Hydrogen Sulfide and Colonic Epithelial Metabolism

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.