetic NOD mice displayed high RONS activity in the epithelial cells of the distal small intestine, in conjunction with a proinflammatory cytokine profile. RONS production was effectively reduced by the CH diet, which also controlled (1) the expression of proinflammatory cytokines and colonisation-dependent RegIIIγ (also known as Reg3g) in ileum; (2) intestinal T cell activation; and (3) islet cytokines. The CH diet diminished microbial colonisation, increased the Bacteroidetes:Firmicutes ratio, and reduced lactic acid and butyric acid production in the gut.
  
  
  CONCLUSIONS
  Epithelial RONS production and proinflammatory T cell activation appears in the ileum of NOD mice after weaning to normal laboratory chow, but not after weaning to an anti-diabetogenic CH diet. Our data suggest a link between dietary factors, microbial colonisation and mucosal immune activation in NOD mice.
authors.affiliation: Department of Medical Microbiology and Immunology, Kiinamyllynkatu 13, Turku, Finland.
authors.forename: R
authors.initials: R
authors.lastname: Emani
authors.forename: M N
authors.initials: MN
authors.lastname: Asghar
authors.forename: R
authors.initials: R
authors.lastname: Toivonen
authors.forename: L
authors.initials: L
authors.lastname: Lauren
authors.forename: M
authors.initials: M
authors.lastname: Söderström
authors.forename: D M
authors.initials: DM
authors.lastname: Toivola
authors.forename: E A F
authors.initials: EA
authors.lastname: van Tol
authors.forename: A
authors.initials: A
authors.lastname: Hänninen
mesh_terms: D000818:Animals; D002364:Caseins / Q000494:pharmacology*; D004032:Diet; D005260:Female; D005434:Flow Cytometry; D005609:Free Radicals / Q000378:metabolism; D007422:Intestines / Q000187:drug effects / Q000276:immunology* / Q000382:microbiology*; D008213:Lymphocyte Activation / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D016688:Mice, Inbred NOD; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D002364:Caseins; D005609:Free Radicals; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; C475729:casein hydrolysate