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Role of Omega-6 and Omega-3 Fatty Acids in Inflammatory Bowel Disease

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Part of the book series: AAPS Advances in the Pharmaceutical Sciences Series ((AAPS,volume 12))

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Abstract

Inflammatory bowel disease (IBD), which includes ulcerative colitis and Crohn’s disease, is a chronic relapsing intestinal inflammatory disorder of the gastrointestinal tract. IBD is occurring with increasing frequency among Western populations and is emerging in countries that have traditionally had a low prevalence of the component diseases. IBD is a multifactorial, heterogeneous disease that occurs in genetically susceptible individuals in response to environmental and immunological factors associated with a dysregulated intestinal mucosal immunological response. The increase in incidence of IBD parallels the increase in dietary intake of omega-6 (n-6) polyunsaturated fatty acids and the change in balance of intake of n-6 to n-3 fatty acids. Experimental data suggest that high intake of n-6 fatty acids may contribute to the development and severity of IBD through increased synthesis and membrane incorporation of arachidonic acid (ARA) with the accompanying production of pro-inflammatory mediators, and increased oxidative stress in n-6 fatty acid rich membranes. Conversely, the n-3 polyunsaturated fatty acids eicosapentaenoic acid and docosahexaenoic acid (DHA) partly replace ARA in cell membranes and are metabolized to weaker pro-inflammatory eicosanoids and to strong pro-resolving mediators with roles in inflammation cessation. Consequently, high dietary n-6 fatty acid intake and high n-6–n-3 fatty acid ratios may be an important environmental modifier that contributes to the development of IBD in genetically susceptible individuals, while increased intake of n-3 fatty acids may lower risk of IBD and could be therapeutic.

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References

  1. Miron N, Cristea V (2012) Enterocytes: active cells in tolerance to food and microbial antigens in the gut. Clin Exp Immunol 167:405–412

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  2. North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition; Colitis Foundation of America, Bousvaros A, Antonioli DA, Colletti RB, Dubinsky MC, Glickman JN, Gold BD, Griffiths AM, Jevon GP, Higuchi LM, Hyams JS, Kirschner BS, Kugathasan S, Baldassano RN, Russo PA (2007) Differentiating ulcerative colitis from Crohn disease in children and young adults: report of a working group of the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition and the Crohn’s and Colitis Foundation of America. J Pediatr Gastroenterol Nutr 44:653–674

    Article  PubMed  Google Scholar 

  3. Monteleone G, Biancone L, Marasco R, Morrone G, Marasco O, Luzza F, Pallone F (1997) Interleukin 12 is expressed and actively released by Crohn's disease intestinal lamina propria mononuclear cells. Gastroenterology 112:1169–1178

    Article  CAS  PubMed  Google Scholar 

  4. Liu Z, Colpaert S, D'Haens GR, Kasran A, de Boer M, Rutgeerts P, Geboes K, Ceuppens JL (1999) Hyperexpression of CD40 ligand (CD154) in inflammatory bowel disease and its contribution to pathogenic cytokine production. J Immunol 163:4049–4057

    CAS  PubMed  Google Scholar 

  5. Neurath MF, Weigmann B, Finotto S, Glickman J, Nieuwenhuis E, Iijima H, Mizoguchi A, Mizoguchi E, Mudter J, Galle PR, Bhan A, Autschbach F, Sullivan BM, Szabo SJ, Glimcher LH, Blumberg RS (2002) The transcription factor T-bet regulates mucosal T cell activation in experimental colitis and Crohn's disease. J Exp Med 195:1129–1143

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. Beadling C, Slifka MK (2006) Regulation of innate and adaptive immune responses by the related cytokines IL-12, IL-23, and IL-27. Arch Immunol Ther Exp (Warsz) 54:15–24

    Article  CAS  Google Scholar 

  7. Dambacher J, Beigel F, Zitzmann K, De Toni EN, Göke B, Diepolder HM, Auernhammer CJ, Brand S (2009) The role of the novel Th17 cytokine IL-26 in intestinal inflammation. Gut 58:1207–1217

    Article  CAS  PubMed  Google Scholar 

  8. Brand S (2009) Crohn’s disease: Th1, Th17 or both? The change of a paradigm: new immunological and genetic insights implicate Th17 cells in the pathogenesis of Crohn’s disease. Gut 58:1152–1167

    Article  CAS  PubMed  Google Scholar 

  9. Shen W, Durum SK (2010) Synergy of IL-23 and Th17 cytokines: new light on inflammatory bowel disease. Neurochem Res 35:940–946

