Inflammation

, Volume 32, Issue 1, pp 27–36 | Cite as

The Degradation of Glycosaminoglycans by Intestinal Microflora Deteriorates Colitis in Mice

  • Hye-Sung Lee
  • Song-Yi Han
  • Kwon-Yeul Ryu
  • Dong-Hyun Kim
Article

Abstract

The biosynthesis and modification of mucopolysaccharides and glycosaminoglycans (GAGs), secreted from gastrointestinal mucosal cells, are increased in colitis and influence the viability of the defense barrier. Therefore, to evaluate the role of GAG-degrading intestinal microflora during the progression of colitis, we investigated the degradation activity of intestinal bacterial GAG, cytotoxicity of GAGs and their metabolites, such as iduronic acid, d-uronic acid or d-glucuronic acid and d-galactosamine or d-glucosamine, against intestinal cells. We also tested their deteriorative effects against colitis. Colitis was induced using 2,4,6-trinitrobenzene sulfonic acid (TNBS) with and without antibiotics in mice. The TNBS treatment caused colon shortening, increased myeloperoxidase activity, induced IL-1β, TNF-α, and IL-6 expression in the colon, activated NF-κB, and potentiated the GAG-degrading activities of intestinal microflora. The antibiotic treatment inhibited colon shortening, decreased myeloperoxidase activity, and reduced proinflammatory cytokine expression, NF-κB activation, and GAG degradation, induced by TNBS. Among the GAG metabolites, d-glucosamine and d-galactosamine showed cytotoxicity against intestinal cells, Caco-2 and IEC-18 cells, synergistically deteriorated the cytotoxicity of TNBS as well as the TNBS-induced colitis in mice. Based on these findings, intestinal microflora may degrade GAGs in colitis, their metabolites deteriorate the progress of colitis and antibiotics ameliorate the colitis by the inhibition of GAG-degrading bacterial growth.

KEY WORDS

colitis 2,4,6-trinitrobenzene sulfonic acid (TNBS) glycosaminoglycans (GAG) intestinal microflora antibiotics 

