Skip to main content Accessibility help

DHA protects against experimental colitis in IL-10-deficient mice associated with the modulation of intestinal epithelial barrier function

  • Jie Zhao (a1), Peiliang Shi (a2), Ye Sun (a3), Jing Sun (a1), Jian-Ning Dong (a1), Hong-Gang Wang (a1), Lu-Gen Zuo (a1), Jian-Feng Gong (a1), Yi Li (a1), Li-Li Gu (a1), Ning Li (a1), Jie-Shou Li (a1) and Wei-Ming Zhu (a1)...


A defect in the intestinal barrier is one of the characteristics of Crohn's disease (CD). The tight junction (TJ) changes and death of epithelial cells caused by intestinal inflammation play an important role in the development of CD. DHA, a long-chain PUFA, has been shown to be helpful in treating inflammatory bowel disease in experimental models by inhibiting the NF-κB pathway. The present study aimed at investigating the specific effect of DHA on the intestinal barrier function in IL-10-deficient mice. IL-10-deficient mice (IL-10− / −) at 16 weeks of age with established colitis were treated with DHA (i.g. 35·5 mg/kg per d) for 2 weeks. The severity of their colitis, levels of pro-inflammatory cytokines, epithelial gene expression, the distributions of TJ proteins (occludin and zona occludens (ZO)-1), and epithelial apoptosis in the proximal colon were measured at the end of the experiment. DHA treatment attenuated the established colitis and was associated with reduced infiltration of inflammatory cells in the colonic mucosa, lower mean histological scores and decreased levels of pro-inflammatory cytokines (IL-17, TNF-α and interferon-γ). Moreover, enhanced barrier function was observed in the DHA-treated mice that resulted from attenuated colonic permeability, rescued expression and corrected distributions of occludin and ZO-1. The results of the present study indicate that DHA therapy may ameliorate experimental colitis in IL-10− / − mice by improving the intestinal epithelial barrier function.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the or variations. ‘’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      DHA protects against experimental colitis in IL-10-deficient mice associated with the modulation of intestinal epithelial barrier function
      Available formats

      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      DHA protects against experimental colitis in IL-10-deficient mice associated with the modulation of intestinal epithelial barrier function
      Available formats

      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      DHA protects against experimental colitis in IL-10-deficient mice associated with the modulation of intestinal epithelial barrier function
      Available formats


