Valerylated high-amylose maize starch enabling colon-targeted valerate delivery: Synthesis, characterization, and impact on gut health

Valerate, a postbiotic metabolite derived from gut microbiota, has demonstrated positive impacts on inflammation and metabolism. However, the development of valerate into a drug has been hindered by its poor oral bioavailability. Here, we report that the oral bioavailability of valerate can be improved by conjugating it with high-amylose maize starch (HAMS) to form valerylated HAMS (HAMSV). As a dietary fiber carrier, HAMS resists upper gastrointestinal digestion, reaching the colon where microbial degradation releases the loaded valerate. A series of HAMSV with varying degree of substitution (DS) from 0.1 to 0.55 were synthesized, and the physicochemical properties were thoroughly characterized. In vitro digestion study showed that RS levels for HAMSV of DS 0.2, 0.35, and 0.55 increased from 50.9% (in HAMS) to 64.8%, 71.1%, and 78.8%, respectively, supporting their potential for colon-targeted valerate delivery. In vivo, HAMSV effectively raised colonic valerate levels, with DS 0.35 identified as optimal. Specifically, mice fed 5% HAMSV (DS 0.35) had an approximately 19.9-fold increase in fecal valerate concentration versus Control group. High-dose HAMSV markedly alleviated murine colitis and increased beneficial gut microbiota, showing superior efficacy to oral sodium valerate. As an ideal colon-targeted valerate delivery system, HAMSV holds considerable promise for treating inflammatory diseases.