Inulin hydrogel microspheres delivering catalase-modified probiotics for inflammatory bowel disease therapy

Abstract Probiotic-mediated gut microbiota regulation therapy holds great potential for the treatment of inflammatory bowel disease. However, harsh gastric conditions and persistent inflammation and oxidative stress in diseased intestines reduce probiotic survival and intestinal retention, severely compromising therapeutic efficacy. Herein, we fabricated inulin hydrogel microspheres encapsulating catalase-modified probiotics. This system alleviates the oxidative stress microenvironment in diseased intestinal tracts and regulates gut microbiota via the prebiotic effects of inulin, thereby achieving therapeutic effects against inflammatory bowel disease. First, the coordination complexation between tannic acid and ferric ions as well as intermolecular hydrogen bonds were utilized to stably immobilize catalase on the surface of probiotic bacteria. Subsequently, the modified probiotics were encapsulated within covalently crosslinked methacrylated inulin hydrogel microspheres via emulsion polymerization. Experimental results demonstrated that the functionalized microsphere system significantly mitigates intestinal oxidative injury, boosts the viability of probiotics under inflammatory stress, alleviates intestinal inflammation, reconstructs impaired intestinal barriers, and rebalances gut microbiota in animal models. Combining antioxidant modification with hydrogel microsphere delivery, this work establishes an innovative probiotic therapeutic platform, providing novel insights for adjuvant therapy of inflammatory bowel disease.