Nutrigenomics applied to an animal model of Inflammatory Bowel Diseases: transcriptomic analysis of the effects of eicosapentaenoic acid- and arachidonic acid-enriched diets.
In vivo models of Inflammatory Bowel Diseases (IBD) elucidate important mechanisms of chronic inflammation. Complex intestinal responses to food components create a unique "fingerprint" discriminating health from disease. Five-week-old IL10(-/-) and C57BL/6J (C57; control) mice were inoculated orally with complex intestinal microflora (CIF) and/or pure cultures of Enterococcus faecalis and E. faecalis (EF) aiming for more consistent inflammation of the intestinal mucosa. Inoculation treatments were compared to non-inoculated IL10(-/-) and C57 mice, either kept in specific pathogen free (SPF) or conventional conditions (2x5 factorial design). At 12 weeks of age, mice were sacrificed for intestinal histological (HIS) and transcriptomic analysis using limma and Ingenuity Pathway Analysis Software. Colonic HIS was significantly affected (P<0.05) in inoculated IL10(-/-) mice and accounted for approximately 60% of total intestinal HIS. Inoculation showed a strong effect on colonic gene expression, with more than 2000 genes differentially expressed in EF.CIF-inoculated IL10(-/-) mice. Immune response gene expression was altered (P<0.05) in these mice. The second study investigated the effect of arachidonic (AA) and eicosapentaenoic acid (EPA) on colonic HIS and gene expression to test whether EPA, contrary to AA, diminished intestinal inflammation in EF.CIF IL10(-/-) mice (2 x 4 factorial design). AIN-76A (5% corn oil) and AIN-76A (fat-free) +1% corn oil supplemented with either 3.7% oleic acid (OA), AA or EPA were used. IL10(-/-) mice fed EPA- and AA-enriched diets had at least 40% lower colonic HIS (P<0.05) than those fed control diets (AIN-76A and OA diets). The expression of immune response and 'inflammatory disease' genes (down-regulated: TNFalpha, IL6, S100A8, FGF7, PTGS2; up-regulated: PPARalpha, MGLL, MYLK, PPSS23, ABCB4 with EPA and/or AA) was affected in IL10(-/-) mice fed EPA- and AA-enriched diets, compared to those fed AIN-76A diet.
Roy
Nicole
N
Food, Metabolism & Microbiology Section, Food & Health Group, AgResearch Grasslands, Palmerston North, New Zealand. warren.mcnabb@agresearch.co.nz
Barnett
Matthew
M
Knoch
Bianca
B
Dommels
Yvonne
Y
McNabb
Warren
W
D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology*; D004032:Diet; D004195:Disease Models, Animal; D015118:Eicosapentaenoic Acid / Q000494:pharmacology*; D005231:Fatty Acids, Unsaturated / Q000008:administration & dosage; D020869:Gene Expression Profiling; D023281:Genomics; D006720:Homozygote; D015212:Inflammatory Bowel Diseases / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016753:Interleukin-10 / Q000235:genetics / Q000502:physiology; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020411:Oligonucleotide Array Sequence Analysis; D014158:Transcription, Genetic / Q000187:drug effects*
D005231:Fatty Acids, Unsaturated; D016753:Interleukin-10; D016718:Arachidonic Acid; D015118:Eicosapentaenoic Acid