References

  1. 1.
    Benno, P., C. E. Leijonmarck, U. Monsen, and A. Uribe. 1993. Functional alterations of the microflora in patients with ulcerative colitis. Scand. J. Gastroenterol. 28:839–844. doi: 10.3109/00365529309104019.PubMedCrossRefGoogle Scholar
  2. 2.
    Gorbach, S. L., L. Nahas, A. G. Plaut, L. Weinstein, J. F. Patterson, and R. Levitan. 1968. Studies of intestinal microflora. V. Fecal microbial ecology in ulcerative colitis and regional enteritis: relationship to severity of disease and chemotherapy. Gastroenterology 54:575–587.PubMedGoogle Scholar
  3. 3.
    Chung, K. T., G. E. Fulk, and M. W. Slein. 1975. Tryptophanase of fecal flora as a possible factor in the etiology of colon cancer. J. Natl. Cancer Inst. 54:1073–1078.PubMedGoogle Scholar
  4. 4.
    Radema, S. A., S. J. van Deventer, and A. Cerami. 1991. Interleukin 1 beta is expressed predominantly by enterocytes in experimental colitis. Gastroenterology 100:1180–1186.PubMedGoogle Scholar
  5. 5.
    Rafii, F., R. van Embdin, and L. M. C. van Lieshout. 1999. Changes in bacterial enzymes and PCR profiles of fecal bacteria from a patient with ulcerative colitis before and after antimicrobial treatments. Dig. Dis. Sci. 44:637–642. doi: 10.1023/A:1026634229934.PubMedCrossRefGoogle Scholar
  6. 6.
    Berrebi, D., J. Languepin, L. Ferkdadji, A. Foussat, P. De Lagausie, R. Paris, D. Emilie, J. F. Mougenot, J. P. Cezard, J. Navarro, and M. Peuchmaur. 2004. Cytokines, chemokine receptors, and homing molecule distribution in the rectum and stomach of pediatric patients with ulcerative colitis. J. Pediatr. Gastroenterol. Nutr. 37:300–308. doi: 10.1097/00005176-200309000-00018.Google Scholar
  7. 7.
    Binder, V. 2004. Epidemiology of IBD during the twentieth century: an integrated view. Best Pract. Res. Clin. Gastroenterol. 18:463–479. doi: 10.1016/j.bpg.2003.12.002.PubMedCrossRefGoogle Scholar
  8. 8.
    Chandran, P., S. Satthaporn, A. Robins, and O. Eremin. 2003. Inflammatory bowel disease: dysfunction of GALT and gut bacterial flora (II). Surgeon 1:125–136.PubMedCrossRefGoogle Scholar
  9. 9.
    Rath, H. C., M. Schultz, R. Freitag, L. A. Dieleman, F. Li, H. J. Linde, J. Scholmerich, and R. B. Sartor. 2001. Different subsets of enteric bacteria induce and perpetuate experimental colitis in rats and mice. Infect. Immun. 69:2277–2285. doi: 10.1128/IAI.69.4.2277-2285.2001.PubMedCrossRefGoogle Scholar
  10. 10.
    Neurath, M., I. Fuss, and W. Strober. 2000. TNBS-colitis. Int. Rev. Immunol. 19:51–62. doi: 10.3109/08830180009048389.PubMedCrossRefGoogle Scholar
  11. 11.
    Hill, M. J., and B. S. Drasar. 1975. The normal colonic bacterial flora. Gut 16:318–323. doi: 10.1136/gut.16.4.318.PubMedCrossRefGoogle Scholar
  12. 12.
    Ganguly, N. K. , J. G. Kingham, B. Lloyd, R. S. Lloyd, C. P. Price, D. R. Triger, and R. Wright. 1978. Acid hydrolases in monocytes from patients with inflammatory bowel disease, chronic liver disease, and rheumatoid arthritis. Lancet 1(8073):1073–1075.PubMedCrossRefGoogle Scholar
  13. 13.
    Rhodes, J. M., R. Gallimore, and E. Elias. 1985. Faecal mucus degrading glycosidases in ulcerative colitis and Crohn's disease. Gut 26:761–765. doi: 10.1136/gut.26.8.761.PubMedCrossRefGoogle Scholar
  14. 14.
    Rifkin, G. D., J. Silva Jr., and R. Fekety. 1978. Gastrointestinal and systemic toxicity of fecal extracts from hamsters with clindamycin-induced colitis. Gastroenterology 74:52–57.PubMedGoogle Scholar
  15. 15.
    Wallace, J. L., W. K. Macnaughton, G. P. Morris, and P. L. Beck. 1989. Inhibition of leukotriene synthesis markedly accelerates healing in a rat model of inflammatory bowel disease. Gastroenterology 96:29–36.PubMedGoogle Scholar
  16. 16.
    Belmiro, C. L., H. S. Souza, C. C. Elia, M. T. Castelo-Branco, F. R. Silva, R. L. Machado, and M. S. Pavao. 2005. Biochemical and immunohistochemical analysis of glycosaminoglycans in inflamed and non-inflamed intestinal mucosa of patients with Crohn's disease. Int. J. Colorectal. Dis. 20:295–304. doi: 10.1007/s00384-004-0677-2.PubMedCrossRefGoogle Scholar
  17. 17.
    Gesner, B. M., and C. R. Jenkin. 1961. Production of heaprinase by bacteroides. J. Bacteriol. 81:595–604.PubMedGoogle Scholar
  18. 18.
