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How DSS induces physiological responses that mimic IBD

Chemically induced murine models of intestinal inflammation, such as DSS-induced colitis models, are widely used because they are easy to induce and the onset, duration and severity of inflammation are immediate and controllable. By titrating the amount of DSS up or down, you can model severe to mild inflammatory disease.

DSS works by direct and selective toxicity to epithelial cells. DSS causes a loss of surface epithelium, enabling luminal microbes and their metabolites enter the lamina propria and induce an inflammatory response (Figure 1).

Figure 1. DSS is directly toxic to epithelial cells, causing loss of the surface layer of epithelial cells, enabling gut microorganisms and their products to enter the lamina propria, and stimulating an inflammatory response.

The advantages of DSS-induced models

The DSS-induced colitis model has some advantages when compared to other animal models of colitis. As mentioned above, an acute, chronic, or relapsing model can easily be generated by changing the concentration and administration cycle of DSS in rats and mice. Moreover, dysplasia that resembles the clinical course of human ulcerative colitis (UC) occurs frequently in the chronic phase of DSS-induced colitis.

Studies validating DSS models using various therapeutic agents for human IBD have shown that DSS-induced colitis can be used as a relevant model for the translation of mice data to human disease.

For more on DSS models of colitis, we recommend the review:

Dextran sodium sulfate colitis murine model: An indispensable tool for advancing our understanding of inflammatory bowel diseases pathogenesis

Derrick D Eichele and Kusum K Kharbanda. World J Gastroenterol. 2017 Sep 7; 23(33): 6016–6029. PMCID: PMC5597494.

Creating an IBD model

The protocol for generating a DSS-induced colitis model is simple to implement—simply dissolve the DSS powder in autoclaved drinking water to create a solution of the correct dose. The duration of the treatment will depend on the strain of rodent as well as how you choose to define your model based on your research aims.

Dosage of DSS for different strains of mice
Animal/Strain Dose Days Publication
C57BL/6 2.5% 8 Jia, Q.; Ivanov, I.; Zlatev, Z.; et al. Dietary fish oil and curcumin combine to modulate colonic cytokinetics and gene expression in dextran sodium sulphate-treated mice. Br.J.Nutr. 2011, 106(4), 519-9.
Wild-type C57BL/6J(m) 3% 6 Thiess, A.L.; Laroui, H.; Obertone, T.S.; et al. Nanoparticle-based therapeutic delivery of prohibitin to the colonic epithelial cells ameliorates acute murine colitis. Inflamm. Bowel Dis. 2011, 17(5), 1163-76.
C57BL/6 AhR null, WT 3.5% 7 Arsenescu, R.; Arsenescu, V.; Zhong, J.; et al. Role of xenobiotic receptor in inflammatory bowel disease. Inflamm. Bowel Dis. 2011, 17(5), 1149-2.
C57BL/6 5% 3-14 Nagalingham, N.A.; Kao, J.Y.; Young, V.B. Microbial ecology of the murine gut associated with the development of dextran sodium sulfate-induced colitis. Inflamm, Bowel Disease. 2011, 7(4), 917-26.
C57BL/6 1.5% 7 Ramakers, J.; Verstege, M.I.; Thuijls, G.; et al. The PPARγ agonist rosiglitazone impairs colonic inflammation in mice with experimental colitis. J.Clin.Immunol. 2007, 27(3), 275-283.
BALB/c 1% 10 Palffy, R.; Gardlik, R.; Behuliak, M.; et al. Salmonella-mediated gene therapy in experimental colitis in mice. Ex.Biol.Med. 2011, 236(2), 177-83.
C57BL/6J 3% 5 Shiomi, Y.; Nishiumi, S.; Ooi, M.; et al. GCMS-based metabolomic study in mice with colitis induced by dextran sulfate sodium. Inflamm. Bowel Dis. 2011, 17(11), 2261-74.
BALB/c 1-5% 10 Rochat, T.; Bermudez-Humaran, L.; Gratadoux, J-J.; et al. Anti-inflammatory effects of Lactobacillus casei BL23 producing or not a manganese-dependent catalase on DSSinduced colitis in mice. Microb. CellFact. 2007, 20(6), 22.
BALB/c; NMRI/KI 2.5-5% n/a Bylund-Fellenius, A-C.; Landström, E.; Axelsson, L.G.; et al. Experimental colitis induced by dextran sulphate in normal and germfree mice. Microbial Ecology in Health and Disease. 1994, 7, 207-215.
IL-5-/- and +/+ 2.9%, 5% 9 Stevceva, L.; Pavli, P.; Husband, A.; et al. Eosinophilia is attenuated in experimental colitis induced in IL-5 deficient mice. Genes Immun. 2000, 1(3), 213-8.
BALB/c; athymic nu/nu CD-1 (BR) 2.5-5% 7-35 Axelsson, L.G.; Landström, E.; Bylund-Fellenius, A.C. Experimental colitis induced by dextran sulphate sodium in mice: Beneficial effects of sulphasalazine and olsalazine. Aliment. Pharmacol.Ther. 1998, 12(9), 925-34.
WT; CCR9(-/-); CCL25 (-/-) 2% 7 Wurbel, M.A.; McIntyre, M.G.; Dwyer, P.; et al. CCL25/CCR9 interactions regulate large intestinal inflammation in a murine model of acute colitis. PLoS One. 2011, 6(1), e16442.
Wild-type; DPIV -/- 2% 6 Yazbeck, R.; Howard, G.S.; Butler, R.N.; et al. Biochemical and histological changes in the small intestine of mice with dextran sulfate sodium induced colitis. J.Cell Physiol. 2011, 226(12), 319-24.
BALB/c 5% 7 Kumar, G.K.; Dhamotharan, R.; Kulkarni, N.M. Embelin ameliorates dextran sodium sulfate-induced colitis in mice. Int. Immunopharmacol. 2011, E.
Dosage of DSS for different strains of rats
Animal/Strain Dose Days Publication
Wistar 2% 2 weeks to 6 months Tamaru, T.; Kobayashi, H.; Kishimoto, S.; et al. Histochemical study of colonic cancer in experimental colitis of rats. Dig. Dis. Sci. 1993, 38, 529-537.
Sprague-Dawley 5% 9

