Double-layer probiotic encapsulation for enhanced bacteriotherapy against inflammatory bowel disease

Inflammatory bowel disease (IBD) is inflammatory intestinal disorders associated with dysregulated gut microbiota. Bacteriotherapy that leverages bacteria as therapeutics has shown tremendous promise in resolving gut dysbiosis and reducing inflammatory mediators to treat IBD. Orally delivered probiotics, such as Escherichia coli Nissle 1917 (EcN), can produce beneficial ingredients, competitively inhibit the proliferation of pathogens, and promote the restoration of gut microbiome homeostasis. However, environmental stresses (such as gastric acids) in the gastrointestinal (GI) tract pose an enormous challenge to the probiotics following oral administration, leading to decreases in viability and activity of probiotics. Meanwhile, the inferior mucoadhesive capability of probiotics results in low colonization efficacy, further compromising their therapeutic effect. Coating probiotics with functional biomaterials may protect them from elimination and prolong their retention in the GI tract. Here, we developed a facile double-layer electrostatic assembly technique to encapsulate EcN bacteria in protective layers of mucoadhesive chitosan (CS) and immunomodulatory hyaluronic acid (HA) to generate HA-CS-EcN. These biomaterials confer the coated EcN resistance to environmental assault and enhanced mucoadhesion in the GI tract. The probiotics equipped with the multifunctional shield can thus suppress inflammation and reshape the intestinal microenvironment to enhance therapeutic efficacy for the prevention and treatment of IBD. Collectively, this study presents a novel probiotic coating strategy to augment the outcome of bacteriotherapy to combat IBD.