pH-Responsive Hydrogels Encapsulating Solubilized Ellagic Acid Enhance Microbial Conversion to Urolithin A

Abstract Microbial conversion of poorly soluble ellagic acid (EA) to urolithin A (UroA) is limited by poor aqueous performance and gastrointestinal presentation. Here, we combined pH-shift-assisted sono-assembly with CaCO3/GDL-mediated internal gelation to integrate EA physicochemical-state modification with gastrointestinal delivery. Solubilized EA (sEA) showed improved aqueous retention and equilibrium solubility, while pH-responsive alginate encapsulation restricted gastric release to below 15% and enhanced EA preservation during digestion. The 1.5% alginate internal-gelation hydrogel encapsulating sEA (IG1.5%@sEA) retained 88.21% of EA after digestion and produced the highest UroA concentration (36.86 μg/mL at 48 h) with urolithin metabotype A microbiota. Comparisons with sEA and IG1.5%@EA, together with fermentation at the same postdigestion EA concentrations, showed that both gastrointestinal preservation and the physicochemical state of EA after solubilization contributed to enhanced microbial conversion. These findings support delivery systems coordinating gastrointestinal protection with control of substrate physicochemical state to enhance microbial conversion of poorly soluble polyphenols.