Orally Administrable H2S‐Scavenging Metal–Organic Framework Prepared by Co‐Flow Microfluidics for Comprehensive Restoration of Intestinal Milieu

Abstract Intestinal milieu disorders are strongly related to the occurrence of inflammatory bowel diseases (IBDs), which results from mucosa destruction, epithelium disruption, and tight junction (TJ) proteins loss. Excess of H 2 S in the intestinal milieu produced by the sulfate‐reducing bacteria metabolism contributes to development of IBDs via epithelial barrier breakdown. Conventional interventions, such as surgery and anti‐inflammatory medications, are considered not completely effective because of frequent recurrence and other complications. Herein, a novel oral delivery system, a hydroxypropyl methylcellulose acetate succinate (HPMCAS)‐based polymer‐coated Zr‐based metal–organic framework (UiO‐66) with a Cu x ‐rhodamine B (CR) probe (hereinafter referred to as HUR), is produced via a co‐flow microfluidic approach with the ability to reduce H 2 S levels, thus restoring the intestinal lumen milieu. HPMCAS serves as an enteric coating that exposes UiO‐66@CR at the pH of the intestine but not the acidic pH of the stomach. The synthesized HUR exhibits notable therapeutic efficacy, including mucosa recovery, epithelium integrity restoration, and TJ proteins upregulation via H 2 S scavenging to protect against intestinal barrier damage and microbiome dysbiosis. Thus, HUR is verified to be a promising theranostic platform able to decrease the H 2 S content for intestinal milieu disorder treatment. The presented study therefore opens the door for further exploitation for IBDs therapy.