Genome-Wide Analysis of Dietary Eicosapentaenoic Acid- and Oleic Acid-Induced Modulation of Colon Inflammation in Interleukin-10 Gene-Deficient Mice

Abstract

Background/Aims: Dietary n–3 polyunsaturated fatty acids can reduce inflammation via a range of mechanisms. This study tested the effect of dietary eicosapentaenoic acid (EPA) on intestinal inflammation using interleukin-10 gene-deficient (Il10^–/–) mice. Methods: At 35 days of age, 12 weaned Il10^–/– and 12 C57 mice were randomly assigned to one of two modified AIN-76A diets, supplemented with 3.7% purified ethyl esters of either EPA (n–3) or oleic acid (OA, control). To identify genes relevant to colon inflammation, transcription profiling (microarrays and qRT-PCR) and bioinformatic analyses were used. Results: In this study, dietary EPA reversed the decrease in colon fatty acid β-oxidation gene expression observed in OA-fed Il10^–/– compared to C57 mice. Il10^–/– mice fed the OA diet showed decreased expression of antioxidant enzyme genes, as well as those involved in detoxification of xenobiotics, compared to C57 mice on the same diet. In contrast, dietary EPA increased the expression of these genes in Il10^–/– mice. Conclusions: These data indicate that dietary EPA-induced endogenous lipid oxidation which might have a potential anti-inflammatory effect on colon tissue. This is supported by the activation of the Ppara gene that regulates the expression of pro-inflammatory and immunomodulatory genes and proteins.

The Role of Intestinal Barrier Function in Early Life in the Development of Colitis

“…Black tea has multiple effects on physical aspects of the intestinal barrier in that it can improve tight junction integrity and speed gastrointestinal transit (Chaudhuri et al, 2000;Hashimoto et al, 1997). Some polyunsaturated fatty acids (PUFAs) are able to decrease intestinal permeability (Vine et al, 2002) and reduce intestinal inflammation (Knoch et al, 2009). Some dairy compounds can also enhance barrier function, for example, -lactoglobulin (Hashimoto et al, 1995) and the casein peptide Asn-Pro-Trp-Asp-Gln (Yasumatsu & Tanabe, 2010) improve tight junction integrity.…”

Diversity of caecal bacteria is altered in interleukin-10 gene-deficient mice before and after colitis onset and when fed polyunsaturated fatty acids

“…10642 and 10587. The experimental design of study 1 (time-course; Knoch et al, 2010a) and study 2 (PUFA intervention; Knoch et al, 2009Knoch et al, , 2010b has been previously described. Briefly, male Il10 -/-mice (C57BL/6J background, formal designation B6.129P2-Il10 ,tm1Cgn ./J) raised under SPF conditions and wild-type C57 mice (C57BL/6J) were received from the Jackson Laboratory (Bar Harbor, Maine, USA) at approximately 5 weeks of age.…”

Animal Models of Colitis: Lessons Learned, and Their Relevance to the Clinic

“…We have utilized Il10 -/-mice inoculated with normal intestinal bacteria, including Enterococcus species , to investigate the role of diet in intestinal inflammation. We have shown that food components such as polyunsaturated fatty acids (Knoch et al, 2009;Knoch et al, 2010) can prevent or ameliorate the level of intestinal inflammation, and have characterized changes in gene expression in association with this change in inflammation to better understand the mechanisms through which such food components might be acting. We have also used metabolomic analysis to measure urinary metabolite differences between Il10 -/-and wildtype C57BL/6 mice, and to determine which of these differences were associated with intestinal inflammation (Lin et al, 2010).…”

“…(Knoch et al, 2009;Knoch et al, 2010) CD4+ SCID mice Table 1. Some key observations from studies using mouse models of IBD A variety of models have contributed to progress in understanding the complex interactions occurring within the intestinal tract between the resident microbial population and the host.…”

“…Environment may also play an important role, with diet in particular having an influence, if not in the initiation of the disease, then certainly in the maintenance and/or amelioration of disease symptoms. As part of a long-term research project (Nutrigenomics New Zealand (NuNZ); www.nutrigenomics.org.nz) we have identified a number of foods which are perceived by people with IBD as being either detrimental or beneficial in terms of managing the symptoms of both CD and UC (Petermann et al, 2009b) or show evidence of ameliorating intestinal inflammation in animal studies (Knoch et al, 2009;Nones et al, 2009;Knoch et al, 2010). There is a very real importance in seeking answers to the effective treatment of IBD because it is such a debilitating condition, and its prevalence is increasing (Cosnes et al, 2011).…”