Subcellular Localization Dictates Therapeutic Function: Spatially Targeted Delivery of Amuc_1100 by Engineered <i>Lacticaseibacillus paracasei</i> L9 Enhances Intestinal Barrier in Colitis.

ABSTRACT: Background/Objectives: Impaired intestinal barrier function is a hallmark of inflammatory bowel disease (IBD). Akkermansia muciniphila and its outer membrane protein Amuc_1100 can enhance this barrier, but the clinical application of Amuc_1100 is limited by the fastidious growth of its native host. This study aimed to overcome this by utilizing the robust probiotic Lacticaseibacillus paracasei L9 for targeted Amuc_1100 delivery. Methods: We engineered Lc. paracasei L9 to express Amuc_1100 via intracellular (pA-L9), secretory (pUA-L9), and surface-display (pUPA-L9) strategies. Their efficacy was assessed in Lipopolysaccharide (LPS)-induced macrophages and a dextran sulfate sodium (DSS)-induced colitis mouse model, evaluating inflammation, barrier integrity

SUBMITTER: Dong X 

PROVIDER: S-EPMC12787787 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature