Therapeutic Carbohydrate Esters for Improved Gut Health

Inulin is a dietary fiber that is resistant to digestion, but is fermented by bacteria in the colon. As a prebiotic, inulin enhances the growth of two important genera of beneficial bacteria, Bifidobacterium and Lactobacillus, when fermented in the gut. This bacterial fermentation leads to the production of short chain fatty acids (SCFAs), principally acetate, propionate, and butyrate. Butyrate is especially health-promoting, and has been shown to treat the symptoms of inflammatory bowel disease (IBD). 5-Aminosalicylic acid (5-ASA) is also effective against IBD and is the standard treatment. SCFAs and 5-ASA must be encapsulated or conjugated to a carrier molecule to prevent upper gastrointestinal absorption and reach their site of action in the colon. Thus far, carrier molecules have not been investigated as therapeutic agents. The present thesis describes research on the creation of novel and improved delivery systems for 5-ASA and SCFAs based upon their attachment to the beneficial dietary fiber, inulin. Acetate, propionate, and butyrate were esterified to inulin in the first study, and 5-formyl-ASA (5-fASA) was esterified to inulin in the second. In both studies, the conjugates were subjected to in vitro digestion and fermentation. The release of SCFAs and 5-ASA, and the growth of Bifidobacteria and Lactobacilli, were quantified. The inulin conjugates were generally stable throughout digestion, and the SCFAs and 5-fASA were released by bacterial fermentation. Acylation of the inulin decreased its ability to enhance the growth of Bifidobacteria and Lactobacilli, but the addition of fructooligosaccharides to the acylated inulin during fermentation alleviated this issue. Advisors: Devin J. Rose and Robert W. Hutkin