Hydrogen sulfide and colonic epithelial metabolism - Implications for ulcerative colitis

Hydrogen sulfide (HS-) impairs the oxidation of butyrate in colonocytes and is found in excess in feces of patients with ulcerative colitis. The possi ble pathogenic role of HS- in ulcerative colitis was further investigated. To investigate the metabolic effect of free and bound fecal HS-, isolated r at colonocytes were incubated in the presence of butyrate without and with the addition of (1) HS- in water, (2) sterile filtrates of fecal homogenate s supplemented and incubated with HS- and known sources of fecal HS- produc tion, 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 incuba ted with 2 mmol/liter of butyrate, the further addition of 1.25 and 2.5 mmo l/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 homogen ate supplemented with HS- corresponding to 1.25 and 2.5 mmol/liter of HS- i n 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 a ctive ulcerative colitis. Bound HS- had no or little effect on CO2 producti on. Addition of fecal filtrate of nonsupplemented homogenate to colonocytes significantly reduced the oxidation of butyrate to CO2 about 25%, which co uld not be ascribed to fecal HS-. In conclusion, fecal HS- has little effec t on butyrate oxidation in colonocytes and does not seem to play a pathogen ic role for UC by impairing colonic epithelial metabolism. Other fecal agen ts seem to be more potent metabolic inhibitors than fecal HS-. The role of colonic contents in the pathogenesis of ulcerative colitis remains circumst antial.