    Article  CAS  PubMed  Google Scholar 

  10. Geremia A, Jewell DP (2012) The IL-23/IL-17 pathway in inflammatory bowel disease. Expert Rev Gastroenterol Hepatol 6:223–237

    Article  CAS  PubMed  Google Scholar 

  11. Zorzi F, Monteleone I, Sarra M, Calabrese E, Marafini I, Cretella M, Sedda S, Biancone L, Pallone F, Monteleone G (2013) Distinct profiles of effector cytokines mark the different phases of Crohn's disease. PLoS One 8:e54562

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  12. Duerr RH, Taylor KD, Brant SR, Rioux JD, Silverberg MS, Daly MJ, Steinhart AH, Abraham C, Regueiro M, Griffiths A, Dassopoulos T, Bitton A, Yang H, Targan S, Datta LW, Kistner EO, Schumm LP, Lee AT, Gregersen PK, Barmada MM, Rotter JI, Nicolae DL, Cho JH (2006) A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science 314:1461–1463

    Article  CAS  PubMed  Google Scholar 

  13. Anderson CA, Massey DC, Barrett JC, Prescott NJ, Tremelling M, Fisher SA, Gwilliam R, Jacob J, Nimmo ER, Drummond H, Lees CW, Onnie CM, Hanson C, Blaszczyk K, Ravindrarajah R, Hunt S, Varma D, Hammond N, Lewis G, Attlesey H, Watkins N, Ouwehand W, Strachan D, McArdle W, Lewis CM, Lobo A, Sanderson J, Jewell DP, Deloukas P, Mansfield JC, Mathew CG, Satsangi J, Parkes M, Wellcome Trust Case Control Consortium (2009) Investigation of Crohn's disease risk loci in ulcerative colitis further defines their molecular relationship. Gastroenterology 136:523–529

    Article  PubMed Central  PubMed  Google Scholar 

  14. Elding H, Lau W, Swallow DM, Maniatis N (2013) Refinement in localization and identification of gene regions associated with Crohn disease. Am J Hum Genet 92:107–113

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Wiekowski MT, Leach MW, Evans EW, Sullivan L, Chen SC, Vassileva G, Bazan JF, Gorman DM, Kastelein RA, Narula S, Lira SA (2001) Ubiquitous transgenic expression of the IL-23 subunit p19 induces multiorgan inflammation, runting, infertility, and premature death. J Immunol 166:7563–7570

    Article  CAS  PubMed  Google Scholar 

  16. Langrish CL, Chen Y, Blumenschein WM, Mattson J, Basham B, Sedgwick JD, McClanahan T, Kastelein RA, Cua DJ (2005) IL-23 drives a pathogenic T cell population that induces autoimmune inflammation. J Eex Med 201:233–240

    Article  CAS  Google Scholar 

  17. Bettelli E, Carrier Y, Gao W, Korn T, Strom TB, Oukka M, Weiner HL, Kuchroo VK (2006) Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature 441:235–238

    Article  CAS  PubMed  Google Scholar 

  18. Mangan PR, Harrington LE, O'Quinn DB, Helms WS, Bullard DC, Elson CO, Hatton RD, Wahl SM, Schoeb TR, Weaver CT (2006) Transforming growth factor-β induces development of the Th17 lineage. Nature 441:231–234

    Article  CAS  PubMed  Google Scholar 

  19. Parronchi P, Romagnani P, Annunziato F, Sampognaro S, Becchio A, Giannarini L, Maggi E, Pupilli C, Tonelli F, Romagnani R (1997) Type 1 T-helper cell predominance and interleukin-12 expression in the gut of patients with Crohn's disease. Am J Pathol 150:823–832

    CAS  PubMed Central  PubMed  Google Scholar 

  20. Pflanz S, Timans JC, Cheung J, Rosales R, Kanzler H, Gilbert J, Hibbert L, Churakova T, Travis M, Vaisberg E, Blumenschein WM, Mattson JD, Wagner JL, To W, Zurawski S, McClanahan TK, Gorman DM, Bazan JF, de Waal Malefyt R, Rennick D, Kastelein RA (2002) IL-27, a heterodimeric cytokine composed of EBI3 and p28 protein, induces proliferation of naive CD4(+) T cells. Immunity 16:779–790

    Article  CAS  PubMed  Google Scholar 

  21. Takeda A, Hamano S, Yamanaka A, Hanada T, Ishibashi T, Mak TW, Yoshimura A, Yoshida H (2003) Cutting edge: role of IL-27/WSX-1 signaling for induction of T-bet through activation of STAT1 during initial Th1 commitment. J Immunol 170:4886–4890

    Article  CAS  PubMed  Google Scholar 

  22. Schmidt C, Giese T, Ludwig B, Mueller-Molaian I, Marth T, Zeuzem S, Meuer SC, Stallmach A (2005) Expression of interleukin-12-related cytokine transcripts in inflammatory bowel disease: elevated interleukin-23p19 and interleukin-27p28 in Crohn's disease but not in ulcerative colitis. Inflamm Bowel Dis 11:16–23

    Article  PubMed  Google Scholar 

  23. Sasaoka T, Ito M, Yamashita J, Nakajima K, Tanaka I, Narita M, Hara Y, Hada K, Takahashi M, Ohno Y, Matsuo T, Kaneshiro Y, Tanaka H, Kaneko K (2011) Treatment with IL-27 attenuates experimental colitis through the suppression of the development of IL-17-producing T helper cells. Am J Physiol Gastrointest Liver Physiol 300:G568–G576

    Article  CAS  PubMed  Google Scholar 

  24. Hoeve MA, Savage ND, de Boer T, Langenberg DM, de Waal Malefyt R, Ottenhoff TH, Verreck FA (2006) Divergent effects of IL-12 and IL-23 on the production of IL-17 by human T cells. Eur J Immunol 36:661–670

    Article  CAS  PubMed  Google Scholar 

  25. Rovedatti L, Kudo T, Biancheri P, Sarra M, Knowles CH, Rampton DS, Corazza GR, Monteleone G, Di Sabatino A, Macdonald TT (2009) Differential regulation of interleukin 17 and interferon gamma production in inflammatory bowel disease. Gut 58:1629–1636

    Article  CAS  PubMed  Google Scholar 

  26. Jupp J, Hillier K, Elliott DH, Fine DR, Bateman AC, Johnson PA, Cazaly AM, Penrose JF, Sampson AP (2007) Colonic expression of leukotriene-pathway enzymes in inflammatory bowel diseases. Inflamm Bowel Dis 13:537–546

    Article  PubMed  Google Scholar 

  27. Chen H, Qin J, Wei P, Zhang J, Li Q, Fu L, Li S, Ma C, Cong B (2009) Effects of leukotriene B4 and prostaglandin E2 on the differentiation of murine Foxp3+ T regulatory cells and Th17 cells. Prostaglandins Leukot Essent Fatty Acids 80:195–200

    Article  CAS  PubMed  Google Scholar 

  28. Sheibanie AF, Yen JH, Khayrullina T, Emig F, Zhang M, Tuma R, Ganea D (2007) The proinflammatory effect of prostaglandin E2 in experimental inflammatory bowel disease is mediated through the IL-23 → IL-17 axis. J Immunol 178:8138–8147

    Article  CAS  PubMed  Google Scholar 

  29. IBD in EPIC Study Investigators, Tjonneland A, Overvad K, Bergmann MM, Nagel G, Linseisen J, Hallmans G, Palmqvist R, Sjodin H, Hagglund G, Berglund G, Lindgren S, Grip O, Palli D, Day NE, Khaw KT, Bingham S, Riboli E, Kennedy H, Hart A (2009) Linoleic acid, a dietary n-6 polyunsaturated fatty acid, and the aetiology of ulcerative colitis: a nested case-control study within a European prospective cohort study. Gut 58:1606–1611

    Article  PubMed  Google Scholar 

  30. Iwakura Y, Ishigame H (2006) The IL-23/IL-17 axis in inflammation. J Clin Invest 116:1218–1222

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  31. Zhang Z, Andoh A, Inatomi O, Bamba S, Takayanagi A, Shimizu N, Fujiyama Y (2005) Interleukin-17 and lipopolysaccharides synergistically induce cyclooxygenase-2 expression in human intestinal myofibroblasts. J Gastroenterol Hepatol 20:619–627

    Article  CAS  PubMed  Google Scholar 

  32. Fuss IJ, Neurath M, Boirivant M, Klein JS, de la Motte C, Strong SA, Fiocchi C, Strober W (1996) Disparate CD4+ lamina propria (LP) lymphokine secretion profiles in inflammatory bowel disease. Crohn's disease LP cells manifest increased secretion of IFN-gamma, whereas ulcerative colitis LP cells manifest increased secretion of IL-5. J Immunol 157:1261–1270

