Digestive Diseases and Sciences

, Volume 46, Issue 8, pp 1722–1732 | Cite as

Hydrogen Sulfide and Colonic Epithelial Metabolism

  • Jimmy Jørgensen
  • Per Brøbech Mortensen


Hydrogen sulfide (HS) impairs the oxidation of butyrate in colonocytes and is found in excess in feces of patients with ulcerative colitis. The possible pathogenic role of HS in ulcerative colitis was further investigated. To investigate the metabolic effect of free and bound fecal HS, isolated rat colonocytes were incubated in the presence of butyrate without and with the addition of (1) HS in water, (2) sterile filtrates of fecal homogenates supplemented and incubated with HS and known sources of fecal HS production, and (3) HS incubated with fecal agents known to bind HS. Oxidation rates were obtained by quantifying the production of CO2. Total and free HS, as well as the fecal ability to bind HS, were determined in health and ulcerative colitis. Compared to the production of CO2 by colonocytes incubated with 2 mmol/liter of butyrate, the further addition of 1.25 and 2.5 mmol/liter of HS in water reduced the production of CO2 by 57.6 ± 10.0 and 98.9 ± 1.4%, respectively. However, when adding fecal filtrate of homogenate supplemented with HS corresponding to 1.25 and 2.5 mmol/liter of HS in water, the reduction of CO2 production was only 30.7 ± 12.0 and 53.2 ± 14.0%, respectively. Neither the fecal level of total or free HS nor the remarkable fecal ability to bind HS differed in health or quiescent and active ulcerative colitis. Bound HS had no or little effect on CO2 production. Addition of fecal filtrate of nonsupplemented homogenate to colonocytes significantly reduced the oxidation of butyrate to CO2 about 25%, which could not be ascribed to fecal HS. In conclusion, fecal HS has little effect on butyrate oxidation in colonocytes and does not seem to play a pathogenic role for UC by impairing colonic epithelial metabolism. Other fecal agents seem to be more potent metabolic inhibitors than fecal HS. The role of colonic contents in the pathogenesis of ulcerative colitis remains circumstantial.

