A montmorillonite-based oral fermentation system enables long-lasting in-situ biosynthesis to restore intestinal homeostasis.

The disruption of intestinal homeostasis represents a hallmark of different diseases. Here, we report a montmorillonite-based oral fermentation system (MOFS) that achieves long-lasting in-situ preparation of beneficial bioproducts for intestinal homeostasis restoration. MOFS is fabricated by loading metabolic substrates in the lamellar structure of montmorillonite via cation replacement and adsorbing the substrate-related bacteria through electrostatic interactions. The water-impermeable property and mucoadhesive ability of montmorillonite endow MOFS with high oral availability and extended retention in the gut. The continuous release of loaded substrates and the formation of biofilms by carried bacteria enable long-term yet efficient synthesis of beneficial metabolites in the intestine, which comprehensively improve gut microbiota composition, suppress intestinal inflammation, and increase the integrity of the gut barrier. In murine models of imbalanced intestinal homeostasis, MOFS demonstrates superior efficacies by alleviating the associated symptoms, even in comparison to clinical therapeutics.