    CAS  PubMed  Google Scholar 

  33. Berrebi D, Besnard M, Fromont-Hankard G, Paris R, Mougenot JF, De Lagausie P, Emilie D, Cezard JP, Navarro J, Peuchmaur M (1998) Interleukin-12 expression is focally enhanced in the gastric mucosa of pediatric patients with Crohn's disease. Am J Pathol 152:667–672

    CAS  PubMed Central  PubMed  Google Scholar 

  34. Heller F, Florian P, Bojarski C, Richter J, Christ M, Hillenbrand B, Mankertz J, Gitter AH, Bürgel N, Fromm M, Zeitz M, Fuss I, Strober W, Schulzke JD (2005) Interleukin-13 is the key effector Th2 cytokine in ulcerative colitis that affects epithelialtight junctions, apoptosis, and cell restitution. Gastroenterology 129:550–564

    Article  CAS  PubMed  Google Scholar 

  35. Biesiada G, Czepiel J, Ptak-Belowska A, Targosz A, Krzysiek-Maczka G, Strzalka M, Konturek SJ, Brzozowski T, Mach T (2012) Expression and release of leptin and proinflammatory cytokines in patients with ulcerative colitis and infectious diarrhea. J Physiol Pharmacol 63:471–481

    CAS  PubMed  Google Scholar 

  36. Raza A, Yousaf W, Giannella R, Shata MT (2012) Th17 cells: interaction with pathogenesis factors in the immunopathogenesisof Inflammatory bowel disease. Expert Rev Clin Immunol 8:161–168

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  37. Verdier J, Begue B, Cerf-Bensussan N, Ruemmele FM (2012) Compartmentalized expression of Th1 and Th17 cytokines in pediatric inflammatory bowel diseases. Inflamm Bowel Dis 18:1260–1266

    Article  CAS  PubMed  Google Scholar 

  38. Benchimol EI, Fortinsky KJ, Gozdyra P, Van den Heuvel M, Van Limbergen J, Griffiths AM (2011) Epidemiology of pediatric inflammatory bowel disease: a systematic review of international trends. Inflamm Bowel Dis 17:423–439

    Article  PubMed  Google Scholar 

  39. Molodecky NA, Soon IS, Rabi DM, Ghali WA, Ferris M, Chernoff G, Benchimol EI, Panaccione R, Ghosh S, Barkema HW, Kaplan GG (2012) Increasing incidence and prevalence of the inflammatory bowel diseases with time, based on systematic review. Gastroenterology 142:46–54

    Article  PubMed  Google Scholar 

  40. Carr I, Mayberry JF (1999) The effects of migration on ulcerative colitis: a three-year prospective study among Europeans and first- and second-generation South Asians in Leicester (1991–1994). Am J Gastroenterol 94:2918–2922

    CAS  PubMed  Google Scholar 

  41. Tsironi E, Feakins RM, Probert CS, Rampton DS (2004) Incidence of inflammatory bowel disease is rising and abdominal tuberculosis is falling in Bangladeshis in East London, United Kingdom. Am J Gastroenterol 99:1749–1755

    Article  PubMed  Google Scholar 

  42. Pinsk V, Lemberg DA, Grewal K, Barker CC, Schreiber RA, Jacobson K (2007) Inflammatory bowel disease in the South Asian pediatric population of British Columbia. Am J Gastroenterol 102:1077–1083

    Article  PubMed  Google Scholar 

  43. Stephen AM, Wald NJ (1990) Trends in individual consumption of dietary fat in the United States, 1920–1984. Am J Clin Nutr 52:457–469

    CAS  PubMed  Google Scholar 

  44. Raper NR, Cronin FJ, Exler J (1992) Omega-3 fatty acid content of the US food supply. J Am Coll Nutr 11:304–308

    Article  CAS  PubMed  Google Scholar 

  45. Cavadini C, Siega-Riz AM, Popkin BM (2000) US adolescent food intake trends from 1965 to 1996. West J Med 173:378–383

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  46. Popkin BM, Siega-Riz AM, Haines PS, Jahns L (2001) Where's the fat? Trends in U.S. diets 1965–1996. Prev Med 32:245–254

    Article  CAS  PubMed  Google Scholar 

  47. Innis SM, Elias SL (2003) Intakes of essential n−6 and n−3 polyunsaturated fatty acids among pregnant Canadian women. Am J Clin Nutr 77:473–478

