Oral Targeted MXenzyme – Armed Probiotic Regulates Intestinal Redox and Microbiota Homeostasis to Synergistically Ameliorate Ulcerative Colitis

Abstract Ulcerative colitis (UC) leads to complex alterations in the intestinal microenvironment, with gut microbiota dysbiosis and excessive reactive oxygen species (ROS) being major drivers. Previously, microecological preparations have been used to restore intestinal homeostasis and demonstrated considerable potential; however, efficacy is hindered due to the hostile environment in the gastrointestinal tract and high ROS levels at lesion sites. Accordingly, a multienzyme mimicking vanadium carbide (V2C) MXenzyme armored colon‐colonizing Akkermansia muciniphila (Akk) probiotic is designed to synchronously alleviate inflammation and regulate the microbiota. V2C is induced on boron hydroxyl groups and coated onto the probiotic via boronic acid vicinal‐diol‐based click reactions and called Akk@V2C. Akk@V2C targets UC lesional sites via Akk colonizing capabilities and electrostatic interactions. Akk@V2C effectively scavenges ROS and enhances Akk colonialization in a UC mouse model and colon tissue biopsies from patients with UC. Furthermore, Akk@V2C exhibits notable curative effects by alleviating inflammation, reprogramming macrophage polarization, and regulating microbiota homeostasis, thus promoting short chain fatty acid production and restoring intestinal barriers. Moreover, this approach exerts a negligible impact on bacterial viability and has shown potential to other probiotics. Collectively, given its flexibility and favorable biocompatibility, this approach is promising for probiotic and biomaterial delivery in biomedical applications.