Hydrogen Sulfide and Colonic Epithelial Metabolism

Abstract

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.