    CAS  PubMed  Google Scholar 

  48. Innis SM, Vaghri Z, King DJ (2004) n−6 Docosapentaenoic acid is not a predictor of low docosahexaenoic acid status in Canadian preschool children. Am J Clin Nutr 80:768–773

    CAS  PubMed  Google Scholar 

  49. Lambert J, Agostoni C, Elmadfa I, Hulshof K, Krause E, Livingstone B, Socha P, Pannemans D, Samartín S (2004) Dietary intake and nutritional status of children and adolescents in Europe. Br J Nutr 92(Suppl 2):S147–S211

    Article  CAS  PubMed  Google Scholar 

  50. Bates B, Lennox A, Prentice A, Bates C, Swan G (2012) National Diet and Nutrition Survey: headline results from years 1, 2 and 3 (combined) of the rolling programme (2008/2009-2-10/11). Department of Health and Food Standards Agency, London. http://media.dh.gov.uk/network/261/files/2012/07/NDNS-Y3-report_All-TEXT-docs-combined.pdf

  51. Calder PC (2013) Omega-3 polyunsaturated fatty acids and inflammatory processes: nutrition or pharmacology? Br J Clin Pharmacol 75:645–662

    CAS  PubMed Central  PubMed  Google Scholar 

  52. Innis SM, Dai C, Wu X, Buchan AM, Jacobson K (2010) Perinatal lipid nutrition alters early intestinal development and programs the response to experimental colitis in young adult rats. Am J Physiol Gastrointest Liver Physiol 299:G1376–G1385

    Article  CAS  PubMed  Google Scholar 

  53. Astudillo AM, Balgoma D, Balboa MA, Balsinde J (1821) Dynamics of arachidonic acid mobilization by inflammatory cells. Biochim Biophys Acta 2012:249–256

    Google Scholar 

  54. Ricciotti E, FitzGerald GA (2011) Prostaglandins and inflammation. Arterioscler Thromb Vasc Biol 31:986–1000

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  55. Shoda R, Matsueda K, Yamato S, Umeda N (1996) Epidemiologic analysis of Crohn disease in Japan: increased dietary intake of n-6 polyunsaturated fatty acids and animal protein relates to the increased incidence of Crohn disease in Japan. Am J Clin Nutr 63:741–745

    CAS  PubMed  Google Scholar 

  56. Cottrell EC, Ozanne SE (2008) Early life programming of obesity and metabolic disease. Physiol Behav 94:17–28

    Article  CAS  PubMed  Google Scholar 

  57. Langley-Evans SC (2006) Developmental programming of health and disease. Proc Nutr Soc 65:97–105

    Article  PubMed Central  PubMed  Google Scholar 

  58. Innis SM (2004) Polyunsaturated fatty acids in human milk: an essential role in infant development. Adv Exp Med Biol 554:27–43

    Article  CAS  PubMed  Google Scholar 

  59. Innis SM (2005) Essential fatty acid transfer and fetal development. Placenta 26(Suppl A):S70–S75

    Article  PubMed  Google Scholar 

  60. Jacobson K, Mundra H, Innis SM (2005) Intestinal responsiveness to experimental colitis in young rats is altered by maternal diet. Am J Physiol Gastrointest Liver Physiol 289:G13–G20

    Article  CAS  PubMed  Google Scholar 

  61. Lee TH, Sperling RI, Ravalese J 3rd, Spur BW, Robinson DR, Corey EJ, Lewis RA, Austen KF (1985) Effect of dietary enrichment with eicosapentaenoic and docosahexaenoic acids on in vitro neutrophil and monocyte leukotriene generation and neutrophil function. N Engl J Med 312:1217–1224

    Article  CAS  PubMed  Google Scholar 

  62. Sperling RI, Benincaso AI, Knoell CT, Larkin JK, Austen KF, Robinson DR (1993) Dietary omega-3 polyunsaturated fatty acids inhibit phosphoinositide formation and chemotaxis in neutrophils. J Clin Invest 91:651–660

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  63. Schmidt EB, Pedersen JO, Varming K, Ernst E, Jersild C, Grunnet N, Dyerberg J (1991) n-3 fatty acids and leukocyte chemotaxis. Effects in hyperlipidemia and dose-response studies in healthy men. Arterioscler Thromb 11:429–435

    Article  CAS  PubMed  Google Scholar 

  64. Hughes DA, Pinder AC, Piper Z, Johnson IT, Lund EK (1996) Fish oil supplementation inhibits the expression of major histocompatibility complex class II molecules and adhesion molecules on human monocytes. Am J Clin Nutr 63:267–272

