Human milk inhibits the diarrhea associated with the stable toxin (ST) of Escherichia coli in the suckling mouse, an established model for ST activity in humans. During the past five years, we have isolated the single component of human milk responsible for this activity, and have partially characterized this molecule. It is a small fucosylated oligosaccharide, which we have designated QV, pending its structural definition. Over the next five years, we propose to perform the following: a) Isolate and fully characterize the molecular structure of QV b) Determine the mechanism whereby QV protects against ST c) Develop an analytical method for measuring QV levels in milk d) Test the relationship between QV levels in milk and ST-related disease in the nursling e) Synthesize QV, or find suitable alternate natural sources f) Test the efficacy of QV in preventing ST-related disease in humans. Thus, the overall direction of this project is to move from a clinical observation (lower incidence of gastroenteritis in breastfed infants) to the isolation and characterization of a specific non-immunoglobulin human milk factor that inhibits ST-induced secretory diarrhea in the infant mouse model, to understanding its mechanism of action, producing large amounts of the active factor, and testing its efficacy in preventing gastroenteritis in a human population. this work not only directly addresses the problem of ST-related diarrhea, but is a model for a potential role for other putative pathogen receptor analogs from human milk which protect nursing infants from enteric pathogens.
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