hydrogen sulfide ulcerative colitis butyrate feces colonocyte detoxification 


  1. 1.
    Roediger WEW: Role of anaerobic bacteria in the metabolic welfare of the colonic mucosa in man. Gut 21:793–798, 1980Google Scholar
  2. 2.
    Roediger WEW: Utilization of nutrients by isolated epithelial cells of the rat colon. Gastroenterology 83:424–429, 1982Google Scholar
  3. 3.
    Roediger WEW: The colonic epithelium in ulcerative colitis- an energy deficiency disease? Lancet 2:712–715, 1980Google Scholar
  4. 4.
    Reiffenstein RJ, Hulbert WC, Roth SH: Toxicology of hydrogen sulfide. Annu Rev Pharmacol Toxicol 109–134, 1992Google Scholar
  5. 5.
    Roediger WEW, Duncan A, Kapaniris O, Millard S: Sulphide impairment of substrate oxidation in rat colonocytes: a biochemical basis for ulcerative colitis? Clin Sci 85:623–627, 1993Google Scholar
  6. 6.
    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, 1993Google Scholar
  7. 7.
    Florin THJ, Gibson GR, Neal G, Cummings JH: A role for sulfate reducing bacteria in ulcerative colitis. Gastroenterology 98:A170, 1990Google Scholar
  8. 8.
    Roediger WEW, Babidge W: Human colonocyte detoxification (review). Gut 41:731–734, 1997Google Scholar
  9. 9.
    Suarez F, Furne J, Springfield J, Levitt M: Production and elimination of sulfur-containing gases in the rat colon. Am J Physiol 274:G727–G733, 1998Google Scholar
  10. 10.
    Florin THJ: Hydrogen sulphide and total acid-volatile sulphide in faeces, determined with a direct spectrophotometric method. Clin Chim Acta 196:127–134, 1991Google Scholar
  11. 11.
    Tangerman A: A quantitative analysis of free hydrogen sulfide and bound sulfide in human feces. Gastroenterology 106:A634, 1994Google Scholar
  12. 12.
    Hove H, Mortensen PB: Influence of intestinal inflammation (IBD) and small and large bowel length on fecal short-chain fatty acids and lactate. Dig Dis Sci 40:1372–1380, 1995Google Scholar
  13. 13.
    Curtis CG, Bartholomew TC, Rose FA, Dodgson KS: Detoxication of sodium 35S-sulphide in the rat. Biochem Pharmacol 21:2313–2321, 1972Google Scholar
  14. 14.
    Jørgensen JR, Mortensen PB: Influence of feces from patients with ulcerative colitis on butyrate oxidation in rat colonocytes. Dig Dis Sci 44:2099–2109, 1999Google Scholar
  15. 15.
    Roediger WEW, Truelove SC: Method of preparing isolated colonic epithelial cells (colonocytes) for metabolic studies. Gut 20:484–488, 1979Google Scholar
  16. 16.
    Krebs HA, Henseleit K: Untersuchungen über die harnstoffbildung im tierkörper. Hoppe-Seyler' Z Physiol Chem 210:33–66, 1932Google Scholar
  17. 17.
    Sigma Catalog: Tissue culture media and reagents. Sigma chemical Co., St. Louis, Missouri, 1997, pp 1752–1753Google Scholar
  18. 18.
    Cline JD: Spectrophotometric determination of hydrogen sul-fide and reducible sulfide in natural waters. Limnol Oceanogr 14:454–458, 1969Google Scholar
  19. 19.
    Zijlstra JB, Beukema J, Wolthers BG, Byrne BM, Groen A, Donkert L: Pretreatment methods prior to gas chromatographic analysis of volatile fatty acids from faecal samples. Clin Chim Acta 78:243–250, 1977Google Scholar
  20. 20.
    Williamson DH, Mellanby J: D-3-Hydroxybutyrate. In Methods of Enzymatic Analysis. HU Bergmeyer (ed). New York, Academic Press, 1974, pp 1836–1839Google Scholar
  21. 21.
    Mellanby J, Williamson DH: Acetoacetate. In Methods of Enzymatic Analysis. HU Bergmeyer (ed). New York, Academic Press, 1974, pp 1840–1843Google Scholar
  22. 22.
    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
  23. 23.
    Gibson GR, Cummings JH, Macfarlane GT, Alison C, Segal I, Vorster HH, Walker ARP: Alternative pathways for hydrogen disposal during fermentation in the human colon. Gut 31:679–683, 1990Google Scholar
  24. 24.
    Strocchi A, Furne JK, Levitt MD: A modification of the methylene blue method to measure bacterial sulfide production in feces. J Microbiol Methods 15:75–82, 1992Google Scholar
  25. 25.
    Darcy-Vrillon B, Cherbuy C, Morel M-T, Durand M, Dueé P-H: Short chain fatty acid and glucose metabolism in isolated pig colonocytes: modulation by NH4 +. Moll Cell Biochem 156:145–151, 1996Google Scholar
  26. 26.
    Suarez FL, Furne JK, Springfield J, Levitt MD: Bismuth subsalicylate markedly decreases hydrogen sulfide release in the human colon. Gastroenterology 114:923–929, 1998Google Scholar
  27. 27.
    Pullan RD, Ganesh S, Mani V, Morris J, Evans BK, Williams GT, Rhodes J: Comparison of bismuth citrate and 5-aminosalicylic acid enemas in distal ulcerative colitis: A controlled trial. Gut 34:676–679, 1993Google Scholar
  28. 28.
    Fine KD, Lee EL: Efficacy of open-label bismuth subsalicylate for the treatment of microscopic colitis. Gastroenterology 114:29–36, 1998Google Scholar
  29. 29.
    Moore JWE, Roediger WEW, Babidge WJ: Colonic luminal hydrogen sulphide is not elevated in ulcerative colitis. Dig Dis Sci 43:162–165, 1998Google Scholar
  30. 30.
    Martensson J: The effects of short-term fasting on the excretion of sulfur compounds in healthy subjects. Metabolism 31:487–492, 1982Google Scholar
  31. 31.
    Jørgensen JR, Clausen MR, Mortensen PB: Oxidation of short-and medium-chain C2-C8 fatty acids in Sprague-Dawley rat colonocytes. Gut 40:400–405, 1997Google Scholar
  32. 32.
    Moore JW, Millard S, Babidge W, Rowland R, Roediger WE: Hydrogen sulphide produces diminished fatty acid oxidation in the rat colon in vivo: Implications for ulcerative colitis. Aust NZ J Surg 67:245–249, 1997Google Scholar
  33. 33.
    Pitcher MC, Beatty ER, Cummings JH: The contribution of sulphate reducing bacteria and 5-aminosalicylic acid to faecal sulphide in patients with ulcerative colitis. Gut 46:64–72, 2000Google Scholar

Copyright information

© Plenum Publishing Corporation 2001

Authors and Affiliations

  • Jimmy Jørgensen
    • 1
  • Per Brøbech Mortensen
    • 1
  1. 1.Department of Medicine CA 2121, Section of GastroenterologyCopenhagen University Hospital, The RigshospitalCopenhagenDenmark

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