    CAS  PubMed  Google Scholar 

  65. Endres S, Ghorbani R, Kelley VE, Georgilis K, Lonnemann G, van der Meer JWM, Cannon JG, Rogers TS, Klempner MS, Weber PC, Schaefer EJ, Wolff SM, Dinarello CA (1989) The effect of dietary supplementation with n-3 polyunsaturated fatty acids on the synthesis of interleukin-1 and tumor necrosis factor by mononuclear cells. N Engl J Med 320:265–271

    Article  CAS  PubMed  Google Scholar 

  66. Caughey GE, Mantzioris E, Gibson RA, Cleland LG, James MJ (1996) The effect on human tumor necrosis factor alpha and interleukin 1 beta production of diets enriched in n-3 fatty acids from vegetable oil or fish oil. Am J Clin Nutr 63:116–122

    CAS  PubMed  Google Scholar 

  67. Meydani SN, Endres S, Woods MM, Goldin BR, Soo C, Morrill-Labrode A, Dinarello CA, Gorbach SL (1991) Oral (n-3) fatty acid supplementation suppresses cytokine production and lymphocyte proliferation: comparison between young and older women. J Nutr 121:547–555

    CAS  PubMed  Google Scholar 

  68. Abbate R, Gori AM, Martini F, Brunelli T, Filippini M, Francalanci I, Paniccia R, Prisco D, Gensini GF, Neri Serneri GG (1996) n-3 PUFA supplementation, monocyte PCA expression and interleukin-6 production. Prostaglandins Leukot Essent Fatty Acids 54:439–444

    Article  CAS  PubMed  Google Scholar 

  69. Trebble T, Arden NK, Stroud MA, Wootton SA, Burdge GC, Miles EA, Ballinger AB, Thompson RL, Calder PC (2003) Inhibition of tumour necrosis factor-alpha and interleukin 6 production by mononuclear cells following dietary fish-oil supplementation in healthy men and response to antioxidant co-supplementation. Br J Nutr 90:405–412

    Article  CAS  PubMed  Google Scholar 

  70. Trebble TM, Wootton SA, Miles EA, Mullee M, Arden NK, Ballinger AB, Stroud MA, Burdge GC, Calder PC (2003) Prostaglandin E2 production and T cell function after fish-oil supplementation: response to antioxidant cosupplementation. Am J Clin Nutr 78:376–382

    CAS  PubMed  Google Scholar 

  71. Grimble RF, Howell WM, O'Reilly G, Turner SJ, Markovic O, Hirrell S, East JM, Calder PC (2002) The ability of fish oil to suppress tumor necrosis factor alpha production by peripheral blood mononuclear cells in healthy men is associated with polymorphisms in genes that influence tumor necrosis factor alpha production. Am J Clin Nutr 76:454–459

    CAS  PubMed  Google Scholar 

  72. Markovic O, O'Reilly G, Fussell HM, Turner SJ, Calder PC, Howell WM, Grimble RF (2004) Role of single nucleotide polymorphisms of pro-inflammatory cytokine genes in the relationship between serum lipids and inflammatory parameters, and the lipid-lowering effect of fish oil in healthy males. Clin Nutr 23:1084–1095

    Article  CAS  PubMed  Google Scholar 

  73. Monk JM, Hou TY, Turk HF, Weeks B, Wu C, McMurray DN, Chapkin RS (2012) Dietary n-3 polyunsaturated fatty acids (PUFA) decrease obesity-associated Th17 cell-mediated inflammation during colitis. PLoS One 7:e49739

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  74. Hekmatdoost A, Wu X, Morampudi V, Innis SM, Jacobson K (2013) Dietary oils modify the host immune response and colonic tissue damage following Citrobacter rodentium-infection in mice. Am J Physiol Gastrointest Liver Physiol 304(10):G917–G928

    Article  CAS  PubMed  Google Scholar 

  75. Vilaseca J, Salas A, Guarner F, Rodriguez R, Martinez M, Malagelada J-R (1990) Dietary fish oil reduces progression of chronic inflammatory lesions in a rat model of granulomatous colitis. Gut 31:539–544

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  76. Andoh A, Tsujikawa T, Ishizuka I, Araki Y, Sasaki M, Koyama S, Fujiyama Y (2003) N-3 fatty acid-rich diet prevents early response of interleukin-6 elevation in trinitrobenzene sulfonic acid-induced enteritis. Int J Mol Med 12:721–725

