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[Webinar] Kopi & C Talk with RSC: Study of gut microbiota for inflammatory bowel disease (SG)

 

 

The guest for this episode of Kopi & C Talk is from MP Biomedicals, represented by Dr. Tan Yong Xing, a life science research scientist.

Find out more about how MP Biomedicals DSS induces physiological responses that mimic IBD in the research against colorectal cancer.

 

How DSS induces physiological responses that mimic IBD

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.

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).

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 degree of induced experimental colitis in weanling rats. J.Pediatric Gastro. Nutrition. 2003, 37, 481-486.
ACI 5% 14 Hirono, I.; Kuhara, K.; Hosaka, S.; et al. Induction of intestinal tumors in rats by dextran sulfate sodium. J.Natl.Cancer Inst. 1981, 66(3), 579-583.
Dosage of DSS for other animals
Animal/Strain Dose Days Publication
Hamster 2.5% 6 Karlsson, A.; Jägervall, A.; Pettersson, M.; et al. Dextran sulphate sodium induces acute colitis and alters hepatic function in hamsters. Int. Immunopharmacol. 2008, 8(1), 20-27
Hamster 1% N/A Yamada, M.; Ohkusa, T.; Ohkusa, I. Occurence of dysplasia and adenocarcinoma after experimental chronic ulcerative colitis in hamsters induced by dextran sulphate sodium. Gut. 1992, 33, 1521-1527
Guinea Pig 3% 4 Iwanaga, T.; Hoshi, O.; Han, H.; et al. Morphological analysis of acute ulcerative colitis experimentally induced by dextran sulfate sodium in the guinea pig: Some possible mechanisms of cecal ulceration. J. Gastroenterol. 1994, 29(4), 430-438.
Pig (Yorkshire) 1.25 g/kg BW 5 Young, D.; Ibuki, M.; Nakamori, T.; et al. Soy-derived di-and tripeptides alleviate colon and ileum inflammation in pigs with dextran sodium sulfate-induced colitis. J.Nutr. 2012, 142(2), 363-8.

Dextran Sodium Sulfate, Colitis Grade

Our DSS is the most widely cited product on the market for generating DSS-induced colitis models

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Verifying your IBD model

A successful IBD model can be verified quickly and easily using standard laboratory procedures

  • The body mass of treated mice will drop rapidly over the course of seven days.
  • At the tissue level, histological examination of the colon by Hematoxylin & Eosin staining on will show gross structural changes, including the destruction of the epithelial lining.

Getting the most out of your DSS colitis model

MP Biomedicals delivers sample preparation solutions to help you with the downstream analysis of your DSS colitis model. Our diverse collection of products ensure you can find reliable and easy-to-use tools to enhance your experiments.

Our FastPrep systems can be used to efficiently isolate DNA, RNA, protein, and lipids from your tissues, allowing you to uncover the molecular mechanisms of interest in your DSS-induced colitis model. FastPrep is suitable for use with a variety of sample types, including fecal matter and tissue biopsies.

FastPrep Systems

Our FastPrep systems allow you to extract biological materials from even the most challenging samples in under 30 minutes

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Feeding your animals

An important feature of a successful IBD model is the accompanying diet. MP Biomedicals offers a complete range of high quality and customizable rodent diets and supplements to suit any research needs, including:

  • High-fat diets
  • Low-fat diets
  • High carbohydrate diets
  • Choline deficient diets

Animal Diets and Feed

Explore our high-quality animal research diets

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Kopi C & Talk QnA

 

Question 1: Does MP Biomedicals have microbiome research group in Singapore? Is there any person that we can liaise with regarding microbiome related products and issues?
Answer: We do not have a microbiome research group in Singapore. Yes, there is a product manager that can liaise with you on microbiome related products. Please send in your contact to us and we will be happy to get back to you on your enquiry. Thank you.

Question 2: Could you comment on the use of bioacoustic sensing for bowel disease detection?
Answer: Bioacoustic sensing technology can be a potential cost-effective, non-invasive, simple yet powerful tool for diagnosis of several gastrointestinal conditions. However, there will be much more development work on the technology before it can be applied in clinical practice.

Question 3: IBD is a field that i am very interested in, but I do not commonly see research institutes doing this field of research. Are there any other labs that does this field of IBD research?
Answer: While IBD is a niched area of study, as mentioned in the seminar, the research applications and potential therapeutics are countless. In Singapore, based on our sales records of Dextran Sodium Sulphate, in the academia arena, there are a few labs in National University of Singapore, Nanyang Technological University working on IBD. There are also some Biologics companies working on IBD related research as well.

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