The idiopathic inflammatory bowel diseases (IBD), Crohn's disease and ulcerative colitis, afflict approximately 0.1% of the population of the western world and result from multifactorial interactions between IBD susceptibility genes and environmental agents. The working model of this proposal addresses the role of sulfate-reducing bacteria (SRB) in the initiation and progression of IBD. Sulfidogenic bacteria are members of the normal intestinal microbiota and are characterized by their ability to use sulfate as a terminal electron acceptor, culminating in the production of the toxic gas hydrogen sulfide (H2S). The investigator postulates that exogenous sulfate can enhance H2S production and thereby trigger colonic inflammation. They further propose that IBD may reflect a predisposing genetic background that causes abnormal sensitivity to SRB-generated H2S. Damage of the colonic epithelium by H2S would promote translocation of bacterial and food antigens, resulting in inflammatory responses to normally benign antigens, an outcome consistent with much circumstantial data and the histopathological features of IBD. The experimental approach uses a novel molecular ecology strategy to examine the development of SRB population in the mouse intestine and to define the effects of drinking water sulfate on their diversity and metabolic activities. A mouse model of IBD is then used to test the hypothesis that drinking water sulfate can trigger colonic inflammation through bacterial H2S production. Confirmation of a role for bacterial-generated sulfide in experimental colitis would represent the first conclusive evidence for environmental modulation of normal gut bacteria contributing to a genetically encoded inflammatory disorder. That finding would intensify efforts to obtain corroborative data from human subjects and would present a novel target for prophylactic or therapeutic treatments for IBD.
| Deplancke, Bart; Finster, Kai; Graham, W Vallen et al. (2003) Gastrointestinal and microbial responses to sulfate-supplemented drinking water in mice. Exp Biol Med (Maywood) 228:424-33 |
| Deplancke, B; Hristova, K R; Oakley, H A et al. (2000) Molecular ecological analysis of the succession and diversity of sulfate-reducing bacteria in the mouse gastrointestinal tract. Appl Environ Microbiol 66:2166-74 |
