Modified montmorillonite armed probiotics with enhanced on-site mucus-depleted intestinal colonization and H2S scavenging for colitis treatment

Inflammatory bowel diseases (IBD) are often associated with dysregulated gut microbiota and excessive inflammatory microenvironment. Probiotic therapy combined with inflammation management is a promising approach to alleviate IBD, but the efficacy is hindered by the inferior colonization of probiotics in mucus-depleted inflammatory bowel segments. Here, we present modified montmorillonite armed probiotic Escherichia coli Nissle 1917 (MMT-Fe@EcN) with enhanced intestinal colonization and hydrogen sulfide (H 2 S) scavenging for synergistic alleviation of IBD. The montmorillonite layer that can protect EcN against environmental assaults in oral delivery and improve on-site colonization of EcN in the mucus-depleted intestinal segment due to its strong adhesive capability and electronegativity, with a 22.6-fold increase in colonization efficiency compared to EcN. Meanwhile, MMT-Fe@EcN can manage inflammation by scavenging H 2 S, which allows for enhancing probiotic viability and colonization for restoring the gut microbiota. As a result, MMT-Fe@EcN exhibits extraordinary therapeutic effects in the dextran sulfate sodium-induced mouse colitis models, including alleviating intestinal inflammation and restoring disrupted intestinal barrier function, and gut microbiota. These findings provide a promising strategy for clinical IBD treatment and potentially other mucus-depletion-related diseases.