RESUMEN
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 (H2S) 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 H2S, 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.
RESUMEN
The effective delivery and colonization of probiotics are recommended for therapeutic interventions during colitis, the efficacy of which is hampered by abnormally colonized Enterobacteriaceae at pathological sites. To improve the delivery and colonization of probiotics, a calcium tungstate microgel (CTM)-based oral probiotic delivery system is proposed herein. CTM can selectively disrupt the ecological niche occupied by abnormally expanded Enterobacteriaceae during colitis to facilitate probiotic colonization. In addition, the calcium-binding protein, calprotectin, which is highly expressed in colitis, efficiently extracts calcium from CTM and releases tungsten to inhibit Enterobacteriaceae by displacing molybdenum in the molybdenum enzyme, without affecting the delivered probiotics. Moreover, CTM demonstrated resistance to the harsh environment of the gastrointestinal (GI) tract and to intestinal adhesion. The synergistic reduction of Enterobacteriaceae by 45 times and the increase in probiotic colonization by 25 times, therefore, result in a remarkable treatment for colitis, including restoration of colonic length, effective downregulation of the inflammatory response, restoration of the damaged mucosal barrier, and restoration of gut microbiome homeostasis.
RESUMEN
Therapeutic approaches that reprogram the gut microbiome are promising strategies to alleviate and cure inflammatory bowel disease (IBD). However, abnormal expansion of Escherichia coli during inflammation can promote pathogenic bacteria occupying ecological niches to resist reprogramming of the microbiome. Herein, a bionic regulator (CaWO4 @YCW) is developed to efficiently and precisely regulate the gut microbiome by specifically suppressing the abnormal expansion of E. coli during colitis and boosting probiotic growth. Inspired by the binding of E. coli strains to the mannose-rich yeast cell wall (YCW), YCW is chosen as the bionic shell to encapsulate CaWO4 . It is demonstrated that the YCW shell endows CaWO4 with superior resistance to the harsh environment of the gastrointestinal tract and adheres to the abnormally expanded E. coli in colitis, specifically as a positioner. Notably, the high expression of calprotectin at the colitis site triggers the release of tungsten ions through calcium deprivation in CaWO4 , thus inhibiting E. coli growth by replacing molybdenum in the molybdopterin cofactor. Moreover, YCW functions as a prebiotic and promotes probiotic growth. Consequently, CaWO4 @YCW can efficiently and precisely reprogram the gut microbiome by eliminating pathogenic bacteria and providing prebiotics, resulting in an extraordinary therapeutic advantage for DSS-induced colitis.