    CAS  PubMed  Google Scholar 

  77. Hirata I, Murano M, Nitta M, Sasaki S, Toshina K, Maemura K, Katsu K (2001) Estimation of mucosal inflammatory mediators in rat DSS-induced colitis. Possible role of PGE(2) in protection against mucosal damage. Digestion 63(Suppl 1):73–80

    Article  CAS  PubMed  Google Scholar 

  78. Barros KV, Xavier RA, Abreu GG, Martinez CA, Ribeiro ML, Gambero A, Carvalho PO, Nascimento CM, Silveira VL (2010) Soybean and fish oil mixture increases IL-10, protects against DNA damage and decreases colonic inflammation in rats with dextran sulfate sodium (DSS) colitis. Lipids Health Dis 9:68

    Article  PubMed Central  PubMed  Google Scholar 

  79. Empey LR, Jewell LD, Garg ML, Thomson AB, Clandinin MT, Fedorak RN (1991) Fish oil-enriched diet is mucosal protective against acetic acid-induced colitis in rats. Can J Physiol Pharmacol 69:480–487

    Article  CAS  PubMed  Google Scholar 

  80. Chapkin RS, Davidson LA, Ly L, Weeks BR, Lupton JR, McMurray DN (2007) Immunomodulatory effects of (n-3) fatty acids: putative link to inflammation and colon cancer. J Nutr 137(Suppl 1):200S–204S

    CAS  PubMed  Google Scholar 

  81. Monk JM, Jia Q, Callaway E, Weeks B, Alaniz RC, McMurray DN, Chapkin RS (2012) Th17 cell accumulation is decreased during chronic experimental colitis by (n-3) PUFA in Fat-1 mice. J Nutr 142:117–124

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  82. Arita M, Yoshida M, Hong S, Tjonahen E, Glickman JN, Petasis NA, Blumberg RS, Serhan CN (2005) Resolvin E1, an endogenous lipid mediator derived from omega-3 eicosapentaenoic acid, protects against 2,4,6-trinitrobenzene sulfonic acid-induced colitis. Proc Natl Acad Sci U S A 102:7671–7676

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  83. John S, Luben R, Shrestha SS, Welch A, Khaw KT, Hart AR (2010) Dietary n-3 polyunsaturated fatty acids and the aetiology of ulcerative colitis: a UK prospective cohort study. Eur J Gastroenterol Hepatol 22:602–606

    Article  CAS  PubMed  Google Scholar 

  84. Uchiyama K, Nakamura M, Odahara S, Koido S, Katahira K, Shiraishi H, Ohkusa T, Fujise K, Tajiri H (2010) N-3 polyunsaturated fatty acid diet therapy for patients with inflammatory bowel disease. Inflamm Bowel Dis 16:1696–1707

    Article  PubMed  Google Scholar 

  85. Belluzzi A, Brignola C, Campieri M, Pera A, Boschi S, Miglioli M (1993) Effect of an enteric-coated fish-oil preparation on relapses in Crohn’s disease. N Engl J Med 334:1557–1560

    Article  Google Scholar 

  86. Turner D, Shah PS, Steinhart AH, Zlotkin S, Griffiths AM (2011) Maintenance of remission in inflammatory bowel disease using omega-3 fatty acids (fish oil): a systematic review and meta-analyses. Inflamm Bowel Dis 17:336–345

    Article  PubMed  Google Scholar 

  87. Feagan BG, Sandborn WJ, Mittmann U, Bar-Meir S, D'Haens G, Bradette M, Cohen A, Dallaire C, Ponich TP, McDonald JW, Hébuterne X, Paré P, Klvana P, Niv Y, Ardizzone S, Alexeeva O, Rostom A, Kiudelis G, Spleiss J, Gilgen D, Vandervoort MK, Wong CJ, Zou GY, Donner A, Rutgeerts P (2008) Omega-3 free fatty acids for the maintenance of remission in Crohn disease: the EPIC Randomized Controlled Trials. JAMA 299:1690–1697

    Article  CAS  PubMed  Google Scholar 

  88. Hawthorne AB, Daneshmend TK, Hawkey CJ, Belluzzi A, Everitt SJ, Holmes GK, Malkinson C, Shaheen MZ, Willars JE (1992) Treatment of ulcerative colitis with fish oil supplementation: a prospective 12 month randomised controlled trial. Gut 33:922–928