    Corfield, A. P., N. Myerscough, N. Bradfield, C. D. A. Corfield, M. Gough, J. R. Clamp, P. Durdey, B. F. Warren, D. C. C. Bartolo, K. R. King, and J. M. Williams. 1996. Colonic mucins in ulcerative colitis: evidence for loss of sulfation. Glycoconjugate J. 13:89–822. doi: 10.1007/BF00702345.CrossRefGoogle Scholar
  19. 19.
    Greenberg, G. R. 2004. Antibiotics should be used as first-line therapy for Crohn’s disease. Inflamm. Bowel Dis. 10:318–320. doi: 10.1097/00054725-200405000-00021.PubMedCrossRefGoogle Scholar
  20. 20.
    Sartir, R. B. 2004. Therapeutic manipulation of the enteric microflora in inflammatory bowel diseases: antibiotics, probiotics, and prebiotics. Gastroenterology 126:1620–1633. doi: 10.1053/j.gastro.2004.03.024.CrossRefGoogle Scholar
  21. 21.
    Mullane, K. M., R. Kraemer, and B. Smith. 1985. Myeloperoxidase activity as a quantitative assessment of neutrophil infiltration into ischemic myocardium. J. Pharmacol. Methods 14:157–167. doi: 10.1016/0160-5402(85)90029-4.PubMedCrossRefGoogle Scholar
  22. 22.
    Choo, M. K., N. Kawasaki, P. Singhirunnusorn, K. Koizumi, S. Sato, S. Akira, I. Saiki, and H. Sakurai. 2006. Blockade of transforming growth factor-beta-activated kinase 1 activity enhances TRAIL-induced apoptosis through activation of a caspase cascade. Mol. Cancer Ther. 5:2970–2976. doi: 10.1158/1535-7163.MCT-06-0379.PubMedCrossRefGoogle Scholar
  23. 23.
    Lee, D. S., Y. S. Kim, C. N. Ko, K. H. Cho, H. S. Bae, K. S. Lee, J. J. Kim, E. K. Park, and D. H. Kim. 2002. Fecal metabolic activities of herbal components to bioactive compounds. Arch. Pharm. Res. 25:165–169. doi: 10.1007/BF02976558.PubMedCrossRefGoogle Scholar
  24. 24.
    Carmichael, J., W. G. DeGreff, A. F. Gazdar, J. D. Minna, and J. B. Mitchell. 1987. Evaluation of a tetrazolium-based semiautomated colorimetric assay: assessment of radiosensitivity. Cancer Res. 47:936–940.PubMedGoogle Scholar
  25. 25.
    Keighley, M. R., and Y. Arabi. 1978. Influence of inflammatory bowel disease on intestinal microflora. Gut 19:1099–1104. doi: 10.1136/gut.19.12.1099.PubMedCrossRefGoogle Scholar
  26. 26.
    Onderdonk, A. B., J. A. Aermos, and J. G. Barblett. 1979. The role of the intestinal microflora in experimental colitis. Am. J. Clin. Nutr. 30:1819–1825.Google Scholar
  27. 27.
    Appleton, I., A. Tomlinsom, and D. A. Willoughby. 1996. Induction of cyclo-oxygenase and nitric oxide synthase in inflammation. Adv. Pharmacol. 35:27–78. doi: 10.1016/S1054-3589(08)60274-4.PubMedCrossRefGoogle Scholar
  28. 28.
    Sartor, R. B. 1994. Cytokines in intestinal inflammation: pathophysiological and clinical considerations. Gastroenterology 106:533–539.PubMedGoogle Scholar
  29. 29.
    Singer, I. I., D. W. Kawka, S. Schloemann, R. Tessner, T. Riehl, and W. F. Stenson. 1998. Cyclooxygenase 2 is induced in colonic epithelial cells in inflammatory bowel disease. Gastroenterology 115:297–306. doi: 10.1016/S0016-5085(98)70196-9.PubMedCrossRefGoogle Scholar
  30. 30.
    Gesner, B. M., and C. R. Jenkin. 1961. Production of heparinase by Bacteroides. J. Bacteriol. 81:595–604.PubMedGoogle Scholar
  31. 31.
    Salyers, A. A., J. R. Vercellotti, S. H. E. West, and T. D. Wilkins. 1977. Fermentation of mucin and plant polysaccharides by strains of Bacteroides from the human colon. Appl. Environ. Microbiol. 34:319–322.Google Scholar
  32. 32.
    Hong, S. W., B. T. Kim, H. Y. Shin, W. S. Kim, K. S. Lee, Y. S. Kim, and D. H. Kim. 2002. Purification and characterization of novel chondroitin ABC and AC lyases from Bacteroides stercoris HJ-15, a human intestinal anaerobic bacterium. Eur. J. Biochem. 269:2934–2940.PubMedCrossRefGoogle Scholar
  33. 33.
    Salyers, A. A., M. Pajeau, and R. E. McCarthy. 1988. Importance of mucopolysaccharides as substrates for Bacteroides thetaiotaomicron growing in intestinal tracts of exgermfree mice. Appl. Environ. Microbiol. 54:1970–1976.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Hye-Sung Lee
    • 1
  • Song-Yi Han
    • 2
  • Kwon-Yeul Ryu
    • 1
  • Dong-Hyun Kim
    • 1
    • 2
  1. 1.Department of Life and Nanopharmaceutical SciencesKyung Hee UniversitySeoulSouth Korea
  2. 2.Department of Pharmaceutical ScienceKyung Hee UniversitySeoulSouth Korea

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