Effect of fish oil enriched enteral diet on inflammatory bowel disease tissues in organ culture: Differential effects on ulcerative colitis and Crohn's disease

摘要

AIM: To investigate the influence of fish oil enriched enteral diet on intestinal tissues taken from Crohn's disease (CD), ulcerative colitis (UC) and non-inflamed non-IBD control patients in vitro.METHODS: Colonoscopic biopsies from patients with active CD (n = 4), active UC (n = 7), and non-inflamed non-IBD control patients (n = 4) were incubated (three dilutions of 1:20, 1:10, and 1:5) with Waymouth's culture medium and enteral elemental diet (EO28, SHS, Liverpool, UK) modified in the fatty acid composition with fish oil (EF) in an organ culture system for 24 h. In each experimental set-up, incubation with Waymouth's medium alone as control was included. Tissue viability was assessed by adding bromodeoxyuridine (BrdU) to the culture fluid and immunohistochemically staining for BrdU uptake. Cytokine ratio of IL-1ra/IL-1β (low ratio indicative of inflammation) and production of those cytokines as a percentage of medium control were assayed in the culture supernatant. RESULTS: Incubation of CD-affected tissue with EF (1:20, 1:10, and 1:5) modestly and non-significantly increased IL-1ra/IL-1β ratio as compared with medium control (CD 39.1±16.1; 26.5±7.8, 47.1±16.8 vs control 13.0±2.2), but incubation of UC-affected tissues increased IL-1ra/IL-1β ratio significantly in all three dilutions (UC 69.1±32.2, P＜0.05; 76.1±36.4, P = 0.05;84.5±37.3, P＜0.02; vs control 10.2±3.7). Incubation of non-inflamed non-IBD control tissue did not increase the IL-1ra/IL-1β ratio in any dilution compared to medium control (69.3±47.0, 54.1±30.6, 79.4±34.0 vs control 76.1±37.3). Average percentage production of IL-1β indexed against medium control was significantly less in UC after EF incubation as compared with CD (UC 24.0±4.8 vs CD 51.8±8.1; P＜0.05). Average percentage production of IL-1ra was markedly higher in UC (135.9±3.4) than that in control patients (36.5±4.3) (P＜0.0001).CONCLUSION: IBD tissues, after incubation with elemental diet modified in its fatty acid composition with fish oil, show an increase in IL-1ra/IL-1β cytokine ratio. This effect of ω-3 fatty acid modulation is significantly more marked in UC compared with CD and is accompanied by both a reduction of IL-1β and increase of IL-1ra. The positive direct anti-inflammatory effect of elemental diet with fish oil in tissue affected with UC suggests dietary treatment of UC may be possible.