Our research concerns host-intestinal microbiota interactions as they pertain to inflammatory disorders and colorectal cancer. Specific focus of current efforts include:
- Defining molecular and cellular mechanisms underlying host mucogenic responses to external stimuli and determining the extent to which goblet cells participate in innate defense responses and serve as the guardians of redox homeostasis in the intestinal mucosa; and
- Defining the role of sulfate-reducing bacteria (SRB) in the initiation or progression of chronic human intestinal disorders.
Sulfate-reducing bacteria are members of the normal intestinal microbiota and have a major impact on terminal fermentative processes that occur in the mammalian colon. The metabolic pathways used by SRB culminate in the production of the toxic gas hydrogen sulfide. Using novel reagents and approaches for studying both SRBs and host epithelial cell responses to sulfide, we have demonstrated that host sulfomucins are a likely key source of sulfate for dissimilatory sulfate respiration by SRBs and that sulfide is genotoxic. Accordingly, we are exploring the working model that multifactorial interactions between polymorphic genes (alleles) that influence SRB colonization and those that influence epithelial responses to the environmental agent sulfide may contribute to IBD-associated or sporadic colorectal cancer.
