Probiotic-based self-crosslinking bio-coating for the treatment of colitis by increasing probiotic colonization

Probiotic-based therapies have great potential to treat inflammatory bowel disease (IBD). Still, their success is limited by difficulties in ensuring survival, colonization, and targeted effects within the harsh environment of the gastrointestinal tract. This study presents a bio-coated probiotic strategy for treating colitis in mice, using self-crosslinking mussel adhesive protein (Map) to form a protective layer around Bifidobacterium longum (BL). Because Map contains abundant lysine residues that confer positive charges, it interacts electrostatically with negatively charged alginate (Alg) to form the BL@Map@Alg formulation. Compared to uncoated BL, BL@Map@Alg increased survival under oxygen exposure by 19.6-fold, showed a 76.8-fold increase in resistance to simulated stomach acid, and exhibited a 6.2-fold boost in intestinal colonization. It also demonstrated superior ROS scavenging ability, decreasing ROS levels by 41.1%. In a mouse colitis model, BL@Map@Alg reduced weight loss, colon shortening, and inflammatory cytokines compared to untreated colitis. It also helped restored intestinal barrier function by increasing the levels of tight junction proteins ZO-1 and claudin-1, which were diminished in DSS-treated mice. 16S rRNA sequencing showed that BL@Map@Alg lowered Escherichia abundance from 27.5% to 0.042% while increasing Akkermansia from 0.73% to 9.3%. These results highlight the potential for BL@Map@Alg to enhance probiotic therapy by improving survival, colonization, and gut microbiota, offering a promising strategy for personalized and precision medicine. Schematic illustration of the synthesis of multifunctional bio-coated probiotics (BL@Map@Alg) and their therapeutic mechanism for colitis treatment. (A) Preparation process of BL@Map@Alg. (B) Schematic illustration of the intestinal adhesion mechanism of BL@Map@Alg. In the gastric environment, sodium alginate undergoes ion exchange (Na + replaced by H + ), resulting in reduced solubility that protects the probiotics. In the intestine, mussel adhesive protein promotes the adhesion of probiotics to the mucosal surface through hydrogen bonding, π–π interactions, and coordination with metal ions, thereby enhancing their colonization capacity. (C) Schematic illustration of the therapeutic mechanism of BL@Map@Alg, including modulation of gut microbiota, suppression of pro-inflammatory cytokine expression, and restoration of the intestinal barrier. • A self-crosslinking bio-coating with Bifidobacterium longum constructs a multifunctional therapeutic platform with targeting, adhesion, and anti-inflammatory properties. • A self-crosslinking bio-coating enhances Bifidobacterium longum survival and colonization, enabling long-term storage and applicability to anaerobic strains. • Probiotic-based self-crosslinking bio-coating confers multi-modal therapeutic effects including barrier repair, anti-inflammation, and microbiota remodeling.