Gastrointestinal\nSelf-Adaptive and Nutrient Self-Sufficient <i>Akkermansia muciniphila</i>–Gelatin Porous Microgels\nfor Synergistic Therapy of Ulcerative Colitis

To realize effective and long-term synergistic therapy\nof ulcerative\ncolitis (UC) with probiotics, we developed gastrointestinal self-adaptive\nand nutrient self-sufficient <i>Akkermansia muciniphila</i> (AKK)–gelatin porous microgels (AKK@GPMGs). In AKK@GPMGs,\nAKK was covered with sequential layers of proanthocyanidins (PAs),\nmucin (MUC), and phosphatidylcholine (PC) to obtain AKK@PAs-MUC-PC\n(AKK@PMP), and then encapsulated within the methacrylate-modified\ngelatin porous microgels. AKK@GPMGs provide sufficient mucus as a\nnutrition source for AKK and boost resistance to stomach acid by 30.49-fold,\nand colonization in the intestines is enhanced by 83.46 times. The\nmicrogels can be dissociated by matrix metalloproteinase at the inflammatory\nsites of the intestine, and release AKK@PMP, which acts as “band-aid”\nthat adheres to the inflamed colon for a long time and offers improved\nsynergistic therapy for UC. Compared to uncoated AKK, AKK@GPMGs increase\nreactive oxygen species scavenging capacity by 26.47 times, improve\nthe intestinal mucus layer thickness by 5.63 times, increase the goblet\ncells abundance by 3.93 times, reduce intestinal permeability by 5.60\ntimes and significantly enhance beneficial gut microbiota while repressing\nharmful microbiota. These results indicate that AKK@GPMGs can restore\nmucus layer and tight junction integrity, reduce inflammation and\noxidative stress, and regulate gut microbiota homeostasis to effectively\ntreat intestinal inflammation.