Biofilm Armor: A Novel Approach for Enhancing Probiotic Efficacy in Ulcerative Colitis Treatment

Ulcerative colitis (UC) is primarily associated with disruptions in the intestinal barrier function and dysbiosis of the gut microbiota. Utilizing probiotics to modulate intestinal barrier integrity and restore gut microbiota balance has emerged as a promising approach for both preventing and treating UC. Nonetheless, the harsh gastrointestinal (GI) environment and rapid passage of body fluids often reduce the viability and colonization of unencapsulated probiotics in the gut. Drawing inspiration from the protective properties of biofilms, we utilized a self- produced biofilm to act as a protective "armor" for the probiotic strain <em>Bacillus paralicheniformis</em>, enhancing its tolerance to the GI tract and its ability to colonize sites of inflammatory bowel disease. In our approach, the biofilm-coated <em>B. paralicheniformis</em> (BCBP) demonstrated significant therapeutic efficacy in UC mice. Compared to uncoated <em>B. paralicheniformis</em> (BP), BCBP exhibited a 4.3-fold increase in survival rate following a 2-hour exposure to simulated gastric fluid. Moreover, BCBP colonization at sites of intestinal inflammation was 2.7-fold higher than that of BP. Importantly, the extracellular polymeric substances within the biofilm bolstered the strain's ability to fortify the intestinal barrier, mitigate inflammation, and restore gut microbiota balance, thereby exerting a synergistic effect in alleviating UC symptoms. In summary, this study not only offers a bio-inspired delivery strategy with strong potential for the treatment of UC, but also proposes a novel paradigm for the delivery of probiotics in the form of biofilms.