Casein hydrolysate diet controls intestinal T cell activation, free radical production and microbial colonisation in NOD mice

R Emani, Muhammad Nadeem Asghar, R Toivonen, L Lauren, M Söderström, Diana Toivola, van Tol EAF, A Hänninen

Research output: Contribution to journalArticleScientificpeer-review

13 Citations (Scopus)

Abstract

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.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.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 RegIII gamma (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.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.
Original languageUndefined/Unknown
Pages (from-to)1781–1791
Number of pages11
JournalDiabetologia
Volume56
Issue number8
DOIs
Publication statusPublished - 2013
MoE publication typeA1 Journal article-refereed

Keywords

  • Casein hydrolysate
  • Guanine and cytosine profiling
  • Gut immune system
  • In vivo imaging system
  • Laser capture microscopy
  • Microbiota analysis
  • Nonobese diabetic (NOD) mouse
  • Reactive oxygen and nitrogen species
  • dietary intervention

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