Gastrointestinal and Microbial Responses to Sulfate-Supplemented Drinking Water in Mice

Abstract

There is increasing evidence that hydrogen sulfide (H₂S), produced by intestinal sulfate-reducing bacteria (SRB), may be involved in the etiopathogenesis of chronic diseases such as ulcerative colitis and colorectal cancer. The activity of SRB, and thus H₂S production, is likely determined by the availability of sulfur-containing compounds in the intestine. However, little is known about the impact of dietary or inorganic sulfate on intestinal sulfate and SRB-derived H₂S concentrations. In this study, the effects of short-term (7 day) and long-term (1 year) inorganic sulfate supplementation of the drinking water on gastrointestinal (GI) sulfate and H₂S concentrations (and thus activity of resident SRBs), and the density of large intestinal sulfomucin-containing goblet cells, were examined in C3H/HeJBir mice. Additionally, a PCR-denaturing gradient gel electrophoresis (DGGE)-based molecular ecology technique was used to examine the impact of sulfate-amended drinking water on microbial community structure throughout the GI tract. Average H₂S concentrations ranged from 0.1 mM (stomach) to 1 mM (cecum). A sulfate reduction assay demonstrated in situ production of H₂S throughout the GI tract, confirming the presence of SRB. However, H₂S generation and concentrations were greatest in the cecum and colon. Sulfate supplementation of drinking water did not significantly increase intestinal sulfate or H₂S concentrations, suggesting that inorganic sulfate is not an important modulator of intestinal H₂S concentrations, although it altered the bacterial profiles of the stomach and distal colon of 1-year-old mice. This change in colonic bacterial profiles may reflect a corresponding increase in the density of sulfomucin-containing goblet cells in sulfate-supplemented compared with control mice.