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In vitro digestion and fermentation of 5-formyl-aminosailcylate-inulin: A potential prodrug of 5-aminosalicylic acid

Hartzell, Annette L., Maldonado-Gómez, María X., Yang, Junyi, Hutkins, Robert W., Rose, Devin J.
Bioactive carbohydrates and dietary fibre 2013 v.2 no.1 pp. 8-14
bacteria, butyrates, colon, dietary fiber, drugs, esterification, fermentation, in vitro digestion, inflammation, inflammatory bowel disease, intestinal microorganisms, inulin, polymers, short chain fatty acids
Many carbohydrate polymers that have been used as carriers for colon-targeted drugs have shown benefits against colonic diseases. The objectives of this project were to (1) synthesize a derivative of 5-aminosalicylic acid (5-ASA), a drug used to treat inflammatory bowel disease, containing inulin, a carbohydrate polymer that has shown benefits against inflammatory bowel disease; (2) quantify the release of 5-ASA from the conjugate during in vitro digestion and fermentation; and (3) determine the in vitro fermentation properties of the conjugated inulin. Inulin was esterified with 5-formyl-aminosalicylic acid (5-fASA), a derivative of 5-ASA, with a degree of substitution of 0.185±0.014. During in vitro digestion and fermentation, 56.2±6.5% of 5-fASA was released in 24h. Gut bacteria did not deformylate 5-fASA to 5-ASA as anticipated. Though conjugation of inulin with 5-fASA reduced bifidogenicity at 24h compared with native inulin (8.26±0.03logcfu/g versus 8.59±0.09logcfu/g, respectively, p<0.01), conjugated 5-fASA-inulin showed protracted fermentation with higher short chain fatty acid (SCFA) and equivalent butyrate concentration at 24h (9.02±0.68μmol SCFA/mg carbohydrate versus 7.54±0.53μmol SCFA/mg carbohydrate, p<0.01; 2.16±0.22μmol butyrate/mg carbohydrate versus 2.34±0.17μmol butyrate/mg carbohydrate, respectively, p=0.09). These data suggest that conjugation of inulin with 5-fASA may support SCFA and especially butyrate-producing bacteria through inulin fermentation in the distal colon, an important site of inflammation, together with delivery of 5-fASA. However, gut bacteria were unable to hydrolyze the formyl group from 5-fASA; thus alternative strategies to conjugate 5-ASA to inulin or remove the formyl group from 5-fASA are needed.