Gastrointestinal-Responsive Jelly Fig–Alginate Microgels for Restoring Intestinal Barrier Homeostasis through Microbiota–Metabolite Remodeling

Abstract Oral biomaterials capable of protecting natural bioactives during gastrointestinal transit while restoring intestinal barrier function offer a promising strategy for inflammatory bowel disease intervention. Here, we developed edible Jelly Fig (Ficus awkeotsang Makino, JF) pectin–alginate composite microgels (Mgel) through Ca2+-mediated ionic crosslinking as a gastrointestinal-responsive oral biomaterial. The resulting microgels exhibited uniform spherical morphology, enhanced mechanical robustness, gastric stability, and intestinal responsiveness, thereby improving the delivery performance of JF-derived bioactive components. Phytochemical and HPLC analyses showed that the ethanol-soluble fraction of JF was enriched in phenolic constituents and displayed potent antioxidant, anti-inflammatory, and epithelial barrier-protective effects in macrophage and intestinal epithelial cell models. In dextran sulfate sodium-induced colitis mice, orally administered Mgel showed superior protective efficacy compared with unformulated JF hydrogel at an equivalent dose, as evidenced by reduced body weight loss, disease activity, colon shortening, histological injury, inflammatory cytokine production, oxidative stress, and intestinal permeability. Mgel further restored mucus and tight junction barrier markers, promoted epithelial regeneration, and improved mucosal healing. Moreover, 16S rRNA sequencing combined with targeted metabolite profiling revealed that Mgel remodeled the gut microbiota, enriched beneficial taxa such as Lactobacillus and Akkermansia, and restored short-chain fatty acid and secondary bile acid metabolism. These findings demonstrate that Jelly Fig–alginate microgels serve as a food-grade, gastrointestinal-responsive oral biomaterial platform for coordinated restoration of epithelial barrier integrity and microbiota–metabolite homeostasis in colitis.