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  89. Hillier K, Jewell R, Dorrell L, Smith CL (1991) Incorporation of fatty acids from fish oil and olive oil into colonic mucosal lipids and effects upon eicosanoid synthesis in inflammatory bowel disease. Gut 32:1151–1155

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  90. Lorenz R, Weber PC, Szimnau P, Heldwein W, Strasser T, Loeschke K (1989) Supplementation with n-3 fatty acids from fish oil in chronic inflammatory bowel disease—a randomized, placebo-controlled, double-blind cross-over trial. J Intern Med Suppl 731:225–232

    Article  CAS  PubMed  Google Scholar 

  91. McCall TB, O'Leary D, Bloomfield J, O'Morain CA (1989) Therapeutic potential of fish oil in the treatment of ulcerative colitis. Aliment Pharmacol Ther 3:415–424

    Article  CAS  PubMed  Google Scholar 

  92. Stenson WF, Cort D, Rodgers J, Burakoff R, DeSchryver-Kecskemeti K, Gramlich TL, Beeken W (1992) Dietary supplementation with fish oil in ulcerative colitis. Ann Intern Med 116:609–614

    Article  CAS  PubMed  Google Scholar 

  93. Shimizu T, Fujii T, Suzuki R, Igarashi J, Ohtsuka Y, Nagata S, Yamashiro Y (2003) Effects of highly purified eicosapentaenoic acid on erythrocyte fatty acid composition and leukocyte and colonic mucosa leukotriene B4 production in children with ulcerative colitis. J Pediatr Gastroenterol Nutr 37:581–585

    Article  CAS  PubMed  Google Scholar 

  94. Trebble TM, Arden NK, Wootton SA, Calder PC, Mullee MA, Fine DR, Stroud MA (2004) Fish oil and antioxidants alter the composition and function of circulating mononuclear cells in Crohn disease. Am J Clin Nutr 80:1137–1144

    CAS  PubMed  Google Scholar 

  95. Lorenz-Meyer H, Bauer P, Nicolay C, Schulz B, Purrmann J, Fleig WE, Scheurlen C, Koop I, Pudel V, Carr L (1996) Omega-3 fatty acids and low carbohydrate diet for maintenance of remission in Crohn’s disease. A randomized controlled multicenter trial. Study Group Members (German Crohn’s Disease Study Group). Scand J Gastroenterol 31:778–785

    Article  CAS  PubMed  Google Scholar 

  96. MacLean CH, Mojica WA, Morton SC, Pencharz J, Hasenfeld Garland R, Tu W, Newberry SJ, Jungvig LK, Grossman J, Khanna P, Rhodes S, Shekelle P (2004) Effects of omega-3 fatty acids on lipids and glycemic control in type II diabetes and the metabolic syndrome and on inflammatory bowel disease, rheumatoid arthritis, renal disease, systemic lupus erythematosus, and osteoporosis. Evid Rep Technol Assess (Summ) 89:1–4

    Google Scholar 

  97. MacLean CH, Mojica WA, Newberry SJ, Pencharz J, Garland RH, Tu W, Hilton LG, Gralnek IM, Rhodes S, Khanna P, Morton SC (2005) Systematic review of the effects of n-3 fatty acids in inflammatory bowel disease. Am J Clin Nutr 82:611–619

    CAS  PubMed  Google Scholar 

  98. Turner D, Zlotkin SH, Shah PS, Griffiths AM (2009) Omega 3 fatty acids (fish oil) for maintenance of remission in Crohn's disease. Cochrane Database Syst Rev (1):CD006320

    Google Scholar 

  99. Turner D, Steinhart AH, Griffiths AM (2007) Omega 3 fatty acids (fish oil) for maintenance of remission in ulcerative colitis. Cochrane Database Syst Rev (3):CD006443

    Google Scholar 

  100. De Ley M, de Vos R, Hommes DW, Stokkers P (2007) Fish oil for induction of remission in ulcerative colitis. Cochrane Database Syst Rev (4):CD005986

    Google Scholar 

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Correspondence to Kevan Jacobson or Philip C. Calder .

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Jacobson, K., Calder, P.C. (2014). Role of Omega-6 and Omega-3 Fatty Acids in Inflammatory Bowel Disease. In: Folkerts, G., Garssen, J. (eds) Pharma-Nutrition. AAPS Advances in the Pharmaceutical Sciences Series, vol 12. Springer, Cham. https://doi.org/10.1007/978-3-319-06151-1_5

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