Schreiber, O.; Petersson, J.; Phillipson, M.; et al. Lactobacillus reuteri prevents colitis by reducing P-selectin associated leukocyte- and platelet-endothelial cell interactions.

Am.J.Physiol.Gastrointest.Liver. 2009, 296, G534-542. Dicksved, J.; Schreiber, O.; Willing, B.; et al. Lactobacillus reuteri maintains a functional mucosal barrier during DSS treatment despite mucus layer dysfunction. PLoS One. 2012, 7(9), e46399.

Petersson, J.; Schreiber, O.; Steege, A.; et al. eNOS involved in colitis-induced mucosal blood flow increase. Am.J.Physiol.Gastrointest.Liver. 2007, 293, G1281-1287.

Sprague-Dawley 5% 6 Vasina, V.; Broccoli, M.; Ursino, M.G.; et al. Non-peptidyl low molecular weight radical scavenger IAC attenuates DSS-induced colitis in rats. World J.Gastroenterol. 2010, 16(29), 3642-50.
Sprague-Dawley 5% 7 Shi, X.Z.; Winston, J.H.; Sarna, S.K. Differential immune and genetic responses in rat models of Crohn’s colitis and ulcerative colitis. Am.J.Physiol.Gastrointest.Liver Physiol. 2011, 300(1), G41-51.
Wistar 2.5% 7 Aoi, Y.; Terashima, S.; Ogura M.; et al. Roles of nitric oxide (NO) and NO synthases in healing of dextran sulfate sodium-induced rat colitis. J Physio Pharmacol. 2008, 59(2), 315-36.
Wistar 5% 10 Lopez-Posadeas, R.; Requena, P.; Gonzalez, R.; et al. Bovine glycomacropeptide has intestinal antiinflammatory effects in rats with dextran-sulfate induced colitis. J.Nutr. 2010, 140(11), 2014-2019.
Wistar 2-4% 7 Shimizu, T.; Suzuki, M.; Fujimura, J.; et al. The relationship between the concentration of dextran sodium sulfate and the deg