Corresponding author

* Corresponding author: W. Zhu, email


Hide All
1 Kaser, A, Zeissig, S & Blumberg, RS (2010) Inflammatory bowel disease. Am J Clin Nutr 28, 573621.
2 Xavier, RJ & Podolsky, DK (2007) Unravelling the pathogenesis of inflammatory bowel disease. Nature 448, 427434.
3 Harhaj, NS & Antonetti, DA (2004) Regulation of tight junctions and loss of barrier function in pathophysiology. Int J Biochem Cell Biol 36, 12061237.
4 Juric, M, Xiao, F, Amasheh, S, et al. (2013) Increased epithelial permeability is the primary cause for bicarbonate loss in inflamed murine colon. Inflamm Bowel Dis 19, 904911.
5 Schulzke, JD, Ploeger, S, Amasheh, M, et al. (2009) Epithelial tight junctions in intestinal inflammation. Ann N Y Acad Sci 1165, 294300.
6 Clayburgh, DR, Shen, L & Turner, JR (2004) A porous defense: the leaky epithelial barrier in intestinal disease. Lab Invest 84, 282291.
7 Schumann, M, Gunzel, D, Buergel, N, et al. (2012) Cell polarity-determining proteins Par-3 and PP-1 are involved in epithelial tight junction defects in coeliac disease. Gut 61, 220228.
8 Su, L, Nalle, SC, Shen, L, et al. (2013) TNFR2 activates MLCK-dependent tight junction dysregulation to cause apoptosis-mediated barrier loss and experimental colitis. Gastroenterology 145, 407415.
9 Carter, PR, Watts, MN, Kosloski-Davidson, M, et al. (2013) Iron status, anemia, and plasma erythropoietin levels in acute and chronic mouse models of colitis. Inflamm Bowel Dis 19, 12601265.
10 Yin, H, Li, X, Zhang, B, et al. (2013) Sirolimus ameliorates inflammatory responses by switching the regulatory T/T helper type 17 profile in murine colitis. Immunology 139, 494502.
11 Goettel, JA, Scott, AH, Olivares-Villagomez, D, et al. (2011) KSR1 protects from interleukin-10 deficiency-induced colitis in mice by suppressing T-lymphocyte interferon-gamma production. Gastroenterology 140, 265274.
12 Ouyang, W, Rutz, S, Crellin, NK, et al. (2011) Regulation and functions of the IL-10 family of cytokines in inflammation and disease. Annu Rev Immunol 29, 71109.
13 Wang, H, Dong, J, Zuo, L, et al. (2014) Anti-mouse CD52 monoclonal antibody ameliorates iron-deficient anaemia in IL-10 knockout mice. Br J Nutr 111, 987995.
14 Kaser, A, Zeissig, S & Blumberg, RS (2010) Inflammatory bowel disease. Annu Rev Immunol 28, 573621.
15 Borrelli, O, Cordischi, L, Cirulli, M, et al. (2006) Polymeric diet alone versus corticosteroids in the treatment of active pediatric Crohn's disease: a randomized controlled open-label trial. Clin Gastroenterol Hepatol 4, 744753.
16 Froslie, KF, Jahnsen, J, Moum, BA, et al. (2007) Mucosal healing in inflammatory bowel disease: results from a Norwegian population-based cohort. Gastroenterology 133, 412422.
17 Hashimoto, T, Perlot, T, Rehman, A, et al. (2012) ACE2 links amino acid malnutrition to microbial ecology and intestinal inflammation. Nature 487, 477481.
18 Hokari, R, Matsunaga, H & Miura, S (2013) Effect of dietary fat on intestinal inflammatory diseases. J Gastroenterol Hepatol 28, Suppl. 4, 3336.
19 Ananthakrishnan, AN, Khalili, H, Konijeti, GG, et al. (2014) Long-term intake of dietary fat and risk of ulcerative colitis and Crohn's disease. Gut 63, 776784.
20 Hou, JK, Abraham, B & El-Serag, H (2011) Dietary intake and risk of developing inflammatory bowel disease: a systematic review of the literature. Am J Gastroenterol 106, 563573.
21 Neuman, MG & Nanau, RM (2012) Inflammatory bowel disease: role of diet, microbiota, life style. Transl Res 160, 2944.
22 Lev-Tzion, R, Griffiths, AM & Leder, O, et al. (2014) Omega 3 fatty acids (fish oil) for maintenance of remission in Crohn's disease. The Cochrane Database of Systematic Review 2014, issue 2, CD006320.
23 Marion-Letellier, R, Savoye, G, Beck, PL, et al. (2013) Polyunsaturated fatty acids in inflammatory bowel diseases: a reappraisal of effects and therapeutic approaches. Inflamm Bowel Dis 19, 650661.
24 Pizato, N, Bonatto, S, Piconcelli, M, et al. (2006) Fish oil alters T-lymphocyte proliferation and macrophage responses in Walker 256 tumor-bearing rats. Nutrition 22, 425432.
25 Draper, E, Reynolds, CM, Canavan, M, et al. (2011) Omega-3 fatty acids attenuate dendritic cell function via NF-κB independent of PPAR-γ. J Nutr Biochem 22, 784790.
26 Calder, PC (2006) n-3 Polyunsaturated fatty acids, inflammation, and inflammatory diseases. Am J Clin Nutr 83, 1505S1519S.
27 Weylandt, KH, Chiu, CY, Gomolka, B, et al. (2012) Omega-3 fatty acids and their lipid mediators: towards an understanding of resolvin and protectin formation. Prostaglandins Other Lipid Mediat 97, 7382.
28 Beguin, P, Errachid, A, Larondelle, Y, et al. (2013) Effect of polyunsaturated fatty acids on tight junctions in a model of the human intestinal epithelium under normal and inflammatory conditions. Food Funct 4, 923931.
29 Singh, UP, Singh, S, Taub, DD, et al. (2003) Inhibition of IFN-γ-inducible protein-10 abrogates colitis in IL-10− / − mice. J Immunol 171, 14011406.
