Digestive Diseases and Sciences

, Volume 41, Issue 12, pp 2477–2481 | Cite as

Antagonistic effects of sulfide and butyrate on proliferation of colonic mucosa

A potential role for these agents in the pathogenesis of ulcerative colitis
  • Stefan U. Christl
  • Hans-Dieter Eisner
  • Gerda Dusel
  • Heinrich Kasper
  • Wolfgang Scheppach
Intestinal Disorders, Inflammatory Bowel Disease, And Irritable Bowel Syndrome


It has been shown that feces of patients with ulcerative colitis uniformly contain sulfate reducing bacteria. Sulfide produced by these bacteria interferes with butyrate-dependent energy metabolism of cultured colonocytes and may be involved in the pathogenesis of ulcerative colitis. Mucosal biopsies from the sigmoid rectum of 10 patients (no caner, polyps, inflammatory bowel disease) were incubated with either NaCl, sodium hydrogen sulfide (1 mmol/L), a combination of both sodium hydrogen sulfide and butyrate (10 mmol/L), or butyrate. Mucosal proliferation was assessed by bromodeoxyuridine labeling of cells in S-phase. Compared to NaCl, sulfide increased the labeling of the entire crypt significantly, by 19% (p < 0.05). This effect was due to an expansion of the proliferative zone to the upper crypt (compartments 3–5), where the increase in proliferation was 54%. Sulfide-induced hyperproliferation was reversed when samples were coincubated with sulfide and butyrate. The study shows that sodium hydrogen sulfide induces mucosal hyperproliferation. Our data support a possible role of sulfide in the pathogenesis of UC and confirm the role of butyrate in the regulation of colonic proliferation and in the treatment of UC.

Key words

ulcerative colitis sulfide sulfate reduction butyrate proliferation 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Beerens H, Romond C: Sulfate reducing anaerobic bacteria in human feces. Am J Clin Nutr 30:1770–1779, 1977PubMedGoogle Scholar
  2. 2.
    Gibson GR, Macfarlane GT, Cummings JH: Occurrence of sulphate reducing bacteria in human feces and the relationship of dissimilatory sulphate reduction to methanogenesis in the large gut. J Appl Bacteriol 65:103–111, 1988PubMedGoogle Scholar
  3. 3.
    Gibson GR, Macfarlane S, Macfarlane GT: Metabolic interactions involving sulphate reducing and methanogenic bacteria in the large intestine. FEMS Microbiol Ecol 12:117–123, 1993Google Scholar
  4. 4.
    Postgate JR: The Sulphate Reducing Bacteria, 2nd ed. Cambridge, UK, Cambridge University Press, 1984Google Scholar
  5. 5.
    Florin THJ, Gibson GR, Neale G, Cummings JH: A role of sulfate reducing bacteria in ulcerative colitis. Gastroenterology 98:A170, 1990Google Scholar
  6. 6.
    Gibson GR, Cummings JH, Macfarlane GT: Growth and activities of sulphate reducing bacteria in gut contents of healthy subjects and patients with ulcerative colitis. FEMS Microbiol Ecol 86:103–112, 1991Google Scholar
  7. 7.
    Gibson GR, Cummings JH, Macfarlane GT, Allison C, Segal J, Vorster HH, Walker ARP: Alternative pathways for hydrogen disposal during fermentation in the human colon. Gut 31:679–683, 1990PubMedGoogle Scholar
  8. 8.
    Gossel TA, Bricker JD: Principles of Clinical Toxicology. New York, Raven, 1990Google Scholar
  9. 9.
    Weiseger RA, Pinkus LM, Jacoby WB: Thiol S-methyltransferase: Suggested role in detoxication of intestinal hydrogen sulfide. Biochem Pharmacol 29:2885–2887, 1980PubMedGoogle Scholar
  10. 10.
    Marcus R, Watt J: Seaweeds and ulcerative colitis in laboratory animals. Lancet 2:489, 1969PubMedGoogle Scholar
  11. 11.
    Kitano A, Matsumoto T, Hiki M, Hashimura H, Yoshihasu K, Okawa K, Kuwajiama S, Kobayashi K: Epithelial dysplasia of the rabbit colon induced by degraded carrageenan. Cancer Res 46:1374–1376, 1986PubMedGoogle Scholar
  12. 12.
    Yamada M, Okusha T, Okayasu I: Occurrence of dysplasia and adenocarcinoma after experimental chronic ulcerative colitis in hamsters induced by dextrane sulphate sodium. Gut 33:1521–1527, 1992PubMedGoogle Scholar
  13. 13.
    Roediger WEW, Duncan A, Kapaniris O, Millard S: Reducing sulfur compounds of the colon impair colonocyte nutrition: Implications for ulcerative colitis. Gastroenterology 104:802–809, 1993PubMedGoogle Scholar
  14. 14.
    Roediger WEW, Duncan A, Lapaniris O, Millard S: Sulphide impairment of sulphide oxidation in rat colonocytes: A biochemical basis for ulcerative colitis? Clin Sci 85:623–627, 1993PubMedGoogle Scholar
  15. 15.
    Roediger WEW: Utilization of nutrients by isolated cells of the rat colon. Gastroenterology 83:424–429, 1982PubMedGoogle Scholar
  16. 16.
    Whitehead RH, Young GP, Bhathal PS: Effects of short chain fatty acids on a new human colon carcinoma cell line (LIM1215). Gut 27:1457, 1986PubMedGoogle Scholar
  17. 17.
    Kim YS, Tsao D, Siddiqui B, Whitehead JS, Arnstein P, Bennett J, Hicks J: Effects of sodium butyrate and dimethylsulfoxide on biochemical properties of human colon cancer cells. Cancer 45:1185–1192, 1980PubMedGoogle Scholar
  18. 18.
    Harig JM, Soergel KH, Komorowski RA, Wood CM: Treatment of diversion colitis with short chain fatty acid irrigation. N Engl J Med 320:23–26, 1989PubMedGoogle Scholar
  19. 19.
    Scheppach W, Sommer H, Kirchner T, Paganelli GM, Bartram P, Christl S, Richter F, Dusel G, Kasper H: Effect of butyrate enemas on the colonic mucosa in distal ulcerative colitis. Gastroenterology 103:51–56, 1992PubMedGoogle Scholar
  20. 20.
    Breuer RI, Buto SK, Christ ML, Bean J, Vernia P, Paoluzi P, Di Polo MC, Caprilli R: Rectal irrigation with short chain fatty acids for distal ulcerative colitis. Dig Dis Csi 36:185–192, 1991Google Scholar
  21. 21.
    Gibson PR, Vam de Pol E, Maxwell LE, Gabriel A, Doe WF: Isolation of colonic crypts that maintain structural and metabolic viability in vitro. Gastroenterology 96:283–291, 1989PubMedGoogle Scholar
  22. 22.
    Bartram HP, Scheppach W, Schmid H, Hofmann A, Dusel G, Richter F, Richter A, Kasper H: Proliferation of human colonic mucosa as an intermediate biomarker of carcinogenesis: Effects of butyrate, deoxycholate, calcium, ammonia, and pH. Cancer Res 53:3283–3288, 1993PubMedGoogle Scholar
  23. 23.
    Lipkin M: Biomarkers of increased susceptibility to gastrointestinal cancer: New application to studies of cancer prevention in human subjects. Cancer Res 48:235–245, 1988PubMedGoogle Scholar
  24. 24.
    Lipkin M: Application of intermediate biomarkers to studies of cancer prevention in the gastrointestinal tract: Introduction and perspective. Am J Clin Nutr 54:188S-192S, 1991PubMedGoogle Scholar
  25. 25.
    Scheppach W, Bartram P, Richter A, Richter F, Liepold H, Dusel G, Hofstetter G, Ruthlein J, Kasper H: Effect of short-chain fatty acids on the human colonic mucosa in vitro. J Parent Enteral Nutr 16:43–48, 1992Google Scholar
  26. 26.
    Moore WEC, Johnsos JL, Holdeman LV: Emendation of Bacteroidaceae and Butyvibrio and descriptions of Desulfomonas gen. nov. and ten new species in the genera Desulfomonas, Butyvibrio, Eubacterium, Clostridum and Ruminococcus. Int J Syst Microbiol 26:238–246, 1976Google Scholar
  27. 27.
    Christl SU, Gibson GR, Cummings JH: Role of dietary sulfate in the regulation of methanogenesis in the human large intestine. Gut 33:1234–1238, 1992PubMedGoogle Scholar
  28. 28.
    Florin THJ, Neale G, Gibson GR, Christl SU, Cummings JH: Metabolism of dietary sulphate: Absorption and excretion in humans. Gut 32:766–773, 1991PubMedGoogle Scholar
  29. 29.
    Vercellotti JR, Salyers AA, Bullard WS, Wilkins S: Breakdown of mucin and plant polysaccharides in the human colon. Can J Biochem 55:1190–1196, 1977PubMedGoogle Scholar
  30. 30.
    Gibson GR, Cummings JH, Macfarlane GT: Use of a three-stage continuous culture system to study the effect of mucin on dissimilatory sulfate reduction and methanogenesis by mixed populations of human gut bacteria. Appl Environ Microbiol 54:2750–2755, 1988PubMedGoogle Scholar
  31. 31.
    Macfarlane GT, Gibson GR, Cummings JH: Comparison of fermentation reactions in different regions of the colon. J Appl Bacteriol 72:57–64, 1992PubMedGoogle Scholar
  32. 32.
    Watt J, Marcus R: Ulcerative colitis in rats fed degraded carrageenan. J Pharm Pharmacol 22:130–131, 1970PubMedGoogle Scholar
  33. 33.
    Onderdonk AB, Hermos JA, Bartlett JG: The role of the intestinal microflora in experimental colitis. Am J Clin Nutr 30:1819–1825, 1977PubMedGoogle Scholar
  34. 34.
    Onderdonk AB, Hermos JA, Dzink JL, Bartlett JG: Protective effect of metronidazole in experimental ulcerative colitis. Gastroenterology 74:521–527, 1978PubMedGoogle Scholar
  35. 35.
    Roediger WEW, Babidge W, Millard S: Methionine derivatives diminish sulphide damage to colonocytes—implication for ulcerative colitis. Gut 39:77–81, 1996PubMedGoogle Scholar
  36. 36.
    Cummings JH: Fermentation in the human large intestine: Evidence and implications for health. Lancet 1:1206–1209, 1983PubMedGoogle Scholar
  37. 37.
    Macfarlane GT, Cummings JH: The colonic flora, fermentation, and large bowel digestive function.In The Large Intestine: Physiology, Pathophysiology, and Disease, S Philips, JH Pemberton, RG Shorter (eds). New York, Raven Press, 1991, p 51Google Scholar

Copyright information

© Plenum Publishing Corporation 1996

Authors and Affiliations

  • Stefan U. Christl
    • 1
  • Hans-Dieter Eisner
    • 1
  • Gerda Dusel
    • 1
  • Heinrich Kasper
    • 1
  • Wolfgang Scheppach
    • 1
  1. 1.Department of MedicineUniversity of WürzburgWürzburgGermany

Personalised recommendations