Aquaculture is the fastest growing food-producing sector in the world and accounts for approximately 50% of the seafood consumed throughout the world. However, the demand for farm raised fish has pushed fish production densities to new limits and this has increased the incidence and spread of disease. There have been very few drugs developed for treating and preventing diseases in fish. We have discovered that a family of compounds called cyclodextrins (cyclicoligosaccharides) are extremely potent stimulators of the fish innate immune system and can protect against lethal lipopolysaccharide challenge. We propose to use these compound asimmuno modulators to treat aqua cultured fish in the diet to enhance their defense against pathogens. These compounds are stable and water-soluble and are classified by the FDA to be Generally Recognized As Safe as food additives. However, before developing this compound further, we need to demonstrate that cyclodextrins can protect fish against a live pathogen challenge. Thus, the primary objective of this proposal is to treat rainbow trout with a cyclodextrin-containing diet and then challenge with a bacterial (Vibrio anguillarum) pathogen and determine the level of protection. Diamond V, a manufacturer of fermented products for a variety of purposes including aquaculture, is developing a novel in-feed technology containing specific metabolites produced through a natural microbial fermentation processes. The research in the current proposal will help Diamond V produce a novel product for enhancing fish health that contains CycloDextrins, which are naturally occurring bacterial fermentation products.