30 Arrieta, MC, Madsen, K, Doyle, J, et al. (2009) Reducing small intestinal permeability attenuates colitis in the IL10 gene-deficient mouse. Gut 58, 4148.
31 Gu, L, Li, N, Gong, J, et al. (2011) Berberine ameliorates intestinal epithelial tight-junction damage and down-regulates myosin light chain kinase pathways in a mouse model of endotoxinemia. J Infect Dis 203, 16021612.
32 Clayburgh, DR, Barrett, TA, Tang, Y, et al. (2005) Epithelial myosin light chain kinase-dependent barrier dysfunction mediates T cell activation-induced diarrhea in vivo . J Clin Invest 115, 27022715.
33 Wang, H, Zhang, W, Zuo, L, et al. (2014) Intestinal dysbacteriosis contributes to decreased intestinal mucosal barrier function and increased bacterial translocation. Lett Appl Microbiol 58, 384392.
34 Wang, H, Dong, J, Shi, P, et al. (2015) Anti-mouse CD52 mAb ameliorates intestinal epithelial barrier function in IL-10 knockout mice with spontaneous chronic colitis. Immunology 144, 254262.
35 Stewart, M, Day, AS & Otley, A (2011) Physician attitudes and practices of enteral nutrition as primary treatment of paediatric Crohn disease in North America. J Pediatr Gastroenterol Nutr 52, 3842.
36 Cabre, E, Manosa, M & Gassull, MA (2012) Omega-3 fatty acids and inflammatory bowel diseases – a systematic review. Br J Nutr 107, Suppl. 2, S240S252.
37 Lee, D, Albenberg, L, Compher, C, et al. (2015) Diet in the pathogenesis and treatment of inflammatory bowel diseases. Gastroenterology (Epublication ahead of print version) .
38 Tapia, G, Valenzuela, R, Espinosa, A, et al. (2014) n-3 Long-chain PUFA supplementation prevents high fat diet induced mouse liver steatosis and inflammation in relation to PPAR-α upregulation and NF-κB DNA binding abrogation. Molec Nutr Food Res 58, 13331341.
39 Adkins, Y & Kelley, DS (2010) Mechanisms underlying the cardioprotective effects of omega-3 polyunsaturated fatty acids. J Nutr Biochem 21, 781792.
40 Berg, DJ, Davidson, N, Kuhn, R, et al. (1996) Enterocolitis and colon cancer in interleukin-10-deficient mice are associated with aberrant cytokine production and CD4(+) TH1-like responses. J Clin Invest 98, 10101020.
41 Mbodji, K, Charpentier, C, Guerin, C, et al. (2013) Adjunct therapy of n-3 fatty acids to 5-ASA ameliorates inflammatory score and decreases NF-κB in rats with TNBS-induced colitis. J Nutr Biochem 24, 700705.
42 Campos, FG, Waitzberg, DL, Habr-Gama, A, et al. (2002) Impact of parenteral n-3 fatty acids on experimental acute colitis. Br J Nutr 87, Suppl. 1, S83S88.
43 Abraham, C & Cho, JH (2009) Inflammatory bowel disease. N Engl J Med 361, 20662078.
44 Hering, NA, Fromm, M & Schulzke, JD (2012) Determinants of colonic barrier function in inflammatory bowel disease and potential therapeutics. J Physiol 590, 10351044.
45 Watson, AJ, Chu, S, Sieck, L, et al. (2005) Epithelial barrier function in vivo is sustained despite gaps in epithelial layers. Gastroenterology 129, 902912.
46 Vandenbroucke, RE, Dejonckheere, E, Van Hauwermeiren, F, et al. (2013) Matrix metalloproteinase 13 modulates intestinal epithelial barrier integrity in inflammatory diseases by activating TNF. EMBO Mol Med 5, 932948.
47 Vivinus-Nebot, M, Frin-Mathy, G, Bzioueche, H, et al. (2014) Functional bowel symptoms in quiescent inflammatory bowel diseases: role of epithelial barrier disruption and low-grade inflammation. Gut 63, 744752.
48 Poritz, LS, Harris, LR, Kelly, AA, et al. (2011) Increase in the tight junction protein claudin-1 in intestinal inflammation. Dig Dis Sci 56, 28022809.
49 Jansson, J, Willing, B, Lucio, M, et al. (2009) Metabolomics reveals metabolic biomarkers of Crohn's disease. PLoS One 4, e6386.
50 Hekmatdoost, A, Feizabadi, MM, Djazayery, A, et al. (2008) The effect of dietary oils on cecal microflora in experimental colitis in mice. Indian J Gastroenterol 27, 186189.
51 Knoch, B, Nones, K, Barnett, MP, et al. (2010) Diversity of caecal bacteria is altered in interleukin-10 gene-deficient mice before and after colitis onset and when fed polyunsaturated fatty acids. Microbiology 156, 33063316.
52 Wang, X, Pan, L, Lu, J, et al. (2012) n-3 PUFAs attenuate ischemia/reperfusion induced intestinal barrier injury by activating I-FABP–PPARγ pathway. Clin Nutr 31, 951957.
53 Bansal, T, Alaniz, RC, Wood, TK, et al. (2010) The bacterial signal indole increases epithelial-cell tight-junction resistance and attenuates indicators of inflammation. Proc Natl Acad Sci U S A 107, 228233.
54 Zeissig, S, Burgel, N, Gunzel, D, et al. (2007) Changes in expression and distribution of claudin 2, 5 and 8 lead to discontinuous tight junctions and barrier dysfunction in active Crohn's disease. Gut 56, 6172.
Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

British Journal of Nutrition
  • ISSN: 0007-1145
  • EISSN: 1475-2662
  • URL: /core/journals/british-journal-of-nutrition
Please enter your name
Please enter a valid email address
Who would you like to send this to? *



Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed