Autonomously Assembled Living Capsules by Microbial Coculture for Enhanced Bacteriotherapy of Inflammatory Bowel Disease

Abstract

Microorganism-mediated self-assembling of living formulations holds great promise for disease therapy. Here, we constructed a prebiotic-probiotic living capsule (PPLC) by coculturing probiotics (EcN) with <i>Gluconacetobacter xylinus</i> (<i>G. xylinus</i>) in a prebiotic-containing fermentation broth. Through shaking the culture, <i>G. xylinus</i> secretes cellulose fibrils that can spontaneously encapsulate EcN to form microcapsules under shear forces. Additionally, the prebiotic present in the fermentation broth is incorporated into the bacterial cellulose network through van der Waals forces and hydrogen bonding. Afterward, the microcapsules were transferred to a selective LB medium, which facilitated the colonization of dense probiotic colonies within them. The <i>in vivo</i> study demonstrated that PPLC-containing dense colonies of EcN can antagonize intestinal pathogens and restore microbiota homeostasis by showing excellent therapeutic performance in treating enteritis mice. The <i>in situ</i> self-assembly of probiotics and prebiotics-based living materials provides a promising platform for the treatment of inflammatory bowel disease.